Applicability of the surgical risk calculator by the American College of Surgeons in the setting of German patients undergoing complete pancreatectomy: multicentre study using data from the StuDoQ|Pancreas registry.

INTRODUCTION: Surgical risk calculators can estimate risk probabilities for postoperative outcomes utilizing patient-specific risk factors. They provide meaningful information for obtaining informed consent. The aim of the present paper was to evaluate the predictive value of the surgical risk calculators by the American College of Surgeons in German patients undergoing total pancreatectomy. METHODS: Data for patients who underwent total pancreatectomy between 2014 and 2018 were acquired from the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery. Risk factors were entered manually into the surgical risk calculators and calculated risks were compared with actual outcomes. RESULTS: Of the 408 patients analysed, predicted risk was higher in patients with complications except for the prediction of re-admission (P = 0.127), delayed gastric emptying (P = 0.243), and thrombosis (P = 0.256). In contrast, classification of patients into below, above, or average risk by the surgical risk calculators only produced meaningful results for discharge to nursing facility (P < 0.001), renal failure (P = 0.003), pneumonia (P = 0.001), serious complications, and overall morbidity (both P < 0.001). Assessment of discrimination and calibration showed poor results (scaled Brier scores 8.46 per cent or less). CONCLUSION: Overall surgical risk calculator performance was poor. This finding promotes the development of a specific surgical risk calculator applicable to the German healthcare system.

Long-term effects of total vs. partial pancreatectomy among patients with pancreatic cancer: a population-based study.

Background: Total pancreatectomy (TP) for pancreatic cancer (PC) has been limited historically for fear of elevated perioperative morbidity and mortality. With advances in perioperative care, TP may be an alternative option to partial pancreatectomy (PP). Limited evidence clarified the indication for these two procedures in PC patients, especially in patients with different tumor staging and location. Thus, this study aims to compare the outcomes after TP and PP for PCs of different T stages and locations. Methods: The study identified 14,456 PC patients with potentially curable primary tumor (T1-3) who received TP or PP from the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2016. Detailed clinical and tumor covariates were all collected. Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints of interest in this study. OS and CSS were compared between patients after TP and PP using log-rank analysis. Results: For all patients, except for tumor location, TP group was comparable to the PP group. OS and CSS of the TP group were worse than of the PP group (median OS: 19 vs. 20 months, P=0.0058; median CSS: 24 vs. 26 months, P=0.00098, respectively). In stratifying analyses, TP was significantly related to worse OS and CSS than PP in pancreatic head and neck cancer patients with T2-stage tumors (median OS: 18 vs. 19 months, P=0.0016; median CSS: 22 vs. 24 months, P=0.00055, respectively), whereas for patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer, OS and CSS of the two groups were similar (all P>0.05). Conclusions: Compared with PP, TP offered worse prognosis in pancreatic head and neck cancer patients with T2-stage tumors, furthermore, TP and PP achieved comparable prognosis in patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer.

Combination of Fat-Free Muscle Index and Total Spontaneous Portosystemic Shunt Area Identifies High-Risk Cirrhosis Patients.

