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Metabolic dysfunctions after pancreatoduodenectomy (PD) need to be considered when pancreatic head resection is likely to lead to long-term survival.Medline, Embase and Cochrane Library were searched for studies reporting measured data of metabolic function after PD and duodenum-sparing total pancreatic head resection (DPPHR). Data from 23 cohort studies comprising 1019 patients were eligible; 594 and 910 patients were involved in systematic review and meta-analysis, respectively.The cumulative incidence of postoperative new onset of diabetes mellitus (pNODM) after PD for benign tumors was 46 of 321 patients (14%) measured after follow-up of in mean 36 months postoperatively. New onset of postoperative exocrine insufficiency (PEI) was exhibited by 91 of 209 patients (44%) after PD for benign tumors measured in mean 23 months postoperatively. The meta-analysis indicated pNODM after PD for benign tumor in 32 of 208 patients (15%) and in 10 of 178 patients (6%) after DPPHR (p = 0.007; OR 3.01; (95%CI:1.39-6.49)). PEI was exhibited by 80 of 178 patients (45%) after PD and by 6 of 88 patients (7%) after DPPHR (p 0.001). GI hormones measured in 194 patients revealed postoperatively a significant impairment of integrated responses of gastrin, motilin, insulin, secretin, PP and GIP (p 0.050-0.001) after PD. Fasting and stimulated levels of GLP-1 and glucagon levels displayed a significant increase (p 0.020/p 0.030). Following DPPHR, responses of gastrin, motilin, secretin and CCK displayed no change compared to preoperative levels.After PD, duodenectomy, rather than pancreatic head resection is the main cause for long-term persisting, postoperative new onset of DM and PEI.

OBJECTIVE To assess metabolic dysfunctions and steatohepatosis after standard and local pancreatic resections for benign and premalignant neoplasms. SUMMARY OF BACKGROUND DATA Duodenopancreatectomy, hemipancreatectomy, and parenchyma-sparing, limited pancreatic resections are currently in use for nonmalignant tumors. METHODS Medline, Embase, and Cochrane libraries were searched for studies reporting measured data of metabolic functions following PD, pancreatic left resection (PLR), duodenum-sparing pancreatic head resection (DPPHR), pancreatic middle segment resection (PMSR), and tumor enucleation (TEN). Forty cohort studies comprising data of 2729 patients were eligible. RESULTS PD for benign tumor was associated in 46 of 327 patients (14.1%) with postoperative new onset of diabetes mellitus (pNODM) and in 109 of 243 patients (44.9%) with postoperative new onset of pancreatic exocrine insufficiency measured after a mean follow-up of 32 months. The meta-analysis displayed pNODM following PD in 32 of 204 patients (15.7%) and in 10 of 200 patients (5%) after DPPHR [P < 0.01; OR: 0.33; (95%-CI: 0.15-0.22)]. PEI was found in 77 of 174 patients following PD (44.3%) and in 7 of 104 patients (6.7%) following DPPHR (P < 0.01;OR: 0.15; 95%-CI: 0.07-0.32). pNODM following PLR was reported in 107 of 459 patients (23.3%) and following PMSR 23 of 412 patients (5.6%) (P < 0.01; OR: 0.20; 95%-CI: 0.12-0.32). Postoperative new onset of pancreatic exocrine insufficiency was found in 17% following PLR and in 8% following PMSR (P < 0.01). pNODM following PPPD and tumor enucleation was observed in 19.7% and 5.7% (P < 0.03) of patients, respectively. Following PD/PPPD, 145 of 608 patients (23.8%) developed a nonalcoholic fatty liver disease after a mean follow-up of 30.4 months. Steatohepatosis following DPPHR developed in 2 of 66 (3%) significantly lower than following PPPD (P < 0.01). CONCLUSION Standard pancreatic resections for benign tumor carry a considerable high risk for a new onset of diabetes, pancreatic exocrine insufficiency and following PD for steatohepatosis. Parenchyma-sparing, local resections are associated with low grade metabolic dysfunctions.

The aim of this study was to assess the frequency and severity of new onset of diabetes mellitus (NODM) and pancreatic exocrine insufficiency (PEI) after pancreaticoduodenectomy (PD) for benign and malignant tumors.When PD is performed on patients for benign tumors, the question of long-term metabolic dysfunctions becomes of importance.Medline/PubMed, Embase, and Cochrane Library were searched for articles reporting results of measuring endocrine and exocrine pancreatic functions after PD. The methodological quality of 19 studies was assessed by means of the Newcastle-Ottawa scale and Moga-Score. The mean weighted overall percentages of NODM and PEI after PD were calculated with a 95% confidence interval (CI).Of 1295 patients, data valid-for-efficacy-analysis are based on 845 patients measuring pancreatic endocrine and on 964 patients determining exocrine functions after PD. The cumulative incidence of NODM was 40 of 275 patients (14.5%; 95% CI: 10.3-18.7) in the benign tumor group, 25 of 161 (15.5%; 95% CI: 9.9-21.2) in the malignant tumor group, and 91 of 409 patients (22.2%; 95% CI: 18.2-26.3) in the benign and malignant tumor group. Comparing the frequency of NODM after PD revealed significant differences between the groups (benign vs benign and malignant P0.0121; malignant vs benign and malignant P0.0017). Exocrine pancreatic insufficiency was found in the benign tumor group in 76 of 301 patients (25.2%; 95% CI: 20.3-30.7) and in the malignant tumor group in 80 of 163 patients (49.1%, 95% CI: 41.4-56.8) (P0.0001).The results of a significant increase of NODM after PD for benign and malignant tumors and a significant decrease of exocrine functions contribute to a rational weighting of metabolic long-term risks following PD.

