Thilo Hackert

Pancreatic cancer surgery in the new millennium: better prediction of outcome.

Background: Surgery is the only therapy with potentially curative intention in pancreatic cancer. This analysis aimed to determine prognostic parameters in a patient cohort with resected pancreatic adenocarcinoma with a special focus on the revised R1-definition. Methods: Between October 2001 and August 2009, data from 1071 consecutively resected patients with pancreatic adenocarcinoma were prospectively collected in an electronical database. Parameters tested for survival prediction in univariate analysis included patient, tumor, and resection characteristics as well as adjuvant therapy. The parameters with significant results were used for multivariate survival analysis. Identified parameters with positive or negative prognostic effect were used to define risk groups and to assess the effects on patient survival. Results: Age, ASA-score, CEA and CA19–9 levels, preoperative insulin-dependent diabetes mellitus, T-, N-, M-, R-, G-tumor classification, advanced disease, and LNR were all significant in univariate analysis, whereas gender, NYHA score, BMI, insurance status, type of surgical procedure, and adjuvant therapy were not. In multivariate analysis, age ≥70 years, preoperative insulin-dependent diabetes, CA19–9 ≥400 U/mL, T4-, M1- or G3-status, and LNR > 0.2 were independent negative predictors, whereas Tis/T1/T2-status, G1-differentiation, and R0-status (revised definition) were independently associated with good prognosis. Using these risk factors, patients were stratified into 4 risk-groups with significantly different prognosis; 5-year survival varied between 0% and 54.5%. Risk stratification resulted in improved survival prognostication within the predominant AJCC IIA and AJCC IIB stages. Conclusions: A newly defined prognostic profiling including the revised R1-definition discriminates survival of patients with resectable pancreatic adenocarcinoma better than the AJCC staging system, and may be of particular relevance for patient-adjusted therapy in the heterogeneous group of AJCC stage II tumors.

Small (Sendai negative) branch-duct IPMNs: not harmless.

Objective:The aim of this study was to evaluate existing management guidelines for branch-duct intraductal papillary mucinous neoplasms (IPMNs). Background:According to current treatment guidelines (Sendai criteria), patients with asymptomatic branch-duct type IPMNs of the pancreas less than 3 cm in diameter without suspicious features in preoperative imaging should undergo conservative treatment with yearly follow-up examinations. Nevertheless, the risk of harboring malignancy or invasive cancer remains a significant matter of consequence. Methods:All patients who were surgically resected for branch-duct IPMNs between January 2004 and July 2010 at the University Clinic of Heidelberg were analyzed. Clinical characteristics of the patients and preoperative imaging were examined with regard to the size of the lesions, presence of mural nodules, thickening of the wall, dilation of the main pancreatic duct, and tumor markers. Results were correlated with histopathological features and were discussed with regard to the literature. Results:Among a total of 287 consecutively resected IPMNs, 123 branch-duct IPMNs were identified analyzing preoperative imaging. Some 69 branch-duct IPMNs were less than 3 cm in size, without mural nodules, thickening of the wall, or other features characteristic for malignancy (“Sendai negative”). Of all the Sendai negative branch-duct IPMNs, 24.6% (17/69) showed malignant features (invasive carcinoma or carcinoma in situ) upon histological examination of the surgical specimen. Conclusions:Although many branch-duct IPMNs are small and asymptomatic, they harbor a significant risk of malignancy. We believe that both main-duct and branch-duct IPMNs represent premalignant lesions. This should be taken into account for adequate therapeutic management. With regard to these results, the current Sendai criteria for branch-duct IPMNs need to be adjusted.

The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After

Background. In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods. The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results. Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former “grade A postoperative pancreatic fistula” is now redefined and called a “biochemical leak,” because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion. This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.

Postoperative pancreatic fistula

Postoperative pancreatic fistula is an important complication after pancreatic resection. The frequency of its incidence varies between 3% after pancreatic head resections and up to 30% following distal pancreatectomy. In recent years, the international definition of pancreatic fistula has been standardised according to the approach of the International Study Group on Pancreatic Fistula (ISGPF). Consequently, results from different studies have become comparable and the historically reported fistula rates can be evaluated more critically. The present review summarises the currently available data on incidence, risk factors, fistula-associated complications and management of postoperative pancreatic fistula.

Multivisceral resection for pancreatic malignancies: risk-analysis and long-term outcome.

Objective:To evaluate the safety and outcome of multivisceral pancreatic resections for primary pancreatic malignancies. Background:Curative resection is the only potential cure for patients with pancreatic cancer, but some patients present with advanced tumors that are not resectable by a standard pancreatic resection. Data on risk and survival analysis of extended pancreatic resections is limited. Methods:One hundred one patients who had a multivisceral pancreatic resection between 10/2001 and 12/2007 were identified from a prospective database, and perioperative and long-term results were compared with those of 202 matched patients with a standard pancreatic resection. Uni- and multivariate regression analysis were performed to identify parameters that are associated with perioperative morbidity. Long-term survival was evaluated. Results:Colon, stomach, adrenal gland, liver, hepatic or celiac artery, kidney, or small intestine were resected in 37.6%, 33.7%, 27.7%, 18.8%, 16.8%, 11.9%, and 6.9% of the 101 patients with multivisceral resection, respectively. Additional portal vein resection was performed in 20.8% of patients. Overall and surgical morbidity but not mortality was significantly increased compared with standard pancreatic resections (55.5% vs. 42.8%, 37.6 vs. 25.3%, and 3.0% vs. 1.5%, respectively). Uni- and multivariate analysis identified a long operative time and the extended multivisceral resection of 2 or more additional organs as independent risk factors for intraabdominal complications or need for relaparotomy. Median survival was comparable to that of standard pancreatic resections. Conclusions:Multivisceral resections can be performed with increased morbidity but comparable mortality and long-term prognosis as compared with standard pancreatic resections at high volume centers. Increased morbidity is related to extended multivisceral resections with a long operative time.

