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John L Cameron

Publications and source records attributed to John L Cameron.

At least 19 recordsLinked to original sources
PubMed2006

Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up.

BACKGROUND: Many studies have reported 5-year survival data after pancreaticoduodenectomy for periampullary adenocarcinoma. This study evaluates 10-year survival in patients surviving 5 years after initial surgery. METHODS: We reviewed all patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma from April 1970 to July 1999 at a single institution. All 5-year survivors were identified, and their subsequent 5-year survival was compared with the actuarial survival of the general population starting at 70 years of age. RESULTS: Nine hundred fifteen patients underwent pancreaticoduodenectomy for periampullary adenocarcinoma. Follow-up was complete on 890 patients. There were 201 (23%) 5-year survivors with a median age of 65 years at initial surgery; 51% were male and 92% were Caucasian. For the 5-year survivors, the carcinoma origin was pancreatic in 46%, ampullary in 25%, distal bile duct in 17%, and duodenal in 12%. For all 5-year survivors, the subsequent 5-year actuarial survival rate was 65%, with a median survival after achieving the 5-year landmark of 7.9 additional years. The subsequent 5-year survival by site of tumor origin was 55% for pancreatic, 66% for ampullary, 74% for bile duct, and 85% for duodenal cancer. For the age-matched population, the 5-year survival rate was 87% (P<.001 when compared with those with all periampullary cancers). CONCLUSIONS: While the 5-year survival rate for all patients with resected periampullary adenocarcinoma is only 23%, these data imply that attainment of the 5-year survival landmark carries with it an improved survival for the subsequent 5 years. While the survival rate was less than that of the age-matched population, 65% of 5-year survivors survived 5 more years, bringing them to the 10-year postresection landmark.

Adenocarcinoma↗
PubMed2006

MKK4 status predicts survival after resection of gastric adenocarcinoma.

HYPOTHESIS: Lack of expression of the tumor-suppressor gene MKK4 is significantly correlated with poor survival after resection of gastric adenocarcinoma. DESIGN: Retrospective review of medical records after construction and immunolabeling of tissue microarrays for clinical correlation. SETTING: The Johns Hopkins Hospital, Baltimore, Md. PATIENTS: Patients operated on because of gastric adenocarcinoma between 1983 and 1995. Main Outcome Measure Long-term survival and MKK4 status. RESULTS: Primary tumors (N = 124) were scored as 0 (no labeling), 1+ (weak labeling), or 2+ (strong labeling) in 9 (7%), 80 (65%), and 35 (28%) patients, and 5-year survival in these patients was 0%, 21%, and 28%, respectively. Given the small size (7%) of the MKK4-negative group (as expected, given the 5%-10% incidence of genetic loss in carcinomas), a Cox proportional hazards analysis was performed, adjusting for age, sex, and tumor stage. This multivariate analysis revealed a 5-fold increased risk of death (P<.001) in patients whose primary tumors were MKK4-negative. Furthermore, the addition of MKK4 status significantly improved the Cox model, changing log likelihood from -1410 to -369, confirming that MKK4 status was truly the effector of the survival difference and not a bystander. CONCLUSIONS: The lack of expression of the tumor-suppressor gene MKK4 in resected gastric adenocarcinoma is robustly associated with poor survival. This finding may provide a useful prognostic tool in patients with gastric adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Differences in survival for patients with resectable versus unresectable metastases from pancreatic islet cell cancer.

