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.

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.

Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients.

OBJECTIVE: Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. DESIGN: We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: <5%; intermediate: ≥5% to <15%; high: ≥15% to <35%; and very high: ≥35%). RESULTS: Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). CONCLUSION: In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.

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.

[Premalignant cystic neoplasms and neuroendocrine tumors of the pancreatic head-Is the Kausch-Whipple resection an adequate treatment?] / Prämaligne, zystische Neoplasien und neuroendokrine Tumoren des Pankreaskopfes ­ Ist die Kausch-Whipple-Resektion eine adäquate Therapie?

Currently, the most frequently used surgical treatment for symptomatic, benign, premalignant cystic and neuroendocrine neoplasms of the pancreatic head is the Whipple procedure or pylorus-preserving pancreatoduodenectomy (PD). However, when performed for treatment of benign tumors, PD is a multiorgan resection involving loss of pancreatic and extrapancreatic tissue and functions. PD for benign neoplasm is associated with the risk of considerable early postoperative complications and an in-hospital mortality of up to 5%. Following the Whipple procedure a new onset of diabetes mellitus is observed in 14-20% and new exocrine insufficiency in 25-45%, leading to metabolic dysfunction and impairment of quality of life persisting after resection of benign tumors. Symptomatic neoplasms are indication for surgery. Patients with asymptomatic pancreatic tumors are treated according to the criteria of surveillance protocols. The goal of surgical treatment for asymptomatic patients is, according to the guideline criteria, interruption of the surveillance program before the development of an advanced stage cancer associated with the neoplasm. Tumor enucleation and duodenum-preserving pancreatic head resection, either total or partial, are parenchyma-sparing resections for benign neoplasms of the pancreatic head. The first choice for small tumors is enucleation; however, enucleation is associated with an increased risk of pancreatic fistula B + C following pancreatic main duct injury. Duodenum-preserving total or partial pancreatic head resection has the advantage of low postoperative surgery-related complications, a mortality of < 0.5% and maintenance of the endocrine and exocrine pancreatic functions. Parenchyma-sparing pancreatic head resections should replace classical Whipple procedures for neoplasms of the pancreatic head.

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.

Whipple Resection for Benign Tumors and Premalignant Neoplasms of the Pancreatic Head: Surgery-Associated Risk for Complications and Late Metabolic Morbidity Matters.

Benign and premalignant neoplasms of the pancreas are increasingly detected and recommended for surgical treatment. For tumors of the pancreatic head, the challenging decision is: multiorgan resection or local tumor extirpation? Compared with pancreaticoduodenectomy, duodenum-preserving pancreatic head resection is associated with significantly fewer surgery-related serious and severe complications and lower in-hospital mortality. The decisive advantage of duodenum-preserving pancreatic head resection is the maintenance of endocrine and exocrine pancreatic and upper gastrointestinal tract functions.

Patient-centered developments in colon- and rectal cancer with a multidisciplinary international team: From translational research to national guidelines.

Rarely, scientific developments centered around the patient as a whole are published. Our multidisciplinary group, headed by gastrointestinal surgeons, applied this research philosophy considering the most important aspects of the diseases "colon- and rectal cancer" in the long-term developments. Good expert cooperation/knowledge at the Comprehensive Cancer Center Ulm (CCCU) were applied in several phase III trials for multimodal treatments of primary tumors (MMT) and metastatic diseases (involving nearly 2000 patients and 64 centers), for treatment individualization of MMT and of metastatic disease, for psycho-oncology/quality of life involving the patients' wishes, and for disease prevention. Most of the targets initially were heavily rejected/discussed in the scientific communities, but now have become standards in treatments and national guidelines or are topics in modern translational research protocols involving molecular biology for e.g., "patient centered individualized treatment". In this context we also describe the paths we had to tread in order to realize our new goals, which at the end were highly beneficial for the patients from many points of view. This description is also important for students and young researchers who, with an actual view on our recent developments, might want to know how medical progress was achieved.

