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AU  - Allison DC
AU  - Bose KK
AU  - Hruban RH
AU  - Piantadosi S
AU  - Dooley WC
AU  - Boitnott JK
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Pancreatic cancer cell DNA content correlates with long-term
      survival after pancreatoduodenectomy.
SO  - Ann Surg 1991 Dec;214(6):648-56
AB  - The DNA content of 47 adenocarcinomas arising in the head of the
      pancreas from patients who had undergone successful
      pancreatoduodenectomy was measured. The DNA measurements of each
      tumor were made without knowledge of the clinical course by
      absorption cytometry performed on Feulgen-stained nuclei that had
      been disaggregated from pancreatic cancer tissue blocks. Forty-
       seven evaluable DNA distributions were obtained from specimens
taken
      between 1975 and 1988. Of the 47 tumors, 19 (40%) were diploid and
      28 (60%) were aneuploid cancers. The 19 patients with diploid
      cancers had a median survival time of 25 months. Median survival of
      the 28 patients with aneuploid cancers was 10.5 months. This
      difference was statistically significant (p = 0.003). A multivariate
      life table regression analysis demonstrated that the ploidy and
      proliferative index as determined by absorption cytometry were
      independent prognostic factors, as strong as or stronger than the
      number of positive nodes and tumor size. Thus cellular DNA content
      appears to be one of the most important predictors of survival in
      patients with adenocarcinoma of the head of the pancreas who have
      successfully undergone a pancreaticoduodenectomy.
 

With permission from Annals of Surgery, ©1991.

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Bluemke DA, Cameron JL, Hruban RH, Pitt HA, Siegelman SS, Soyer P,
Fishman EK.
Potentially resectable pancreatic adenocarcinoma: spiral CT assessment
with surgical and pathologic correlation.  Radiology 1995 Nov;197(2):381-5 
PURPOSE: To evaluate the accuracy of spiral computed tomography (CT)
      in assessing the resectability of small pancreatic ductal
      adenocarcinoma and to correlate the CT findings with histopathologic
      and surgical findings. MATERIALS AND METHODS: Spiral CT scans
      obtained in 64 patients who underwent surgery for potentially
      resectable pancreatic adenocarcinoma were prospectively assessed for
      tumor resectability. CT findings were correlated with surgically
      assessed extent of tumor and pathologic findings. RESULTS:
      Fifty-seven (89%) of 64 carcinomas were detected with spiral CT.
      Twenty-four carcinomas were resectable at surgery and 40 were not.
      The average size of resectable tumors was 3.1 cm (range, 1.0-7.5
      cm). The overall accuracy of spiral CT for assessing resectability
      was 70%. Of resected tumors, 14 were hypoattenuating compared with
      the remaining pancreas and 10 were isoattenuating. Eleven tumors
      showed neointimal proliferation in arterioles at histologic
      examination. CONCLUSION: Further progress in preoperative staging of
      pancreatic ductal adenocarcinoma with spiral CT should be directed
      toward improving detection of small pancreatic tumors and assessment
      of early metastatic disease.
 

With permission from the Radiological Society of North America, ©1995.

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AU  - Bose KK
AU  - Allison DC
AU  - Hruban RH
AU  - Piantadosi S
AU  - Zahurak M
AU  - Dooley WC
AU  - Lin P
AU  - Cameron JL
IN  - Department of Surgery, Medical College of Ohio, Toledo 43699-0008.
TI  - A comparison of flow cytometric and absorption cytometric DNA values
      as prognostic indicators for pancreatic carcinoma.
SO  - Cancer 1993 Feb 1;71(3):691-700
AB  - BACKGROUND. The DNA content of 30 adenocarcinomas of the head of the
      pancreas was measured by flow and absorption cytometric analysis.
      METHODS. Each of the patients in this study had curative
      pancreatoduodenectomy. The absorption cytometric measurements were
      done in a research laboratory, and the flow cytometric measurements
      were performed in a commercial laboratory. The DNA measurements were
      done on nuclei disaggregated from pancreatic cancer tissue blocks
      without the examiner knowing whether the patient had survived.
      RESULTS. Twenty-one of the 30 cancers were found to be aneuploid by
      absorption cytometric analysis, whereas only 1 of the 30 cancers was
      aneuploid by flow cytometric analysis. This difference was
      statistically significant (P < 0.001). CONCLUSIONS. Univariate and
      multivariate analyses showed that the absorption cytometric DNA
      measurements were stronger prognostic determinants for patient
      survival than were the flow cytometric DNA measurements, indicating
      that some caution may be warranted in the interpretation of
      commercially obtained DNA distributions of pancreatic carcinomas.

With permission from Cancer, ©1993.

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AU  - Caldas C
AU  - Hahn SA
AU  - da Costa LT
AU  - Redston MS
AU  - Schutte M
AU  - Seymour AB
AU  - Weinstein CL
AU  - Hruban RH
AU  - Yeo CJ
AU  - Kern SE
IN  - Department of Oncology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland 21205.
TI  - Frequent somatic mutations and homozygous deletions of the p16
      (MTS1) gene in pancreatic adenocarcinoma [published erratum appears
      in Nat Genet 1994 Dec;8(4):410].
SO  - Nat Genet 1994 Sep;8(1):27-32
AB  - The MTS1 gene on chromosome 9p21 encodes the p16 inhibitor of
      cyclinD/Cdk-4 complexes, and is deleted or mutated in a variety of
      tumour types. We found allelic deletions of 9p21-p22 in 85% of
      pancreatic adenocarcinomas. Analysis of MTS1 in pancreatic
      carcinomas (27 xenografts and 10 cell lines) showed homozygous
      deletions in 15 (41%) and sequence changes in 14 (38%). These
      included eight point mutations (four nonsense, two missense and two
      splice site mutations) and six deletions/insertions, all accompanied
      by loss of the wild-type allele. Sequencing of MTS1 from primary
      tumours confirmed the mutations. Coexistent inactivations of both
      MTS1 and p53 was common and suggests that abnormal regulation of
      cyclin-dependent kinases may play an important role in the biology
      of pancreatic carcinoma.

With permission from Nature Genetics, ©1994.

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AU  - Caldas C
AU  - Hahn SA
AU  - Hruban RH
AU  - Redston MS
AU  - Yeo CJ
AU  - Kern SE
IN  - Department of Oncology, Johns Hopkins University School of Medicine,
      Baltimore, Maryland 21205.
TI  - Detection of K-ras mutations in the stool of patients with
      pancreatic adenocarcinoma and pancreatic ductal hyperplasia.
SO  - Cancer Res 1994 Jul 1;54(13):3568-73
AB  - Pancreatic adenocarcinoma is the fifth leading cause of cancer death
      in the United States. Mutations in the K-ras oncogene occur in 85%
      of pancreatic adenocarcinomas and have also been identified in 75%
      of pancreatic ducts with mucinous cell hyperplasia seen in
      association with chronic pancreatitis. We identified K-ras mutations
      in 65% of duct lesions associated not only with chronic pancreatitis
      but also with pancreatic adenocarcinoma and distal common bile duct
      carcinoma (cholangiocarcinoma). These observations make K-ras a
      potential candidate for a gene-based diagnostic test. Indeed, K-ras
      mutations have been demonstrated in the pancreatic secretions of
      patients with pancreatic carcinoma and pancreatic intraductal
      neoplasia. We analyzed stool specimens for mutated K-ras sequences
      using a plaque hybridization assay in patients with pancreatic
      adenocarcinoma, cholangiocarcinoma, and chronic pancreatitis. K-ras
      mutations were detected in stool specimens from 6 of 11 patients
      with pancreatic adenocarcinoma, from 2 of 3 patients with
      cholangiocarcinoma, and from 1 of 3 patients with chronic
      pancreatitis. The K-ras mutations found in stool specimens from
      patients with pancreatic carcinoma were identical to those in the
      primary cancer in five cases. Mutations found in the stool specimens
      from one patient with pancreatic cancer, one patient with chronic
      pancreatitis, and two patients with cholangiocarcinoma were the same
      as those identified in pancreatic ductal mucinous cell hyperplasia
      lesions present in the resected pancreas specimens. Our data suggest
      that the K-ras mutations originating from cells of pancreatic
      adenocarcinomas and from cells shed by abnormal pancreatic duct
      epithelium can be detected in the stool. These results support the
      further exploration of stool K-ras analysis as a potential screening
      assay for the early detection of pancreatic adenocarcinoma and
      precursor lesions such as pancreatic ductal mucinous cell
      hyperplasia.

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AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore.
TI  - Carcinoma of the pancreas: are we making progress?.
SO  - Md Med J 1990 Apr;39(4):361-3
AB  - Over the past several decades no disease has frustrated clinicians
      more than carcinoma of the pancreas. At the time of diagnosis most
      patients have been unresectable. Recent reports suggest that when
      resection is possible, pancreaticoduodenectomy can be performed
      safely and survival extended by adjuvant therapy.
 

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AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins University School of Medicine,
      Baltimore, Maryland 21205, USA.
TI  - The current management of carcinoma of the head of the pancreas.
      [Review]
SO  - Annu Rev Med 1995;46:361-70
AB  - Carcinoma of the head of the pancreas can be diagnosed and staged
      effectively by computed tomography (CT) scan and by visceral
      angiography. If the tumor appears to be resectable, no further
      studies such as percutaneous biopsy are required.
      Pancreaticoduodenectomy is the only potentially curable treatment.
      This operation can be performed with a hospital mortality rate of
      approximately 2%. If the resection is curative, five-year survival
      in excess of 20% can be anticipated. Utilizing multivariate
      analysis, negative lymph node status, the absence of microscopic
      evidence of blood vessel involvement, and two or fewer blood
      transfusions during surgery are all independent predictors of
      long-term survival. Adjuvant therapy is effective and should be used
      routinely. [References: 7]

With permission from the Annual Review of Medicine, Volume 46, ©1995, by Annual Reviews, Inc.

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AU  - Cameron JL
AU  - Crist DW
AU  - Sitzmann JV
AU  - Hruban RH
AU  - Boitnott JK
AU  - Seidler AJ
AU  - Coleman J
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland 21205.
TI  - Factors influencing survival after pancreaticoduodenectomy for
      pancreatic cancer.
SO  - Am J Surg 1991 Jan;161(1):120-4; discussion 124-5
AB  - Eighty-nine patients with carcinoma of the head of the pancreas
      underwent pancreaticoduodenectomies. The actuarial 5-year survival
      for all 89 patients was 19%, with a median survival of 11.9 months.
      The 81 hospital survivors were analyzed in an effort to determine
      factors influencing long-term survival. Negative lymph nodes and the
      absence of blood vessel invasion both favored long-term survival.
      The strongest predictive factor was negative lymph node status with
      a median survival of 55.8 months, compared with 11 months with lymph
      nodes involved with tumor (p less than 0.05). Blood transfusions
      were also predictive, with patients receiving two or fewer units
      having a median survival of 24.7 months, compared with 10.2 months
      for those receiving three or more units (p less than 0.05). The most
      important determinant of long-term survival after
      pancreaticoduodenectomy for pancreatic cancer is biology of the
      tumor (lymph node status, blood vessel invasion). However,
      performance of the resection (units of blood transfused) also
      appears to be an important factor influencing survival.
 