Background Parenchyma-sparing, local pancreatic head resection, but not pancreaticoduodenectomy (PD) preserves tissue and maintains the pancreatic metabolic functions. Methods PubMed/Medline, Embase, and Cochrane library collections were systematically searched. Twenty-six cohort studies with 523 cumulative patients, who underwent duodenum-sparing pancreatic head resection (DPPHR), were retrieved. The meta-analysis was based on 14 controlled studies. Results In total, 338 patients suffered cystic neoplasms and 59 PNETs, IPMN-174, MCN-43 and SPN-23 patients. Eighty-one patients (15.5%) histo-pathologically displayed a low-malignant tumor, of which 27 were carcinoma in-situ. Tumor recurrence was observed after a mean follow-up of 47.1 months in 11 patients. In-hospital and late mortality after DPPHR was 0.6% and 1.7%, respectively. The meta-analysis was based on 318 DPPHR compared to 404 PD patients. DPPHR was performed for premalignant neoplasm and PNET in 164 and 46 patients, and PD in 181 and 46 patients, respectively. Events of recurrence displayed no statistically significant difference between the DPPHR and PD groups. Conclusion DPPHR is associated with oncologically complete tumor resection for patients suffering premalignant IPMN, MCN, or SPN and for low-risk cancer.

Background Potential benefits of local extirpation of benign pancreatic head tumors are tissue conservation of pancreas, stomach, duodenum and common bile duct (CBD) and maintenance of pancreatic functions. Methods Medline/PubMed, Embase and Cochrane Library databases were searched to identify studies applying duodenum-preserving total or partial pancreatic-head resection (DPPHRt/p) and reporting short- and long-term outcomes. Twenty-four studies, including 416 patients who underwent DPPHRt/p, were identified for systematic analysis. The meta-analysis was based on 10 prospective controlled and 4 retrospective controlled cohort studies, comparing 293 DPPHRt/p resections with 372 pancreato-duodenectomies (PD). Results, systematic analysis Of 416 patients, 75.7% underwent total and 24.3% partial head resection, while 47.1% included segmentectomy of duodenum and CBD. The most common pathology was cystic neoplasm (65.8%) and endocrine tumors (13.4%). The frequencies of severe postoperative complications of 8.8%, pancreatic fistula of 19.2%, re-operation of 1.7% and hospital mortality of 0.48%, indicate a low level of early post-operative complications. Meta-analysis DPPHRt/p significantly preserved the level of exocrine (IV = −0.67, 95% CI −0.98 to −0.35, p = 0.0001) and endocrine (IV = 18.20, fixed, 95% CI −0.92 to 25.48, p = 0.0001) pancreatic functions compared to PD when the pre- and postoperative functional status in both groups are analyzed. There were no significant differences between DPPHRt/p and PD in frequency of pancreatic fistula, delayed gastric emptying or hospital mortality. Conclusion DPPHRt/p for benign neoplasms and neuro-endocrine tumors of the pancreatic head is associated with a low level of early-postoperative complications and a better conservation of exocrine and endocrine functions.

Purpose: In pancreatic cancer median survival times range around 6, 6 to 6,9 months. Here we retrospectively analyzed the outcome of immunotherapy in the additional palliative treatment of pancreatic cancer with long antigen exposition dendritic cell therapy (LANEX-DC ® ) in 138 patients who were treated at our institution. Patients: Data were available of 134 patients (97.1%). The median interval between first diagnosis and start of treatment was 1.4 months. Results: Therapy was well tolerated and no serious side effects were observed. The survival rate after 6 months was 72.2 % and afters 9 month 50.4%. The median survival time according to Kaplan- Meier regression analysis was 8.9 months. Median survival was significantly higher in the group of patients who started immunotherapy within 2 months following diagnosis (p=0.029) or repeated immunotherapy (p=0.027). Interestingly, younger patients 60 years of age (p = 0.022). Conclusion: We were able to demonstrate in a large retrospective analysis that additional treatment with dendritic cells (LANEX-DC ® ) is highly effective and extends the median survival times up to 8.9 months. Furthermore we were able to demonstrate that median survival can be increased by early beginning and repetition of LANEX-DC ® treatment.

Cystic neoplasms of the pancreas are being detected and surgically treated increasingly more frequently. Intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are primary benign lesions; however, the 5-year risk for malignant transformation has been estimated to be 63 % and 15 %, respectively. Surgical extirpation of a benign cystic tumor of the pancreas is a cancer preventive measure. The duodenum-preserving total pancreatic head resection technique (DPPHRt) is being used more frequently for cystic neoplasms of the pancreatic head. The complete resection of the pancreatic head can be applied as a duodenum-preserving technique or with segmental resection of the peripapillary duodenum. Borderline lesions, carcinoma in situ or T1N0 cancer of the papilla and the peripapillary common bile duct are also considered to be indications for segmental resection of the peripapillary duodenum. A literature search for cystic neoplastic lesions and DPPHRt revealed the most frequent indications to be IPMN, MCN and SCA lesions and 28 % suffered from a cystic neoplasm with carcinoma in situ or a peripapillary malignoma. The hospital mortality rate was 0.52 %. Compared to the Whipple type resection the DPPHRt exhibits significant benefits with respect to a low risk for early postoperative complications and a low hospital mortality rate of < 1 %. Exocrine and endocrine pancreatic functions after DPPHR are not impaired compared to the Whipple type resection.

Cystic neoplastic lesions of the pancreas are found in up to 10% of all pancreatic lesions. A malignant transformation of cystic neoplasia is observed in intraductal papillary mucinous tumor (IPMN) lesions in 60% and in mucinous cystic tumor (MCN) lesions in up to 30%. For cystic neoplasia located monocentrically in the pancreatic head and that do not have an association with an invasive pancreatic cancer, the duodenum-preserving total head resection has been used in recent time as a limited surgical procedure.An indication to duodenum-preserving total pancreatic head resection is considered for patients who do not have clinical signs of an advanced cancer in the lesion and who have main-duct IPMN and monocentric MCN lesions. In 104 patients with cystic neoplastic lesions in the Ulm series, 32% finally had a carcinoma in situ or an advanced pancreatic cancer. The application of a duodenum-preserving total pancreatic head resection in patients with asymptomatic cystic lesion is based on the size of the tumor and the tumor relation to the pancreatic ducts. For patients who have preoperatively clinical signs of malignancy, a Kausch-Whipple type of oncologic resection is recommended.Duodenum-preserving total pancreatic head resection is used in several modifications. The surgical procedure is a limited pancreatic head resection which necessitates segmental resection of the peripapillary duodenum. Hospital mortality is very low; in most published series it is 0%. The long-term outcome is determined by completeness of resection for both -- benign and malignant -- entities. Careful evaluation of the frozen section results has a pivotal role for intraoperative decision making.A duodenum-preserving total pancreatic head resection is a limited surgical procedure for patients who suffer a local monocentric, cystic neoplastic lesion in the pancreatic head. Absence of an advanced pancreatic cancer and completeness of extirpation of the benign tumor determine the long-term outcome. In regards to the location of the lesion in the pancreatic head, several modifications have been applied with low hospital morbidity and mortality below 1%.