Background: Sarcopenia and spontaneous portosystemic shunts (SPSSs) are common complications of liver cirrhosis, and both are associated with higher rates of hepatic encephalopathy (HE) development in these patients. This study aimed to evaluate the simultaneous impact of skeletal muscle mass and spontaneous portosystemic shunting, measured from routine diagnostic CT on outcomes in patients with liver cirrhosis. Methods: Retrospective analysis of patients with cirrhosis. Skeletal muscle mass [including fat-free muscle index (FFMI) as a surrogate for sarcopenia] and total cross-sectional spontaneous portosystemic shunt area (TSA) were quantified from CT scans. The primary endpoint was the development of HE, while the secondary endpoint was 1-year mortality. Results: One hundred fifty-six patients with liver cirrhosis were included. Patients with low (L-) FFMI and large (L-)TSA showed higher rates of HE development. In multivariable analysis, L-FFMI and L-TSA were independent predictors of HE development (L-FFMI HR = 2.69, CI 1.22-5.93; L-TSA, HR = 2.50, CI = 1.24-4.72) and 1-year mortality (L-FFMI, HR = 7.68, CI 1.75-33.74; L-TSA, HR = 3.05, CI 1.32-7.04). The simultaneous presence of L-FFMI and L-TSA exponentially increased the risk of HE development (HR 12.79, CI 2.93-55.86) and 1-year mortality (HR 13.66, CI 1.75-106.50). An easy sequential algorithm including FFMI and TSA identified patients with good, intermediate, and poor prognoses. Conclusion: This study indicates synergy between low skeletal muscle mass and large TSA to predict exponentially increased risk of HE development and mortality in liver cirrhosis. Simultaneous screening for sarcopenia and TSA from routine diagnostic CT may help to improve the identification of high-risk patients using an easy-to-apply algorithm. Clinical Trial registration: [ClinicalTrials.gov], identifier [NCT03584204].

Cranial stent position is independently associated with the development of TIPS dysfunction.

Complications of portal hypertension can be treated with transjugular intrahepatic portosystemic shunt (TIPS) in selected patients. TIPS dysfunction is a relevant clinical problem. This study investigated the prognostic value of two-dimensional (2D) TIPS geometry for the development of TIPS dysfunction. Three hundred and seven patients undergoing TIPS procedure between 2014 and 2019 were analyzed in this monocentric retrospective study. 2D angiograms from the patients with and without TIPS dysfunction were reviewed to determine geometric characteristics including insertion and curve angles and the location of the stent. Primary outcome was the development of TIPS dysfunction. A total of 70 patients developed TIPS dysfunction and were compared to the dysfunction-free (n = 237) patients. The position of the cranial stent end in the hepatic vein and the persistence of spontaneous portosystemic shunts were significantly associated with the development of TIPS dysfunction. Among significant parameters in univariable regression analysis (portal vein-pressure after TIPS, Child-Pugh Score before TIPS, MELD before TIPS and white blood cell count before TIPS), multivariable models showed cranial stent position (p = 0.027, HR 2.300, 95% CI 1.101-4.806) and SPSS embolization (p = 0.006, HR 0.319, 95% CI 0.140-0.725) as the only predictors of TIPS dysfunction. This monocentric study demonstrates that the position of the cranial stent end is independently associated with the development of TIPS dysfunction. The distance of the cranial stent end to the IVC at the time of TIPS placement should be less than 1 cm in 2D angiography.

Impact of pylorus preservation on delayed gastric emptying after pancreaticoduodenectomy-analysis of 5,000 patients based on the German StuDoQ|Pancreas-Registry.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreatic head resection. It leads to increased length of hospital stay, high costs for healthcare systems and reduced quality of life. The primary aim of the study was to assess the impact of pylorus preservation, respectively resection on the occurrence of DGE in patients undergoing pancreaticoduodenectomy (PD). METHODS: All cases of pylorus-resecting PD (PRPD) and pylorus-preserving PD (PPPD) entered in the StuDoQ|Pancreas nationwide registry of the German Society of General and Visceral Surgery from 01/01/2014 until 31/12/2018 including demographics, surgical techniques, histopathological and perioperative data were retrospectively analyzed. This study was approved by the ethics committee of the Ruhr-University Bochum, Germany. RESULTS: Data of 5,080 patients were enrolled. PPPD was the method of choice (70.4%). Pylorus preservation had no impact on the occurrence of DGE (20.3% vs. 21.5%, P=0.33), but further risk factors could be identified. The comparison of PPPD and PRPD groups showed statistically significant differences in the surgical approach (primary open approach, 94.8% vs. 98.0%, P<0.001), duration of surgery (326.4 vs. 352.1 minutes, P<0.001), technique of pancreatic anastomosis (pancreaticojejunostomy vs. pancreaticojejunostomy), 78.6% vs. 85.2%, P<0.001). CONCLUSIONS: Patient factors, intraoperative factors, duration of surgery and postoperative factors (postoperative pancreatic fistula, biliary leakage and other surgical complications) were identified as risk factors for DGE. Future research should focus on register-based, prospective, randomised-controlled studies such as the currently recruiting "PyloResPres trial".