Well-differentiated islet cell tumors can be associated with aggressive biology, resulting in early metastases to the liver. This study was carried out to determine whether survival for patients with malignant islet cell tumors and synchronous liver metastases is affected by complete surgical resection. Thirty-one patients with synchronous liver metastases from islet cell cancer underwent surgical exploration with the intent for complete tumor resection, and all patients underwent resection of the pancreatic primary. The patients were divided into two groups, those with resectable versus unresectable liver metastases. Twenty-six of 31 (84%) patients underwent complete resection of both the primary tumor and all liver metastases, and 5 (16%) patients underwent only complete resection of the pancreatic primary without liver resection. To extirpate the primary tumor, a pancreaticoduodenectomy was performed in 11 of the 26 (42%) completely resected patients and in 4 of the 5 (80%) incompletely resected patients, P = NS. The remainder of the patients underwent distal pancreatectomy. There were no statistical differences in primary tumor size, lymph node metastases, or adjuvant treatments between patients with resected and unresected liver metastases. The median overall survival for the completely resected group was 78 months, longer than the 17 months for the group with unresectable liver metastases (P = 0.06). Complete tumor resection (or the tumor biology that allows such complete resection) affords a survival advantage to patients with metastatic islet cell tumors of the pancreas. Patterns of liver metastases from islet cell tumors, specifically multiple bilobar metastases that are not amenable to resection and/or ablation, predict a poor outcome despite resection of the primary pancreatic tumor.

Adult↗
PubMed2006

Abdominal lymphangiomas in adults.

Abdominal lymphangiomas are rare benign cystic tumors that can become locally invasive and often require resection. They arise in all ages and have a variable presentation. We performed a retrospective review of a single institution surgical experience with this lesion in adults. The pathology prospective database was reviewed to identify patients with surgically resected abdominal lymphangiomas from January 1986 to May 2004. Retrospective review and follow-up was performed for each patient. The six patients with abdominal lymphangiomas ranged in age from 38 to 66 years. They presented with a variety of signs and symptoms. All underwent CT scan that demonstrated a cystic lesion, but in only one third was the diagnosis made preoperatively. Tumors were located in the retroperitoneum, small bowel mesentery, liver, and pancreas. Five of the six tumors were completely resected. Two of the six required resection of adjacent or involved organs. Follow-up ranged between 6 months and 18 years. All had symptomatic relief after resection, and no patient showed evidence of recurrence in this time period. Abdominal lymphangiomas are rare. The correct diagnosis often remains elusive until tissue is obtained. The treatment of choice is complete surgical resection. When completely resected, these lesions seem not to recur, and the overall prognosis is excellent.

Abdominal Neoplasms↗
PubMed2006

Benign pneumatosis intestinalis in the setting of celiac disease.

Pneumatosis intestinalis is an uncommon finding that may indicate the presence of several alarming pathological conditions, including bowel ischemia, that require urgent surgical intervention. We report the case of a 51-year-old man with celiac disease who underwent resection of a large duodenal adenocarcinoma. Although he initially recovered rapidly from his procedure, he subsequently developed abdominal distention and leukocytosis. Abdominal imaging revealed extensive small bowel pneumatosis and pneumoperitoneum. Emergent surgical exploration revealed only bowel wall air cysts and dilated bowel but failed to demonstrate any intra-abdominal pathology. The patient recovered uneventfully and was discharged without any further complications or recurrence of symptoms. We review the current literature on the rare finding of pneumatosis intestinalis in the setting of celiac disease. In all reported cases, even when pneumatosis is accompanied by pneumoperitoneum, these alarming findings have proved to be of "benign" origin, that is with no evidence of bowel ischemia, perforation, or peritonitis. The available evidence suggests that pneumatosis in the setting of celiac disease may reflect the dissection of intraluminal gas into the inflamed bowel wall without accompanying intra-abdominal pathology. We conclude that pneumatosis intestinalis, even with accompanying pneumoperitoneum, does not uniformly mandate surgical exploration in patients with celiac disease.

Adenocarcinoma↗
PubMed2006

Pancreaticoduodenectomy in the very elderly.

