Long-Term Oncologic Outcome following Duodenum-Preserving Pancreatic Head Resection for Benign Tumors, Cystic Neoplasms, and Neuroendocrine Tumors: Systematic Review and Meta-analysis.

BACKGROUND: Pancreatoduodenectomy (PD) has a considerable surgical risk for complications and late metabolic morbidity. Parenchyma-sparing resection of benign tumors has the potential to cure patients associated with reduced procedure-related short- and long-term complications. MATERIALS AND METHODS: Pubmed, Embase, and Cochrane libraries were searched for studies reporting surgery-related complications following PD and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. A total of 38 cohort studies that included data from 1262 patients were analyzed. In total, 729 patients underwent DPPHR and 533 PD. RESULTS: Concordance between preoperative diagnosis of benign tumors and final histopathology was 90.57% for DPPHR. Cystic and neuroendocrine neoplasms (PNETs) and periampullary tumors (PATs) were observed in 497, 89, and 31 patients, respectively. In total, 34 of 161 (21.1%) patients with intraepithelial papillar mucinous neoplasm exhibited severe dysplasia in the final histopathology. The meta-analysis, when comparing DPPHRt and PD, revealed in-hospital mortality of 1/362 (0.26%) and 8/547 (1.46%) patients, respectively [OR 0.48 (95% CI 0.15-1.58); p = 0.21], and frequency of reoperation of 3.26 % and 6.75%, respectively [OR 0.52 (95% CI 0.28-0.96); p = 0.04]. After a follow-up of 45.8 ± 26.6 months, 14/340 patients with intraductal papillary mucinous neoplasms/mucinous cystic neoplasms (IPMN/MCN, 4.11%) and 2/89 patients with PNET (2.24%) exhibited tumor recurrence. Local recurrence at the resection margin and reoccurrence of tumor growth in the remnant pancreas was comparable after DPPHR or PD [OR 0.94 (95% CI 0.178-5.34); p = 0.96]. CONCLUSIONS: DPPHR for benign, premalignant neoplasms provides a cure for patients with low risk of tumor recurrence and significantly fewer early surgery-related complications compared with PD. DPPHR has the potential to replace PD for benign, premalignant cystic and neuroendocrine neoplasms.

Duodenum-Preserving Pancreatic Head Resection for Benign and Premalignant Tumors-a Systematic Review and Meta-analysis of Surgery-Associated Morbidity.

BACKGROUND: Pancreatic benign, cystic, and neuroendocrine neoplasms are increasingly detected and recommended for surgical treatment. In multiorgan resection pancreatoduodenectomy or parenchyma-sparing, local extirpation is a challenge for decision-making regarding surgery-related early and late postoperative morbidity. METHODS: PubMed, Embase, and Cochrane Libraries were searched for studies reporting early surgery-related complications following pancreatoduodenectomy (PD) and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. Thirty-four cohort studies comprising data from 1099 patients were analyzed. In total, 654 patients underwent DPPHR and 445 patients PD for benign tumors. This review and meta-analysis does not need ethical approval. RESULTS: Comparing DPPHRt and PD, the need for blood transfusion (OR 0.20, 95% CI 0.10-0.41, p<0.01), re-intervention for serious surgery-related complications (OR 0.48, 95% CI 0.31-0.73, p<0.001), and re-operation for severe complications (OR 0.50, 95% CI 0.26-0.95, p=0.04) were significantly less frequent following DPPHRt. Pancreatic fistula B+C (19.0 to 15.3%, p=0.99) and biliary fistula (6.3 to 4.3%; p=0.33) were in the same range following PD and DPPHRt. In-hospital mortality after DPPHRt was one of 350 patients (0.28%) and after PD eight of 445 patients (1.79%) (OR 0.32, 95% CI 0.10-1.09, p=0.07). Following DPPHRp, there was no mortality among the 192 patients. CONCLUSION: DPPHR for benign pancreatic tumors is associated with significantly fewer surgery-related, serious, and severe postoperative complications and lower in-hospital mortality compared to PD. Tailored use of DPPHRt or DPPHRp contributes to a reduction of surgery-related complications. DPPHR has the potential to replace PD for benign tumors and premalignant cystic and neuroendocrine neoplasms of the pancreatic head.

Long-term Metabolic Morbidity and Steatohepatosis Following Standard Pancreatic Resections and Parenchyma-sparing, Local Extirpations for Benign Tumor: A Systematic Review and Meta-analysis.

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.

Resection of the duodenum causes long-term endocrine and exocrine dysfunction after Whipple procedure for benign tumors - Results of a systematic review and meta-analysis.