TIPS for the management of stomal variceal bleeding due to cirrhotic and non-cirrhotic portal hypertension.

BACKGROUND: Portal hypertension (PH) is associated with the development of esophageal or gastric varices, which can cause bleedings with high mortality. Varices can also manifest at sites of stomata. These parastomal varices can cause recurrent variceal bleedings (VB) despite local therapies. We present a case series of parastomal VB due to PH that were managed with implantation of transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We retrospectively included all patients (pt) from 2 tertiary medical centers with parastomal VB between January 2014 and February 2020 who underwent the TIPS procedure. RESULTS: Nine pt were included. Seven pt had liver cirrhosis, mostly alcohol-related. Two pt had non-cirrhotic PH due to porto-sinusoidal vascular disease (PSD). Four pt had a colostomy, 1 an ileostomy, and 4 an ileal conduit. Malignancy was the leading cause of stoma surgery. All 9 pt suffered from recurrent parastomal VB despite non-selective beta-blocker and/or local therapy (e.g., compression, coagulation, suture ligation, or surgical stoma revision). All pt received TIPS implantation. In 7 pt, TIPS implantation led to sustainable hemostasis. Two pt suffered a bleeding relapse that was attributable to TIPS dysfunction. TIPS revision with coil embolization of the varices terminated the VB sustainably in both pt. CONCLUSIONS: In pt presenting with recurrent stomal bleedings, parastomal varices as a rare complication of PH must be taken into consideration as an underlying cause. In our case series, we managed to sustainably cease parastomal VB by TIPS implantation with or without coil embolization of the ectopic varices.

Pancreatic Apoplexy: Fulminant Necrotizing Pancreatitis Leading to Completion Pancreatectomy Within 3 Days After Partial Pancreaticoduodenectomy.

OBJECTIVES: Patient characteristics with postoperative acute necrotizing pancreatitis and completion pancreatectomy (CP) after pancreaticoduodenectomy (PD) remain unclear. METHODS: Data from all patients who underwent a PD with need for CP (January 2011-December 2019) at a German University Hospital were analyzed regarding the indications and timing of CP, laboratory and histopathological findings, and overall outcome. RESULTS: Six hundred twelve patients underwent PD, 33 (5.4%) of them needed a CP. Indications were grade C pancreatic fistula with or without biliary leak (46% and 12%), biliary leak (6%), and hemorrhage due to pancreatic fistula (36%). Eight patients (24%) underwent CP within 3 days after PD. These fulminant courses ("pancreatic apoplexy") were accompanied by significantly higher levels of lactate dehydrogenase, C-reactive protein, serum amylase, serum lipase, drain amylase, and drain lipase compared with patients with CP after the third day. Pancreatic apoplexy was histologically associated with higher rates of pancreatic necrosis (P = 0.044) and hemorrhage (P = 0.001). A trend toward higher mortality was observed (75% vs 36%, P = 0.058). CONCLUSIONS: Pancreatic apoplexy, defined as fulminant necrotizing pancreatitis after PD leading to CP within 3 days, is associated with characteristic laboratory and histopathological findings and a trend to higher mortality.

Late recurrences of pancreatic cancer in patients with long-term survival after pancreaticoduodenectomy.