It is estimated that by 2050, there will be a 300% increase in the elderly population (> or =65 years) and a corresponding increase in elderly patients presenting for surgical evaluation. Surgical decision-making in this population can be difficult because outcomes in the elderly are poorly defined. We reviewed 2698 consecutive pancreaticoduodenectomies (PDs) at our institution over a 35-year period (April 1970 through March 2005), with the last 1000 resections being done in the last 4 years. Data collected included surgical indication, mortality (defined as 30-day or in-hospital mortality), complications, and survival. Patients were divided by age into three groups (<80, 80-89, and > or =90 years) and evaluated using multiple logistic regression. Two hundred seven patients > or =80 years old underwent a PD (7.7% of 2698). Patients 80-89 years of age had a mortality rate of 4.1% (8 of 197) and a complication rate of 52.8% (99 of 197), whereas patients < or =79 years of age had a mortality of 1.7% and a complication rate of 41.6% (P < 0.05). There were no perioperative deaths among the 10 patients > or =90 years of age, and their complication rate was 50% (5 of 10). One-year survival for patients 80-89 years of age was 59.1%, and that for patients > or =90 years was 60%. Age was not an independent risk factor for perioperative mortality and morbidity following PD after adjusting for preoperative comorbidities. We demonstrate that PD can be safely performed in patients over 80 years of age and conclude that age alone should not be a contraindication to pancreatic resection. The advent of improved surgical outcomes and an aging population will likely result in a significant increase in the number of PDs performed in the next few decades.

Age Factors↗
PubMed2006

Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial.

Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy (PD) with encouraging results in both retrospective and prospective studies. We performed a prospective randomized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD. Two hundred thirty-eight patients were randomized to either receive a pancreatic stent (S) or no stent (NS), and stratified according to the texture of the pancreatic remnant (soft/normal versus hard). Four patients were excluded from the study; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed. Patients who randomized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis. In patients with a soft pancreas, 57 randomized to the S group and 56 randomized to the NS group. In patients with a hard pancreas, 58 randomized to the S group and 63 randomized to the NS group. The S and NS groups for the entire study population, as well as for the subgroup of high-risk patients with soft pancreata, were similar as regard to demographics, past medical history, preoperative symptoms, preoperative procedures, and intraoperative data. The pancreatic fistula rate for the entire study population was 9.4%. The fistula rates in the S and NS subgroups with hard pancreata were similar, at 1.7% and 4.8% (P = 0.4), respectively. The fistula rates in the S and NS subgroups with soft pancreata were also similar, at 21.1% and 10.7% (P = 0.1), respectively. A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation (e.g., anastomotic technique, anastomotic orientation, pancreatic duct size, and number of intra-abdominal drains placed). In patients with soft pancreata, 63% percent of the pancreatic fistulas in stented patients required adjustment to the clinical pathway (including two deaths), compared to 47% of the pancreatic fistulas in patients in the NS group (P = 0.3). Internal pancreatic duct stenting does not decrease the frequency or the severity of postoperative pancreatic fistulas.

Adult↗
PubMed2006

Hospital readmission after pancreaticoduodenectomy.

Data exist on the morbidity and mortality of patients undergoing pancreaticoduodenectomy (PD), but there are few reports about hospital readmissions after this procedure. Our aim was to evaluate the number of and reasons for readmission after PD and the factors influencing readmission. We reviewed the initial hospitalization and readmissions for 1643 patients undergoing PD compared patients requiring readmission to patients that did not require readmission. Twenty-six percent of patients were readmitted a total of 678 times after PD. Patients readmitted were younger than those not readmitted (61.8 versus 64.6 years, P < 0.0001). Vessel resection, abscess formation, wound infection, postoperative percutaneous biliary stents, estimated blood loss >1000 ml, and age < or =65 years were independently associated with readmission. The length of stay for all patients decreased over time, from 10.5 days in 1996 to 7 days in 2003. The percentage of patients being readmitted also decreased from 33% in 1996 to 20% (P = 0.004) in 2003. The readmission rate after PD was 26%. Younger age, blood loss, postoperative complications, and vessel resection were independent risk factors for readmission. The early hospital readmission rate has not increased in association with a decreased LOS, supporting the idea that reduction in LOS did not lead to increased readmission rates.