Cystic neoplastic lesions of the pancreas are now found with increasing frequency. Duodenum-preserving pancreatic head resection with segmental resection of the duodenum has been introduced for the surgical treatment of inflammatory and neoplastic lesions. We report the following data from 15 patients treated surgically for cystic neoplastic lesions of the pancreas head.Duodenum-preserving total pancreatic head resection (DPPHRt) with segmental resection of the duodenum (SD) was performed in eight patients, five with intraductal papillary mucinous neoplasm (IPMN), two with mucinous cystic neoplasm (MCN), and one with cystic endocrine neoplasm (EN). In four patients, a subtotal pancreatic head resection was performed, but recurrence of the IPMN lesion was observed in two patients. Ten patients suffered cystadenoma, three patients had a borderline lesion, and two patients had an in-situ carcinoma.Eight patients had a DPPHRt with SD resection, two patients had a resection of the uncinate process including segmental resection of the inferior duodenal segment, and one patient had a duodenum-and spleen-preserving total pancreatectomy. In four patients a DPPHR with subtotal pancreatic head resection was carried out. Postoperative local complications occurred in eight patients: there was a recurrence of the IPMN lesion in the remnant pancreatic head in two patients; and there was intraabdominal bleeding in one patient, pancreatic fistula in one patient, and delay of gastric emptying in four patients. Seven patients showed signs of acute pancreatitis. Hospital mortality was 0%, and postoperative length of hospital stay was 10. 4 days (range, 8-18 days).Duodenum-preserving total pancreatic head resection for IPMN, MCN, serous cystadenoma (SCA), and cystic EN lesions is a safe and beneficial surgical procedure. Segmental resection of the duodenum was applied for an oncologically complete resection. In regard to long-term outcome, the procedure is, additionally, a pancreatic cancer preventive strategy.

Pancreatic head resection is a major surgical procedure and even today is linked to considerable risk for severe complications. In high-volume centers, morbidity and mortality after pancreatic head resection decreased to below 5%. In the authors’ monoinstitutional experiences including 1315 patients with malignant lesion and benign tumor, the frequency and severity of local as well as systemic complications after pancreatic head resection are reported. Between 1982 and 2004, 1315 patients underwent several types of pancreatic head resections including 549 patients with periampullary cancer, 57 with cystic neoplastic lesions, 61 with neoplasia of the papilla, 18 with endocrine tumors, and 630 with inflammatory head tumors in chronic pancreatitis. Kausch-Whipple resection was applied in 208 patients, pylorus-preserving pancreatic head resection in 412, duodenum-preserving pancreatic head resection in 571, total pancreatectomy in 36, and ampullectomy in 61 patients. Pancreatic fistula was observed in 6.8% and a breakdown of pancreaticojejunostomosis in 2.5% of the patients. Gastrointestinal leakage occurred in 0.5%. Pancreatic fistula was managed nonsurgically in 84 of 89 patients. However, the breakdown of pancreatic anastomosis requiring completion pancreatectomy developed in 29 of 33 patients. The hospital mortality of the breakdown of pancreaticojejunostomosis rose up to 34.5%; hospital mortality in patients with pancreatic fistula was 3.6%. The total hospital mortality in 1315 patients after head resection was 2.05%. Risk factors with significant relation to outcome criteria on nonsurvival are the breakdown of pancreaticojejunostomosis, severe intra-abdominal bleeding, intra-abdominal abscess, and postoperative multiorgan dysfunction syndrome. Pancreatic fistula as well as biliary leakage did not significantly determine outcome. Pancreatic head resection for neoplastic and benign tumor lesions of the pancreatic head using different resection techniques is still a major surgical procedure but with a low risk for severe complications in a high-volume center. Pancreatic fistula is a local complication that results in a prolongation of hospital stay but does not contribute to mortality and reoperation. However, the breakdown of pancreaticojejunostomosis is a life-threatening complication causing abdominal sepsis.

The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat. Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection. Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8–25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not. In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.

We investigated the immune status in 32 pancreatic cancer patients (PC) in comparison with healthy controls (HC).Using flow cytometry, peripheral blood lymphocytes (PBL) were characterized by the expression of surface markers for T helper cells (CD4), T suppressor cells (CD8), B cells (CD19) and NK cells (CD56). The blastogenic response of PBL was analyzed after stimulation with concavalin A (ConA), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and anti-CD3 antibodies. The serum levels of TNF-alpha, IL-1beta, IL-2, IL-10, IL-12, IL-18, IL-1RA, sIL-2R and TGF-beta were determined by ELISA.No differences in the distribution of peripheral immunocytes in PC were found, whereas the blastogenic response of peripheral blood lymphocytes (PBL) after stimulation with PHA or anti-CD3 antibodies was significantly decreased in PC. In PC, we found reduced serum levels of IL-2 and significantly elevated levels of TNF-alpha, TGF-beta1, IL-10, IL-2R, IL-1beta and IL-1RA.These data provide evidence for a systemic immune dysfunction in pancreatic cancer patients characterized by a shift towards a T helper cell type 2 cytokine profile, a significant elevation of substances related to T cell suppression and a reduced blastogenic response to PHA and anti-CD3 antibodies of PBL.

