Drainage and irrigation on demand may decrease severe septic complications and mortality in pancreatic resections.

PURPOSE: The necessity of routine drain placement in pancreatic resections is controversial. Some randomized controlled trials have shown that the omission of drainage is safe for some patients, whereas reintervention rates and mortality rates are substantial for others. The present study aimed to assess fistula-associated outcomes in the setting of routine drain placement and drain irrigation on demand. METHODS: Between 01/2017 and 12/2022, perioperative and outcome data from patients who underwent consecutive pancreatoduodenectomies (PD, n = 253) or distal pancreatectomies (DP, n = 72) were prospectively collected in the electronic StuDoQ database and analysed. All patients underwent intraoperative drain placement. Drains were removed starting at postoperative day 2 in PD or at day 5 in DP after testing for amylase concentration. In case of high amylase levels or macroscopically suspicious pancreatic fistulas, drain irrigation was started. Nondrained fluid collections underwent percutaneous radiologic or transluminal endoscopic evacuation. RESULTS: Clinically relevant pancreatic fistulas were detected in 53 of 325 patients (POPF grade B 16.3%, grade C 1.2%). 43.3% of those had drain irrigation. Additional interventional or endoscopic drainage was necessary in 14 and 5 patients, respectively (overall 5.8%), and were observed in 4.0% of patients with PD and in 12.5% with DP (p = 0.009). Delayed fistula-associated postpancreatectomy haemorrhage (PPH) was present in 1.2% (4/325) of patients. The fistula- and delayed PPH-associated reoperation rate was 1.5% (5/325). The 30-day and in-hospital mortality rates were both 1.5% (5/325), and the rate of fistula-associated mortality was 0.6% (2/325). The overall 90-day mortality rate was 4.5%. CONCLUSIONS: In pancreatectomies, a standardized drainage protocol including on-demand drain irrigation results in very low fistula-associated morbidity and mortality and an infrequent need for interventional or surgical reintervention as compared to previously published drainage studies.

Outcomes and risks in palliative pancreatic surgery: an analysis of the German StuDoQ|Pancreas registry.

BACKGROUND: Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC. METHODS: From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed. RESULTS: Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days [SD 1.7] vs. 1.9 [3.6], 2.0 [2.8] or 2.1 [2.8]; P < 0.0001) and in the hospital (median 7 days [IQR 4-11] vs. 12 [10-18], 12 [8-19] or 12 [9-17]; P < 0.0001), and complications occurred less frequently (22/127 [17.3%] vs. 37/92 [40.2%], 29/65 [44.6%] or 48/105 [45.7%]; P < 0.0001). In multivariable logistic regression, biliary stents were associated with less major (Clavien-Dindo grade ≥ IIIa) complications (OR 0.49 [95% CI 0.25-0.96], P = 0.037), whereas-compared to exploration only-biliary, gastroenteric, and double bypass were associated with more major complications (OR 3.58 [1.48-8.64], P = 0.005; 3.50 [1.39-8.81], P = 0.008; 4.96 [2.15-11.43], P < 0.001). CONCLUSIONS: In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered.

Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions.

Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated. Targeted Next Generation Sequencing (NGS) applied on cytology smears was retrospectively evaluated in a cohort of 37 resected PCL. Usefulness of NGS on fresh cyst fluids was tested in a prospective cohort of patients with newly diagnosed PCL (n = 71). In the retrospective cohort, cytology plus NGS displayed higher sensitivity (94.1% vs. 87.1%) and specificity (100% vs. 50%) than cytology alone for the detection of mucinous neoplasms. In the prospective cohort, sensitivity and specificity of conventional cytology alone were 54.2% and 100% for the detection of mucinous neoplasia and 50.0% and 100% for the detection of high-grade dysplasia, respectively. Adding NGS, all lesions which underwent histopathologic verification (12/71, 17%) could be classified without false positive or false negative results regarding the detection of mucinous neoplasm so far. NGS analysis of cfDNA in PCL fluids is feasible and can increase diagnostic accuracy in the detection of mucinous neoplasms compared to cytology alone. However, algorithms for the detection of high-risk lesions need further improvement.

Oligometastatic pulmonary metastasis in pancreatic cancer patients: Safety and outcome of resection.