With permission from the American Journal of Surgery, ©1991.

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AU  - Cameron JL
AU  - Pitt HA
AU  - Yeo CJ
AU  - Lillemoe KD
AU  - Kaufman HS
AU  - Coleman J
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - One hundred and forty-five consecutive pancreaticoduodenectomies
      without mortality.
SO  - Ann Surg 1993 May;217(5):430-5; discussion 435-8
AB  - OBJECTIVE: A review of mortality and morbidity for
      pancreaticoduodenectomy was performed for 145 consecutive patients
      who underwent the operative procedure between 1988 and 1991. SUMMARY
      BACKGROUND DATA: In the past, pancreaticoduodenectomy has carried a
      high hospital morbidity and mortality. During the 1970s, many
      considered that the operation should be abandoned. Recent data,
      however, suggest that a marked drop in both morbidity and mortality
      have occurred for this operative procedure. METHODS: Among the 145
      consecutive patients who underwent pancreaticoduodenectomy, 108
      patients were 69 years of age or younger, and 37 were 70 years of
      age or older. Four patients were 80 years of age or older. One
      hundred and seven patients had a malignant neoplasm, whereas 38
      patients had benign disease. There were no significant differences
      in preoperative risk factors when the younger and older, and benign
      disease and malignant disease groups were compared. RESULTS: Mean
      operative time was 7.3 hours. Median blood loss was 0, indicating
      that more than one-half of the patients underwent
      pancreaticoduodenectomies without blood transfusions. There were no
      significant differences in postoperative complications when the
      younger and older, and benign disease and malignant disease groups
      were compared. There was no hospital or 30-day mortality.
      CONCLUSIONS: With appropriate preoperative selection, virtually any
      patient in any age group, with benign or malignant disease, can
      undergo pancreaticoduodenectomy with minimal risk of hospital
      mortality.
 

With permission from Annals of Surgery, ©1993.

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AU  - Chakravarthy A
AU  - Abrams RA
IN  - Johns Hopkins Oncology Center, Division of Radiation Oncology,
      Baltimore, MD 21287-8922.
TI  - Radiation therapy in the management of patients with malignant
      carcinoid tumors.
SO  - Cancer 1995 Mar 15;75(6):1386-90
AB  - BACKGROUND. The purpose of this study was to analyze the
      effectiveness of radiotherapy for symptomatic, metastatic, and/or
      unresectable carcinoid tumors. METHODS. From 1975 to 1991, 18
      patients with histologically proven carcinoid tumors, including 7
      with symptomatic hepatic involvement, received radiotherapy to a
      total of 31 anatomic sites of metastatic or unresectable carcinoid
      tumors. Symptomatic response to treatment, date of symptomatic or
      radiographic progression, and survival after diagnosis and
      completion of radiotherapy were determined. Clinical improvement was
      defined as symptomatic relief and/or objective reduction in size of
      tumor mass sustained for at least 4 weeks. RESULTS. After
      radiotherapy of 31 sites in 18 patients, 3 patients died in less
      than 3 months. Of the remaining 15 patients, survival from initial
      radiotherapy ranged from 8 to 108 months (median, 23 months), and 8
      (53%) died without symptomatic progression in the treated region.
      Clinical improvement occurred in 27/31 sites (87%). Acute side
      effects were mild, and no late side effects were recorded. Median
      survivals from diagnosis were: 39 months for patients with primary
      tumors of the lung, 33 months for patients with brain metastases,
      and 32 months for patients with hepatic involvement. Patients with
      the carcinoid syndrome responded in 19/22 sites (86%) compared with
      8/9 sites (89%) for patients without the syndrome (P = not
      significant). CONCLUSIONS. Radiation therapy can achieve symptomatic
      palliation for patients with metastatic/unresectable malignant
      carcinoid tumors, and it is well tolerated. Clinical improvement
      occurs after irradiation in patients with or without the carcinoid
      syndrome.
 

With permission from Cancer, ©1995.

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AU  - Crist DW
AU  - Sitzmann JV
AU  - Cameron JL
TI  - Improved hospital morbidity, mortality, and survival after the
      Whipple procedure.
SO  - Ann Surg 1987 Sep;206(3):358-65
AB  - Between 1969 and 1986, 88 patients had a Whipple resection for
      adenocarcinoma of the pancreas (N = 50), ampulla (N = 19), distal
      bile duct (N = 10), and duodenum (N = 9). Forty-nine patients were
      men, 39 were women, and the mean age was 58 years (range: 34-84
      years). The patients were divided into two groups on the basis of
      two different time periods: those operated on from 1969 to 1980 (N =
      41) and those operated on from 1981 to 1986 (N = 47). There were no
      significant differences between the two groups in terms of mean age,
      sex distribution, duration of symptoms before presentation, or mean
      weight loss. Likewise, preoperative laboratory data were similar for
      both groups of patients. In addition, mean tumor size for patients
      with pancreatic cancer (3.5 cm vs. 3.2 cm) and patients with
      nonpancreatic periampullary cancer (1.9 cm vs. 2.2 cm) was similar
      in both groups, as was the incidence of positive lymph nodes. Among
      the 41 patients operated on during the first period, hospital
      morbidity and mortality rates were 59% and 24%, respectively. In
      contrast, hospital morbidity and mortality rates were 36% and 2%,
      respectively, among the 47 patients operated on during the recent
      period. During the recent period, more Whipple procedures were
      performed each year (7.8 vs. 3.4) and by fewer surgeons (3.4
      operations/surgeon vs. 1.9 operations/surgeon). In addition, between
      1981 and 1986, there were fewer total pancreatectomies (9% vs. 39%),
      fewer vagotomies (26% vs. 76%), and more pyloric-preserving
      procedures (30% vs. 0) performed compared with the earlier period.
      During the recent period, mean operative time (7.8 vs. 9.0 hours),
      mean estimated blood loss (1694 vs. 3271 mL), and mean
      intraoperative blood replacement (3.6 vs. 6.3 units) were all
      significantly less than in the earlier period. These findings
      suggest that the recent decline in operative morbidity and mortality
      may be due to fewer surgeons performing more Whipple resections in
      less time and with less blood loss. The actuarial 5-year survival
      rate for the 38 patients with nonpancreatic periampullary cancer was
      34%. Surprisingly, the actuarial 5-year survival rate among the 50
      patients with pancreatic cancer was 18%. Moreover, in the absence of
      positive lymph node involvement, the 5-year actuarial survival rate
      among patients with pancreatic cancer was 48%. No explanation is
      obvious for the improvement in survival among patients with
      pancreatic cancer.
 

With permission from Annals of Surgery, ©1987.

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AU  - Danner DB
AU  - Hruban RH
AU  - Pitt HA
AU  - Hayashi R
AU  - Griffin CA
AU  - Perlman EJ
IN  - Department of Pathology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Primitive neuroectodermal tumor arising in the pancreas.
SO  - Mod Pathol 1994 Feb;7(2):200-4
AB  - Peripheral primitive neuroectodermal tumors (PNETs) are extra
      cranial primitive small round blue cell tumors showing histologic,
      immunohistochemical or electron microscopic evidence of
      neuroectodermal differentiation. They are most commonly encountered
      in the soft tissue or bone in children and young adults. We report
      an unusual case of a PNET arising in the pancreas. A 17-yr-old male
      presented with a pancreatic mass and underwent a
      pancreatoduodenectomy. Histologically, the neoplasm was composed of
      sheets of small round cells that stained for cytokeratin, neuron
      specific enolase, and 12E7 but not muscle specific action, desmin,
      common leukocyte antigen, chromogranin, synaptophysin, or other
      islet cell markers. The diagnosis of PNET in this unusual location
      was confirmed by cytogenetic analysis which showed the chromosomal
      translocation characteristics of PNETs, t(11;12)(q24;q12). This case
      highlights the difficulty in the diagnosis of PNET when it is
      present in visceral organs where other neuroendocrine neoplasms and
      adenocarcinomas are more common.
 

With permission from Modern Pathology, Volume 7, ©1994.

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AU  - DiGiuseppe JA
AU  - Hruban RH
AU  - Goodman SN
AU  - Polak M
AU  - van den Berg FM
AU  - Allison DC
AU  - Cameron JL
AU  - Offerhaus GJ
IN  - Department of Pathology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Overexpression of p53 protein in adenocarcinoma of the pancreas. SO
- Am J Clin Pathol 1994 Jun;101(6):684-8
AB  - Mutations in the p53 tumor suppressor gene are frequently identified
      in human neoplasms. These mutations may be associated with
      stabilization and, therefore, with overexpression of the p53 protein
      product as determined by immunohistochemical staining. Using a new
      antigen retrieval method and a polyclonal antibody to p53 (CM-1),
      the authors examined 48 formalin-fixed paraffin-embedded
      adenocarcinomas of the pancreas for overexpression of the p53 gene
      product. These 48 carcinomas were obtained from a series of patients
      with well-documented clinical histories and extensive follow-up. The
      carcinomas had been analyzed previously for K-ras gene mutations,
      tumor ploidy, and tumor proliferating index. Specific diffuse
      nuclear staining for the p53 protein was identified in 19 of the 48
      (40%) infiltrating carcinomas examined. Focal or negative staining
      was seen in the remaining 29 cases (60%). In addition, 17 of the
      neoplasms contained synchronous in situ carcinomas; two (12%) of
      these displayed diffuse nuclear staining for the p53 protein.
      Overexpression of p53 was associated with aneuploidy (P = .05),
      which had been a poor prognosticator in this series of
      adenocarcinomas of the pancreas. Although overexpression of p53
      appeared to be associated with poor prognosis (hazard ratio, 1.8; P
      = .07), this was not statistically significant. Overexpression of
      p53 was not significantly associated with K-ras oncogene mutations
      or tumor proliferating index. The authors conclude that
      overexpression of the p53 protein occurs frequently in invasive
      adenocarcinomas of the pancreas and in some in situ carcinomas, as
      well.
 

Used with permission of Lippincott-Raven Publishers, 227 E. Washington Square, Philadelphia, PA 19106-3780. DiGiuseppe JA et al. American Journal of Clinical Pathology, vol. 101:684-688, ©1994.

