A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Metastatic pancreatic tumors: what is the optimal treatment?

Although rare, metastases to the pancreas from other primary tumors are increasingly recognized in clinical practice, but the optimal treatment remains unclear. When a careful staging is performed and widespread disease is excluded, the indication of pancreatectomy may arise. This study was designated to review the published literature on the results of surgical treatment for the most common malignancies metastasizing to the pancreas. Analysis of the reports show that resection can be performed safely, but long term survival is substantially influenced by the tumor's biology. There are convincing evidences that pancreatic resection for metastasis from renal cell cancer may offer excellent results in term of prolonged survival, while for other type of cancer, pancreatic resection should be considered only a palliative procedure, with only anedoctical reported long-term survivors. So, comparison of the results of surgical and non-surgical management of metastatic tumors to the pancreas is very difficult to perform. There is a need of studies evaluating the role of chemotherapy in the neoadjuvant setting or the best sequential use of multimodality treatment (targeted therapy, radiotherapy, surgery, etc.). At the moment, pancreatic resection for metastasis should be reserved to patients in good health conditions, with isolated disease from renal cell cancer. For other types of tumor, surgery should be performed only in individual basis.

Outcome of pancreaticoduodenectomy in octogenarians: Single institution's experience and review of the literature.

INTRODUCTION: Pancreatic and perampullary neoplasms in patients aged 80 or older trouble the surgeons because of the risk of surgical treatment. We have reviewed our experience and literature's reports of pancreaticoduodenectomy in octogenarians, evaluating early results and long-term survival in pancreatic cancer group. METHODS: Three hundred eighty-five patients who underwent pancreaticoduodenectomy for neoplasms from 1998 to 2011 were included in the study, and were divided in two groups: group 1, patients younger than 80 years of age, and group 2, patients 80 years of age and older. Operative morbidity, mortality, disease-free and long-term survival were analysed. English literature was systematically searched for pancreatic resection's outcome in octogenarians. RESULTS: There were 385 pancreaticoduodenectomies: 362 patients were in group 1 and 23 patients in group 2. There was no significant difference regarding gender, and pathologic findings between the two groups. Complications' rate (40 vs. 43%), mortality rate (4% vs. 0%), and overall median survival for pancreatic cancer patients were not statistically different in the two groups (median 21 vs. 19 months). Literature's review showed 14 reports of pancreatic resection in octogenarians. Most of the studies (particularly in centres with high-volume pancreatic surgery) showed that outcome after pancreatectomy was not different in octogenarians or in younger patients. CONCLUSION: Pancreaticoduodenectomy is an acceptable option for elderly patients. Age alone should not be considered a contraindication to major pancreatic resection, but a careful preoperative evaluation and an accurate postoperative management are mandatory.

Pancreaticoduodenojejunostomy for chronic pancreatitis presenting with an inflammatory mass in the head of the pancreas.

An inflammatory mass in the head of the pancreas is reported in 18-50% of patients with chronic pancreatitis. When the clinical history is misleading, differential diagnosis between chronic pancreatitis and pancreatic cancer may be very difficult. Pancreaticoduodenectomy is considered the treatment of choice, if cancer is still suspected despite negative biopsy. From January 1987 to December 1992 we performed 42 pancreaticoduodenectomies, 36 for malignancies of the pancreaticoduodenal area and 6 for chronic pancreatitis suspected to have a pancreatic cancer. In three additional cases of chronic pancreatitis, we performed a pancreaticoduodenojejunal anastomosis after complete opening of the pancreatic duct and excision of the papilla of Vater. Frozen section and definitive histological examination of the pancreas and ampulla excluded malignance in all three patients. They are alive and well 60, 36, and 20 months after operation. With this procedure, frozen-section examination of the distal part of the pancreatic and biliary duct, the papilla, and the periductal pancreatic tissue can be performed, while this is impossible with the usual pancreaticojejunostomy. We can therefore reasonably exclude a small cancer of the periampullary area and perform a wider derivative procedure, instead of a pancreaticoduodenectomy, in patients with an inflammatory mass of the head of the pancreas.