BACKGROUND: Pancreatic cancer remains a relevant clinical problem due to poor prognosis. Even after curative pancreaticoduodenectomy tumor recurrences occur in up to 80%. Risk factors for postoperative tumor recurrences have been identified before, but data on risk factors for tumor recurrences in patients with long-term-survival is scarce. METHODS: In this retrospective study consecutive long-term survival-patients (defined as at least 60 months survival) undergoing pancreaticoduodenectomy for pancreatic cancer from 2007-2014 were identified in the 2nd largest pancreatic surgery center in Germany. Clinical, pathohistological and laboratory values were analyzed to identify risk factors for tumor recurrence. RESULTS: Thirty-four of one-hundred-sixty-seven patients were identified as long-term-survival-patients in the study period. Of those, 10 patients (29.4%) suffered from tumor recurrence. Lymph vessel invasion was identified as an independent risk factor (P=0.031, hazard ratio 13.127, 95% confidence interval: 1.270-135.698). Median postoperative time to tumor recurrence in long-term-survival-patients was 49 months. Overall survival after diagnosis of tumor recurrence was 33 months. 80% (N=8) of the patients were asymptomatic. Half of the patients (N=5) suffered from local disease, with 40% undergoing curative tumor resection. CA 19-9 levels were significantly elevated at 57 U/mL (normal <27 U/mL). CONCLUSIONS: Tumor recurrence in long-term-survival-patients is typically asymptomatic. Especially long-term-survival-patients with lymph vessel invasion are more likely to develop tumor recurrence. Therefore, a structured follow-up program including CT-scans and CA 19-9 surveillance must be continued in all patients undergoing pancreaticoduodenectomy even in cases of long-term-survival.

Recurrence of Pancreatic Ductal Adenocarcinoma after Complete Histopathological Remission Caused by FOLFIRINOX.

We previously reported 2 cases of pathologic complete response (pCR) of a pancreatic cancer (PC) following neoadjuvant FOLFIRINOX treatment. We now complete our report by a follow-up on both patients. Patient 1 achieved a disease-free survival of 12 months after initial resection until she developed a singular hepatic metastasis. Treatment by FOLFIRINOX and complete removal of the metastasis by atypical liver resection after 6 months allowed for another 12 months of disease control. After intra-abdominal tumor recurrence and development of intracerebral metastases, the patient died 34 months after primary diagnosis. Patient 2 developed hepatic tumor recurrence only 3 months after initial resection. However, treatment by FOLFIRINOX led to a stable disease for 27 months after resection and was followed by atypical liver resection of multiple segments. Six months later, another hepatic recurrence was suspected. Via next-generation sequencing (NGS) of the tumor genome, a deleterious mutation in the ataxia telangiectasia-mutated (ATM) gene, causing a BRCAness, was detected. After initial treatment by FOLFOX, maintenance therapy with the poly-ADP-ribose-polymerase (PARP) inhibitor olaparib was initiated. The patient is now alive for 54 months after initial diagnosis of metastasized pancreatic adenocarcinoma. Tumor recurrence is possible even after pCR of PC and remains challenging. In case of multifocal tumor recurrence, chemotherapy remains the standard treatment. Recently, genetic sequencing allows individualized treatments. In selected cases, highly specialized teams can offer a variety of therapeutic options leading to previously unseen clinical courses.

Is surgery for serous cystic neoplasms of the pancreas still indicated? Sixteen years of experience at a high-volume center.

BACKGROUND: Current guidelines discourage surgery for serous cystic neoplasms (SCN) of the pancreas, because of their benign character, slow growth, and excellent prognosis. Nevertheless, SCN continue to contribute up to 30% of resected cystic pancreatic lesions worldwide. METHODS: Spectrum of indications and outcomes of surgery were analysed in a retrospective series of 133 SCN at a single high-volume center in Germany between 2004 and 2019. RESULTS: Relevant symptoms justified surgery in 60% of patients with SCN, while 40% underwent surgery because of preoperative diagnostic uncertainty about suspected malignancy. There were 4 malignant SCN (3%). Ninety-day mortality was 0.75%, major morbidity - 15%, 10-year survival - 95%. Risks of malignant transformation and of postoperative mortality were similarly low. CONCLUSIONS: Surgery is reasonable and safe for symptomatic patients with SCN. Preoperative diagnostic uncertainty is the main reason for futile resections of benign asymptomatic SCN. Conservative management with close initial surveillance should be the first choice for this population. Surgery for supposed SCN without symptoms is justified only in carefully selected patients with suspected malignancy.