Limited surgical procedures for benign cystic neoplasms and endocrine tumours of the pancreas have the potential advantage of pancreatic tissue sparing compared to standard oncological resections. Searching PubMed/MedLine, Embase and Cochrane Library identified 86 full papers: 25 reporting on enucleation (EN), 38 on central pancreatectomy (CP) and 23 on duodenum-preserving total/partial pancreatic head resection (DPPHRt/p). The results are based on analysis of data of 838, 912 and 431 patients for EN, CP and DPPHRt/s, respectively. The indication for EN for cystic neoplasms and neuro-endocrine tumours to EN was 20.5 and 73 %; for CP 62.9 and 31 %; and for DPPHRt/p 69.6 and 10.2 %, respectively. The estimated mean tumour sizes were in EN-group 2.4 cm, in CP-group 2.9 cm and in DPPHRt/p-group 3.1 cm (DPPHRt/p vs EN, p = 0.035). Postoperative severe complications developed after EN, CP and DPPHRt/p in 9.6, 16.8 and 11.5 % of patients; pancreatic fistula in 36.7, 35.2 and 20.1 %; and reoperation was required in 4.7, 6.5 and 1.8 %, respectively. Hospital mortality after EN was 0.95 %; after CP 0.72 %; and after DPPHRt/p 0.49 %. Compared to EN and CP, DPPHRt/p exhibited significant lower frequency of reoperation (p = 0.029, p

Conflicting results have been published about the effects of carbon dioxide (CO 2 ) pneumoperitoneum on splanchnic and liver perfusion. Several experimental studies described a pressure-related reduction in hepatic blood flow, whereas other investigators reported an increase as long as the intraabdominal pressure (IAP) remained less than 16 mm Hg. Our goal in the present study was to investigate the effects of insufflated CO 2 on hepatic blood flow during laparoscopic surgery in healthy adults. Blood flow in the right and middle hepatic veins was assessed in 24 patients undergoing laparoscopic surgery by use of transesophageal Doppler echocardiography. Hepatic venous blood flow was recorded before and after 5, 10, 20, 30, and 40 min of pneumoperitoneum, as well as 1 and 5 min after deflation. Twelve patients undergoing conventional hernia repair served as the control group. The induction of pneumoperitoneum produced a significant increase in blood flow of the right and middle hepatic veins. Five minutes after insufflation of CO 2 the median right hepatic blood flow index increased from 196 mL/min/m 2 (95% confidence interval (CI), 140-261 mL/min/m 2 ) to 392 mL/min/m 2 (CI, 263-551 mL/min/m 2 ) (P < 0.05) and persisted during maintenance of pneumoperitoneum. In the middle hepatic vein the blood flow index increased from 105 mL/min/m 2 (CI, 71-136 mL/min/ m 2 ) to 159 mL/min/m 2 (CI, 103-236 mL/min/m 2 ) 20 min after insufflation of CO 2 . After deflation blood flow returned to baseline values in both hepatic veins. Conversely, in the control group hepatic blood flow remained unchanged over the entire study period. We conclude that induction of CO 2 pneumoperitoneum with an IAP of 12 mm Hg is associated with an increase in hepatic perfusion in healthy adults.

The outcome of severe acute pancreatitis is determined by the development of the systemic inflammatory response and subsequent multiorgan dysfunction. Using the taurocholate-induced model of acute pancreatitis in rats, we investigated the relationship between early polymorphonuclear (PMN)-mediated pancreatic tissue damage and the systemic inflammatory response. The respiratory burst of PMN leukocytes was increased in animals with acute pancreatitis and was reduced by anti-ICAM-1 antibody and oxygen radical scavenger treatment after 24 hr. In acute pancreatitis a reduced number of peripheral helper T cells was evident, most likely due to L-selectin-mediated increased lymphocyte homing. After 24 hr the CD45RC(high)/CD45RC(low) ratio of helper T cells, a critical factor in T cell-mediated disease was increased due to a reduction of regulatory CD45RC(low) cells. Only the treatment with anti-ICAM-1 mAb affected these changes, indicating that immunological changes in necrotizing pancreatitis are only in part affected by early PMN leukocyte-mediated pancreatic damage.

Adenocarcinoma of the pancreas is associated with the worst survival of any form of gastrointestinal malignancy. In spite of the progress in surgical treatment, resulting in increasing resection rates and a decrease in treatment-related morbidity and mortality, the true figures of cure are even today below 3%. The dissemination of pancreatic cancer behind the local tissue compartments restricts the short-term (3 years) and long-term outcome for patients who have undergone resection. By histological evaluation, less than 15% of the patients undergoing R(0) resection have a pN(0) status, more than 60% suffer from lymph angiosis carcinomatosa, and more than 50% suffer extrapancreatic nerve plexus infiltration. Hematoxylin and eosin-negative lymph nodes were found to be cancer positive when reverse transcriptase polymerase chain reaction (RT- PCR) or immunostaining was applied to the HE-negative lymph nodes. Cancer of the uncinate process has a very poor prognosis because there are no early symptoms; vessel wall involvement occurs early and frequently; a high association of liver metastasis exists as well. Surgery offers a low success rate, but it provides the only chance of cure. Ductal pancreatic cancer is diagnosed in more than 95% of the cases in an advanced stage; potentially curative resection can be performed only in about 10%-15% of these patients. Major contributions of surgery to improved treatment results are the reduction of surgical morbidity--e.g., early postoperative local and systemic complications--and a decrease of hospital mortality below 3%-5%. In most recently published prospective trials, R(0) resection has been reported to result in an increase in short-term survival beyond that recorded for patients with residual tumor. However, R(0) resection fails to improve long-term survival. In many published R(0) series, standard tissue resection of pancreatic head cancer with the Kausch-Whipple procedure failed to include remote cancer cell-positive tissues in the operative specimen; e.g., N(2)-lymph nodes, nerve plexus, and perivascular extrapancreatic and retropancreatic tissues were not excised. Cancer recurrence after so-called R(0) resection with curative intent is frequently the consequence of cancer left behind. Thus, long-term survival (5 years) is observed in a very small group of patients, contradicting the published 5-year actuarial survival rates of 20%-45% for resected patients. The assessment of clinical benefit from surgical or medical cancer treatment should therefore be based on several end points, not only on actuarial survival. Publication of actuarial survival figures must include the number of observed (actual) survivals, the definition of the subset of patients followed after resection, and the total number of patients in the study group; anything less is misleading. In reporting pancreatic cancer treatment trial results after oncological resections, more convincing primary end points to evaluate treatment efficacy are median survival (in months), actual survival at 1-5 years, and progression-free survival (in months). In series with multimodality treatment, clinical benefit response as well as quality of life measurements using the EORTC Quality of Life index C30 (QLQ-C30) are of importance in evaluating survival data. Adjuvant treatment improves survival after oncological resection; however, the short-term and long-term benefit after adjuvant chemotherapy in R(0) as well as in R(1)-(2) resected patients has not yet been underscored by data from controlled clinical trials. The survival benefit (median survival time) of adjuvant chemotherapy or radiochemotherapy has been demonstrated to be 6-10 months. Therefore, after oncological resection of pancreatic cancer each patient should be offered adjuvant treatment. A neoadjuvant treatment protocol for pancreatic cancer, however, has not been established.

