Endoscopic and surgical treatment of necrotizing pancreatitis-a comparison of short- and long-term outcome.

BACKGROUND: Acute necrotizing pancreatitis is still related to high morbidity and mortality rates. Minimal-invasive treatment options, such as endoscopic necrosectomy, may decrease peri-interventional morbidity and mortality. This study aims to compare the initial operative with endoscopic treatment on long-term parameters, such as endocrine and exocrine functionality, as well as mortality and recurrence rates. METHODS: We included 114 patients, of whom 69 were treated with initial endoscopy and 45 by initial surgery. Both groups were further assessed for peri-interventional and long-term parameters. RESULTS: In the post-interventional phase, patients in the group of initial surgical treatment (IST) showed significantly higher rates of renal insufficiency (p < 0.001) and dependency on invasive ventilation (p < 0.001). The in-house mortality was higher in the surgical group, with 22% vs. 10.1% in the group of patients following initial endoscopic treatment (IET; p = 0.077). In long-term follow-up, the overall mortality was 45% for IST and 31.3% for IET (p = 0.156). The overall in-hospital stay and intensive care unit (ICU) stay were significantly shorter after IET (p < 0.001). In long-term follow-up, the prevalence of endocrine insufficiency was 50% after IST and 61.7% after IET (p = 0.281). 57.1% of the patients following IST and 16.4% of the patients following IET had persistent exocrine insufficiency at that point (p = < 0.001). 8.9% of the IET and 27.6% of the IST patients showed recurrence of acute pancreatitis (p = 0.023) in the long-term phase. CONCLUSION: In our cohort, an endoscopic step-up approach led to a reduced in-hospital stay and peri-interventional morbidity. The endocrine function appeared comparable in both groups, whereas the exocrine insufficiency seemed to recover in the endoscopic group in the long-term phase. These findings advocate for a preference for endoscopic treatment of acute necrotizing pancreatitis whenever feasible.

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Internal drainage for interdisciplinary management of anastomotic leakage after pancreaticogastrostomy.

BACKGROUND: Anastomotic leakage and postoperative pancreatic fistula (POPF) may occur after pancreatic head resection, also in the setting of pancreato-gastric reconstruction. For adequate complication management, a variety of non-standardized treatments are available. Still, data on clinical evaluation of endoscopic methods remain scarce. Based on our interdisciplinary experience on endoscopic treatment of retro-gastric fluid collections after left-sided pancreatectomies, we developed an innovative endoscopic concept with internal peri-anastomotic stent placement for patients with anastomotic leakage and/or peri-anastomotic fluid collection. METHODS: Over the period of 6 years (2015-2020) we retrospectively evaluated 531 patients after pancreatic head resections at the Department of Surgery, Charité-Unversitätsmedizin Berlin. Of these, 403 received reconstruction via pancreatogastrostomy. We identified 110 patients (27.3%) with anastomotic leakage and/or peri-anastomotic fluid collection and could define four treatment groups which received either conservative treatment (C), percutaneous drainage (PD), endoscopic drainage (ED), and/or re-operation (OP). Patients were grouped in a step-up approach for descriptive analyses and in a stratified, decision-based algorithm for comparative analyses. The study's primary endpoints were hospitalization (length of hospital stay) and clinical success (treatment success rate, primary/secondary resolution). RESULTS: We characterized an institutional, post-operative cohort with heterogenous complication management following pancreato-gastric reconstruction. The majority of patients needed interventional treatments (n = 92, 83.6%). Of these, close to one-third (n = 32, 29.1%) were treated with endoscopy-guided, peri-anastomotic pigtail stents for internal drainage as either primary, secondary and/or tertiary treatment modality. Following a decision-based algorithm, we could discriminate superior primary-(77,8% vs 53.7%) and secondary success rates (85.7% vs 68.4%) as well as earlier primary resolutions (11.4 days, 95%CI (5.75-17.13) vs 37.4 days, 95%CI (27.2-47.5)] in patients receiving an endoscopic compared to percutaneous management. CONCLUSION: This study underscores the importance of endoscopy-guided approaches for adequate treatment of anastomotic leakage and/or peri-anastomotic fluid collections after pancreatoduodenectomy. We herein report a novel, interdisciplinary concept for internal drainage in the setting of pancreato-gastric reconstruction.

Robotic versus laparoscopic versus open major hepatectomy - an analysis of costs and postoperative outcomes in a single-center setting.