Aged↗
PubMed2006

1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience.

Pancreaticoduodenectomy (PD) with the possible addition of neoadjuvant or adjuvant therapy is the standard of care in the United States for adenocarcinoma originating in the pancreatic head, neck, and uncinate process. We reviewed 1423 patients who underwent a PD for a malignancy originating in the pancreas at our institution between 1970 and 2006. We examined 1175 PDs for ductal adenocarcinomas in greater detail. Eighteen different histological types of pancreatic cancer were identified; the most common diagnoses included ductal adenocarcinoma, neuroendocrine carcinoma, and IPMN with invasive cancer. Patients with ductal adenocarcinoma were analyzed in detail. The median age was 66 years, with patients in the present decade significantly older (68 years), on average, than patients in the three prior decades (e.g., 60 years in 1970, P = 0.02). The median tumor diameter was 3 cm; 42% of the resections had positive margins and 78% had positive lymph nodes. The perioperative morbidity was 38%. The median postoperative stay declined over time, from 16 days in the 1980s to 8 days in the 2000s (P < 0.001). The perioperative mortality declined from 30% in the 1970s to 1% in the 2000s (P < 0.001). The median survival for all patients with ductal adenocarcinoma was 18 months (1-year survival = 65 %, 2-year survival = 37%, 5-year survival = 18%). In a Cox proportional hazards model, pathological factors having a significant impact on survival included tumor diameter, resection margin status, lymph node status, and histologic grade. This is the largest single-institution experience with PD for pancreatic cancer. Patients who have cancers with favorable pathological features have a statistically significant improved long-term survival.

Adult↗
PubMed2006

Incidence and outcome of biliary strictures after pancreaticoduodenectomy.

OBJECTIVE: This single-institution review examined the incidence of biliary stricture formation after pancreaticoduodenectomy (PD) for benign and malignant periampullary disease. BACKGROUND: The incidence and course of stricture of the hepaticojejunostomy have not been documented after PD. METHODS: Between January 1995 and April 2003, 1595 patients underwent PD for periampullary disease (392 benign, 1203 malignant). A retrospective analysis of a prospectively collected database was performed to determine the incidence of biliary stricture after PD. RESULTS: Forty-two of the 1595 patients (2.6%) who underwent PD developed postoperative jaundice secondary to a stricture of the biliary-enteric anastomosis. There was no difference in the incidence of biliary strictures after resection for benign (n = 10, 2.6%) or malignant disease (n = 32, 2.6%). The median time to stricture formation resulting in jaundice was 13 months (range, 1-106 months) and was similar for patients with benign and malignant disease. Preoperative jaundice did not protect against biliary stricture formation. By univariate analysis, biliary strictures were associated with preoperative percutaneous biliary drainage (odds ratio [OR] = 2.11, P = 0.02) and postoperative biliary stenting (OR = 2.11, P = 0.013). Postoperative chemoradiotherapy in patients with malignant disease was not associated with stricture formation. All strictures were initially managed with percutaneous biliary balloon dilatation and stenting, and only 2 patients required redo hepaticojejunostomy. Recurrent neoplastic disease was discovered in only 3 of the 32 patients (9%) with malignant disease. All 3 of these patients had cholangiocarcinoma as their initial diagnosis. CONCLUSIONS: Biliary stricture formation is an infrequent complication after PD and can be managed successfully with percutaneous biliary dilatation and short-term stenting in most patients. The only significant univariate predictors for biliary stricture formation were preoperative and postoperative percutaneous biliary drainage. The development of a biliary stricture in patients who have undergone PD for malignant disease is usually benign and should not be automatically attributed to anastomotic tumor recurrence.

Cholestasis↗
PubMed2006

Periampullary and pancreatic incidentaloma: a single institution's experience with an increasingly common diagnosis.