Die neoadjuvante Chemotherapie bei Pankreaskarzinom ist bisher nicht standardisiert. Die Applikation erfolgt als Radiochemotherapie innerhalb von 5–8 Wochen mit fraktionierter Radiotherapie zwischen 40 und 54 Gy und 5 FU als Radiosensitator.Bei Patienten mit resezierbaren Pankreaskarzinomen (UICC-Stadium II) bewirkt neoadjuvante Radiochemotherapie eine Verlangerung der Uberlebenschancen mit medianen Uberlebenszeiten zwischen 15 und 30 Monaten. Bei ca.15% der Patienten mit resektablen Karzinomen (Stadium I–III) kann durch neoadjuvante Radiochemotherapie ein Downstaging erreicht werden.Neoadjuvante Radiochemotherapie bewirkt in Kombination mit einer R0-Resektion eine Verminderung des lokalen Tumorrezidivs.Kontrollierte Studienergebnisse sind zur sicheren Bewertung der Vorteile einer neoadjuvanten Radiochemotherapie erforderlich.

Oxidative stress is an important factor in the pathogenesis of acute pancreatitis, as shown in vivo by the beneficial effects of scavenger treatment and in vitro by the potential of free radicals to induce acinar cell damage. However, it is still unclear whether oxygen free radicals (OFR) act only as mediators of tissue damage or represent the initiating event in acute pancreatitis in vivo as well. In the present study the authors aimed to address this issue in an experimental set-up.Two hundred male Wistar rats were randomly assigned to one of the following experimental groups. In two groups, acute necrotizing pancreatitis was induced by retrograde intraductal infusion of 3% sodium taurocholate. Through the abdominal aorta, a catheter was advanced to the origin of the celiac artery for continuous regional arterial (CRA) pretreatment with isotonic saline (NP-S group) or superoxide dismutase/catalase (NP-SOD/CAT group). In another group, oxidative stress was generated by CRA administration of xanthine oxidase and intravenous administration of hypoxanthine (HX/XOD group). Sham-operated rats received isotonic saline both arterially and intraductally. After observation periods of 5 and 30 minutes and 3 and 6 hours, the pancreas was removed for light microscopy and determination of reduced glutathione (GSH), oxidized glutathione (GSSG), conjugated dienes (CD), and malondialdehyde as a marker for OFR-induced lipid peroxidation as well as myeloperoxidase as a parameter for polymorphonuclear leukocyte accumulation.A significant decrease of GSH was paralleled by an increased ratio of GSSG per total glutathione and elevated CD levels after 5 minutes in the NP-S group versus the sham-operated group. Thereafter, the percentage of GSSG and GSH returned to normal levels until the 6-hour time point. After a temporary decrease after 30 minutes, CD levels increased again at 3 hours and were significantly higher at 6 hours in contrast to sham-operated rats. Myeloperoxidase levels were significantly elevated at 3 and 6 hours after pancreatitis induction. In contrast to NP-S rats, treatment with SOD/CAT significantly attenuated the changes in glutathione metabolism within the first 30 minutes and the increase of CDs after 6 hours. HX/XOD administration lead to changes in levels of GSH, GSSG, and CDs at 5 minutes as well as to increased myeloperoxidase levels at 3 hours; these changes were similar to those observed in NP-S rats. Acinar cell damage including necrosis was present after 5 minutes in both NP groups, but did not develop in HX/XOD rats. In addition, serum amylase and lipase levels did not increase in the latter group. SOD/CAT treatment significantly attenuated acinar cell damage and inflammatory infiltrate compared with NP-S animals during the later time intervals.OFRs are important mediators of tissue damage. However, extracellular OFR generation alone does not induce the typical enzymatic and morphologic changes of acute pancreatitis. Factors other than OFRs must be involved for triggering acute pancreatitis in vivo.

Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.

Von Januar 1979 bis August 1996 wurden an der Chirurgischen Universitatsklinik Ulm 178 Patienten aufgrund eines Lebertraumas chirurgisch versorgt. Es handelte sich dabei zu 91,6 % um stumpfe und nur zu 8,4 % um penetrierende Traumen. Bei 110 Fallen (62 %) handelte es sich um leichte Verletzungen der Schweregrade I und II, wahrend sich bei 68 Patienten (38 %) schwere Traumen der Grade III, IV und V fanden. Die Letalitatsrate wird vom Schweregrad der Leberruptur und der Begleitverletzung bestimmt. Die Gesamtletalitat lag bei 32 % (57 Patienten). Davon sind 28 Patienten an den Folgen der Leberverletzung verstorben. Dies bedeutet, die reine Sterblichkeit aufgrund der Leber betrug 15,7 %. Keiner der Patienten mit einer penetrierenden Verletzung ist verstorben. Die Komplikationsrate lag bei 55 %, wobei die Hamatombildung die am haufigsten beobachtete Komplikation darstellte (12,9 %), an zweiter Stelle folgte die Nachblutung mit 9,6 %. Die Abscesrate lag bei 2,8 %. Bei einem kreislaufstabilen Patienten sollte grundsatzlich die konservative Therapie angestrebt werden, sofern er die gegebenen Voraussetzungen erfullt. Bei kreislaufinstabilen Patienten ist ein operatives Vorgehen unumganglich. Das chirurgische Vorgehen hangt vom Schweregrad der Leberverletzung ab. Bei leichter Blutung steht die „einfache“ Versorgung durch Coagulation oder Naht im Vordergrund. Liegt eine schwere Blutung vor, so empfiehlt sich die Hepatotomie, die gezielte Blutstillung und Debridement (Pachters Vorgehen). Ist die Blutung nicht unter Kontrolle zu bringen, ist die perihepatische Bauchtuchtamponade das Mittel der Wahl.