Pancreatic head resection for noninflammatory benign lesions of the head of the pancreas.

INTRODUCTION: Duodenum-preserving pancreatic head resection (DPPHR) has been safely performed in patients with chronic pancreatitis. The procedure has rarely been used to remove benign or borderline lesions of the head of the pancreas. AIMS: To review our experience with 13 patients who underwent DPPHR and to review reports in the literature on the same subject. METHODOLOGY: From October 1991 to September 2000, 13 patients underwent DPPHR to resect endocrine pancreatic tumors (n = 4), beta cell hyperplasia (n = 1), pancreatic pseudocysts (n = 2), serous cystadenomas (n = 3), congenital (n = 1) and choledochal (n = 1) cysts, and intraductal papillary mucinous tumor (n = 1). The Kocher maneuver was performed in seven patients (group 1) and avoided in six (group 2). Type 1, 2, and 3 DPPHR were defined depending on the amount of pancreatic tissue left at the inner surface of the duodenum. Ten patients underwent evaluation that included an oral glucose tolerance test and exocrine pancreatic function test. RESULTS: The mortality rate was zero; the complication rate was 69%. Patients in whom the Kocher maneuver was not performed (group 2) experienced fewer complications, shorter stay on nasogastric tube and abdominal drain(s), and earlier water intake and discharge. Type of DPPHR did not influence the postoperative course. One patient died 3 months after surgery of unrelated disease. Twelve patients were alive and well 2 months to 8 years after surgery. CONCLUSION: DPPHR is a low-risk procedure in patients with benign or borderline noninflammatory lesions of the head of the pancreas in whom pylorus-preserving pancreaticoduodenectomy is otherwise indicated. Whenever possible, the Kocher maneuver should be avoided.

Clinical evaluation and safety of loxiglumide (CCK-A receptor antagonist) in nonresectable pancreatic cancer patients. Italian Pancreatic Cancer Study Group.

The effects and safety of loxiglumide, a cholecystokinin-A (CCK-A) receptor antagonist, on advanced pancreatic cancer were investigated in humans. A perspective, controlled (2.4 g/day vs. placebo), randomized, double-blind, parallel-group study was performed in 64 patients affected by nonresectable histologically diagnosed pancreatic cancer. The patients were stratified according to sex and stage (A, T3/N0-N1/M0; B, T1-T2-T3/N0-N1/M1; C, relapse after surgical exeresis). Tumor size (by computed tomography scan) and mortality rate were evaluated as efficacy criteria. Clinical symptoms and physical signs, laboratory tests, and adverse reactions were checked every 6 weeks as efficacy/tolerability criteria. Forty-two male and twenty-two female patients were considered. A homogeneous distribution of the patients was demonstrated in the two treatment groups. Group C was not statistically evaluated for survival and tumor evolution because of its small number. Three patients dropped out for causes not related to the therapy. No toxic reactions to the drug were reported. Tumor size monitoring within groups A and B demonstrated a similar increase in both the loxiglumide and the placebo group. Survival in group A was higher than in group B (p = 0.0003). In group B, survival was lower in females (F) than in males (M) (F = 61.00 +/- 6.47 days, M = 140.44 +/- 22.15 days; p = 0.012), while survival by sex was similar in group A and in global analysis. Survival by treatment was similar for groups A and B. Survival by surgery was higher (p = 0.049) for surgical palliation than for nonoperated patients. The tumor grade affected survival but it did not vary by therapy. In conclusion, sure efficacy of loxiglumide in advanced pancreatic cancer was not demonstrated by our results. In consideration of its documented tumor growth inhibiting action, we suggest that loxiglumide be tested for recurrence prevention after resective surgery.

Evaluation of carbohydrate antigens 19-9 and 12-5 in patients with pancreatic cancer.