BACKGROUND: While incidental masses in certain organs have received particular attention, periampullary and pancreatic incidentalomas (PIs) remain poorly characterized. METHODS: We reviewed 1944 consecutive pancreaticoduodenectomies (PD) over an 8-year period (April 1997 to October 2005). A total of 118 patients (6% of all PDs) presented with an incidental finding of a periampullary or pancreatic mass. The PI patients were analyzed and compared with the rest of the cohort (NI, nonincidentaloma group, n = 1826). RESULTS: Thirty-one percent of the PI patients (n = 37) had malignant disease (versus 76% of the NI patients, P < 0.001), 47% (n = 55) had premalignant disease, and the remaining 22% (n = 26) had little or no risk for malignant progression. The 3 most common diagnoses in the PI group were IPMN without invasive cancer (30%), cystadenoma (17%), and pancreatic ductal adenocarcinoma (10%). The PI group had a higher overall complication rate (55% versus 43%, P = 0.02), due in part to a significantly increased rate of pancreatic fistulas (18.4% PI versus 8.5% NI, P < 0.001). Patients in the PI group with malignant disease had a superior long-term survival (median, 30 months, P = 0.01) compared with patients in the NI group with malignant disease (median, 21 months). CONCLUSIONS: Incidentally discovered periampullary and pancreatic masses comprise a substantial proportion of patients undergoing PD. Roughly three fourths of these lesions are malignant or premalignant, and amenable to curative resection. Resected malignant PIs have favorable pathologic features as compared with resected malignant NIs, and resection of these early lesions in asymptomatic individuals is associated with improved survival, compared with patients with symptomatic disease.

Adolescent↗
PubMed2006

One thousand consecutive pancreaticoduodenectomies.

OBJECTIVE: To trace the evolution of pancreaticoduodenectomy from the decade of the 1960s through the first decade of the new Millenium, through the experience of one surgeon doing 1000 consecutive operations. SUMMARY BACKGROUND DATA: A regional resection of the head of the pancreas was first performed successfully by Kausch in 1909. The operation was popularized by Whipple in 1935, who reported 3 pancreaticoduodenectomies. Because of a hospital mortality of approximately 25%, the operation was performed infrequently until the 1980s. From the 1980s on, experience with this complex alimentary tract operation increased, and high-volume centers developed. This resulted in a significant drop in hospital mortality and allowed institutions and individuals to gain large experiences. METHODS: Between March 1969 and May 2003, 1000 consecutive pancreaticoduodenectomies were performed by a single surgeon. A retrospective review of a prospectively maintained database was performed to determine the management and outcome of these patients, as well as to document the evolution of this operative procedure over 5 decades. RESULTS: The median operative time decreased significantly over the decades, being 8.8 hours in the 1970s and 5.5 hours during the 2000s. Postoperative length of stay dropped from a median of 17 days in the 1980s to 9 days in the 2000s. There were only 10 postoperative/hospital deaths, for a mortality of 1%. A total of 405 patients underwent pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Overall 5-year survival was 18%; for the lymph node-negative patients, it was 32%; and for node-negative, margin-negative patients, it was 41%. CONCLUSIONS: Pancreaticoduodenectomy has become a commonly performed operation in many tertiary care centers. Operative time, blood loss, and length of stay have dropped substantially. The operation has become safe, with a low hospital mortality. It has become an effective operation for pancreatic cancer in those patients in whom their tumor is margin negative and node negative.

Adolescent↗
PubMed2006

Assessment of complications after pancreatic surgery: A novel grading system applied to 633 patients undergoing pancreaticoduodenectomy.