OBJECTIVE: To assess the perioperative and long-term outcome following pulmonary resection in patients with metachronous metastasis of pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Most patients with PDAC relapse or develop tumor spread to secondary organs. Currently, it remains unclear how to proceed with pulmonary metastasis in the metachronous setting. In particular, the role of surgery remains controversial. METHODS: Data of patients with pulmonary metachronous metastasis after PDAC collected from 2003 to 2015 in databases of two high-volume pancreatic cancer centers were retrospectively analyzed. Clinical and pathological aspects of primary PDAC as well as the perioperative and long-term outcome following pulmonary metastasectomy (PM) was evaluated, respectively. Patients with synchronous liver metastasis or metastasis to other secondary organs were excluded. Univariate survival analysis was performed. RESULTS: We identified 15 patients undergoing pulmonary resection for suspected metastasis after primary pancreatic resection. Operative and histopathologic evaluation revealed resectable pancreatic pulmonary metastasis in 11 patients (73.3%). The median disease-free survival (DFS) and overall survival (OS) after PM diagnosis was 18 months and 26 months, respectively. The median time to metachronous metastasis (TMM) was 17 months [3-64 months]. Perioperative morbidity was low with only one readmission (8.3%). There was no perioperative mortality. Patients who developed pulmonary metastasis later than 17 months after primary surgery showed better OS compared to those who did earlier (32.2 vs. 14.75 months, p = 0.025). In addition, patients with high-grade tumors had worse survival (12.4 vs. 31 months, p = 0.02). Elevated serum CEA levels or CA 19-9 levels were also not associated with shortened OS. CONCLUSIONS: This study suggests that pulmonary metastasectomy after PDAC is safe and effective. Patients with extended DFS after primary pancreatic surgery as well as favorable tumor grading seem to particularly benefit from pulmonary surgery.

Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas.

OBJECTIVES: Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). METHODS: Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1ß, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). RESULTS: Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. CONCLUSIONS: Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.

Temporary Intra-Operative Portocaval Shunts, Post-Operative Infections, and Mid-Term Survival after Cava-Sparing Liver Transplantation.

BACKGROUND: Temporary intra-operative portocaval shunts (TPCS) are believed to improve outcomes after cava-sparing liver transplantation. We hypothesize that decompression of the portal venous system via a TPCS reduces gut congestion, thereby decreasing bacterial translocation. Thus, we sought to clarify whether transplantation with a TPCS alters rates of post-operative infections and survival. PATIENTS AND METHODS: Patients undergoing liver transplantation (n = 189) were stratified by usage of a TPCS and the type of intra-operative antibiotic prophylaxis. Rates of post-operative infections were analyzed using the χ2 test. The log-rank test was used to compare 120-d survival. RESULTS: The analysis of patients transplanted with a TPCS and meropenem revealed increased infection rates with gut-specific pathogens (Escherichia coli, Escherichia faecalis, Escherichia faecium; p = 0.04) and equal 120-d survival in comparison with patients transplanted without a TPCS. When vancomycin was added to meropenem infection rates did not differ and patients transplanted with a TPCS had better survival in comparison with patients transplanted without a TPCS (p = 0.02). Within the TPCS group, the administration of meropenem and vancomycin was associated with improved survival in comparison with meropenem only (p = 0.03). CONCLUSION: Survival of patients may be improved by usage of a TPCS when gut-specific pathogens are covered by intra-operative antibiotic prophylaxis.

3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer.

The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases). The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate. The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment.

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery.

BACKGROUND: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. METHODS: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. RESULTS: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. CONCLUSION: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.

Pancreatic anastomosis after pancreatoduodenectomy: A position statement by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: Clinically relevant postoperative pancreatic fistula (grades B and C of the ISGPS definition) remains the most troublesome complication after pancreatoduodenectomy. The approach to management of the pancreatic remnant via some form of pancreatico-enteric anastomosis determines the incidence and severity of clinically relevant postoperative pancreatic fistula. Despite numerous trials comparing diverse pancreatico-enteric anastomosis techniques and other adjunctive strategies (pancreatic duct stenting, somatostatin analogues, etc), currently, there is no clear consensus regarding the ideal method of pancreatico-enteric anastomosis. METHODS: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the best contemporary literature concerning pancreatico-enteric anastomosis and worked to develop a position statement on pancreatic anastomosis after pancreatoduodenectomy. RESULTS: There is inherent risk assumed by creating a pancreatico-enteric anastomosis based on factors related to the gland (eg, parenchymal texture, disease pathology). None of the technical variations of pancreaticojejunal or pancreaticogastric anastomosis, such as duct-mucosa, invagination method, and binding technique, have been found to be consistently superior to another. Randomized trials and meta-analyses comparing pancreaticogastrostomy versus pancreaticojejunostomy yield conflicting results and are inherently prone to bias due to marked heterogeneity in the studies. The benefit of stenting the pancreatico-enteric anastomosis to decrease clinically relevant postoperative pancreatic fistula is not supported by high-level evidence. While controversial, somatostatin analogues appear to decrease perioperative complications but not mortality, although consistent data across the more than 20 studies addressing this topic are lacking. The Fistula Risk Score is useful for predicting postoperative pancreatic fistula as well as for comparing outcomes of pancreatico-enteric anastomosis across studies. CONCLUSION: Currently, no specific technique can eliminate development of clinically relevant postoperative pancreatic fistula. While consistent practice of any standardized technique may decrease the rate of clinically relevant postoperative pancreatic fistula, experienced surgeons can have lower postoperative pancreatic fistula rates performing a variety of techniques depending on the clinical situation. There is no clear evidence on the benefit of internal or external stenting after pancreatico-enteric anastomosis. The use of somatostatin analogues may be important in decreasing morbidity after pancreatoduodenectomy, but it remains controversial. Future studies should focus on novel approaches to decrease the rate of clinically relevant postoperative pancreatic fistula with appropriate risk adjustment.

Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma.

PURPOSE: Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1 % of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC. METHODS: Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively. RESULTS: A substantial antitumor activity was observed for treatment regimens containing 5-FU and oxaliplatin with partial responses or prolonged disease stabilizations (>12 months) observed in 6 out of 7 patients (86 %). Activity was also observed for single-agent 5-FU and its oral prodrugs. Serum lipase levels were elevated in 7 of 12 patients with advanced disease (58 %), whereas CEA and CA 19-9 seemed to be of minor importance for ACC (elevated pre-treatment levels in 4/12 and 3/12 cases, respectively). In selected patients, repeated serum lipase measurements were available and accurately predicted response to chemotherapy and relapse after surgery. CONCLUSIONS: 5-FU- and oxaliplatin-containing regimens are active in advanced ACC. Lipase kinetics may be a useful novel tool to monitor the course of disease as well as treatment effects in ACC.

Open Surgical versus Minimal Invasive Necrosectomy of the Pancreas-A Retrospective Multicenter Analysis of the German Pancreatitis Study Group.

BACKGROUND: Necrotising pancreatitis, and particularly infected necrosis, are still associated with high morbidity and mortality. Since 2011, a step-up approach with lower morbidity rates compared to initial open necrosectomy has been established. However, mortality and complication rates of this complex treatment are hardly studied thereafter. METHODS: The German Pancreatitis Study Group performed a multicenter, retrospective study including 220 patients with necrotising pancreatitis requiring intervention, treated at 10 hospitals in Germany between January 2008 and June 2014. Data were analysed for the primary endpoints "severe complications" and "mortality" as well as secondary endpoints including "length of hospital stay", "follow up", and predisposing or prognostic factors. RESULTS: Of all patients 13.6% were treated primarily with surgery and 86.4% underwent a step-up approach. More men (71.8%) required intervention for necrotising pancreatitis. The most frequent etiology was biliary (41.4%) followed by alcohol (29.1%). Compared to open necrosectomy, the step-up approach was associated with a lower number of severe complications (primary composite endpoint including sepsis, persistent multiorgan dysfunction syndrome (MODS) and erosion bleeding: 44.7% vs. 73.3%), lower mortality (10.5% vs. 33.3%) and lower rates of diabetes mellitus type 3c (4.7% vs. 33.3%). Low hematocrit and low blood urea nitrogen at admission as well as a history of acute pancreatitis were prognostic for less complications in necrotising pancreatitis. A combination of drainage with endoscopic necrosectomy resulted in the lowest rate of severe complications. CONCLUSION: A step-up approach starting with minimal invasive drainage techniques and endoscopic necrosectomy results in a significant reduction of morbidity and mortality in necrotising pancreatitis compared to a primarily surgical intervention.

Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

BACKGROUND: The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. METHODS: A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2) were also utilized. RESULTS: Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. CONCLUSION: This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation.

Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p < 0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p = 0.03). Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic.

Autologous but not Fibrin Sealant Patches for Stump Coverage Reduce Clinically Relevant Pancreatic Fistula in Distal Pancreatectomy: A Systematic Review and Meta-analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) causes significant morbidity and mortality after distal pancreatectomy. Patch coverage of the pancreatic stump is often used with the intention to prevent POPF. Despite numerous investigations, the effects of patch coverage remain unclear. The present meta-analysis aims to clarify the effects of patch coverage in distal pancreatectomy on the incidence of POPF. METHODS: A systematic search of MEDLINE/PubMed and the Cochrane Database according to the PRISMA Statement was performed. Subsequently a meta-analysis on rates and overall incidence of POPF and length of hospital stay was carried out. By applying the inverse variance weighting method, the combined effect size and 95 % confidence interval were calculated. Heterogeneity was assessed using I 2 statistics. RESULTS: Five randomized controlled trials and six observational clinical studies were included for final analysis. A cumulative incidence of 43 % of POPF grades A-C was identified. Patch coverage in distal pancreatectomy is significantly associated with a decreased rate of POPF grade C (p = 0.006). Patches of autologous vascularized tissue significantly reduce the overall incidence of POPF (p = 0.04) and clinically relevant POPF grade B and C (p = 0.002). Fibrin sealant patches do not influence rates of POPF after distal pancreatectomy. None of the outcomes evaluated showed adverse results for the patch group. CONCLUSIONS: Patch coverage after distal pancreatectomy can reduce the rate of POPF. Patch coverage with autologous vascularized tissue but not fibrin sealant patches may be used to reduce clinically relevant POPF and postoperative morbidity in distal pancreatectomy.