BACKGROUND: Metabolic dysfunctions after pancreatoduodenectomy (PD) need to be considered when pancreatic head resection is likely to lead to long-term survival. METHODS: 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. RESULTS: 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. CONCLUSIONS: After PD, duodenectomy, rather than pancreatic head resection is the main cause for long-term persisting, postoperative new onset of DM and PEI.

Parenchyma-sparing, local pancreatic head resection for premalignant and low-malignant neoplasms - A systematic review and meta-analysis.

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.

New Onset of Diabetes and Pancreatic Exocrine Insufficiency After Pancreaticoduodenectomy for Benign and Malignant Tumors: A Systematic Review and Meta-analysis of Long-term Results.

OBJECTIVE: 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. SUMMARY BACKGROUND DATA: When PD is performed on patients for benign tumors, the question of long-term metabolic dysfunctions becomes of importance. METHODS: 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). RESULTS: 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 P < 0.0121; malignant vs benign and malignant P < 0.0017). 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) (P < 0.0001). CONCLUSION: 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.

Duodenum-preserving total and partial pancreatic head resection for benign tumors--systematic review and meta-analysis.

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.

Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

BACKGROUND: 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. OBJECTIVES: 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. PATIENTS: 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. RESULTS: 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. CONCLUSION: Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

The use of antibiotics for acute pancreatitis: is there a role?

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.

Duodenum-preserving total pancreatic head resection for cystic neoplasm: a limited but cancer-preventive procedure.

BACKGROUND: 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. PATIENTS: 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. RESULTS: 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. CONCLUSION: 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%.

Duodenum-preserving total pancreatic head resection for cystic neoplastic lesions in the head of the pancreas.

BACKGROUND/PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 cancer--low survival rates.

INTRODUCTION: Cancers of the pancreas are identified in 11 800 to 13 500 patients each year in Germany. Epidemiological studies prove smoking and chronic alcohol consumption as causes of about 30% of pancreatic cancers. METHODS: Selective literature review. RESULTS: Only patients within TNM stage I and II have after oncologic tumor extirpation a chance for long term survival. Controlled prospective clinical trials demonstrated adjuvant chemotherapy yielding an additional significant survival benefit. The 3- and 5-year-survival after R0-resection and adjuvant chemotherapy are about 30% and below 15% respectively. Using the criteria of observed 5-year-survival less than 2% of all pancreatic cancer patients are alive. After R0-resection the median survival time is between 17 and 28 months, after R1/2-resection between 8 and 22 months. DISCUSSION: Pancreatic cancer is even today for more than 95% of the patients incurable. Strategies to prevent pancreatic cancer are intended to stop smoking and chronic alcohol consumption and early surgical extirpation of cystic neoplastic lesions. For patients with established pancreatic cancer risk a follow-up protocol is discussed.

The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer.

BACKGROUND/AIMS: Recently we have shown that NSC-631570 (Ukrain) is a safe and effective drug in the treatment of unresectable pancreatic cancer. The aim of this study was to determine the effectiveness of the combined treatment with Gemcitabine and NSC-631570 in the adjuvant treatment of resected advanced pancreatic cancer. METHODOLOGY: 30 patients received adjuvant chemotherapy following surgical resection for pancreatic cancer. Chemotherapy consisted of Gemcitabine according to the Burris-protocol with weekly infusions of 1000 mg/sqm. Immediately following Gemcitabine infusion 20mg of NSC-631570 were administered intravenously over 15 minutes. RESULTS: WHO grade II toxicities were observed in 53%, no WHO grade III or IV toxicities occurred. In 80% of the patients recurrence of the disease was observed. The relapse-free survival time was 21.7 months. The actuarial survival rates were 86.7% after one year, 76.6% after two years, 46.7% after three years and 23.3% after five years. The median survival time according to Kaplan-Meier regression analysis was 33.8 months. CONCLUSIONS: Adjuvant chemotherapy in advanced stages of pancreatic cancer using the combination of Gemcitabine and NSC-631570 is a safe treatment and seems to lead to a prolonged survival. Although further investigation is needed to confirm these results, the combined treatment of Gemcitabine and NSC-631570 is a promising therapy for the adjuvant treatment of resectable advanced pancreatic cancer.

Effect of early and late antibiotic treatment in experimental acute pancreatitis in rats.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Systemic immune dysfunction in pancreatic cancer patients.

BACKGROUND AND AIMS: We investigated the immune status in 32 pancreatic cancer patients (PC) in comparison with healthy controls (HC). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The effects of intraabdominally insufflated carbon dioxide on hepatic blood flow during laparoscopic surgery assessed by transesophageal echocardiography.

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.

Influence of PMN leukocyte-mediated pancreatic damage on the systemic immune response in severe acute pancreatitis in rats.

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.

Treatment of pancreatic cancer: challenge of the facts.

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.

Duodenum-preserving pancreatic head resection leads to relief of common bile duct stenosis.

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.