Is primary total pancreatectomy in patients with high-risk pancreatic remnant justified and preferable to pancreaticoduodenectomy? -a matched-pairs analysis of 200 patients.

BACKGROUND: Total pancreatectomy (TP) eliminates the risk of postoperative pancreatic fistula (POPF) and its associated secondary complications. Hence, it may theoretically offer advantages over pancreaticoduodenectomy (PD) regarding early postoperative outcome of patients with high-risk pancreatic remnant. METHODS: Ninety-day mortality and morbidity of 100 TP vs. 100 PD for pancreatic head lesions were retrospectively compared. Groups were matched for pancreatic texture, pancreatic duct size, final histology, age, gender and surgeon. Only patients at high risk for POPF due to soft pancreatic texture and small pancreatic duct <3 mm were included. RESULTS: Preoperatively, the TP-group was characterized by poorer general condition, more comorbidities and more pronounced obesity than the PD-group. Postoperatively, overall morbidity was lower after TP (63% vs. 88%, P<0.001) due to less mild complications. Postpancreatectomy hemorrhage rate was lower after TP than after PD (2% vs. 12%, P=0.014). Duration of surgery, hospital stay, major morbidity (30%) and mortality (7% vs. 5%) were the same. POPF was the most common complication after PD with 32%. Emergency completion pancreatectomy was necessary in 10% of PD with a significantly higher mortality compared to elective TP (50% vs. 7%, P=0.001). CONCLUSIONS: TP may reduce severe POPF-associated complications and prevent mortality related to emergency completion pancreatectomy in some elderly, obese and polymorbid patients with high-risk pancreatic remnant. Careful individual selection by an experienced pancreatic surgeon is mandatory.

Risk factors for perforated marginal ulcers following pancreaticoduodenectomy and prospective analysis of marginal ulcer development.

BACKGROUND: Perforated marginal ulcers (PMUs) are a feared long-term complication following pancreaticoduodenectomy (PD), which always require relaparotomy compared to marginal ulcers. METHODS: First, we performed a retrospective chart review for all patients who underwent PD from 2007-2016 to identify incidence and risk factors associated with PMUs. Second, we analyzed follow up gastroscopies in all patients undergoing PD from 2007-2011 to identify the overall incidence of marginal ulcers. RESULTS: A total of 725 patients underwent PD in the retrospective study period. 17 patients (2.3%) suffered from PMU at a median postoperative time of 13 months. These patients were significantly younger (median age: 49 vs. 62 years; P=0.02) and suffered most often from chronic pancreatitis (P<0.001). Smoking and alcohol consumption were significantly more common (P=0.01 and P=0.023). An elevated level of carcinoembryonic antigen and chronic pancreatitis were identified as independent risk factors. Overall, 373 patients were enrolled for prospective analysis. Marginal ulcers occurred in 5-5.9% over a postoperative period of 5 years. CONCLUSIONS: Continuous treatment with proton-pump inhibitors for at least 5 years, immediate smoking cessation and follow-up gastroscopies are obligate for patients undergoing PD to avoid marginal ulcers and PMUs.

Does autologous fibrin sealant (vivostat©) reduce the incidence of postoperative pancreatic fistula after distal pancreatectomy? - a matched pairs analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most common complication following distal pancreatectomy. This retrospective study investigated the effects of autologous fibrin sealant (Vivostat©) in reducing the incidence of POPF after distal pancreatectomy. METHODS: A matched pairs analysis was performed to compare the incidence of clinically relevant POPF of 41 patients who underwent a distal pancreatectomy with application of autologous fibrin sealant (Vivostat©) with a historical control group. RESULTS: Clinically relevant POPF were present in 11 patients in the study group (27%) and in 13 patients in the control group (32%, p = .639). No patient of the study group required emergency angiographic treatment for postoperative hemorrhage due to POPF, whereas three patients were identified in the control group (7%, p = .079). CONCLUSIONS: POPF cannot be prevented under treatment with autologous fibrin sealant (Vivostat©). We observed the tendency of a lower rate of postoperative pancreatic hemorrhage due to POPF. However, prospective randomized controlled studies are required.