PURPOSE: In the era of minimal-invasive surgery, the introduction of robotic liver surgery (RS) was accompanied by concerns about the increased financial expenses of the robotic technique in comparison to the established laparoscopic (LS) and conventional open surgery (OS). Therefore, we aimed to evaluate the cost-effectiveness of RS, LS and OS for major hepatectomies in this study. METHODS: We analyzed financial and clinical data on patients who underwent major liver resection for benign and malign lesions from 2017 to 2019 at our department. Patients were grouped according to the technical approach in RS, LS, and OS. For better comparability, only cases stratified to the Diagnosis Related Groups (DRG) H01A and H01B were included in this study. Financial expenses were compared between RS, LS, and OS. A binary logistic regression model was used to identify parameters associated with increased costs. RESULTS: RS, LS and OS accounted for median daily costs of 1,725 €, 1,633 € and 1,205 €, respectively (p < 0.0001). Median daily (p = 0.420) and total costs (16,648 € vs. 14,578 €, p = 0.076) were comparable between RS and LS. Increased financial expenses for RS were mainly caused by intraoperative costs (7,592 €, p < 0.0001). Length of procedure (hazard ratio [HR] = 5.4, 95% confidence interval [CI] = 1.7-16.9, p = 0.004), length of stay (HR [95% CI] = 8.8 [1.9-41.6], p = 0.006) and development of major complications (HR [95% CI] = 2.9 [1.7-5.1], p < 0.0001) were independently associated with higher costs. CONCLUSIONS: From an economic perspective, RS may be considered a valid alternative to LS for major liver resections.

Challenges of single-stage pancreatoduodenectomy: how to address pancreatogastrostomies with robotic-assisted surgery.

INTRODUCTION: Establishing a sufficient pancreatico-enteric anastomosis remains one of the most important challenges in open single stage pancreatoduodenectomy as they are associated with persisting morbidity and mortality. Applicability on a robotic-assisted approach, however, even increases the requirements. With this analysis we introduce a dorsal-incision-only invagination type pancreatogastrostomy (dioPG) to the field of robotic assistance having been previously proven feasible in the field of open pancreatoduodenectomy and compare initial results to the open approach by means of morbidity and mortality. METHODS: An overall of 142 consecutive patients undergoing reconstruction via the novel dioPG, 38 of them in a robotic-assisted and 104 in an open approach, was identified and further reviewed for perioperative parameters, complications and mortality. RESULTS: We observed a comparable R0-resection rate (p = 0.448), overall complication rate (p = 0.52) and 30-day mortality (p = 0.71) in both groups. Rates of common complications, such as postoperative pancreatic fistula (p = 0.332), postoperative pancreatic hemorrhage (p = 0.242), insufficiency of pancreatogastrostomy (p = 0.103), insufficiency of hepaticojejunostomy (p = 0.445) and the re-operation rate (p = 0.103) were comparable. The procedure time for the open approach was significantly shorter compared to the robotic-assisted approach (p = 0.024). DISCUSSION: The provided anastomosis appeared applicable to a robotic-assisted setting resulting in comparable complication and mortality rates when compared to an open approach. Nevertheless, also in the field of robotic assistance establishing a predictable pancreatico-enteric anastomosis remains the most challenging aspect of modern single-stage pancreatoduodenectomy and requires expertise and experience.

Robotic vs. laparoscopic liver surgery: a single-center analysis of 600 consecutive patients in 6 years.

BACKGROUND: While laparoscopic liver surgery has become a standard procedure, experience with robotic liver surgery is still limited. The aim of this prospective study was to evaluate safety and feasibility of robotic liver surgery and compare outcomes with conventional laparoscopy. METHODS: We here report the results of a single-center, prospective, post-marketing observational study (DRKS00017229) investigating the safety and feasibility of robotic liver surgery. Baseline characteristics, surgical complexity (using the IWATE score), and postoperative outcomes were then compared to laparoscopic liver resections performed at our center between January 2015 and December 2020. A propensity score-based matching (PSM) was applied to control for selection bias. RESULTS: One hundred twenty nine robotic liver resections were performed using the da Vinci Xi surgical system (Intuitive) in this prospective study and were compared to 471 consecutive laparoscopic liver resections. After PSM, both groups comprised 129 cases with similar baseline characteristics and surgical complexity. There were no significant differences in intraoperative variables, such as need for red blood cell transfusion, duration of surgery, or conversion to open surgery. Postoperative complications were comparable after robotic and laparoscopic surgery (Clavien-Dindo ≥ 3a: 23% vs. 19%, p = 0.625); however, there were more bile leakages grade B-C in the robotic group (17% vs. 7%, p = 0.006). Length of stay and oncological short-term outcomes were comparable. CONCLUSIONS: We propose robotic liver resection as a safe and feasible alternative to established laparoscopic techniques. The object of future studies must be to define interventions where robotic techniques are superior to conventional laparoscopy.

Safety and feasibility of robotic liver resection after previous abdominal surgeries.

BACKGROUND: While minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches. METHODS: Clinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses. RESULTS: Out of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien-Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery. CONCLUSIONS: We propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.

Robotic versus open pancreatic surgery: a propensity score-matched cost-effectiveness analysis.