The diagnostic value of the tumor-associated antigens Ca 19-9 and Ca 12-5 was tested in 130 subjects (38 healthy controls, 37 carcinomas of the pancreas, 23 chronic pancreatitis, 23 extrapancreatic gastrointestinal cancers, 9 endocrine pancreatic tumors). Ca 19-9 levels above 37 U/ml were obtained in 67.6% and Ca 12-5 levels above 39 U/ml in 45.9% of carcinomas of the pancreas, 4.3 and 8.7%, respectively, of chronic pancreatis, 21.7 and 17.4% of extrapancreatic gastrointestinal tumors, and 0 and 11.1% of endocrine pancreatic tumors and in none of the healthy controls. Results of preoperative determination of Ca 19-9 and Ca 12-5 gave a sensitivity of 67.6 and 45.9%, a specificity of 91.8 and 90.9%, a predictive value of a positive test of 80.6 and 70.8%. When elevation of both antigens was required, sensitivity decreased to 32.4% but specificity rose to 97.3%. All but one of the pancreatic cancer patients were at stage 3 and 4. The only patient with pancreatic cancer in stage 1 had normal levels of both markers. Ca 19-9 and Ca 12-5, whether alone or associated, represent a good diagnostic test for differentiating pancreatic cancer from chronic pancreatitis. Due to the low sensitivity of both markers, the tests are of limited value when any other diagnostic evidence of pancreatic cancer is absent.

Ductal adenocarcinoma of the body and tail of the pancreas.

BACKGROUND: Carcinoma arising from the body and tail of the pancreas is less frequent than pancreatic head cancer, and its prognosis is known to be worse. This aggressive behavior is reported by few large clinical studies. STUDY DESIGN: We retrospectively reviewed our 24 years experience on adenocarcinoma of the body and tail of the pancreas and analyzed survival and longterm results after resection. Recent large series on cancer of the distal pancreas were also reviewed. RESULTS: Among 148 patients observed, 109 were surgically treated. Resectability rate was 16%; ductal adenocarcinoma in 22% of patients who underwent surgery was resectable. Macroscopic radical resection was achieved in only 16 cases. Overall 5-year survival rate was 2%. In resected cancers the actual 5-year survival rate was 12.5%. Patients with unresectable cancers did not survive more than 17 months. All three patients who survived more than 5 years had a small tumor (T1 according to TNM staging). In the literature, among 360 evaluable resected patients, only 7 survived at 5 years (2%). CONCLUSIONS: The prognosis for patients with adenocarcinoma of the distal pancreas is poor, even after resection of the tumor; however, the results are not substantially different for those reported after resection for pancreatic head carcinoma. Surgical resection can offer longterm survival for patients with localized cancer.

Median pancreatectomy for tumors of the neck and body of the pancreas.

BACKGROUND: When enucleation is too risky because of possible damage of the main pancreatic duct, benign tumors located in the neck or body of the pancreas are usually removed by a left (spleno)-pancreatectomy or by a pancreatoduodenectomy. But standard pancreatic resection results in an important loss of normal pancreatic parenchyma and may cause impairment of exocrine and endocrine function. The aim of this study was to evaluate early and longterm results of median pancreatectomy, a limited resection of the midportion of the pancreas, in selected patients with benign or borderline tumors of the pancreas. STUDY DESIGN: Records of patients at Ospedale Busonera between November 1985 and September 1998 were reviewed. Ten patients with tumors of the neck or body of the pancreas underwent median pancreatectomy; the cephalic stump was sutured and the distal stump was anastomosed with a Roux-en-Y jejunal loop. Followup included clinical evaluation and routine laboratory tests: abdominal ultrasonography, exocrine and endocrine pancreatic function with fecal chymotrypsin, and an oral glucose tolerance test. RESULTS: Pathologic examination showed: insulinoma (n = 3), mucinous cystadenoma (n = 3), nonfunctioning endocrine tumor (n = 1), papillary-cystic neoplasm (n= 1), serous cystadenoma (n = 1), and intraductal mucinous tumor (n = 1). Operative mortality and morbidity were 0% and 40%, respectively; pancreatic fistula occurred in three patients. At mean followup of 62.7 months, no recurrence was found and no patient had exocrine insufficiency or glucose metabolism impairment. CONCLUSIONS: Median pancreatectomy is a safe and effective alternative to major pancreatic resection in selected patients with benign or low-malignant lesions of the pancreas. This procedure carries a surgical risk similar to that of the standard operation, but avoids extensive pancreatic resection and pancreatic function impairment.