Long-term survival after pancreaticoduodenectomy in patients with ductal adenocarcinoma of the pancreatic head.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignant tumors due to unavailable screening methods, late diagnosis with a low proportion of resectable tumors and resistance to systemic treatment. Complete tumor resection remains the cornerstone of modern multimodal strategies aiming at long-term survival. This study was performed to investigate the overall rate of long-term survival (LTS) and its contributing factors. METHODS: This was a retrospective single-center analysis of consecutive patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2007 and 2014 at the St. Josef Hospital, Ruhr University Bochum, Germany. Clinical and laboratory parameters were assessed and evaluated for prediction of LTS with Cox regression analysis. RESULTS: The overall rate of LTS after PD for PDAC was 20.4% (34/167). Median survival was 24 months regardless of adjuvant treatment. Carbohydrate antigen 19-9 levels, tumor grade, lymph vessel invasion, perineural invasion and reduced general condition were significantly associated with LTS in univariate analysis (P < 0.05). Serum levels of carbohydrate antigen 19-9, American Joint Committee on Cancer stage, tumor grade, abdominal pain, male, exocrine pancreatic insufficiency and duration of postoperative hospital stay were independent predictors of cancer survival in multivariable analysis. CONCLUSIONS: Cancer related characteristics are associated with LTS in multimodally treated patients after curative PDAC surgery.

Long term follow-up of a simplified and less burdened pancreatic duct ligation model of exocrine pancreatic insufficiency in Goettingen Minipigs.

BACKGROUND: Pancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows the study of digestive processes and pancreatic enzyme replacement therapies. However, detailed descriptions of the surgical procedure, perioperative management, a determination of exocrine pancreatic insufficiency are scarce in the literature. Data of the long-term health status of minipigs upon EPI induction are still not available. Therefore, the present study describes in detail an experimental approach to the induction of exocrine pancreatic insufficiency via pancreatic duct ligation in minipigs and the long term follow up of the animal's health state. METHODS: 14 Goettingen minipigs underwent pancreatic duct ligation via midline laparotomy for the induction of exocrine pancreatic insufficiency. Fecal fat content, fat absorption, chymotrypsin levels, body weight and blood vitamin and glucose levels were determined. RESULTS: Exocrine pancreatic insufficiency was successfully induced in 12 Goettingen minipigs. Two minipigs failed to develop exocrine insufficiency most likely due to undetected accessory pancreatic ducts. All animals tolerated the procedure very well and gained weight within 8 weeks after surgery without requiring pancreatic enzyme replacement therapy. The follow up for approx. 180 weeks showed a stable body weight and health state of the animals with normal blood glucose levels (Table 1). From approx. 130 weeks post pancreatic duct ligation, all animals were supplemented with pancreatic enzymes and vitamins resulting in blood concentrations almost within the reference range. CONCLUSIONS: Pancreatic duct ligation in minipigs is an excellent method of inducing exocrine pancreatic insufficiency. It is important to identify and ligate accessory pancreatic ducts since persistence of accessory ducts will lead to maintenance of exocrine pancreatic function. The EPI model caused no persistent side effects in the animals and has the potential to be used in long-term EPI studies with up to 100 weeks post-OP without supplementation with enzymes and vitamins.

Alteration of contrast enhanced ultrasound (CEUS) of hepatocellular carcinoma in patients with cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS).