Aus epidemiologischen Untersuchungen ist bekannt, das bei ca. 50 % der Kinder mit einseitiger Leistenhernie auf der Gegenseite ebenfalls ein offener Processus vaginalis vorliegt. 10–25 % dieser Kinder entwickeln in der Folge eine kontralaterale Hernie. Seit 1996 wird in unserer Klinik bei Sauglingen und Kindern mit klinisch unilateraler Leistenhernie mittels intraoperativer Laparoskopie durch den eroffneten Bruchsack der kontralaterale innere Leistenring inspiziert. Vorgehen: Bisher wurden 112 Kinder untersucht (Alter: 6 Monate bis 7 Jahre; 78 Jungen, 34 Madchen). Nach Freipraparation des Bruchsacks wurde dieser eroffnet und ein 5,5-mm-Trokar durch den inneren Leistenring eingebracht. Nach Anlage des Pneumoperitoneums erfolgte mit einer 5-mm-(30 °)-Optik zunachst die orientierende Laparoskopie, anschliesend mit der 70 °-Optik die Inspektion des kontralateralen inneren Leistenrings. Ergaben sich Hinweise fur einen breit offenen Processus vaginalis (Typ III nach Chin), wurde in gleicher Narkose diese Seite ebenfalls offen chirurgisch exploriert. Ergebnisse: Laparoskopisch fand sich bei 19 Patienten (17 %) ein nach oben genannten Kriterien pathologischer Befund (6 Madchen, 13 Jungen). Diese wurden auf der Gegenseite operiert und die laparoskopische Diagnose in allen Fallen bestatigt. Verfahrensbedingte Komplikationen traten nicht auf. Die Eingriffe erfolgten im Rahmen der Eintageschirurgie. Die Operationsdauer erhohte sich durch die intraoperative Laparoskopie um im Median 6 min (3–11 min). Deutlich haufiger fanden sich pathologische Befunde bei Patienten unter 2 Jahren (14 von 19 Patienten). Schlusfolgerungen: Das beschriebene Verfahren erlaubt ohne nennenswerten zusatzlichen Zeitbedarf, Patienten zu selektionieren, die von einer einzeitigen offenen Exploration der gegenseitigen Leistenregion profitieren. Somit konnen Zweitoperationen mit erneuter Narkose und Hospitalisierung vermieden werden. Zusatzlich erlaubt die intraoperative Laparoskopie die allgemeine Beurteilung der Abdominalorgane sowie Klarung spezieller Fragen wie, z. B. die Vitalitat reponierter Darmschlingen.

Approximately 40% of children with a clinical unilateral inguinal hernia display a patent processus vaginalis on the contralateral side; half of these children subsequently develop an inguinal hernia. The management of this problem is still controversial. Different strategies to identify patients who profit from an open contralateral exploration have been applied (diagnostic pneumoperitoneum, herniography, ultrasound). The purpose of this study was to evaluate the usefulness of intraoperative laparoscopy in a no-puncture technique through the opened hernia sack. In 75 children (age 6 months to 7 years) with clinical unilateral hernia laparoscopy (5-mm Laparoscope, 30 degrees and 70 degrees ), in cases of wide-open contralateral internal inguinal ring (Type III) an open surgical exploration was performed. Twelve patients (17%) fulfilled the laparoscopic criteria of a Type III ring. The diagnose was confirmed during open contralateral exploration. Seven children (8%) showed a patent but small processus vaginalis with a shallow internal ring. These patients were treated conservatively. In the follow-up period (median 6 months) one subsequent hernia developed. There was no technical failure, and no associated complications were seen. The median time for laparoscopy was 6 minutes. Intraoperative laparoscopy during unilateral hernia repair allows the identification of patients who profit from bilateral open surgery during the same operation with little additional operating time, and so far with no resulting complications. Application of this method may avoid a second hospitalization and operation as well as unnecessary routine bilateral open exploration. As an additional source of information through excellent visualization of the abdominal cavity, this method proved helpful to examine the incarcerated bowel after repositioning.

We investigated the effects of endogenously produced and exogenously applied nitric oxide (NO) on cell proliferation rates and cell cycle regulation in senescent human fibroblasts (WI38). Induction of inducible nitric oxide synthase by tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta inhibited cell proliferation and led to a G1 arrest. These effects were partially reversible by N(G)-monomethyl-arginine (NMA). Addition of the NO donors sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) increased cell proliferation rates as well as the S/G2 fraction. This points to a functional role of NO in cell cycle regulation and cell proliferation in human fibroblasts which depends on the mode of NO generation as well as the culture conditions used.

Anti-p53-autoantibodies (a-p53-aabs) may suppress the development of distant metastases, but not lymph node metastases. This could explain the significantly prolonged survival of patients with UICC stage III tumors who have a-p53-aabs compared to those without a-p53-aabs.Mutation within the tumor suppressor gene p53 leads to increased intracellular p53 protein levels and an increased antibody formation against this molecule. Altered p53 has been proposed to be associated with poor prognosis, and the present study investigated whether the detection of a humoral response to p53 gives evidence for a prognostic or diagnostic parameter in pancreatic disorders.We screened 145 patients with pancreatic cancer and 95 patients with chronic pancreatitis for the development of a-p53-aab via ELISA and Western-blotting. p53 expression was examined by immunohistochemistry.We found that 41% of the tissues of patients suffering from pancreatic carcinoma overexpressed p53, and 15.9% of the patients suffering from pancreatic cancer developed a-p53-aab. In pancreatic cancer, we could exhibit a significant correlation between grading, p53-overexpression, survival, and antibody response against p53. A-p53-aabs were significantly more frequent in patients with stage III tumors (tumors with lymph node metastases, but not distant metastases, p0.02).