Hormonal treatment of unresectable pancreatic cancer with LHRH analogue (goserelin).

Recently non-controlled clinical trials reported encouraging results using a suppressive endocrine treatment in patients with unresectable pancreatic cancer. In this study 15 patients were given an LHRH analogue every 4 weeks (goserelin 3.6 mg), while 18 patients with advanced stage pancreatic carcinoma were given only symptomatic therapy. All patients treated with goserelin had sexual hormone suppression. Follow-up included abdominal ultrasound or computed tomography scan every 3 months; Ca 19-9 assay and routine laboratory blood tests were performed every month. No partial or complete response, no performance status or Ca 19-9 level changes were found. No significant difference in survival was seen in the two groups of patients. This study suggests that goserelin is unlikely to have a major influence on the survival of patients with advanced pancreatic carcinoma and casts further doubt upon the hormone-dependence of this neoplasm.

Diabetes mellitus in pancreatic cancer follow-up.

The aim of this study was to assess the behavior of fasting serum glucose, C-peptide levels and OGTT in pancreatic cancer follow-up. We studied 49 patients with pancreatic cancer (stage I = 8 pts; II = 16 pts; III = 12 pts; IV = 13 pts). At diagnosis 13/49 patients had fasting serum glucose levels of above 140 mg/dL. Of the remaining 36 pts, 22 underwent OGTT, which indicated diabetes mellitus in 9/22 (41%) and impaired glucose tolerance in 7/22 (32%) cases. C-peptide basal values were within the normal range (0.8-2.0 micrograms/L) in 14/49 (28%), above 2.0 micrograms/L in 6/49 (13%) and below 0.8 micrograms/L in 29/49 (59%) of the cases. No significant correlation was found between tumor stage or size and the presence of diabetes or of a reduced glucose tolerance. Twenty-four patients underwent curative resection (group 1) and 16 palliative resection, while the remaining nine did not undergo surgery (group 2). Group 1 and 2 patients had a follow-up of 2 to 40 months (mean = 14 months) and from 1 to 7.5 months (mean = 3.5 months) respectively. In group 1 patients no significant difference was found between pre- and post-operative fasting serum glucose levels. However, in 11/15 (73%) patients who underwent OGTT before and after surgery, an improvement in glucose tolerance was observed after tumor resection. In group 2 patients, a significant increase in fasting serum glucose levels was found during follow-up. In neither of the groups studied were significant variations found in C-peptide levels during the follow-up, although a slight increase was observed in patients who did not undergo surgery. In conclusion, the reduced glucose tolerance or frank diabetes mellitus, which frequently occurs during the onset of pancreatic cancer, does not seem to be related to tumor stage or size. Curative resection ameliorates glucose intolerance, while tumor persistence can enhance serum glucose levels.

Neural cell adhesion molecule (N-CAM) in gastrointestinal neoplasias.