Isolated pulmonary metastases define a favorable subgroup in metastatic pancreatic cancer.

PURPOSE: Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. METHODS: Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. RESULTS: A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1-31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). CONCLUSIONS: Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup.

Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head is justified in elderly patients: A Retrospective Cohort Study.

BACKGROUND: The increasing elderly population is an inevitable trend worldwide in developed countries. Therefore, we aimed to assess the experience of a tertiary pancreatic center with a very homogenous population comprising only patients diagnosed with PDAC of the pancreatic head in patients older than 75 years of age compared to their younger counterparts regarding the benefit in life expectancy and tumor biological aggressiveness. METHODS: 300 patients underwent partial pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD) for PDAC of the pancreatic head between 2002 and 2012 and were evaluated with regard to their co-morbidities, clinicopathological and perioperative variables, postoperative morbidity, mortality and long term survival. Therefore, two groups according to the age at the procedure (A: <75 years, n = 241, B: ≥75 years, n = 59) were designed. RESULTS: There were no differences between groups with regard to gender, performed procedure (PPPD or PD), operation time, blood loss, tumor invasiveness and grade of tumor differentiation, R-status, lymph node ratio, 30-day mortality, length of stay and adjuvant chemotherapy. Extended resections including total pancreatectomy were slightly more often performed in younger patients (p = 0.071) and trended toward a higher rate of surgical complications in patients <75 years of age (p = 0.183). A higher rate of preoperative co-morbidities in elderly patients (group B), was associated with more postoperative non-surgical complications (p = 0.002) in this group of patients. However, the median overall survival (19.2 vs. 18.4 months) did not differ significantly between groups. CONCLUSIONS: Major pancreatic surgery for ductal adenocarcinoma of the pancreatic head is justified in elderly patients. With careful patients' selection and prudent perioperative management, elderly patients will have a similar long term outcome despite the higher rate of postoperative morbidity based on non-surgical complications.

Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy.

Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria-targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. © 2016 Wiley Periodicals, Inc.

Treatment options for chylous ascites after major abdominal surgery: a systematic review.

BACKGROUND: Chylous leakage is a relevant clinical problem after major abdominal surgery leading to an increased length of stay. DATA SOURCES: A systematic search of MEDLINE/PubMed and the Cochrane Library was performed according to the PRISMA statement. The search for the MeSH terms "chylous ascites" and/or "lymphatic fistula" retrieved a total of 2,348 articles, of which 36 full-text articles were reviewed by 2 independent investigators. RESULTS: Chylous ascites is described with an incidence of up to 11%, especially after pancreatic surgery. The incidence is increasing with the number of lymph nodes harvested. In patients treated with total parenteral nutrition, conservative treatment is demonstrated to be effective in up to 100% of cases. CONCLUSIONS: The extent of abdominal surgery mainly predicts the risk of chylous ascites. Conservative treatment has been shown to be effective in almost all cases and is the treatment of choice.

Interferon-γ, interleukin-10 and interferon-inducible protein 10 (CXCL10) as serum biomarkers for the early allograft dysfunction after liver transplantation.

Orthotopic liver transplantation (LTP) is nowadays a standard procedure, and provides the chance of survival of patients with end-stage non-treatable chronic liver disease or acute liver failure. Despite long-term survival with a good quality of life in the majority of patients, about 20% develop early allograft dysfunction (EAD), which leads to death or the need for re-transplantation. Therefore, the early diagnosis of EAD and evaluation of its risk factors are very important. Many primary pathological processes leading to EAD are accompanied by the release of different mediators and by a change of biochemical parameters detectable in the peripheral blood. The aim of this study was to investigate cytokines as well as soluble mediators in the serum of patients with and without EAD from our LTP bank, and to evaluate their predictive and prognostic values for EAD. We demonstrated for the first time that the level of IFNγ during the nearest preoperative period may serve as a predictive parameter for EAD. We additionally found that IL-10 and CXCL10 (IP-10) levels in the early postoperative period can be prognostic for EAD. We believe our data expand the spectrum of predictive and prognostic parameters for EAD in LTP.