OBJECTIVE: To define a simple and reproducible classification of complications following pancreaticoduodenectomy (PD) based on a therapy-oriented severity grading system. BACKGROUND: While mortality is rare after PD, morbidity rates remain high. The lack of standardization in evaluating morbidity after PD has severely hampered meaningful comparisons over time and among centers. We adapted a novel classification of complication to stratify morbidity by severity after PD, to test whether the incidence of pancreatic fistula has changed over time, and to identify risk factors in a single North American center. METHODS: The classification was applied to a consecutive series of 633 patients undergoing PD between February 2003 and August 2005. Another series of 141 patients treated between 1987 and 1990 was also analyzed to identify changes in the incidence and severity of fistula. Univariate and multivariate analyses were performed to link respective complications with preoperative and intraoperative parameters, length of hospital stay, and long-term survival. RESULTS: A total of 263 (41.5%) patients did not develop any complication, while 370 (58.5%) had at least one complication; 62 (10.0%) patients had only grade I complications (no need for specific intervention), 192 patients (30.0%) had grade II (need for drug therapy such as antibiotics), 85 patients (13.5%) had grade III (need for invasive therapy), and 19 patients (3.0%) had grade IV complications (organ dysfunction with ICU stay). Grade V (death) occurred in 12 patients (2.0%). A total of 57 patients (9.0%) developed pancreatic fistula, of which 33 (58.0%) were classified as grade II, 17 (30.0%) as grade III, 5 (9.0%) as grade IV, and 2 (3.5%) as grade V. Delayed gastric emptying was documented in 80 patients (12.7%); half of them were scored as grade II and the other half as grade III. A significant decrease in the incidence of fistula was observed between the 2 periods analyzed (14.0% vs. 9.0%, P < 0.001), mostly due to a decrease in grade II fistula. Cardiovascular disease was a risk factor for overall morbidity and complication severity, while texture of the gland and cardiovascular disease were risk factors for pancreatic fistula. CONCLUSION: This study demonstrates the applicability and utility of a new classification in grading complications following pancreatic surgery. This novel approach may provide a standardized, objective, and reproducible assessment of pancreas surgery enabling meaningful comparison among centers and over time.

Adult↗
PubMed2006

Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions.

Approximately 23,000 new gastric cancer cases and 12,000 associated deaths occur annually in the United States. Intestinal metaplasia and gastric epithelial dysplasia are precursor lesions to gastric adenocarcinoma, but are not readily detectable clinically, radiographically, or endoscopically. A noninvasive method of precursor detection would require the ability to distinguish precursor lesions from adjacent normal mucosa. In search of such markers, tissue microarrays were prepared for 133 patients of resected gastric adenocarcinoma. Tissue microarrays contained primary cancer, normal stomach, intestinal metaplasia, and gastric epithelial dysplasia and were probed with antibodies against nine potential markers that were either identified in a database of genes overexpressed in gastric adenocarcinoma or were already of interest to our laboratory: claudin-4, mitogen-activated protein kinase kinase 4 (MKK4), 14-3-3sigma (stratifin), S100A4, mesothelin, fascin, topoisomerase IIalpha, HER-2/neu, and epithelial growth factor receptor. Three markers discriminated gastric adenocarcinoma precursor lesions from normal gastric mucosa. Claudin-4 expression was present in 36 intestinal metaplasia lesions (100%) and 14 gastric epithelial dysplasia lesions (100%), but in only 16 normal stomach samples (15%). MKK4 expression was present in 24 intestinal metaplasia lesions (89%) and 12 gastric epithelial dysplasia lesions (100%), but in only 6 normal stomach samples (8%). Stratifin expression was present in 29 intestinal metaplasia lesions (97%) and 8 gastric epithelial dysplasia lesions (100%), but in only 2 normal stomach samples (3%). Sensitivity and specificity for detection of the precursor lesion intestinal metaplasia were 100% and 85%, respectively, for claudin-4; 89% and 92%, respectively, for MKK4; and 97% and 97%, respectively, for stratifin. In primary cancers, 123 of 125 (98.4%) were positive for claudin-4, 116 of 126 (94%) for MKK4, and 111 of 120 (92%) for stratifin. In conclusion, claudin-4, MKK4, and stratifin immunolabeling detects precursor lesions of gastric adenocarcinoma that are otherwise clinically, radiographically, and endoscopically inapparent. These findings may prove useful in the diagnosis and therapeutic targeting of gastric adenocarcinoma precursor lesions.