Hemorrhagic mucosal lesions are produced during intestinal ischemia and after reperfusion due at least in part to the accumulation and activation of polymorphonuclear leukocytes in the tissue. It has been shown in vitro that adenosine is instrumental in attenuating this pathophysiological process. Acadesine [5-amino-4-imidazolecarboxamide (AICA) riboside], a purine nucleoside analogue, increases the availability of adenosine in the tissue. The aim of the study was therefore to assess the influence of acadesine treatment on neutrophil accumulation, purine metabolism, and mucosal damage after intestinal ischemia and reperfusion. Intestinal ischemia was induced in cats by partial occlusion of the superior mesenteric artery for 2 h. Samples of the small intestine were exercised before and at the end of the hypotensive period as well as 10 and 60 min after reperfusion. Conjugated dienes, myeloperoxidase, and reduced and oxidized glutathione, as well as the purine metabolites, were determined in the tissue samples. The tissue was also examined histologically. Six cats received saline, and six cats were treated initially before ischemia with acadesine (2.5 mg/kg body wt i.v.) over 5 min as a bolus. Thereafter, acadesine (0.5 mg.kg-1.min- i.v.) was given continuously during ischemia and 30 min after reperfusion. Acadesine treatment significantly attenuated the mucosal lesions seen during reperfusion. This improvement was due at least in part to the inhibition of neutrophil accumulation, as judged by low myeloperoxidase levels. The prevention of neutrophil activation resulted most likely from increased adenosine concentrations in the intestinal tissue in the early reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment.The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment.Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed.Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ.Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

Background. Carcinoid tumors of the gastrointestinal tract are most common localized in the appendix, followed by the small intestine, the rectum, and the stomach. The localization of these tumors at the ampulla of Vater is extremely seldom. Methods. In the present study the authors describe two patients with carcinoid tumors of the ampulla Vater and review 71 previously published cases. Results. Most patients presented with jaundice, but without carcinoid syndrome. Because the tumor grows submucosally, preoperative diagnosis was correct only in 15%. Most tumors were around 2 cm in size. Metastasis to lymph nodes and/or liver was present in 45%. Standard treatment is Whipple resection or local excision in small tumors. Conclusions. Carcinoid tumors of the ampulla of Vater are an extremely rare clinical entity. Generally, the prognosis is good with a 5-year survival period of 90%.

Background/Aim : In spite of the interest in free radicals as mediators of ischemic damage, most information on these species in biological systems is derived from indirect measurements. Our aim was to obtain more direct information concerning sources of free radical production during ischemia and reperfusion. Methods : We have performed simultaneous measurement of radical generation, purine metabolites, reduced glutathione, neutrophil infiltration and morphological appearance in the cat small intestine in vivo during 60 minutes of ischemia followed by 60 minutes of reperfusion. Results : Radical formation increased abruptly on reperfusion and remained elevated in untreated animals. Inhibition by a monoclonal antibody (IB4) against the neutrophil and by allopurinol treatment was paralleled by improvement of biochemical and morphological parameters. The radicals detected during reperfusion could be divided into one component arising directly from the neutrophils, one due to the xanthine oxidase reaction, and one unknown source. Conclusions : Neutrophils are a major source of radical production during reperfusion after ischemia. Radicals formed in the xanthine oxidase reaction seem to function as a primer for the neutrophils. The nonsignificant linear correlation between radical formation and morphological appearance suggests that factors other than free radicals are important for the development of intestinal damage after a period of ischemia.

Infections due to pancreatic necrosis and abscesses are observed in one third of patients with severe acute pancreatitis (SAP). Based on results of double-blind, randomized, placebo-controlled trials, antibiotic prophylaxis in SAP is ineffective for reducing the frequency of infected necrosis and to decrease hospital mortality. Antibiotic treatment using carbapenems and quinolones is indicated on demand in patients with SAP and multiorgan failure at admission and in those with hemodynamic shock. Patients with biliary acute pancreatitis (AP) and clinically acute cholecystitis and/or cholangitis benefit from antibiotic treatment. Patients with AP associated with bacteremia, positive bronchoalveolar lavage, and urinary tract infection should receive antibiotics. In necrotizing pancreatitis, evidence-based data do not support late use of antibiotic prophylaxis after onset. Further high-quality, randomized, controlled trials are needed to evaluate antibiotic prophylaxis in the first 24 to 48 hours after SAP onset.

For treatment of inflammatory and benign neoplastic lesions of the pancreatic head, a subtotal or total pancreatic head resection is a limited surgical procedure with the impact of replacing the application of a Whipple procedure. The objective of this work is to describe the technical modifications of subtotal and total pancreatic head resection for inflammatory and neoplastic lesions of the pancreas. The advantages of this limited surgical procedure are the preservation of the stomach, the duodenum and the extrahepatic biliary ducts for treatment of benign lesions of the pancreatic head, papilla, and intrapancreatic segment of the common bile duct. For chronic pancreatitis with an inflammatory mass complicated by compression of the common bile duct or causing multiple pancreatic main duct stenoses and dilatations, a subtotal pancreatic head resection results in a long-lasting pain control. Performing, in addition, a biliary anastomosis or a Partington Rochelle type of pancreatic main duct drainage, respectively, is a logic and simple extension of the procedure. The rationale for the application of duodenum-preserving total pancreatic head resection for cystic neoplastic lesions are complete exstirpation of the tumor and, as a consequence, interruption of carcinogenesis of the neoplasia preventing development of pancreatic cancer. Duodenum-preserving total head resection necessitates additional biliary and duodenal anastomoses. For mono-centric IPMN, MCN, and SCA tumors, located in the pancreatic head, total duodenum-preserving pancreatic head resection can be performed without hospital mortality and resurgery for recurrency. Based on controlled clinical trials, duodenum-preserving pancreatic head resection is superior to the Whipple-type resection with regard to lower postoperative morbidity, almost no delay of gastric emptying, preservation of the endocrine function, lower frequency of rehospitalization, early professional rehabilitation, and establishment of a predisease level of quality of life. The limited surgical procedures of subtotal or total pancreatic head resection are simple, safe, ensures free tumour margins and replace in the authors institution the application of a Whipple-type head resection.