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AU  - DiGiuseppe JA
AU  - Hruban RH
AU  - Offerhaus GJ
AU  - Clement MJ
AU  - van den Berg FM
AU  - Cameron JL
AU  - van Mansfeld AD
IN  - Department of Pathology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Detection of K-ras mutations in mucinous pancreatic duct hyperplasia
      from a patient with a family history of pancreatic carcinoma [see
      comments].
SO  - Am J Pathol 1994 May;144(5):889-95
AB  - Mutations in the K-ras oncogene and in the p53 tumor suppressor gene
      are commonly identified in sporadic cases of pancreatic
      adenocarcinoma. Although these genes might serve as useful markers
      for early diagnosis of pancreatic carcinoma in patients at risk for
      the development of this disease, familial pancreatic carcinomas have
      not been studied for these mutations. We recently had the
      opportunity to examine a pancreas prophylactically removed from a
      patient with a strong family history of pancreatic carcinoma. This
      gave us the unique opportunity to study the early events in the
      development of familial adenocarcinoma of the pancreas.
      Histopathological examination of the pancreas revealed multifocal
      papillary and nonpapillary mucinous duct hyperplasia. Seven of these
      foci were microdissected and analyzed for K-ras and p53 mutations.
      The K-ras mutations were detected by combined mutant-enriched
      polymerase chain reaction-restriction fragment length polymorphism
      analysis and characterized further by allele-specific
      oligonucleotide hybridization. Five of the seven duct lesions
      harbored activating point mutations in codon 12 of K-ras; a G to A
      transition was found in four and a G to C transversion in one. In
      contrast, these lesions did not harbor detectable p53 mutations as
      determined by denaturing gradient gel electrophoresis of exons 5 to
      8, nor was there overexpression of the p53 protein as determined by
      immunohistochemistry. These findings suggest that mutations in K-ras
      represent an early event in the pathogenesis of pancreatic
      carcinoma. In addition, monitoring of patients with a strong family
      history of pancreatic carcinoma for K-ras mutations may identify
      patients at risk for the development of invasive carcinoma.
 

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AU  - Dooley WC
AU  - Cameron JL
AU  - Pitt HA
AU  - Lillemoe KD
AU  - Yue NC
AU  - Venbrux AC
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Is preoperative angiography useful in patients with periampullary
      tumors? [see comments].
SO  - Ann Surg 1990 Jun;211(6):649-54; discussion 654-5
AB  - Ninety patients with periampullary tumors, staged by CT scan and
      believed to be resectable, were staged further by visceral
      angiography. Most of these patients (78) had carcinoma of the head
      of the pancreas. Visceral angiography was normal in 62 patients.
      Major vessel encasement (17 patients) or occlusion (11 patients) was
      identified in 28 patients. There were no complications related to
      angiography. Among the 62 patients with normal angiograms, 48
      underwent a pancreaticoduodenectomy, for a resectability rate of
      77%. Among the 17 patients with vessel encasement, the resectability
      rate was 35%. For the 11 patients with vessel occlusion, the
      resectability rate was 0%. Combined with CT scan, visceral
      angiography is a useful adjunct in the staging of patients with
      periampullary tumors. Major vessel occlusion precludes resection,
      and major vessel encasement makes resection unlikely. If visceral
      angiography is normal, it is very likely that the tumor will be
      resectable.
 

With permission from Annals of Surgery, ©1990.

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AU  - Dranoff G
AU  - Jaffee E
AU  - Lazenby A
AU  - Golumbek P
AU  - Levitsky H
AU  - Brose K
AU  - Jackson V
AU  - Hamada H
AU  - Pardoll D
AU  - Mulligan RC
IN  - Whitehead Institute for Biomedical Research, Massachusetts Institute
      of Technology, Cambridge 02142.
TI  - Vaccination with irradiated tumor cells engineered to secrete murine
      granulocyte-macrophage colony-stimulating factor stimulates potent,
      specific, and long-lasting anti-tumor immunity.
SO  - Proc Natl Acad Sci U S A 1993 Apr 15;90(8):3539-43
AB  - To compare the ability of different cytokines and other molecules to
      enhance the immunogenicity of tumor cells, we generated 10
      retroviruses encoding potential immunomodulators and studied the
      vaccination properties of murine tumor cells transduced by the
      viruses. Using a B16 melanoma model, in which irradiated tumor cells
      alone do not stimulate significant anti-tumor immunity, we found
      that irradiated tumor cells expressing murine granulocyte-macrophage
      colony-stimulating factor (GM-CSF) stimulated potent, long-lasting,
      and specific anti-tumor immunity, requiring both CD4+ and CD8+
      cells. Irradiated cells expressing interleukins 4 and 6 also
      stimulated detectable, but weaker, activity. In contrast to the B16
      system, we found that in a number of other tumor models, the levels
      of anti-tumor immunity reported previously in cytokine gene transfer
      studies involving live, transduced cells could be achieved through
      the use of irradiated cells alone. Nevertheless, manipulation of the
      vaccine or challenge doses made it possible to demonstrate the
      activity of murine GM-CSF in those systems as well. Overall, our
      results have important implications for the clinical use of
      genetically modified tumor cells as therapeutic cancer vaccines.
 

With permission from The Proceedings of the National Academy of Sciences USA, ©1993.

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AU  - Gordon TA
AU  - Burleyson GP
AU  - Tielsch JM
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - The effects of regionalization on cost and outcome for one general
      high-risk surgical procedure.
SO  - Ann Surg 1995 Jan;221(1):43-9
AB  - PURPOSE: The effects of regionalization of tertiary care were
      studied by analyzing cost and outcome for pancreaticoduodenectomies
      in a state in which the majority of these high-risk procedures were
      performed in one hospital. METHODS: Using Maryland inpatient
      discharge data via a retrospective study, the authors compared cost
      and outcome data for a hospital with more than one half of the cases
      in the state to all other hospital providers as a group and with
      smaller groupings according to the volume of procedures performed.
      RESULTS: Hospital mortality, length of stay, and costs were
      significantly less at the high-volume regional medical center when
      compared with all other hospitals. Mortality and cost increased as
      volume decreased when hospitals were grouped according to volume.
      CONCLUSIONS: An academic medical center, functioning as a
      high-volume regional provider, can deliver tertiary care services
      with improved outcomes at lower costs than community hospitals.
 

With permission from Annals of Surgery, ©1995.

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AU  - Griffin CA
AU  - Hruban RH
AU  - Long PP
AU  - Morsberger LA
AU  - Douna-Issa F
AU  - Yeo CJ
IN  - Oncology Center, Johns Hopkins University School of Medicine,
      Baltimore, Maryland 21287-8934.
TI  - Chromosome abnormalities in pancreatic adenocarcinoma.
SO  - Genes Chromosom Cancer 1994 Feb;9(2):93-100
AB  - Adenocarcinoma of the pancreas is the fifth most common cause of
      cancer deaths in the United States, yet few cytogenetic studies of
      this tumor have been reported. We analyzed 26 primary tumors to
      identify which chromosome abnormalities occur most frequently in
      this neoplasm. One carcinoma was well differentiated and mucin
      producing, 18 were moderately well differentiated, and seven were
      poorly differentiated. Only normal karyotypes were obtained from
      nine carcinomas. The remaining 17 carcinomas frequently had normal
      metaphase cells in addition to simple to highly complex karyotypes.
      The modal chromosome number in 20 carcinomas was diploid or
      near-diploid; four carcinomas had both a major near-diploid and
      near-triploid or near-tetraploid component, and two were
      near-tetraploid. Numerical abnormalities included loss of whole
      copies of chromosomes 6, 17, and 18, and gains of chromosome 20.
      Structural abnormalities were frequent, with 1p, 2p, 3p, 4q, 6q, 7q,
      11q, and 17p recurrently involved. Results of this study were
      combined with karyotypes of 19 other primary adenocarcinomas of the
      pancreas reported in the literature. The combined data involving 117
      breakpoints suggest that careful analysis of chromosome 20, proximal
      1q, 6q, proximal 8p, and proximal 17p could be productive in
      defining genes involved in adenocarcinoma of the pancreas.
 

Reproducted with permission of John Wiley & Sons, Inc.. © 1994 Wiley-Liiss, Inc.

<--- go back to bibliography
AU  - Griffin CA
AU  - Hruban RH
AU  - Morsberger LA
AU  - Ellingham T
AU  - Long PP
AU  - Jaffee EM
AU  - Hauda KM
AU  - Bohlander SK
AU  - Yeo CJ
IN  - Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA. TI
 - Consistent chromosome abnormalities in adenocarcinoma of the
      pancreas.
SO  - Cancer Res 1995 Jun 1;55(11):2394-9
AB  - Little is known about the somatic genetic changes which characterize
      pancreatic adenocarcinoma. The identification of acquired genomic
      alterations would further our understanding of the biology of this
      neoplasm. We have studied 62 primary pancreatic adenocarcinomas
      obtained from surgical resections using classical cytogenetics and
      fluorescent in situ hybridization methods. Clonally abnormal
      karyotypes were observed in 44 neoplasms. Karyotypes were generally
      complex (greater than three abnormalities) and included both
      numerical and structural chromosome abnormalities. Many tumors
      contained at least one marker chromosome. The most frequent whole
      chromosomal gains were chromosomes 20 (eight tumors) and 7 (seven
      tumors). Losses were much more frequent: chromosome 18 was lost in
      22 tumors followed in frequency by chromosomes 13 (16 tumors), 12
      (13 tumors), 17 (13 tumors), and 6 (12 tumors). Structural
      abnormalities were frequent. Two hundred nine chromosome breakpoints
      were identified. Excluding Robertsonian translocations, the
      chromosomal arms most frequently involved were 1p (12); 6q (11); 7q
      and 17p (9 each); and 1q, 3p, 11p, and 19q (8 each). Portions of the
      long arm of chromosome 6 appeared to be lost in nine tumors. To
      determine whether the apparent losses of portions of 6q are real,
      four tumors with 6q deletions were hybridized with a biotin-labeled
      microdissection probe from 6q24-ter. Loss of one copy of this region
      was verified in three of four tumors. In addition, double minute
      chromosomes were identified in eight cases. To our knowledge, these
      represent the first primary specimens of pancreatic adenocarcinoma
      with cytogenetic evidence of gene amplification.
 

<--- go back to bibliography
AU  - Hahn SA
AU  - Kern SE
IN  - Department of Pathology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland, USA.
TI  - Molecular genetics of exocrine pancreatic neoplasms. [Review] SO  -
Surg Clin North Am 1995 Oct;75(5):857-69
AB  - Molecular genetic studies of pancreatic ductal adenocarcinoma have
      revealed the common co-existence of K-ras, p53, and MTS1 mutations.
      The finding of K-ras mutations in epithelial lesions of ducts
      suggests them as a precursor intraepithelial neoplasm. The clinical
      importance of this line of work can only be anticipated at present,
      and a fuller understanding of genetic alterations in these neoplasms
      is necessary. [References: 62]
 

With permission from Surgical Clinics of North America, ©1995.