BACKGROUND: The neural adhesion molecule N-CAM, a membrane bound glycoprotein, seems to play an important role in the development of normal tissue architecture and in contact-dependent inhibition of cell growth. MATERIALS AND METHODS: We evaluated the behaviour of circulating N-CAM in patients with pancreatic cancer (24 cases) and chronic pancreatitis (15 cases) and compared it with that of 20 controls, 6 patients with colon adenoma, 31 with colorectal cancer or 21 with gastric cancer and ascertained the influence of tumor stage and grade on the findings. RESULTS: N-CAM levels were significantly lower in patients with pancreatic cancer and chronic pancreatitis than in the other groups studied. High levels were found only in few colorectal carcinoma patients (4/31). No correlation was found between tumor stage and N-CAM levels when pancreatic and colorectal cancer were considered. However, low N-CAM levels were found in 50% of advanced, but not in early gastric cancer. When pancreatic, colorectal and gastric cancer were considered, poorly differentiated (G3) had lower levels of N-CAM than well (G1) or moderately (G2) differentiated tumors. The variations found in circulating N-CAM were comparable to those in CEA but not to those in CA 19-9. CONCLUSIONS: a) perhaps because of its higher aggressiveness, pancreatic cancer is associated with low serum N-CAM levels unlike other gastrointestinal neoplasias; b) the association between aggressiveness and reduced N-CAM levels is borne out by the correlation found with the grade of differentiation; c) the reduced levels found in chronic pancreatitis suggest that this molecule plays a role in stromaparenchymal interactions, which might be altered in the presence of fibrotic phenomena.

Forecast of surgical risk in pancreatic cancer.

Over a 22 year period, 305 patients underwent operations for pancreatic cancer. Seventy-one patients who only underwent a laparotomy and 60 patients with defective data were excluded from our study. The remaining 174 patients were analyzed to find a clinically applicable algorithm to allow the preoperative surgical risk to be evaluated in a single patient. One hundred twenty-six had undergone a bypass operation (Group I) and 48, a potentially curative resection (Group II). The two groups were divided into the following three risk groups according to the postoperative course: D, patients who died during the first postoperative month; C, patients with postoperative complications; and U, patients with an uneventful course. Preoperative weight loss, duration of jaundice, serum bilirubin level, total protein level, and age of every patient were collected and transformed into a three-score ordinal scale. Stepwise discriminant analysis of these data enabled us to correctly classify 88 percent of the patients who underwent palliative operations and 83 percent of those who had pancreatic resection. This method is useful in identifying the risk group for a single patient using individual preoperative variables. It may, moreover, suggest the most suitable treatment for each patient with pancreatic cancer.

Epidemiology of pancreatic cancer in Northeastern Italy: incidence, resectability rate, hospital stay, costs and survival (1990-1992).

BACKGROUND: The incidence of pancreatic cancer and relative hospital stay and costs are not well known. AIMS: To define the incidence, hospital stay and cost of pancreatic cancer in a well-defined area of Italy. PATIENTS AND METHODS: Each new case of pancreatic cancer diagnosed between 1990 and 1992 among 669,703 inhabitants in the Veneto Region of Northern Italy was recorded and followed until death or for 5 years after diagnosis. Four types of hospital stay were defined. Type 1: undiagnosed pancreatic cancer; type 2: first diagnosis of pancreatic cancer, treatment excluded; type 3: main treatment; and type 4: follow-up and disease-related complications. Data were analysed for hospital stay-related procedures, costs and survival. RESULTS: Pancreatic cancer was diagnosed in 253 patients (12.6/100,000 per year), 43 patients (17.7%) underwent surgical resection, and 93 (36.8%) palliative surgery. The mean duration of type 3 hospital stay was similar for resection, palliative and exploratory surgery. The estimated hospital cost was significantly higher for surgical resection, almost the same for palliative and exploratory surgery, and only slightly lower for medical treatment. Each patient spent a mean of 57.7 days in the hospital. The hospital mortality rate was 4.6% for surgical resection, 22.1% for palliative surgery, and 18.7% for exploratory laparotomy. Overall, the 1-, 2-, 3- and 5-year survival rates were 20.9%, 5.1%, 2.9% and 1.2%, respectively. CONCLUSIONS: Pancreatic cancer is an expensive, almost incurable disease. Integrated treatments in specialized Centres should reduce the mortality rate and costs.

Central venous catheter guidewire replacement according to the Seldinger technique: usefulness in the management of patients on total parenteral nutrition.