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL).

Mechanisms leading to acute pancreatitis after a fat-enriched meal combined with excess alcohol are incompletely understood. We have studied the effects of alcohol and fat (VLDL) on pancreatic acinar cell (PAC) function, oxidative stress, and repair mechanisms by pancreatic stellate cells (PSC) leading to fibrogenesis. To do so, PAC (rat) were isolated and cultured up to 24 h. Ethanol and/or VLDL were added to PAC. We measured PAC function (amylase, lipase), injury (lactic dehydrogenase), apoptosis (TUNEL, Apo2.7, annexin V binding), oxidative stress, and lipid peroxidation (conjugated dienes, malondialdehyde, chemoluminescence); we also measured PSC proliferation (bromodeoxyuridine incorporation), matrix synthesis (immunofluorescence of collagens and fibronectin, fibronectin immunoassay), and fatty acids in PAC supernatants (gas chromatography). Within 6 h, cultured PAC degraded and hydrolyzed VLDL completely. VLDL alone (50 microg/ml) and in combination with alcohol (0.2, 0.5, and 1% vol/vol) induced PAC injury (LDL, amylase, and lipase release) within 2 h through generation of oxidative stress. Depending on the dose of VLDL and alcohol, apoptosis and/or necrosis were induced. Antioxidants (Trolox, Probucol) reduced the cytotoxic effect of alcohol and VLDL. Supernatants of alcohol/VLDL-treated PAC stimulated stellate cell proliferation and extracellular matrix synthesis. We concluded that, in the presence of lipoproteins, alcohol induces acinar cell injury. Our results provide a biochemical pathway for the clinical observation that a fat-enriched meal combined with excess alcohol consumption can induce acinar cell injury (acute pancreatitis) followed by repair mechanisms (proliferation and increased matrix synthesis in PSC).

Long-term experience on surgical treatment of alveolar echinococcosis.

INTRODUCTION: Alveolar echinococcosis (AE) is life-threatening and reports on surgical procedures and results are rare, but essential. MATERIALS AND METHODS: Longitudinal surveillance and long-term follow-up of patients surgically treated for AE during the periods 1982-1999 (group A) and 2000-2006 (group B). SETTING: University hospital within an endemic area. RESULTS: The median (min-max) follow-up period was 141 (5-417) months. Forty-eight surgical procedures were performed in 36 patients with AE: 63% were partial resections of the liver (additional extrahepatic resection in ten of them), 17% just extrahepatic resections, 10% biliodigestive anastomosis, and 10% exploratory laparotomies. Seventy-five percent of the operations were first-time procedures, 25% done due to a relapse. Forty-two percent of the operations were estimated to be curative (R0), whereas 58% were palliative (R1, R2). All patients had additional medical treatment and periodical follow-up. Two out of 18 (11%) patients, estimated to have had curative surgery, developed a relapse 42 and 54 months later. R0-resection rates depended on the primary, neighboring, metastasis stage of AE (S1, 100%; S2, 100%; S3a, 33%; S3b, 27%; S4, 11%). During the period 2000-2006 elective radical surgery for AE was done only if a safe distance of at least 2 cm was attainable. This concept was associated with an increased R0-resection rate of 87% for group B compared to 24% for group A. Operative procedures done to control complicated courses of AE (jaundice, cholangitis, vascular compression, bacterial superinfection) have not been curative (R2) in 82% because the disease had spread into irresectable structures. Morbidity was 19%. All patients with curative resections are alive. Fifty-six percent of the patients with palliative treatment are alive as long as 14-237 months, 28% died from AE 164-338 months after diagnosis (late lethality), and 17% died due to others diseases 96-417 months after diagnosis of AE. One out of seven (14%) patients suffering from suppurative parasitic necrosis died because it was impossible to control systemic sepsis (3% hospital lethality). CONCLUSION: Curative surgery for AE is feasible if the parasitic mass is removable entirely. The earlier the stage, the more frequent is R0 resectability. The observance of a minimal safe distance increases the rate of R0 resections. The benefit of palliative surgery is uncertain due to favorable long-term results of medical treatment alone. However, necrotic tissue is at risk of bacterial superinfection, which can cause life-threatening sepsis. Palliative surgery is an option to treat complications, which could not be managed otherwise.