A systematic review and meta-analysis of laparoscopic versus open distal pancreatectomy for benign and malignant lesions of the pancreas: it's time to randomize.

BACKGROUND Laparoscopic distal pancreatectomy is regarded as a feasible and safe surgical alternative to open distal pancreatectomy for lesions of the pancreatic tail and body. The aim of the present systematic review was to provide recommendations for clinical practice and research on the basis of surgical morbidity, such as pancreas fistula, delayed gastric empting, safety, and clinical significance of laparoscopic versus open distal pancreatectomy for malignant and nonmalignant diseases of the pancreas. METHODS A systematic literature search (MEDLINE) was performed to identify all types of studies comparing laparoscopic distal pancreatectomy and open distal pancreatectomy. Random effects meta-analyses were calculated after critical appraisal of the included studies and presented as odds ratios or mean differences each with corresponding 95% confidence intervals. RESULTS A total of 4,148 citations were retrieved initially; available data of 29 observational studies (3,701 patients overall) were included in the meta-analyses. Five systematic reviews on the same topic were found and critically appraised. Meta-analyses showed superiority of laparoscopic distal pancreatectomy in terms of blood loss, time to first oral intake, and hospital stay. All other parameters of operative morbidity and safety showed no difference. Data on oncologic radicality and effectiveness are limited. CONCLUSION Laparoscopic distal pancreatectomy seems to be a safe and effective alternative to open distal pancreatectomy. No more nonrandomized trials are needed within this context. A large, randomized trial is warranted and should focus on oncologic effectiveness, defined end points, and cost-effectiveness.

Enucleation in pancreatic surgery: indications, technique, and outcome compared to standard pancreatic resections

PurposePancreatic surgery is a technically challenging intervention with high demands for preoperative diagnostics and perioperative management. A perioperative mortality rate below 5% is achieved in high-volume centers due to the high level of standardization in surgical procedures and perioperative care. Besides standard resections, certain indications may require individualized surgical concepts such as tumor enucleations. The aim of the study was to evaluate the indications, technique, and outcome of this limited local approach compared to major resections.Materials and methodsData from patients undergoing pancreatic surgery were prospectively recorded. All patients with tumor enucleations were compared with classical resections (pancreaticoduodenectomy or left resection) in a matched-pair analysis (1:2). Tumor type, localization, operative parameters, complications, and outcome were evaluated.ResultsFifty-three patients underwent pancreatic tumor enucleation between October 2001 and December 2009. Indications included cystic lesions, IPMNs, and neuroendocrine pancreatic tumors. Enucleations were associated with shorter operation time, less blood loss as well as shorter ICU and hospital stay compared to pancreaticoduodenectomy and left resections. The overall surgical morbidity of enucleations was 28.3% without major complications. Leading clinical problems were ISGPF type A fistulas (20.8%) requiring prolonged primary drainage. No surgical revisions were necessary, and no deaths occurred.ConclusionsPancreatic tumor enucleations can be carried out with good results and no mortality. Decisions regarding enucleations are highly individual compared to standard resections, underlining the importance of treatment in experienced high-volume institutions. Enucleations should be carried out whenever possible and oncologically feasible to prevent the typical complications of major pancreatic resection.

Role of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in distinguishing between benign and invasive intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has malignant potential. Although serum levels of carbohydrate antigen (CA) 19‐9 and carcinoembryonic antigen (CEA) are known to be raised in pancreatic ductal adenocarcinoma, little has been reported about their significance in IPMN.

Advanced-stage pancreatic cancer: therapy options

Pancreatic ductal adenocarcinoma is one of the most aggressive cancers, and surgical resection is a requirement for a potential cure. However, the majority of patients are diagnosed with advanced-stage disease, either metastatic (50%) or locally advanced cancer (30%). Although palliative chemotherapy is the standard of care for patients with metastatic disease, management of locally advanced adenocarcinoma is controversial. Several treatment options, including extended surgical resections, neoadjuvant therapy with subsequent resections, as well as palliative radiotherapy and/or chemotherapy, should be considered. However, there is little evidence available to support treatment options for locally advanced disease. As valid predictive biomarkers for stratification of therapy are not available today, future trials need to define the role of the different treatment options. This Review summarizes the current evidence and discusses available treatment options for both locally advanced and metastatic pancreatic adenocarcinoma.

Bacterial translocation and infected pancreatic necrosis in acute necrotizing pancreatitis derives from small bowel rather than from colon

BACKGROUND The clinical course of acute necrotizing pancreatitis (ANP) is determined by the superinfection of pancreatic necrosis. To date, the pathophysiology of the underlying bacterial translocation is poorly understood. The present study investigated the bacterial source of translocation. METHODS A terminal loop ileostomy was applied in rats. Selective digestive decontamination (SDD) of either the small bowel or the colon was performed. After 3 days of SDD, severe ANP was induced. At 24 hours, bacterial translocation was assessed by cultures of bowel mucosa, mesenteric lymph nodes, and pancreas using a scoring system (0-4). RESULTS Without SDD, pancreatic infection was present in all cases with an average score of 2.67. Colon SDD reduced pancreatic superinfection to 1.67 (not significant). SDD of the small bowel significantly reduced superinfection to 1.0 (P < .005). CONCLUSIONS Bacterial translocation from the colon is less frequent than translocation from the small bowel. Thus, the small bowel seems to be the major source of enteral bacteria in infected pancreatic necrosis.