14-3-3 Proteins↗
PubMed2006

Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer.

We screened 116 patients with a strong family history of pancreatic cancer using a combination of endoscopic ultrasound and computed tomography. Ten of these patients underwent surgical resection at our institution, providing an opportunity to define the morphology of pancreatic precursor lesions in patients with a strong family history of pancreatic cancer. Eight of the 10 pancreata were available and these were entirely submitted for histologic examination. The number of pancreatic intraepithelial neoplasia (PanIN) lesions and intraductal papillary mucinous neoplasms (IPMNs) were compared with age-matched controls. Parenchymal changes were defined. Selected precursor neoplasms from 6 pancreata were microdissected and analyzed for KRAS gene mutations. PanINs were significantly more common in the 8 cases (mean of 10.7% of the duct profiles, range 1.0% to 27.3%) than in the controls (mean 1.9%, range 0% to 9.2%, P<0.01). Different KRAS gene mutations were identified in separately microdissected precursor lesions in 2 of 6 cases. IPMNs were identified in 4 of the 8 cases, including 2 pancreata each having 2 distinct IPMNs. Both the IPMNs and the PanINs, even the low-grade PanIN-1 lesions, were associated with lobular parenchymal atrophy. Some individuals with a strong family history of pancreatic cancer develop multifocal, noninvasive epithelial precursor lesions of the pancreas. PanINs and IPMNs produce obstructive lobular atrophy, and this atrophy is likely the source of the chronic pancreatitis-like changes seen in these patients. The multifocal nature of familial pancreatic neoplasia suggests that surveillance of these patients is warranted after partial pancreatectomy.

Adenocarcinoma, Mucinous↗
PubMed2005

Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms.

Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3sigma and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3sigma, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3sigma and ERM protein expression. Expression of 14-3-3sigma and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3sigma may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.

14-3-3 Proteins↗
PubMed2005

Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: a potential new target for therapy.

Methylthioadenosine phosphorylase (MTAP) plays an important role in the salvage pathway for the synthesis of adenosine. Novel chemotherapeutic strategies exploiting the selective loss of MTAP function in cancers have been proposed. The MTAP gene, on chromosome 9p21, is frequently included within homozygous deletions of the p16INK4A/ CDKN2A gene. Biallelic deletions of the p16INK4A/CDKN2A gene are found in 40% of pancreatic cancers, suggesting that the MTAP gene may be frequently inactivated in pancreatic cancer and that selected patients with pancreatic cancer may benefit from therapies targeting this loss. We immunolabeled six xenografted pancreatic cancers with known MTAP and p16INK4A/CDKN2A gene status and found that immunolabeling mirrored gene status. Loss of expression of both MTAP and p16 was observed only in those pancreatic cancers with homozygous deletions that encompassed both the MTAP and p16INK4A/CDKN2A genes. We then immunolabeled a series of 320 microarrayed infiltrating pancreatic adenocarcinomas, 35 biliary adenocarcinomas, 54 ampullary cancers, and 35 noninvasive intraductal papillary mucinous neoplasms. Immunolabeling for MTAP was lost in 91 of the 300 (30%) evaluable pancreatic cancers, 9 of 54 (17%) ampullary cancers, 4 of 33 (12%) biliary cancers, and in 1 of 35 (3%) IPMNs. All neoplasms with loss of MTAP labeling also demonstrated loss of p16 labeling. These results suggest that MTAP expression is lost in approximately 30% of infiltrating pancreatic cancers and in a lower percentage of other periampullary neoplasms, that this loss is the result of homozygous deletions encompassing both the MTAP and p16INK4A/CDKN2A genes. Thus, pancreatic cancer is a promising cancer type in which to explore novel chemotherapeutic strategies to exploit the selective loss of MTAP function.

Adenocarcinoma↗