Effect of major abdominal surgery on endotoxin release and expression of Toll-like receptors 2/4.

BACKGROUND: Surgery can cause endotoxemia, and endotoxin aggregates to Toll-like receptors and acts proinflammatory; repetitive endotoxin application can cause tolerance. The objective of the study is to characterize early inflammatory response and expression of TLR2/4 during major abdominal surgery. MATERIALS AND METHODS: A prospective controlled study of 20 patients with elective major abdominal surgery was performed. Blood samples were collected before and at a defined time after surgery. Endotoxemia, capability of plasma to inactivate endotoxin, cytokine release of LPS-stimulated mononuclear cells, quantitative TLR mRNA expression, and plasma concentrations of TNFalpha, IL-6, C-reactive protein (CRP), alpha(1)-acid glycoprotein, transferrin, and albumin were measured. RESULTS: Surgery caused endotoxemia (p = 0.053), and the capability of plasma to inactivate endotoxin was reduced (p = 0.0002). Two hours postoperatively, the plasma concentrations of TNFalpha and IL-6 peaked significantly, but the liberation capacity of mononuclear cells for cytokines (TNFalpha, IL-1beta, IL-6) was significantly reduced. The concentration of CRP and alpha(1)-acid glycoprotein peaked 48 h postoperatively, but those of transferrin and albumin were significantly decreased (p < 0.001, respectively). Median mRNA expression of TLR2 and TLR4 of mononuclear cells was not altered, and there was no obvious trend over time. CONCLUSION: Major abdominal surgery is associated with endotoxemia, reduced capability of plasma to inactivate endotoxin, cytokine kinetics resembling those of healthy man after experimentally given LPS, and substantial acute-phase reaction. The cytokine liberation of mononuclear cells suggests a state of postoperative endotoxin tolerance. Despite these substantial changes, trends in TLR2/4 expression are not obvious.

[Duodenum-preserving pancreatic head resection : A local parenchyma-sparing treatment of benign and premalignant tumors of the pancreatic head]. / Die duodenumerhaltende Pankreaskopfresektion : Eine lokale parenchymsparende Therapie benigner und prämaligner Tumoren des Pankreaskopfes.

BACKGROUND: In contrast to the Kausch-Whipple procedure (pancreatoduodenectomy) duodenum-preserving pancreatic head resection (DPPHR) is associated with tissue sparing and maintenance of the pancreatic metabolic functions. AIM: According to the results of controlled clinical trials the DPPHR procedure for benign pancreatic neoplasms is associated with low surgery-related complications and maintenance of glucose metabolism and exocrine pancreatic functions. This overview summarizes the clinical results of the use of DPPHR for chronic pancreatitis and benign tumors of the pancreatic head and the status of the clinical evidence of the results. MATERIAL AND METHODS: The literature review included the results of all prospective, prospective-controlled and randomized clinical trials and meta-analyses, which analyzed and compared pancreatoduodenectomy and DPPHR for chronic pancreatitis and benign neoplasms of the pancreas. RESULTS: Compared to pancreatoduodenectomy, DPPHR exhibits significantly shorter times for surgery, shorter intensive care unit and hospital stays, lower intraoperative blood loss, lower frequency of disorders of gastric emptying and preservation of pancreatic functions. Chronic pancreatitis pancreatic fistula rates, hospital mortality and quality of life were equally low after both operations. The use of DPPHR for benign, premalignant neoplasms in adults and children and for periampullary low-risk malignancies has the advantage of a long-lasting preservation of endocrine and exocrine pancreatic functions and gastrointestinal motility. CONCLUSION: The use of DPPHR for benign, premalignant, cystic and neuroendocrine neoplasms of the pancreatic head is associated with major advantages in the early postoperative course and preservation of gastrointestinal and pancreatic functions.