Cancers of the pancreas are identified in 11 800 to 13 500 patients each year in Germany (1). The mean age at disease onset is 68 years in men and 70 years in women. For some years, women have been observed to develop the disease more frequently than men (1). The growing incidence of pancreatic cancer in the industrialized countries is attributed to overweight (2), increasing age, smoking (4), and chronic alcohol consumption (4). Epidemiological studies have shown smoking to be the cause in about 30% of cases of ductal pancreatic cancer (3); pancreatic diseases with a markedly elevated risk of malignancy – besides the genetically determined syndromes with high pancreatic carcinoma penetrance (5) – are hereditary chronic pancreatitis with up to 40% malignancy (6), chronic alcoholic pancreatitis with 4% to 6 % malignancy (7), and cystic neoplasms with a malignant transformation rate of 20% to 70% (8). Pancreatic cancer is still incurable for more than 95% of patients (9). In preparation for exercising the function of expert (Beger), and as a member of the Surgical Treatment Working Group for drafting of the S3 guidelines of the German Society of Digestive and Metabolic Diseases (DGVS)/ of the Scientific Medical Societies in Germany (AWMF) (Rau), the authors conducted a selective literature review based on their clinical and scientific experience.

Severe acute pancreatitis is considered to be a subgroup of acute pancreatitis with the development of local and/or systemic complications. A significant correlation exists between the development of pancreatic necrosis, the frequency of bacterial contamination of necrosis and the evolution of systemic complications. Bacterial infection and the extent of necrosis are determinants for the outcome of severe acute pancreatitis. The late course of necrotizing pancreatitis is determined by bacterial infection of pancreatic and peripancreatic necroses. Mortality increases from 5-25% in patients with sterile necrosis to 15-28% when infection has occurred. The use of prophylactic antibiotics has been recommended in patients with necrotizing pancreatitis. Several controlled clinical trials demonstrated a significant reduction in pancreatic infections or a significant reduction of hospital mortality. However, the results of these clinical trials are controversial and not convincing. Recently, the largest randomized placebo-controlled, double-blind trial has been able to demonstrate that antibiotic prophylaxis with ciprofloxacin and metronidazole has no beneficial effects with regard to the reduction of pancreatic infection and the decrease of hospital mortality. The clinical data from this placebo-controlled trial do not support antibiotic prophylaxis in all patients with necrotizing pancreatitis, but in specific subgroups of patients with pancreatic necrosis and a complicated course.

Background: Common bile duct stenosis (CBDS) is one of the most frequent complications in chronic pancreatitis with inflammatory mass in the head of the pancreas (IMH) Methods: A total of 474 patients who underwent duodenum-preserving pancreatic head resection (DPPHR) between 1982 and 1998 were reevaluated; 219 patients (46%) with a mean duration of the disease of 45 months had a radiologically proven CBDS. Results: One patient (0.5%) died of septic complications in the early postoperative course, 15 patients (6.8%) had to be reoperated on for complications. A follow-up investigation of 143 patients (92%) revealed a late mortality of 12%; no patient died of biliary complications. Seventy-five percent of the patients were completely free of pain, and 85% of the patients had a constant or even increasing body weight. Conclusions: The high percentage of pain-free patients with improved physical status and economical rehabilitation demonstrates the improvement of the quality of life after DPPHR for complicated chronic pancreatitis.

Introduction: We recently showed that cyclin D1 is overexpressed in human pancreatic carcinoma cells, and that this overexpression correlates significantly with a poor prognosis. Aims: To assess the interrelations of epidermal growth factor (EGF), EGF receptor (EGFR), and cyclin Dl in human pancreatic carcinoma. Methodology and Results: In pancreatic carcinoma cell lines (BxPC-3, AsPC-1), cell cycle analysis revealed an increase in cells in the S/G1 phase between 18 and 30 hours after stimulation with 50 ng/mL EGF. Cyclin Dl mRNA increased after 2 hours, corresponding to an increase in cyclin D1 protein, with the maximum level between 7.5 and 10 hours after stimulation, as demonstrated by Western blot analysis. We performed immunohistochemical analysis on 61 adenocarcinoma tissues for the expression of EGF, EGFR, and cyclin D 1 and demonstrated an overexpression in the tumor cells in 51%, 54%, and 62.3%, respectively, whereas normal human pancreas stained negative for all of the three factors. Interestingly, EGF and EGFR expression correlated significantly with the cyclin Dl expression in human pancreatic tumor cells (p < 0.001 and p < 0.01, respectively). Conclusion: These results demonstrate that cyclin Dl overexpression in the tumor cells of pancreatic carcinoma tissue is at least partly dependent on the mitogenic effects of EG)'signaling through the EGFR.

The hallmark of severe acute pancreatitis (SAP) is massive acinar cell death by necrosis. However, programmed, apoptotic acinar cell death has also been observed. Little is known about the dynamics, localization, and inductive factors of acinar cell apoptosis in SAP. We therefore induced SAP in rats by retrograde infusion of 3% sodium taurocholate. Starting as early as 5 minutes after taurocholate administration, small scattered groups of acinar cells showed zymogen degranulation, loss of cell polarity, cytoplasmic microvacuolization, and nuclear shrinkage, but no DNA degradation, thus featuring necrosis. The areas of necrotic acini extended at later time points giving rise to larger areas of complete parenchymal breakdown after 6 hours. Parenchymal degradation was paralleled by neutrophil infiltration and significant tumor necrosis factor (TNF)-alpha mRNA up-regulation. Up to the 12-hour interval, apoptotic acinar cells detected by TUNEL were as rare as in healthy pancreata. At 24 hours, however, the acinar apoptotic rate in nonnecrotic parenchyma had dramatically increased. Pretreatment of rats with anti-ICAM-1 antibody prior to pancreatitis induction led to a significant reduction of neutrophil infiltration along with decreased TNF-alpha mRNA expression throughout the 24-hour observation period without affecting the presence and dynamics of necrosis. However, anti-ICAM-1 pretreatment decreased the extent of acinar cell damage by necrosis and extensively suppressed acinar cell apoptosis. We conclude that taurocholate induces two sequential patterns of acinar cell death in terms of very early necrosis followed by late apoptosis during the postacute phase of SAP. The progression of necrosis and the late apoptotic acinar cell death seem to be influenced by the local presence of neutrophils via a TNF-alpha-dependent mechanism. In addition to augmenting necrosis, neutrophils might have an apoptosis-inducing potential in SAP.