Transjugular intrahepatic portosystemic shunt (TIPS) can treat portal hypertensive complications and modifies hepatic hemodynamics. Modification of liver perfusion can alter contrast enhancement dynamics of liver nodules. This study investigated the diagnostic performance of contrast-enhanced ultrasound (CEUS) to diagnose hepatocellular carcinoma (HCC) in cirrhosis with TIPS. In this prospective monocentric observational study, CEUS was used to characterize focal liver lesions in patients at risk for HCC with and without TIPS. Times of arterial phase hyperenhancement (APHE) und washout were quantified. Perfusion-index (PI) and resistance-index (RI) of hepatic artery and portal venous flow parameters were measured via doppler ultrasonography. Diagnostic gold standard was MRI/CT or histology. This study included 49 liver lesions [23 TIPS (11 HCC), 26 no TIPS (15 HCC)]. 26 were diagnosed as HCC by gold standard. Sensitivity and specificity of CEUS to diagnose HCC with and without TIPS were 93.3% and 100% vs. 90.9% and 93.3%, respectively. APHE appeared significantly earlier in patients with TIPS compared to patients without TIPS. TIPS significantly accentuates APHE of HCC in CEUS. CEUS has good diagnostic performance for diagnosis of HCC in patients with TIPS.

Facing the surgeon's nightmare: Incidence and management of postoperative pancreatic fistulas grade C after pancreaticoduodenectomy based on the updated definition of the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: Postoperative pancreatic fistulas (POPF) grade C represent a rare but feared complication following pancreaticoduodenectomy (PD). They can contribute significantly to postoperative morbidity and mortality. METHODS: We performed a retrospective chart review for all patients who had undergone pancreatic head resection between 2007 and 2016 to identify those who suffered from POPF grade C according to the updated definition of the International Study Group of Pancreatic Surgery (ISGPS). RESULTS: A total of 722 patients underwent PD. Twenty-three patients (3.19%) developed a POPF grade C. Cardiovascular diseases, soft pancreatic texture and main pancreatic duct diameter were identified as risk factors (P < .05). Reoperation was necessary in all affected patients on postoperative day 12 ± 9 on average. Mortality was significantly associated with POPF grade C (P < .05) being present in 39.1% (9/23). CONCLUSIONS: POPF grade C after PD remains a serious complication with a high level of morbidity and mortality. Surgical treatment is the sole curative therapy and thus the treatment of choice.

Anti-tumorigenic Effects of Emodin and Its' Homologue BTB14431 on Vascularized Colonic Cancer in a Rat Model.

OBJECTIVE: New drugs for cancer treatment are being sought worldwide. Therapeutic agents derived from natural substances can provide cost-efficient options. We evaluated the effect of emodin, an active natural anthraquinone derivate, and it's in-silico homologue the novel substance BTB14431 in vivo. METHOD: CC-531 colon cancer cells were implanted intraperitoneal (ip) and subcutaneous (sc) in 100 WAG/Rij rats. 28 days after tumor cell implantation, solid cancers were treated for 7 days by varying doses of BTB14431 (0.3 mg/kg body weight; 1.7 mg/kg) or emodin (2.5 mg/kg; 5 mg/kg). Treatment was applied either via an intravenous (iv) port catheter or by ip injection. Saline solution served as control. 21 days after final dose all animals were euthanized and ip tumor weight, sc tumor weight and animal body weight (bw) were determined by autopsy. Significant lower total tumor weight occurred after iv treatment with low dose BTB14431 (6.8 g; 90% confidence interval (CI) 5.3 - 8.2 g; p ≤ 0.01) and also low and high concentrations of emodin (9.4 g; CI 7.9 - 10.7 g; p ≤ 0.01 and 8.3 g; CI 7.6 - 9.3; p ≤ 0.01). Iv treatment by high dose BTB14431 did not lead to a decline in tumor weight. High dose ip treatment by emodin led to a lower overall (11.1 g; CI 10.1 - 13.8 g; p ≤ 0.01) and ip tumor weight (8.6 g; CI 6 - 10.4 g; p ≤ 0.01). Sc tumor weight was not affected. All other ip treatments did not result in changes of combined, ip or sc tumor weight. Bw decreased during iv treatment in all animals and increased after treatment was completed. Regain of bw was stronger in animals receiving low dose emodin. CONCLUSION: Our study shows promising anti-cancer properties of BTB14431 and supports the evidence regarding emodin as a natural antitumorigenic agent. Optimal dosing of iv emodin and especially BTB 14431 for maximal efficacy remains unclear and should be a subject of further research. 
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It's not all about the size-characteristics and risk factors for malignancy of mucinous cystic neoplasms of the pancreas.