Surgical approaches to chronic pancreatitis.

Chronic pancreatitis (CP), a benign, inflammatory process of the pancreas, can cause severe pain, diabetes mellitus, steatorrhoea, and weight loss and often leads to a significant reduction in the quality of life. In the past decade our knowledge of the pathophysiology of CP has increased together with the number and quality of treatment options available for this disease. In addition to pharmacological and endoscopic treatment modalities, surgical drainage and resection procedures have become increasingly important since they have the potential to provide superior long-term results in patients with CP. The classical and pylorus-preserving pancreaticoduodenectomy, once the standard operations for patients with CP, have been replaced by organ-sparing procedures like the duodenum preserving pancreatic head resection and its variants. The latter allow better preservation of the exocrine and endocrine pancreatic function, and provide adequate pain relieve and improvement in the quality of life of CP patients.

Treatment of chronic pancreatitis with endotherapy or surgery: critical review of randomized control trials.

The goal of this Society for Surgery of the Alimentary Tract postgraduate course was to review critically the highest level of published evidence focused on treating the disabling chronic abdominal pain due to chronic pancreatitis. Just eight randomized controlled trials (RCTs) have been reported since 1995. All are from Europe. These eight RCTs utilized 380 patients to compare a diverse variety of surgical resections, surgical drainage vs. endotherapy (trans-ampullary pancreatic stents for drainage), or endotherapy with or without shock wave lithotripsy. Therefore, these trials contained a paucity of patients for each treatment compared. Heterogeneity was evident after analysis of the study designs because they used a diverse set of inclusion and exclusion criteria usually not based on objective criteria such as ductal anatomy. All but one had short follow-up. Because of the lack of homogeneity for these study designs that were somewhat underpowered, the RCTs on the treatment of chronic pancreatitis to relieve disabling abdominal pain must be read carefully. In addition to RCTs, the case series still remains a valuable part of our literature.

Endotoxemia and endotoxin tolerance in patients with ARDS.

BACKGROUND: The significance of endotoxemia in man is controversial, induces cytokine release and stimulates the immune system. Exaggerated cytokine release of mononuclear cells was observed in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, repetitive administration of endotoxin can cause tolerance. OBJECTIVE: To investigate endotoxemia, plasma TNFalpha, IL-1beta, IL-6, the liberation capacity of those cytokines from mononuclear cells after LPS challenge (Delta values), and plasma antibodies to endotoxins and alpha-hemolysin of Staphylococcus aureus in ALI/ARDS. DESIGN: A prospective clinical study was conducted. SETTING: The study was carried out at the University Hospital Ulm, Ulm, Germany. SUBJECTS: The respondents were 23 patients with ALI/ARDS. INTERVENTIONS: ALI/ARDS was defined according to the American-European Consensus Conference on ARDS. Blood was collected periodically. Parameters were measured by LAL or ELISA. RESULTS: ARDS (P(a)O(2)/F(i)O(2) < 200) revealed higher endotoxemia (0.22-0.46 [0.06-1.15] EU/mL vs 0.05-0.14 [0.02-0.63] EU/mL) than ALI (P(a)O(2)/F(i)O(2) > 200) but lower DeltaIL-6 (124-209 [10-1214] pg/mL vs 298-746 [5-1797] pg/mL), DeltaTNFalpha (50-100 [6-660] pg/mL vs 143-243 [12-2795] pg/mL), and DeltaIL-1 (2-3 [0-26] pg/mL vs 2-14 [0-99] pg/mL). Endotoxemia correlated negative with P(a)O(2)/F(i)O(2) (r, -0.44 to -0.50). All patients presented antibodies to lipopolysaccharides and alpha-hemolysin, but the level did not correlate with P(a)O(2)/F(i)O(2). CONCLUSIONS: ALI/ARDS is associated with endotoxemia. The more severe the disease, the more intense is endotoxemia but the lower is the capacity of mononuclear cells to release cytokines (tolerance). Antibodies against Gram-positive and Gram-negative bacteria are detectable in the plasma but without relation to P(a)O(2)/F(i)O(2).