<--- go back to bibliography
AU  - Hruban RH
AU  - van Mansfeld AD
AU  - Offerhaus GJ
AU  - van Weering DH
AU  - Allison DC
AU  - Goodman SN
AU  - Kensler TW
AU  - Bose KK
AU  - Cameron JL
AU  - Bos JL
IN  - Department of Pathology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - K-ras oncogene activation in adenocarcinoma of the human pancreas. A
      study of 82 carcinomas using a combination of mutant-enriched
      polymerase chain reaction analysis and allele-specific
      oligonucleotide hybridization. [Review]
SO  - Am J Pathol 1993 Aug;143(2):545-54
AB  - We examined 82 surgically resected or biopsied, formalin-fixed,
      paraffin-embedded primary adenocarcinomas of the pancreas for the
      presence of activating point mutations in codon 12 of the K-ras
      oncogene. Mutations were detected using primer-mediated,
      mutant-enriched, polymerase chain reaction-restriction fragment
      length polymorphism analysis and characterized further by
      allele-specific oligonucleotide hybridization. This combination of
      mutant-enriched polymerase chain reaction-restriction fragment
      length polymorphism analysis and allele-specific oligonucleotide
      hybridization results in a rapid and sensitive characterization of
      the mutations in codon 12 of K-ras. Sixty-eight (83%) of the 82
      carcinomas examined harbored a point mutation. Of the 68 mutations,
      33 (49%) were guanine to adenine transitions, 27 (39%) were guanine
      to thymine transversions, and eight (12%) were guanine to cytosine
      transversions. Mutations were found in carcinomas of the head (61 of
      75, 81%) as well as in carcinomas of the body or tail (seven of
      seven, 100%) of the pancreas. The overall prevalence of K-ras point
      mutations in adenocarcinomas of the pancreas obtained from patients
      who smoked cigarettes at some point during their lives (88%; 86% in
      current smokers and 89% in ex-smokers) was greater than that seen in
      pancreatic adenocarcinomas from patients who never smoked cigarettes
      (68%, P = 0.046). The presence of K-ras point mutations did not
      correlate with tumor ploidy, tumor proliferating index, or patient
      survival. These results demonstrate that primer-mediated,
      mutant-enriched polymerase chain reaction-restriction fragment
      length polymorphism analysis combined with allele-specific
      oligonucleotide hybridization can be used to detect and characterize
      mutations in codon 12 of the K-ras oncogene in formalin-fixed,
      paraffin-embedded tissues, and the results confirm that activating
      point mutations in codon 12 of the K-ras oncogene occur frequently
      in adenocarcinomas of the pancreas. [References: 45]
 

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AU  - Huang AY
AU  - Golumbek P
AU  - Ahmadzadeh M
AU  - Jaffee E
AU  - Pardoll D
AU  - Levitsky H
IN  - Department of Oncology, Johns Hopkins University School of Medicine,
      Baltimore, MD 21205.
TI  - Role of bone marrow-derived cells in presenting MHC class
      I-restricted tumor antigens.
SO  - Science 1994 May 13;264(5161):961-5
AB  - Many tumors express tumor-specific antigens capable of being
      presented to CD8+ T cells by major histocompatibility complex (MHC)
      class I molecules. Antigen presentation models predict that the
      tumor cell itself should present these antigens to T cells. However,
      when conditions for the priming of tumor-specific responses were
      examined in mice, no detectable presentation of MHC class
      I-restricted tumor antigens by the tumor itself was found. Rather,
      tumor antigens were exclusively presented by host bone
      marrow-derived cells. Thus, MHC class I-restricted antigens are
      efficiently transferred in vivo to bone marrow-derived
      antigen-presenting cells, which suggests that human leukocyte
      antigen matching may be less critical in the application of tumor
      vaccines than previously thought.
 

Abstracted with permission from Huang A, Golumbek P, Amazadeh M, Jaffee EM, Pardoll DM, Levitsky H. The role of bone marrow derived cells in presenting MHC class I rstricted tumor antigens. Science 64:961-965, 1994. Copyright 1994, American Association for the Advancement of Science.

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AU  - Jaffee EM
AU  - Dranoff G
AU  - Cohen LK
AU  - Hauda KM
AU  - Clift S
AU  - Marshall FF
AU  - Mulligan RC
AU  - Pardoll DM
IN  - Departments of Oncology, School of Medicine, Johns Hopkins
      University, Baltimore, Maryland 21205.
TI  - High efficiency gene transfer into primary human tumor explants
      without cell selection.
SO  - Cancer Res 1993 May 15;53(10 Suppl):2221-6
AB  - Preclinical studies with murine tumor models have demonstrated that
      autologous tumor cell vaccines engineered to secrete certain
      cytokines in a paracrine fashion elicit systemic immune responses
      capable of eliminating small amounts of established tumor. These
      results have engendered much interest in developing this strategy
      for gene therapy of human cancer. The major limitation to creating
      genetically modified autologous human tumor vaccines is efficient
      gene transfer into primary tumor explants, since the majority of
      human tumors fail to proliferate in long-term culture. Using the
      retroviral vector MFG in conjunction with short-term culture
      techniques, we have achieved, in the absence of selection, a mean
      transduction efficiency of 60% in primary renal, ovarian, and
      pancreatic tumor explants, and we have developed an autologous
      granulocyte-macrophage colony-stimulating factor secreting tumor
      vaccine for clinical trials.
 

<--- go back to bibliography
AU  - Kern SE
AU  - Kinzler KW
AU  - Bruskin A
AU  - Jarosz D
AU  - Friedman P
AU  - Prives C
AU  - Vogelstein B
IN  - Department of Pathology, Johns Hopkins University School of
      Medicine, Baltimore, MD 21231.
TI  - Identification of p53 as a sequence-specific DNA-binding protein. SO
 - Science 1991 Jun 21;252(5013):1708-11
AB  - The tumor-suppressor gene p53 is altered by missense mutation in
      numerous human malignancies. However, the biochemical properties of
      p53 and the effect of mutation on these properties are unclear. A
      human DNA sequence was identified that binds specifically to
      wild-type human p53 protein in vitro. As few as 33 base pairs were
      sufficient to confer specific binding. Certain guanines within this
      33-base pair region were critical, as methylation of these guanines
      or their substitution with thymine-abrogated binding. Human p53
      proteins containing either of two missense mutations commonly found
      in human tumors were unable to bind significantly to this sequence.
      These data suggest that a function of p53 may be mediated by its
      ability to bind to specific DNA sequences in the human genome, and
      that this activity is altered by mutations that occur in human
      tumors.
 

Abstracted with permission from Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C, Vogelstein B. Identification of p53 as a sequence-specific DNA-binding protein. Science 252:1708-1711, 1991. Copyright 1991, American Association for the Advancement of Science.

<--- go back to bibliography
AU  - Kern SE
AU  - Pietenpol JA
AU  - Thiagalingam S
AU  - Seymour A
AU  - Kinzler KW
AU  - Vogelstein B
IN  - Department of Pathology, Johns Hopkins University School of
      Medicine, Baltimore, MD 21231.
TI  - Oncogenic forms of p53 inhibit p53-regulated gene expression. SO  -
Science 1992 May 8;256(5058):827-30
AB  - Mutant forms of the gene encoding the tumor suppressor p53 are found
      in numerous human malignancies, but the physiologic function of p53
      and the effects of mutations on this function are unknown. The p53
      protein binds DNA in a sequence-specific manner and thus may
      regulate gene transcription. Cotransfection experiments showed that
      wild-type p53 activated the expression of genes adjacent to a p53
      DNA binding site. The level of activation correlated with DNA
      binding in vitro. Oncogenic forms of p53 lost this activity.
      Moreover, all mutants inhibited the activity of coexpressed
      wild-type p53, providing a basis for the selection of such mutants
      during tumorigenesis.
 

Abstracted with permission from Kern SE, Pietenpol JA, Thiagalingam S, Seymour A, Kinzler KW, Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science 256:827-830, 1992. Copyright 1992, American Association for the Advancement of Science.

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AU  - Lillemoe KD
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Current management of pancreatic carcinoma. [Review]
SO  - Ann Surg 1995 Feb;221(2):133-48
AB  - OBJECTIVE: The author seeks to provide an update on the current
      management of pancreatic carcinoma, including diagnosis and staging,
      surgical resection and adjuvant therapy for curative intent, and
      palliation. SUMMARY BACKGROUND DATA: During the 1960s and 1970s, the
      operative mortality and long-term survival after
      pancreaticoduodenectomy for pancreatic carcinoma was so poor that
      some authors advocated abandoning the procedure. Several recent
      series have reported a marked improvement in perioperative results
      with 5-year survival in excess of 20%. Significant advances also
      have been made in areas of preoperative evaluation and palliation
      for advanced disease. CONCLUSION: Although carcinoma of the pancreas
      remains a disease with a poor prognosis, advances in the last decade
      have led to improvements in the overall management of this disease.
      Resection for curative intent currently should be accomplished with
      minimal perioperative mortality. Surgical palliation also may
      provide the optimal management of selected patients. [References:
      129]
 

With permission from Annals of Surgery, ©1995.

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AU  - Lillemoe KD
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Pancreatic disease in the elderly patient. [Review]
SO  - Surg Clin North Am 1994 Apr;74(2):317-44
AB  - Pancreatic disease represents a significant health-care problem in
      elderly patients. Although the entire spectrum of benign and
      malignant disease of the pancreas can occur in elderly patients,
      acute gallstone pancreatitis and pancreatic carcinoma are by far the
      most common pancreatic disorders seen in this age group. Although
      the management of both of these conditions is no different in
      elderly patients, aggressive evaluation and therapy are essential
      for optimal results. Specifically, the evidence supports an
      aggressive attitude towards surgical intervention for patients with
      pancreatic cancer. [References: 69]
 

With permission from Surgical Clinics of North America, ©1994.

<--- go back to bibliography
AU  - Lillemoe KD
AU  - Cameron JL
AU  - Kaufman HS
AU  - Yeo CJ
AU  - Pitt HA
AU  - Sauter PK
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Chemical splanchnicectomy in patients with unresectable pancreatic
      cancer. A prospective randomized trial.
SO  - Ann Surg 1993 May;217(5):447-55; discussion 456-7
AB  - OBJECTIVE: A prospective, randomized, double-blind study was
      completed comparing intraoperative chemical splanchnicectomy with
      50% alcohol versus a placebo injection of saline in patients with
      histologically proven unresectable pancreatic cancer. METHODS:
      Standardized assessment of pain, mood, and disability due to pain
      was completed preoperatively and at 2-month intervals until death.
      Chemical splanchnicectomy with alcohol was performed in 65 patients,
      whereas 72 patients received the placebo. The two groups were
      similar with respect to age, sex, location, and stage of tumor,
      operation performed, the use of postoperative chemo- and radiation
      therapy, and initial assessment scores for pain, mood, and
      disability. RESULTS: No differences in hospital mortality or
      complications, return to oral intake, or length of hospital stay
      were observed. Mean pain scores were significantly lower in the
      alcohol group at 2-, 4-, and 6-month follow-up and at the final
      assessment (p < 0.05). To further determine the effect of chemical
      splanchnicectomy, patients were stratified into those with and
      without preoperative pain. In patients without preoperative pain,
      alcohol significantly reduced pain scores and delayed or prevented
      the subsequent onset of pain (p < 0.05). In patients with
      significant preoperative pain, alcohol significantly reduced
      existing pain (p < 0.05). Furthermore, patients with preexisting
      pain who received alcohol showed a significant improvement in
      survival when compared with controls (p < 0.0001). CONCLUSION: The
      results suggest that intraoperative chemical splanchnicectomy with
      alcohol significantly reduces or prevents pain in patients with
      unresectable pancreatic cancer.
 