While on total parenteral nutrition (TPN), 37 patients underwent replacement of a central venous catheter (CVC), during which a wire introducer was used, according to the Seldinger technique. In 25 patients, the CVC was placed in the superior cava via the subclavian, and, in 12, via the jugular vein. Overall, 82 CVC changes were performed.: 74 for assumed CVC sepsis, 6 as preventive treatment, and 2 for partial catheter displacement. Catheter tip culture proved to be positive in 25 of 119 CVC examined. The catheters were defined as sterile when the tip culture was negative; contaminated, when the tip culture was positive and peripheral blood culture was either negative or positive for different bacteria; septic when both tip and blood were positive for the same bacteria. The results indicated that 10 catheters were contaminated and 17 were septic. Eight previously sterile CVC were found positive after the exchange: 3 were removed at the end of TPN in asymptomatic patients, and 5 were successfully resterilized by means of one more change. Guidewire replacement allowed CVC sterilization of 22 of 24 catheters (91.6%). No complications due to the catheter-changing method were seen.

Surgical experience with adenocarcinoma of the ampulla of Vater.

Between 1968 and 1982, 13 patients in this study had a pancreaticoduodenectomy (PD), one patient had a total pancreatectomy, two had an ampullectomy, and one patient had a choledochoduodenostomy for neoplasia of the ampulla of Vater. The operative mortality was zero, and the 5-year actuarial survival rate for the 16 resected patients was 52.6 per cent. From a review of the literature, the authors evaluated 1,894 PDs and 61 ampullectomies. The operative mortality rate was 14 per cent and 3 per cent, respectively. The 5-year survival rate was 21 per cent for PD and 23 per cent for ampullectomy. However, 187 patients with negative lymph nodes who underwent PD had a 5-year survival rate of 39 per cent. PD resection is fully warranted for ampullary tumors. Ampullectomy should be reserved only for high surgical risk patients.

Cystic neoplasms of the pancreas: problems in differential diagnosis.

From 1970 to 1990 we observed 18 patients with histologically proven pancreatic cystic tumors. The average duration of symptoms prior to diagnosis was 14.1 months. A presumptive diagnosis was made preoperatively in nine patients. CT-guided fine needle cytology performed in three cases correctly showed a benign lesion in one patient and malignancy in two patients. Amylase and tumoral marker levels (CEA, CA19-9) were low in cystic fluid of two patients with cystadenomas who underwent preoperative percutaneous aspiration. Intraoperative biopsy of the cystic wall failed to detect epithelial lining in two cases; one patient had internal drainage for cystadenocarcinoma mistaken for pancreatic pseudocyst. Sixteen patients underwent surgery, two of whom died. Of the seven patients with a malignant condition, resection for cure was performed on three. The preoperative diagnosis of these very rare tumors remains difficult. Fine-needle cytology and cystic fluid examination may be a promising technique, but resection of all suspected lesions, whenever possible, is the procedure of choice for diagnosis and treatment.

Mucinous cystadenoma of the pancreas as a cause of acute pancreatitis.

Acute pancreatitis is only rarely the first presentation of a cystic neoplasm of the pancreas. Mucinous cystadenomas have not been reported to be a cause of acute pancreatitis; however, we present two cases of mucinous cystadenoma of the pancreas which have caused acute pancreatitis. Both patients (female) presented acute abdominal pain, with serum amylase elevation and ultrasound scan (US) and computed tomography (CT) evidence of moderate pancreatitis, which resolved with medical treatment; fluid collection in the distal pancreas had been misinterpreted as a pseudocyst. There was no history of alcohol abuse or gallstone disease. After distal pancreatectomy the diagnosis of mucinous cystadenoma was confirmed; in one case a large pseudocyst was associated with this diagnosis. Pre-operative differential diagnosis between inflammatory and neoplastic cysts is difficult, especially when the patient's first presentation is due to an episode of acute pancreatitis. A neoplastic cyst should be considered when acute pancreatitis attacks occur in non-alcoholic women, who do not have gallstone disease.