BACKGROUND: Mucinous cystic neoplasms (MCN) of the pancreas are rare mucin-producing cystic tumors. As they harbor malignant potential, surgical resection is frequently performed. Current guidelines recommend surgery in asymptomatic patients only for MCN exceeding 4 cm. The aim of this study was to identify radiological and clinical risk factors for malignancy in a single-center cohort of MCN. METHODS: All resected MCN from a single high-volume center between 2004 and 2019 were retrospectively analyzed. Patient characteristics, preoperative findings, histopathological results, and data on the postoperative course were recorded. Variables associated with malignancy were evaluated using χ2 and Mann-Whitney U test. Receiver operating characteristic (ROC) curves were used to model predictive capabilities of preoperative tumor marker levels. Furthermore uni- and multivariate logistic regression analysis were performed for binary variables. Survival time was plotted as Kaplan-Meier curves and evaluated by log-rank test. RESULTS: A total of 63 patients were included. Median age was 62 years; 51 (81.0%) of them were women; median tumor size was 3.5 cm (range, 0.5-18.5); 16 (25.4%) of tumors harbored invasive carcinoma and 13 presented intraepithelial dysplasia (20.6%); 7 (43.8%) invasive carcinomas were smaller than 4 cm. All malignant MCN were radiologically suspected of malignancy (calcifications, mural nodules, or wall thickness) preoperatively. Elevated levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were strongly associated with malignancy (odd's ratio 33.600; 7.000-161.270); P<0.001 and odd's ratio 19.250; 3.370-109.970; P<0.001). Other factors associated with malignancy were preoperative weight loss (P=0.015) and higher age (P=0.048). Tumor size, abdominal or back pain or jaundice showed no significant correlation to malignancy in our cohort. CONCLUSIONS: Malignant potential of MCN should not be underestimated and a close clinical and radiological follow-up is mandatory in all suspected cases. This is especially important for small lesions. Risk assessment should not rely only on tumor size but consider all clinical, radiological and laboratory findings of each case. Follow-up should be performed by experienced surgeons and radiologists in high volume centers for pancreatic surgery. Surgery should be performed in all cases in which malignancy is suspected.

Prognostic value and impact of cerebral metastases in pancreatic cancer.

Background: Pancreatic cancer is a fatal disease most often diagnosed at an advanced stage. Most patients already suffer from irresectable tumor or distant metastases being most commonly found in the liver or the lung. However, cerebral metastases occur extremely rare.Methods: We performed a retrospective analysis of our database to identify all patients diagnosed with pancreatic cancer and cerebral metastases who underwent surgical treatment in our department from January 2004 to November 2016.Results: Only 0.2% (4 of 2492) were diagnosed with cerebral metastases. Two patients had surgical resection of the cerebral metastases. One patient underwent palliative radiation therapy and the fourth patient received only palliative therapy. Mean interval between initial diagnosis and development of brain metastases was 8.5 months (range 1-20). Mean survival period after diagnosis of brain metastases was 4.75 months (range 1-10).Conclusions: Cerebral metastases of pancreatic cancer occur extremely rare. They are associated with an advanced tumor stage, commonly liver and lung metastases. All patients presenting with neurological symptoms, multifocal metastases, and significantly elevated CA 19-9 levels are suspicious of sustaining cerebral metastases and should undergo brain imaging.