With permission from Annals of Surgery, ©1993.

<--- go back to bibliography
AU  - Lillemoe KD
AU  - Pitt HA
AU  - Kaufman SL
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Acute cholecystitis occurring as a complication of percutaneous
      transhepatic drainage.
SO  - Surg Gynecol Obstet 1989 Apr;168(4):348-52
AB  - Sepsis is a common occurrence during long term transhepatic biliary
      drainage. Most of these episodes are attributed to cholangitis, are
      relatively minor and can be managed nonoperatively. During a 42
      month period, nine patients who had sepsis develop after biliary
      drainage were found to have acute cholecystitis, a complication not
      previously noted after this procedure. Seven of the nine patients
      had an underlying malignant lesion, and three of these patients had
      undergone percutaneous biliary drainage for palliation of
      unresectable or metastatic tumor. Eight of the nine patients
      underwent cholecystectomy whereas percutaneous cholecystostomy was
      used in one patient with an unresectable cholangiocarcinoma.
      Operative and pathologic evidence of acute cholecystitis was present
      in all, but only two patients had gallstones. Seven patients
      survived the surgical procedure and were discharged at an average of
      11.7 days postoperatively. Based on this series, we propose that
      acute cholecystitis should be considered as a source of sepsis in
      patients undergoing biliary drainage who do not respond to
      antibiotics and catheter manipulations. Moreover, cholecystectomy
      should be performed at the time of laparotomy, if prolonged
      transhepatic drainage is planned for unresectable malignant
      conditions.
 

By Permission of SURGERY, Gynecology & Obstetrics, now known as the JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS.

<--- go back to bibliography
AU  - Lillemoe KD
AU  - Sauter PK
AU  - Pitt HA
AU  - Yeo CJ
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore.
TI  - Current status of surgical palliation of periampullary carcinoma. SO
 - Surg Gynecol Obstet 1993 Jan;176(1):1-10
AB  - In recent years, the use of nonoperative palliation for unresectable
      periampullary carcinoma has increased markedly, in part, because of
      the high morbidity and mortality rates after surgical palliation.
      The current analysis was undertaken to determine whether or not
      decreases in morbidity and mortality rates, recently observed after
      resection of periampullary carcinoma, are now being seen in the
      surgical palliation of unresectable periampullary carcinoma. During
      a 54 month period, 118 consecutive patients underwent surgical
      exploration with the finding of unresectable periampullary
      adenocarcinoma. Jaundice was the most common complaint at admission,
      being present in 73 percent of the patients. Abdominal or back pain,
      or both, was present in 71 percent of the patients and weight loss
      was observed in 61 percent of the patients. The most commonly
      performed procedure was combined biliary bypass and
      gastrojejunostomy, being performed upon 75 percent of the patients.
      A gastrojejunostomy was performed upon 107 of 118 patients (91
      percent). The hospital mortality rate was 2.5 percent. Postoperative
      complications occurred in 37 percent of the patients but were seldom
      life-threatening. Wound infection was the most frequent
      postoperative complication (10 percent), followed by cholangitis (8
      percent) and delayed gastric emptying (8 percent). During the late
      follow-up period, only 4 percent of the patients had gastric outlet
      obstruction, and only 2 percent had recurrent jaundice. The mean
      survival time postoperatively was 7.7 months. These results
      demonstrate that patients with unresectable periampullary carcinoma
      can undergo surgical palliation with minimal perioperative
      mortality, acceptable morbidity and good long term palliation. We
      conclude that surgical palliation is the treatment of choice for
      carefully selected patients with unresectable periampullary
      carcinoma.
 

By Permission of SURGERY, Gynecology & Obstetrics, now known as the JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS.

<--- go back to bibliography
AU  - Long PP
AU  - Hruban RH
AU  - Lo R
AU  - Yeo CJ
AU  - Morsberger LA
AU  - Griffin CA
IN  - Johns Hopkins Oncology Center, Baltimore, MD 21287-8934.
TI  - Chromosome analysis of nine endocrine neoplasms of the pancreas. SO
- Cancer Genet Cytogenet 1994 Oct;77(1):55-9
AB  - Endocrine neoplasms of the pancreas differ from the more common
      adenocarcinomas of the pancreas not only in histologic appearance,
      but also in clinical presentation and biologic behavior. Chromosomes
      were analyzed from nine fresh pancreatic endocrine neoplasms. Clonal
      chromosomal abnormalities were found in five; all were malignant
      neoplasms. One showed only a loss of the Y chromosome and another
      had a small triploid population of cells in addition to a normal
      mainline, with a karyotype of 61-66,XX, -X, -1, -2, -3, -4, +5, -6,
      +7, -11, -14, +17, +18, +20, +mar1,x2, +mar2,inc. Three neoplasms
      had near-haploid clones. One neoplasm had a composite karyotype of
      31-36,X, +1, +3, +5, +7, +9, +10, +17, +18, +mar. Two were from
      the same patient, who had the autosomal dominant syndrome MEN-1. The
      same clone, described as 29,X, +add(1)(p12), +5, +7, +8, +18,
      +19, was found in both the primary pancreatic neoplasm and in the
      metastatic tumor. To our knowledge, this is the first report of a
      haploid clone in both a primary and metastatic solid tumor, and
      suggests that the near-haploid state is at least compatible with
      metastasis. These data, combined with the limited reports of
      cytogenetic data from endocrine pancreatic neoplasms, suggest that
      at least half of such neoplasms will have an abnormal karyotype.
 

Reprinted by permission of the publisher from "Chromosome analysis of nine endocrine neoplasms of the pancreas", Long PP et al. Cancer Genetics and Cytogenetics, Vol. 77 No. 1, pp. 55-59, ©1994 by Elsevier Science Inc.

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AU  - Lumadue JA
AU  - Griffin CA
AU  - Osman M
AU  - Hruban RH
IN  - Department of Pathology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland, USA.
TI  - Familial pancreatic cancer and the genetics of pancreatic cancer.
      [Review]
SO  - Surg Clin North Am 1995 Oct;75(5):845-55
AB  - In our current understanding of pancreatic carcinoma, these
      neoplasms can arise either sporadically or in familial clusters.
      Extensive chromosome abnormalities are frequent, as is loss of
      heterozygosity at loci known to contain the tumor suppressor genes
      DCC, p53, and MTS1. Although the genetic examination of all
      pancreatic cancers is important, the examination of familial cases
      is especially useful in that these allow the identification of
      uniform genetic alterations that are inherited through the germ
      line. Much additional work needs to be done before the genetic basis
      of pancreatic cancer is completely understood. Although our
      knowledge is limited, it is clear that genetic analyses can be used
      to establish the prognosis for a patient with pancreatic cancer and,
      it is hoped, will someday be used in the management, treatment, and
      detection of pancreatic cancer. [References: 61]
 

With permission from Surgical Clinics of North America, ©1995.

<--- go back to bibliography
AU  - Nakeeb A
AU  - Lillemoe KD
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, MD.
TI  - The role of pancreaticoduodenectomy for locally recurrent or
      metastatic carcinoma to the periampullary region.
SO  - J Am Coll Surg 1995 Feb;180(2):188-92
AB  - BACKGROUND: The efficacy of operative resection of metastatic
      lesions to the liver, lung, and brain is well established. However,
      the appropriate management of metastatic or locally recurrent
      malignancies to the periampullary region is less well established.
      STUDY DESIGN: A retrospective review of The Johns Hopkins Hospital
      experience with pancreaticoduodenectomy for metastatic or locally
      recurrent periampullary lesions was performed. RESULTS: From 1988 to
      1993, 27 patients with a past history of malignancy underwent
      pancreaticoduodenectomy. In six patients (22 percent), the lesion
      was determined to be from a metastasis or a local recurrence, and in
      21 patients (78 percent), the lesion was a new primary. Patients
      with metastatic or locally recurrent lesions were younger (51.3
      compared to 67.1 years of age) and presented with a shorter interval
      from their initial neoplasm (33 compared to 120 months). Of the six
      patients undergoing pancreaticoduodenectomy for a metastatic or
      locally recurrent lesion, three patients are alive an average of 38
      months and three patients died an average of 11 months
      postoperatively. This compares favorably with the survival rate of
      the new primary group in which 12 patients are alive a mean of 22
      months and nine patients died a mean of 14 months postoperatively.
      CONCLUSIONS: These results suggest that patients with metastatic or
      locally recurrent lesions in the periampullary region from a
      previously treated neoplasm should be considered candidates for
      pancreaticoduodenectomy.
 

By Permission of the JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS.

<--- go back to bibliography
AU  - Nordback IH
AU  - Hruban RH
AU  - Boitnott JK
AU  - Pitt HA
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland 21205.
TI  - Carcinoma of the body and tail of the pancreas.
SO  - Am J Surg 1992 Jul;164(1):26-31
AB  - Recently, several institutions have reported improved results in the
      treatment of patients with carcinoma of the head of the pancreas. In
      an attempt to determine whether similar trends could be demonstrated
      for patients with carcinoma of the body and tail of the pancreas,
      the records of all 113 patients with an adenocarcinoma of the body
      or tail of the pancreas treated at The Johns Hopkins Hospital
      between 1972 and 1989 were reviewed. The patients were divided into
      two groups: those diagnosed between 1972 and 1982 (41 patients) and
      those between 1983 and 1989 (72 patients). No significant
      differences in tumor stage were observed between the two groups. The
      proportion of patients who underwent surgery decreased from 68% to
      47% (p = 0.02). The number of patients who had bypass operations
      (15% versus 17%) or pancreatic resection (5% versus 10%) was similar
      in the two groups, but the proportion of patients who underwent
      exploratory laparotomy with biopsy only decreased from 49% to 21% (p
      = 0.002). The postoperative 30-day mortality (7% versus 3%),
      postoperative morbidity (18% versus 21%), median survival (4 months
      versus 3 months), and the 1-year survival (8% versus 9%) did not
      differ significantly between the two groups. One patient survived
      for 6 years after resection, and another patient is still alive 3
      years after resection. Thus, unlike adenocarcinoma of the head of
      the pancreas, it appears that treatment results for patients with
      adenocarcinoma of the body or tail of the pancreas have not improved
      in recent years, the only change being a decreased need for
      exploratory laparotomy with biopsy only.
 

With permission from the American Journal of Surgery, ©1992.

<--- go back to bibliography
AU  - Nordback IH
AU  - Hruban RH
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, MD 21205.
TI  - Second primary lesions in the biliary tree after successful
      resection of ampullary carcinoma.
SO  - Surgery 1992 Jul;112(1):111-5
AB  - Two patients are described who had an adenocarcinoma at the site of
      the hepaticojejunostomy 5 and 15 years after pancreaticoduodenectomy
      for an ampullary adenocarcinoma. Both patients had symptoms and
      signs of biliary obstruction. Both tumors were identified by upper
      endoscopy and resected at laparotomy. In both patients the tumor was
      considered a new primary carcinoma rather than a recurrent or
      metastatic carcinoma. Evidence to support this was the finding of an
      intraepithelial component of the tumor in the resection specimens of
      both patients, the fact that the tumors were on the luminal side of
      the distal bile duct in both cases, lack of other evidence of
      recurrent or metastatic tumor, and the time interval between the
      pancreaticoduodenectomy and the development of the new tumor.
 