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%.

The tobacco carcinogen NNK is stereoselectively reduced by human pancreatic microsomes and cytosols.

BACKGROUND/AIMS: Cigarette smoking increases the risk of cancer of the pancreas. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the only known environmental compound that induces pancreatic cancer in laboratory animals. Concentrations of NNK are significantly higher in the pancreatic juice of smokers than in that of nonsmokers. The chiral NNK metabolite, (R,S)-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is itself a potent pancreatic carcinogen in rats. The carcinogenicity of NNAL is related to its stereochemistry; (S)-NNAL is a more potent lung tumorigen in the A/J mouse than is (R)-NNAL. In this study, we determined the potential of the human pancreas to convert NNK into NNAL. MATERIALS AND METHODS: Human pancreatic microsomes and cytosols were incubated with [5-(3)H]NNK, and the metabolic products were determined by high-performance liquid chromatography (HPLC). RESULTS: (S)-NNAL was the predominant isomer formed in all cytosolic incubations. In ten microsomal samples, NNAL was formed at an average rate of 3.8 +/- 1.6 pmol/mg/min; (R)-NNAL was the predominant isomer in this group. The average rate of NNAL formation in 18 other microsomal samples was significantly lower, 0.13 +/- 0.12 pmol/mg/min (p < 0.001); (S)-NNAL was the predominant isomer formed in this group. CONCLUSION: In human pancreatic tissues, there is intraindividual variability regarding the capacity for, and stereoselectivity of, carbonyl reduction of NNK.

Benign Tumors of the Pancreas-Radical Surgery Versus Parenchyma-Sparing Local Resection-the Challenge Facing Surgeons.

Pancreaticoduodenectomy and left-sided pancreatectomy are the surgical treatment standards for tumors of the pancreas. Surgeons, who are requested to treat patients with benign tumors, using standard oncological resections, face the challenge of sacrificing pancreatic and extra-pancreatic tissue. Tumor enucleation, pancreatic middle segment resection and local, duodenum-preserving pancreatic head resections are surgical procedures increasingly used as alternative treatment modalities compared to classical pancreatic resections. Use of local resection procedures for cystic neoplasms and neuro-endocrine tumors of the pancreas (panNETs) is associated with an improvement of procedure-related morbidity, when compared to classical Whipple OP (PD) and left-sided pancreatectomy (LP). The procedure-related advantages are a 90-day mortality below 1% and a low level of POPF B+C rates. Most importantly, the long-term benefits of the use of local surgical procedures are the preservation of the endocrine and exocrine pancreatic functions. PD performed for benign tumors on preoperative normo-glycemic patients is followed by the postoperative development of new onset of diabetes mellitus (NODM) in 4 to 24% of patients, measured by fasting blood glucose and/or oral/intravenous glucose tolerance test, according to the criteria of the international consensus guidelines. Persistence of new diabetes mellitus during the long-term follow-up after PD for benign tumors is observed in 14.5% of cases and after surgery for malignant tumors in 15.5%. Pancreatic exocrine insufficiency after PD is found in the long-term follow-up for benign tumors in 25% and for malignant tumors in 49%. Following LP, 14-31% of patients experience postoperatively NODM; many of the patients subsequently change to insulin-dependent diabetes mellitus (IDDM). The decision-making for cystic neoplasms and panNETs of the pancreas should be guided by the low surgical risk and the preservation of pancreatic metabolic functions when undergoing a limited, local, tissue-sparing procedure.