With permission from SURGERY, ©1992.

<--- go back to bibliography
AU  - Pitt HA
IN  - Department of Surgery, Johns Hopkins University School of Medicine,
      Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
TI  - Curative treatment for pancreatic neoplasms. Standard resection.
      [Review]
SO  - Surg Clin North Am 1995 Oct;75(5):891-904
AB  - In the mid-1990s pancreatoduodenectomy can be performed at regional
      referral centers with an operative mortality of 1% to 2%. In
      addition, a number of centers around the world are now reporting
      5-year survivals between 20% and 30% for patients with resected
      pancreatic cancer. In recent years a debate has continued as to the
      proper extent of resection for these patients, in part because
      numerous resective and reconstructive options are available. In
      broad terms, operations can be categorized as "standard" or
      "radical." In general, standard operations tend to have lower
      postoperative morbidity and mortality. Multiple factors influence
      postoperative survival, including intraoperative blood loss,
      perioperative transfusions, type of operation, hospital mortality,
      tumor biology, and adjuvant therapy. Among these parameters, tumor
      biology is the most important by multivariate analysis. Recent data
      suggest that the quality of survival is better with standard
      operations and best with the pylorus-preserving
      pancreatoduodenectomy. Nevertheless, debate will continue about the
      proper extent of resection until a well-controlled randomized trial
      has addressed this issue. [References: 29]
 

With permission from Surgical Clinics of North America, ©1995.

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AU  - Pitt HA
AU  - Nakeeb A
AU  - Abrams RA
AU  - Coleman J
AU  - Piantadosi S
AU  - Yeo CJ
AU  - Lillemore KD
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland, USA.
TI  - Perihilar cholangiocarcinoma. Postoperative radiotherapy does not
      improve survival.
SO  - Ann Surg 1995 Jun;221(6):788-97; discussion 797-8
AB  - OBJECTIVE: The aims of this analysis were to determine prospectively
      the effects of surgical resection and radiation therapy on the
      length and quality of survival as well as late toxicity in patients
      with perihilar cholangiocarcinoma. BACKGROUND: Retrospective
      analyses have suggested that adjuvant radiation therapy improves
      survival in patients with perihilar cholangiocarcinoma. However, in
      these reports, patients receiving radiotherapy tended to have
      smaller, often resectable tumors, and were relatively fit. In
      comparison, patients who have not received radiotherapy often had
      unresectable tumors, metastatic disease, or poor performance status.
      METHODS: From 1988 through 1993, surgically staged patients with
      perihilar cholangiocarcinoma and 1) no evidence of metastatic
      disease, 2) Karnofsky score > 60, 3) no prior malignancy or
      radiotherapy, and 4) a patent main portal vein were analyzed. Fifty
      patients were stratified by resection (n = 31) versus operative
      palliation (n = 19) and by radiation (n = 23) versus no radiotherapy
      (n = 27). RESULTS: Patients undergoing resection had smaller tumors
      (1.9 +/- 2.8 vs. 2.4 +/- 2.1 cm, p < 0.01) that were less likely to
      invade the hepatic artery (3% vs. 42%, p < 0.05) or portal vein (6%
      vs. 53%, p < 0.05). Multiple parameters that might have affected
      outcome were similar between patients who did and did not receive
      radiation therapy. Resection improved the length (24.2 +/- 2.5 vs.
      11.3 +/- 1.0 months, p < 0.05) and quality of survival. Radiation
      had no effect on the length (18.4 +/- 2.9 vs. 20.1 +/- 2.4 months)
      or quality of survival or on late toxicity. CONCLUSIONS: This
      analysis suggests that in patients with localized perihilar
      cholangiocarcinoma, resection prolongs survival whereas radiation
      has no effect on either survival or late toxicity. Thus, new agents
      or strategies to deliver adjuvant therapy are needed to improve
      survival in these patients.
 

With permission from Annals of Surgery, ©1995.

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AU  - Raben D
AU  - Williams J
AU  - Abrams RA
IN  - Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8922, USA.
TI  - The clinical use of multimodality therapy in the management of
      cancer. [Review]
SO  - In Vivo 1994 Nov-Dec;8(5):635-42
AB  - The essential challenge in managing malignant disease with intent of
      cure is to eradicate the last malignant cell without imposing
      unacceptable burdens regarding toxicity, functional loss, or damaged
      cosmesis. In this review we examine the strengths and limitations of
      surgery, radiotherapy, and systemic chemotherapy when used as single
      modalities and the unique features of each that allow their
      advantageous combination. Finally, we consider newer developments in
      the antineoplastic armamentarium which may soon contribute to the
      challenges of achieving cure with acceptable sequelae. [References:
      58]
 

With permission from In Vivo, ©1994.

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AU  - Redston MS
AU  - Caldas C
AU  - Seymour AB
AU  - Hruban RH
AU  - da Costa L
AU  - Yeo CJ
AU  - Kern SE
IN  - Department of Pathology, Johns Hopkins University School of
      Medicine, Baltimore, Maryland 21205.
TI  - p53 mutations in pancreatic carcinoma and evidence of common
      involvement of homocopolymer tracts in DNA microdeletions.
SO  - Cancer Res 1994 Jun 1;54(11):3025-33
AB  - Pancreatic adenocarcinoma is a major cause of cancer death, and yet
      little is known about its molecular pathogenesis. We identified p53
      mutations in 19 (70%) of 27 primary pancreatic adenocarcinomas. Most
      were missense point mutations, and the mutations were distributed
      primarily within the evolutionarily conserved domains. Transitions
      predominated over transversions, and many of the transitions were at
      CpG dinucleotides. Intragenic deletions accounted for 32% of
      mutations and were associated with decreased survival (P = 0.0016).
      A review of 1937 published p53 mutations revealed that the
      occurrence of small (1-2 base pairs) microdeletions varied among
      different types of human neoplasms and that pancreatic
      adenocarcinoma had one of the highest frequencies (13% of 47
      mutations, P = 0.0036). Many small deletions occurred in iterations
      of single bases, but this did not fully account for their pattern of
      distribution, and there was evidence for the involvement of
      homocopolymer (polypurine:polypyrimidine) tracts. This may represent
      a more widespread phenomenon, because microdeletions occur in
      similar sequence patterns in reports of somatic and germ line
      mutations among genes other than p53.
 

<--- go back to bibliography
AU  - Savader BL
AU  - Fishman EK
AU  - Savader SJ
AU  - Cameron JL
IN  - Russell H. Morgan Department of Radiology, Johns Hopkins Medical
      Institutions, Baltimore, MD.
TI  - CT arterial portography vs pancreatic arteriography in the
      assessment of vascular involvement in pancreatic and periampullary
      tumors.
SO  - J Comput Assist Tomogr 1994 Nov-Dec;18(6):916-20
AB  - OBJECTIVE: Preoperative staging of pancreatic tumors is frequently
      accomplished through a combined effort of CT and arteriography. For
      tumor detection and delineation of disease extent CT is utilized
      routinely, with CT arterial portography (CTAP) being the single most
      accurate study for the detection liver metastases. Arteriography has
      remained the " gold" standard for assessing vascular
involvement. The purpose of this study was to determine whether CTAP could
become the single study of choice for assessing resectability in patients
with pancreatic and periampullary tumors with particular emphasis on its
accuracy in determining vascular involvement. MATERIALS AND METHODS:
Radiologic studies and medical records were reviewed in 20 patients who
had received both CTAP and arteriographic examinations for preoperative
assessment of pancreatic and periampullary tumors. These findings were
correlated with results from either surgery (12 cases) or percutaneous
biopsy and follow-up (8 cases) in 12 nonresectable and 8 resectable
tumors. RESULTS: Arteriography and CTAP correctly concurred in 75% of
cases (15 of 20); CTAP correctly demonstrated vascular involvement not
appreciated on arteriography in 15% (3 of 20) with an overall sensitivity
and specificity of 90 and 100%, respectively. Arteriography was superior
to CTAP in one patient (5%) with an overall sensitivity and specificity of
70 and 90%, respectively, for predicting vascular involvement by tumor.
CONCLUSION: Our experience suggests that CTAP is more accurate than
arteriography for demonstrating tumor involvement of major peripancreatic
vessels. Because CTAP, additionally, has a high sensitivity for detecting
liver metastases, no further studies may be necessary to determine
operability of these patients.
 

Used with permission of Lippincott-Raven Publishers, 227 E. Washington Square, Philadelphia, PA 19106-3780. Savader SJ et al. J Comput Assist Tomogr 18:916-20, 1994.

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AU  - Schutte M
AU  - da Costa LT
AU  - Hahn SA
AU  - Moskaluk C
AU  - Hoque AT
AU  - Rozenblum E
AU  - Weinstein CL
AU  - Bittner M
AU  - Meltzer PS
AU  - Trent JM
AU  - et al
IN  - Department of Pathology, Johns Hopkins Medical Institutions,
      Baltimore, MD 21205-2196, USA.
TI  - Identification by representational difference analysis of a
      homozygous deletion in pancreatic carcinoma that lies within the
      BRCA2 region.
SO  - Proc Natl Acad Sci U S A 1995 Jun 20;92(13):5950-4
AB  - Homozygous deletions have been central to the discovery of several
      tumor-suppressor genes, but their finding has often been either
      serendipitous or the result of a directed search. A recently
      described technique [Lisitsyn, N., Lisitsyn, N. & Wigler, M. (1993)
      Science 259, 946-951] held out the potential to efficiently discover
      such events in an unbiased manner. Here we present the application
      of the representational difference analysis (RDA) to the study of
      cancer. We cloned two DNA fragments that identified a homozygous
      deletion in a human pancreatic adenocarcinoma, mapping to a
      1-centimorgan region at chromosome 13q12.3 flanked by the markers
      D13S171 and D13S260. Interestingly, this lies within the
      6-centimorgan region recently identified as the BRCA2 locus of
      heritable breast cancer susceptibility. This suggests that the same
      gene may be involved in multiple tumor types and that its function
      is that of a tumor suppressor rather than that of a dominant
      oncogene.
 

With permission from The Proceedings of the National Academy of Sciences USA, ©1995.

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AU  - Seymour AB
AU  - Hruban RH
AU  - Redston M
AU  - Caldas C
AU  - Powell SM
AU  - Kinzler KW
AU  - Yeo CJ
AU  - Kern SE
IN  - Department of Pathology, Johns Hopkins University School of
      Medicine, Baltimore, Maryland 21205.
TI  - Allelotype of pancreatic adenocarcinoma.
SO  - Cancer Res 1994 May 15;54(10):2761-4
AB  - Knowledge of the patterns of allelic loss has been useful in
      identifying the spectrum of the tumor suppressor genes involved in
      various tumor types. Such analyses in pancreatic carcinoma have been
      difficult due to the characteristic host desmoplastic reaction to
      the neoplasm. We have assembled the first allelotype of pancreatic
      adenocarcinoma, a survey for allelic loss among each chromosomal
      arm, using seven cryostat-dissected neoplasms. The fractional
      allelic loss in these seven neoplasms was 0.18, a value similar to
      that seen previously in colorectal carcinoma. Alleles of chromosome
      18q (lost in five of six informative tumors) and of chromosome 17p
      (lost in four of five informative tumors) were commonly affected.
      Neither APC mutations (33 neoplasms), allelic shifts of dinucleotide
      repeats (26 neoplasms), nor immunohistochemical evidence of
      retinoblastoma protein underexpression (7 neoplasms) were found.
      Further evaluation of allelic loss in pancreatic cancer would
      benefit from improved methods for the analysis of lost genetic
      material which overcome the problems posed by the high admixture of
      nonneoplastic stromal and inflammatory cells in these tumors.
 

<--- go back to bibliography
AU  - Talamini MA
AU  - Pitt HA
AU  - Hruban RH
AU  - Boitnott JK
AU  - Coleman J
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Spectrum of cystic tumors of the pancreas.
SO  - Am J Surg 1992 Jan;163(1):117-23; discussion 123-4
AB  - The pathologic and clinical classification, as well as the behavior,
      of cystic tumors of the pancreas has been the subject of
      controversy. We retrospectively reviewed 50 patients with a
      diagnosis of cystic tumor of the pancreas observed at The Johns
      Hopkins Hospital from 1984 to 1991. These tumors were classified
      into three broad groups: I, cystadenoma; II, cystadenocarcinoma; and
      III, adenocarcinoma with mucin production or an associated cyst. The
      three groups did not differ with respect to age or sex. The most
      common clinical presentation was abdominal pain. Symptoms and signs
      among the three groups were similar except that patients with
      cystadenomas were less likely (p less than 0.05) to be jaundiced and
      more likely (p less than 0.05) to be asymptomatic. Radiologic
      findings on computerized tomography, cholangiography, and
      arteriography also overlapped, making precise preoperative
      determination of tumor type difficult. Operative classification was
      also often not possible. The resectability rate (Group I, 91%; Group
      II, 67%; Group III, 53%) and 5-year survival rate (Group I, 90%;
      Group II, 72%; Group III, 14%) correlated with careful pathologic
      determination. Cystic tumors of the pancreas represent a spectrum of
      disease ranging from benign cystadenoma to adenocarcinoma
      masquerading as cystadenocarcinoma. We recommend resection whenever
      possible, even when preoperative evaluation suggests benign disease.
 

With permission from the American Journal of Surgery, ©1992.

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AU  - Tamm EP
AU  - Jones B
AU  - Yeo CJ
AU  - Maher MM
AU  - Cameron JL
IN  - Russell H. Morgan Department of Radiology and Radiologic Science,
      Johns Hopkins Hospital, Baltimore, MD 21287, USA.
TI  - Pancreaticogastrostomy and the Whipple procedure: radiographic
      appearance and complications.
SO  - Radiology 1995 Jul;196(1):251-5
AB  - PURPOSE: To evaluate the radiographic appearance of a
      pancreaticogastrostomy (PG) and its complications. MATERIALS AND
      METHODS: Seventy-two patients underwent pancreaticoduodenectomy and
      PG or pancreaticojejunostomy. Those who underwent PG and were
      evaluated postoperatively with T-tube cholangiography and upper
      gastrointestinal (UGI) series constitute the study group (n = 22; 10
      men, 12 women; age range, 33-88 years). RESULTS: Twenty-one of the
      patients had a gastric filling defect radiographically detected.
      Four patients had clinically apparent delayed gastric emptying and
      one patient had a clinically apparent pancreatic fistula not
      detected radiographically. Two patients outside the study group had
      complications: One had a pancreatic fistula seen only with
      sinography, and one had a PG leak seen only with repeat UGI series
      and computed tomography (CT). CONCLUSION: PG caused a gastric
      filling defect in most patients. Suspected pancreatic fistulas are
      best confirmed with sinography, and suspected PG leaks may require
      repeat evaluation and CT. Clinical findings of delayed gastric
      emptying do not correlate with findings of UGI.
 

With permission from Radiology, ©1995.

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AU  - Trerotola SO
AU  - Jones B
AU  - Crist DW
AU  - Cameron JL
IN  - Russell H. Morgan Department of Radiology and Radiological Science,
      Johns Hopkins Medical Institutions, Baltimore, MD 21205.
TI  - Pylorus-preserving Whipple pancreaticoduodenectomy: postoperative
      evaluation.
SO  - Radiology 1989 Jun;171(3):735-8
AB  - The pylorus-preserving Whipple pancreaticoduodenectomy is becoming a
      popular alternative to the standard Whipple operation. Fluoroscopy
      plays an important role in postoperative assessment. The authors
      evaluated images of 50 consecutive patients who had undergone the
      newer procedure. Thirty-one complications were identified. Two
      normal variants that could be confused with abnormalities were
      noted: (a) the featureless appearance of the duodenal bulb may be
      mistaken for extravasation, and (b) contrastmaterial filling of the
      proximal jejunal loop at an end-to-end anastomosis with retained
      invaginated pancreas may be mistaken for intussusception. Another
      pitfall was failure to evaluate the pancreaticojejunostomy
      anastomosis fully, resulting in false-negative radiologic
      interpretations when leaks were present. The approach to
      postoperative examination of patients who have undergone the
      pylorus-preserving Whipple procedure is different from that of
      patients who have undergone the standard procedure. Radiologists
      should be familiar with this approach, the normal postoperative
      anatomy, and pitfalls in imaging so that complications can be
      diagnosed and treated.
 

With permission from Radiology, ©1989.

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AU  - Tulinius H
AU  - Olafsdottir GH
AU  - Sigvaldason H
AU  - Tryggvadottir L
AU  - Bjarnadottir K
IN  - Icelandic Cancer Registry, Reykjavik.
TI  - Neoplastic diseases in families of breast cancer patients. SO  - J
Med Genet 1994 Aug;31(8):618-21
AB  - OBJECTIVE--To investigate whether the risk of cancer at all sites,
      and at individual sites other than breast, prostate, ovaries, and
      endometrium, is increased among relatives of breast cancer patients
      compared with the general population. DESIGN--A cohort of family
      members of breast cancer patients was established. The probands were
      chosen by year of birth or time of diagnosis. Any influence of
      knowledge of the cancer experience of the relatives has been
      avoided. The risk estimates are based on expected numbers computed
      from age and time specific incidence rates for the Icelandic
      population. SETTING--Iceland. SUBJECTS--The population of Iceland.
      MAIN OUTCOME MEASURES--Relative risks by degree of relatedness and
      age of proband. RESULTS--The relative risk of cancer at all sites is
      raised for males and females. This is more than expected based on
      the known familial risk of breast cancer, prostate, and ovarian
      cancer. The excess risk of breast, prostate, and ovarian cancer is
      confirmed, but not that of cancer of the endometrium. The risk of
      cancer of the pancreas in both sexes and the stomach and kidneys in
      females is significantly raised. No evidence was found for decreased
      risk for any cancer type. CONCLUSIONS--The risk of cancer at all
      sites in relatives of breast cancer patients is increased. In
      addition to the risk of breast, prostate, and ovarian cancer, the
      risk of pancreas cancer and cancer of the stomach and kidneys in
      females is raised, but the last mentioned observations need further
      confirmation.
 

With permission from the Journal of Medical Genetics, ©1994.

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AU  - Udelsman R
AU  - Yeo CJ
AU  - Hruban RH
AU  - Pitt HA
AU  - Niederhuber JE
AU  - Coleman J
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Pancreaticoduodenectomy for selected pancreatic endocrine tumors.
      [Review]
SO  - Surg Gynecol Obstet 1993 Sep;177(3):269-78
AB  - Endocrine tumors are distributed throughout the pancreas and can
      usually be removed by local excision or distal pancreatectomy. Those
      tumors arising in the pancreatic head and uncinate process may be
      difficult to enucleate because of size, location or malignant
      extension. In the past, surgeons have been reluctant to perform a
      pancreaticoduodenectomy (Whipple procedure) for these lesions
      because of the high morbidity and mortality rates. In recent years,
      we and others have reported a marked reduction in the morbidity and
      mortality rates after the Whipple procedure and, since 1981, have
      used pancreaticoduodenectomy to resect pancreatic endocrine
      neoplasms successfully in 12 patients. Tumors were resected from six
      men and six women who ranged in age from 28 to 61 years (median of
      49 years). Six of the tumors were benign and included three
      insulinomas, one glucagonoma, one gastrinoma and one nonfunctioning
      islet cell tumor. The six malignant tumors included two insulinomas,
      one VIPoma and three nonfunctioning islet cell tumors. In all
      instances, enucleation could not be performed safely or would have
      resulted in an inadequate excision. Pylorus preservation was used in
      seven of the patients, including the last six. The average operative
      time was 6.8 hours, and six of the patients did not require
      perioperative blood transfusions. There was no hospital mortality.
      Hospital morbidity included three self-limited pancreatic fistulas,
      one gastrocutaneous fistula, one hepatic abscess and one
      postoperative myocardial infarction. One patient with a malignant
      VIPoma died three years postoperatively of metastatic tumor. The
      remaining 11 patients are alive and well with a median follow-up
      period of three and one-half years (range of zero to 9.7 years).
      These data indicate that pancreaticoduodenectomy is an appropriate
      procedure for properly selected patients with pancreatic endocrine
      neoplasms and can be performed with acceptable morbidity and
      mortality rates. [References: 34]
 

By Permission of SURGERY, Gynecology & Obstetrics, now known as the JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS.

<--- go back to bibliography
AU  - Yeo CJ
IN  - Department of Surgery, Johns Hopkins University School of Medicine,
      Baltimore, Maryland, USA.
TI  - Management of complications following pancreaticoduodenectomy.
      [Review]
SO  - Surg Clin North Am 1995 Oct;75(5):913-24
AB  - Pancreaticoduodenectomy remains a formidable procedure, with low
      mortality rates in experienced hands. Postoperative complications
      following pancreaticoduodenectomy are common, and their prompt
      recognition and appropriate management are of great importance in
      contributing to a successful outcome for the majority of patients.
      [References: 49]
 

With permission from Surgical Clinics of North America, ©1995.

<--- go back to bibliography
AU  - Yeo CJ
AU  - Barry MK
AU  - Sauter PK
AU  - Sostre S
AU  - Lillemoe KD
AU  - Pitt HA
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland.
TI  - Erythromycin accelerates gastric emptying after
      pancreaticoduodenectomy. A prospective, randomized,
      placebo-controlled trial.
SO  - Ann Surg 1993 Sep;218(3):229-37; discussion 237-8
AB  - OBJECTIVE: This study tested the hypothesis that erythromycin, a
      motilin agonist, reduces the incidence of early DGE after
      pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Delayed gastric
      emptying (DGE) is a leading cause of morbidity after
      pancreaticoduodenectomy, occurring in up to 40% of patients. The
      pathogenesis of DGE has been speculated to involve factors such as
      peritonitis from anastomotic leaks, ischemia to the antropyloric
      muscles, and gastric atony in response to resection of the duodenal
      pacemaker or reduction in circulating motilin levels. METHODS:
      Between November 1990 and January 1993, 118 patients undergoing
      pancreaticoduodenectomy completed this prospective, randomized,
      placebo-controlled trial. The patients received either 200 mg of
      intravenous erythromycin lactobionate every 6 hours (n = 58), or an
      identical volume of 0.9% saline (n = 60) from the third to tenth
      postoperative days. On the tenth postoperative day, a dual phase
      radionuclide gastric emptying study was performed. RESULTS: The
      erythromycin and control groups were comparable regarding multiple
      preoperative, intraoperative, and postoperative factors. The
      erythromycin group had a 37% reduction in the incidence of DGE (19%
      vs. 30%), a significantly reduced (p < 0.05) need to reinsert a
      nasogastric tube for DGE (6 vs. 15 patients), and a significantly
      reduced (p < 0.01) per cent retention of liquids at 30 minutes and
      solids at 30, 60, 90, and 120 minutes. No major adverse reactions to
      erythromycin were observed. CONCLUSIONS: Erythromycin is a safe,
      inexpensive drug that significantly accelerates gastric emptying
      after pancreaticoduodenectomy and reduces the incidence of DGE by
      37%. These data support the use of erythromycin to decrease early
      DGE after pancreaticoduodenectomy.
 

With permission from Annals of Surgery, ©1993.

<--- go back to bibliography
AU  - Yeo CJ
AU  - Cameron JL
AU  - Lillemoe KD
AU  - Sitzmann JV
AU  - Hruban RH
AU  - Goodman SN
AU  - Dooley WC
AU  - Coleman J
AU  - Pitt HA
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland, USA.
TI  - Pancreaticoduodenectomy for cancer of the head of the pancreas. 201
      patients.
SO  - Ann Surg 1995 Jun;221(6):721-31; discussion 731-3
AB  - OBJECTIVE: This single-institution study examined the outcome after
      pancreaticoduodenectomy in patients with adenocarcinoma of the head
      of the pancreas. SUMMARY OF BACKGROUND DATA: In recent years,
      pancreaticoduodenectomy for adenocarcinoma of the head of the
      pancreas has been associated with decreased morbidity and mortality
      and, in some centers, 5-year survival rates in excess of 20%.
      METHODS: Two hundred one patients with pathologically verified
      adenocarcinoma of the head of the pancreas undergoing
      pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970
      and 1994 were analyzed (the last 100 resections were performed
      between March 1991 and April 1994). This is the largest
      single-institution experience reported to date. RESULTS: The overall
      postoperative in-hospital mortality rate was 5%, but has been 0.7%
      for the last 149 patients. The actuarial 5-year survival for all 201
      patients was 21%, with a median survival of 15.5 months. There were
      11 5-year survivors. Patients resected with negative margins
      (curative resections: n = 143) had an actuarial 5-year survival rate
      of 26%, with a median survival of 18 months, whereas those with
      positive margins (palliative resections; n = 58) fared significantly
      worse, with an actuarial 5-year survival rate of 8% and a median
      survival of 10 months (p < 0.0001). Survival has improved
      significantly from decade to decade (p < 0.002), with the 3-year
      actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in
      the 1990s. Factors significantly favoring long-term survival by
      univariate analyses included tumor diameter < 3 cm, negative nodal
      status, diploid tumor DNA content, tumor S phase fraction < 18%,
      pylorus-preserving resection, < 800 mL intraoperative blood loss, <
      2 units of blood transfused, negative resection margins, and use of
      postoperative adjuvant chemotherapy and radiation therapy.
      Multivariate analyses indicated the strongest predictors of
      long-term survival were diploid tumor DNA content, tumor diameter <
      3 cm, negative nodal status, negative resection margins, and decade
      of resection. CONCLUSIONS: The survival of patients with pancreatic
      adenocarcinoma treated by pancreaticoduodenectomy is improving.
      Aspects of tumor biology, such as DNA content, tumor diameter, nodal
      status and margin status, are the strongest predictors of outcome.
 

With permission from Annals of Surgery, ©1995.

<--- go back to bibliography
AU  - Yeo CJ
AU  - Cameron JL
AU  - Maher MM
AU  - Sauter PK
AU  - Zahurak ML
AU  - Talamini MA
AU  - Lillemoe KD
AU  - Pitt HA
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Maryland, USA.
TI  - A prospective randomized trial of pancreaticogastrostomy versus
      pancreaticojejunostomy after pancreaticoduodenectomy.
SO  - Ann Surg 1995 Oct;222(4):580-8; discussion 588-92
AB  - OBJECTIVE: The authors hypothesized that pancreaticogastrostomy is
      safer than pancreaticojejunostomy after pancreaticoduodenectomy and
      less likely to be associated with a postoperative pancreatic
      fistula. SUMMARY BACKGROUND DATA: Pancreatic fistula is a leading
      cause of morbidity and mortality after pancreaticoduodenectomy,
      occurring in 10% to 20% of patients. Nonrandomized reports have
      suggested that pancreaticogastrostomy is less likely than
      pancreaticojejunostomy to be associated with postoperative
      complications. METHODS: Between May 1993 and January 1995, the
      findings for 145 patients were analyzed in this prospective trial at
      The Johns Hopkins Hospital. After giving their appropriate
      preoperative informed consent, patients were randomly assigned to
      pancreaticogastrostomy or pancreaticojejunostomy after completion of
      the pancreaticoduodenal resection. All pancreatic anastomoses were
      performed in two layers without pancreatic duct stents and with
      closed suction drainage. Pancreatic fistula was defined as drainage
      of greater than 50 mL of amylase-rich fluid on or after
      postoperative day 10. RESULTS: The pancreaticogastrostomy (n = 73)
      and pancreaticojejunostomy (n = 72) groups were comparable with
      regard to multiple parameters, including demographics, medical
      history, preoperative laboratory values, and intraoperative factors,
      such as operative time, blood transfusions, pancreatic texture,
      length of pancreatic remnant mobilized, and pancreatic duct
      diameter. The overall incidence of pancreatic fistula after
      pancreaticoduodenectomy was 11.7% (17/145). The incidence of
      pancreatic fistula was similar for the pancreaticogastrostomy
      (12.3%) and pancreaticojejunostomy (11.1%) groups. Pancreatic
      fistula was associated with a significant prolongation of
      postoperative hospital stay (36 +/- 5 vs. 15 +/- 1 days) (p <
      0.001). Factors significantly increasing the risk of pancreatic
      fistula by univariate logistic regression analysis included
      ampullary or duodenal disease, soft pancreatic texture, longer
      operative time, greater intraoperative red blood cell transfusions,
      and lower surgical volume (p < 0.05). A multivariate logistic
      regression analysis revealed the factors most highly associated with
      pancreatic fistula to be lower surgical volume and ampullary or
      duodenal disease in the resected specimen. CONCLUSIONS: Pancreatic
      fistula is a common complication after pancreaticoduodenectomy, with
      an incidence most strongly associated with surgical volume and
      underlying disease. These data do not support the hypothesis that
      pancreaticogastrostomy is safer than pancreaticojejunostomy or is
      associated with a lower incidence of pancreatic fistula.
 

With permission from Annals of Surgery, ©1995.

<--- go back to bibliography
AU  - Yung BC
AU  - Sostre S
AU  - Yeo CJ
AU  - Pitt HA
AU  - Cameron JL
IN  - Department of Radiology, Johns Hopkins Medical Institutions,
      Baltimore, Maryland 21205.
TI  - Comparison of left anterior oblique, anterior, and geometric mean
      methods in gastric emptying assessment of
      postpancreaticoduodenectomy patients.
SO  - Clin Nucl Med 1993 Sep;18(9):776-81
AB  - Although left anterior oblique (LAO) gastric emptying studies appear
      to be an adequate alternative to geometric mean (GM) measurements in
      patients with normal gastric anatomy, it is not clear whether they
      can be used after gastric or duodenal surgery. In this study,
      dual-phase gastric emptying studies with combined solid-liquid meal
      were performed in 54 patients who had undergone
      pancreaticoduodenectomy (Whipple procedure). Gastric emptying was
      studied with GM, LAO, and anterior (ANT) methods. T1/2 and percent
      gastric retention at 10, 30, 60, 90, and 120 minutes were
      calculated. Results from the three methods were compared using
      correlation analysis and the t test. The t test showed no
      significant difference in T1/2 and percent retention values between
      the GM and LAO or ANT views. The solid emptying T1/2 showed a better
      correlation between GM and LAO values (r = 0.824) than between GM
      and ANT (r = 0.589). For the liquid T1/2, the reverse was true.
      Correlation between GM and ANT (r = 0.939) was better than between
      GM and LAO (r = 0.839); however, both LAO and ANT views correlated
      well with GM liquid emptying. It is concluded that the LAO view can
      replace GM gastric emptying methods in postpancreaticoduodenectomy
      patients for evaluation of both solid and liquid emptying, although
      the ANT view appears completely adequate for the study of liquid
      emptying.
 

Used with permission of Lippincott-Raven Publishers, 227 E. Washington Square, Philadelphia, PA 19106-3780. Yung BC-K et al. Clin Nucl Med 18:776-781, 1993.

<--- go back to bibliography
AU  - Zinner MJ
AU  - Shurbaji MS
AU  - Cameron JL
IN  - Department of Surgery, Johns Hopkins Medical Institutions,
      Baltimore, Md.
TI  - Solid and papillary epithelial neoplasms of the pancreas. SO  -
Surgery 1990 Sep;108(3):475-80
AB  - Seven patients with solid and papillary epithelial neoplasms of the
      pancreas are reported. All were young women with a mean age of 22
      years (range, 16 to 33 years old). Each patient had a large
      asymptomatic abdominal mass. The tumors ranged in size from 7 to 20
      cm (average size, 13 cm) and were evenly distributed throughout the
      head, body, and tail of the pancreas. One patient had a metastatic
      tumor to her liver, which was unresectable. All other patients
      underwent resection, which included two distal pancreatectomies, two
      total pancreatectomies, one pancreaticoduodenectomy, and one local
      excision. Four of the seven patients had evidence of local invasions
      alone, and one had a liver metastasis and local invasion. All
      patients had the characteristic histologic pattern of a solid and
      papillary epithelial pancreatic neoplasm. All patients are alive
      with a mean follow-up of 10 years (range, 4 to 20 years). This is an
      unusual malignant neoplasm of the pancreas occurring predominantly
      in young women. Even though they are locally invasive, long-term
      survival is the rule. Surgical therapy should be aggressive, since
      liver metastasis may occur.
 

With permission from SURGERY, ©1990.

<--- go back to bibliography


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