BACKGROUND: Robotic pancreatic surgery (RPS) is associated with high intraoperative costs compared to open pancreatic surgery (OPS). However, it remains unclear whether several advantages of RPS such as reduced surgical trauma and a shorter postoperative recovery time could lead to a reduction in total costs outweighing the intraoperative costs. The study aimed to compare patients undergoing OPS and RPS with regards to cost-effectiveness in a propensity score-matched (PSM) analysis. METHODS: Patients undergoing OPS and RPS between 2017 and 2019 were included in this monocentric, retrospective analysis. The controlling department provided financial data (costs and revenues, net loss/profit). A propensity score-matched analysis was performed or OPS and RPS (matching criteria: age, American society of anesthesiologists (ASA) score, gender, body mass index (BMI), and type of pancreatic resection) with a caliper 0.2. RESULTS: In total, 272 eligible OPS cases were identified, of which 252 met all inclusion criteria and were thus included in the further analysis. The RPS group contained 92 patients. The matched cohorts contained 41 patients in each group. Length of hospital stay (LOS) was significantly shorter in the RPS group (12 vs. 19 days, p = 0.003). Major postoperative morbidity (Dindo/Clavien ≥ 3a) and 90-day mortality did not differ significantly between OPS and RPS (p > 0.05). Intraoperative costs were significantly higher in the RPS group than in the OPS group (7334€ vs. 5115€, p < 0.001). This was, however, balanced by other financial categories. The overall cost-effectiveness tended to be better when comparing RPS to OPS (net profit-RPS: 57€ vs. OPS: - 2894€, p = 0.328). Binary logistic regression analysis revealed major postoperative complications, longer hospital stay, and ASA scores < 3 were linked to the risk of net loss (i.e., costs > revenue). CONCLUSIONS: Surgical outcomes of RPS were similar to those of OPS. Higher intraoperative costs of RPS are outweighed by advantages in other categories of cost-effectiveness such as decreased lengths of hospital stay.

The influence of the COVID-19 pandemic on surgical therapy and care: a cross-sectional study.

BACKGROUND: Due to the COVID-19 pandemic, an extensive reorganisation of healthcare resources was necessary-with a particular impact on surgical care across all disciplines. However, the direct and indirect consequences of this redistribution of resources on surgical therapy and care are largely unknown. METHODS: We analysed our prospectively collected standardised digital quality management document for all surgical cases in 2020 and compared them to the years 2018 and 2019. Periods with high COVID-19 burdens were compared with the reference periods in 2018 and 2019. RESULTS: From 2018 to 2020, 10,723 patients underwent surgical treatment at our centres. We observed a decrease in treated patients and a change in the overall patient health status. Patient age and length of hospital stay increased during the COVID-19 pandemic (p = 0.004 and p = 0.002). Furthermore, the distribution of indications for surgical treatment changed in favour of oncological cases and less elective cases such as hernia repairs (p < 0.001). Postoperative thromboembolic and pulmonary complications increased slightly during the COVID-19 pandemic. There were slight differences for postoperative overall complications according to Clavien-Dindo, with a significant increase of postoperative mortality (p = 0.01). CONCLUSION: During the COVID-19 pandemic we did not see an increase in the occurrence, or the severity of postoperative complications. Despite a slightly higher rate of mortality and specific complications being more prevalent, the biggest change was in indication for surgery, resulting in a higher proportion of older and sicker patients with corresponding comorbidities. Further research is warranted to analyse how this changed demographic will influence long-term patient care.

Feasibility of robotic-assisted pancreatic resection in patients with previous minor abdominal surgeries: a single-center experience of the first three years.

BACKGROUND: Robotic-assisted pancreatic surgery is limited to specialized high-volume centers and selected patient cohorts. Especially for patients with a history of previous abdominal surgeries, the standard procedure remains open surgery due to the fear of complications caused by abdominal adhesions. METHODS: Clinical data of all consecutive patients undergoing robotic-assisted pancreatic surgery using the daVinci Xi system (Intuitive Surgical) at our center (Department of Surgery, Universitätsmedizin Berlin, Germany) were collected prospectively and further analyzed from October 2017 to October 2020. Prior abdominal surgeries were specified according to the surgical approach and localization. In univariate and multivariate analysis, baseline and perioperative parameters of patients with a history of prior abdominal surgeries (PS) were compared to those of patients with no history of prior abdominal surgeries (NPS). RESULTS: Out of 131 patients undergoing robotic-assisted pancreatic surgery, 62 (47%) had a history of abdominal surgery. Previous procedures included most often appendectomy (32%) followed by gynecological surgery (29%) and cholecystectomy (27%). 24% of PS had received multiple surgeries prior to the robotic-assisted pancreatic resections. Baseline characteristics and comorbidities were comparable between the groups. We did not detect differences in the duration of surgery (262 min), conversion rates (10%), and postoperative complications between NPS and PS. Postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), and in-house mortality showed no significant differences between the two groups. Multivariate analysis revealed male sex and high BMI as a potential predictive factor for severe postoperative complications. Other characteristics like the type of pancreatic resection, ASA, and underlying malignancy showed no difference in the multivariable analysis. CONCLUSIONS: We propose robotic-assisted pancreatic surgery to be safe and feasible for patients with a history of minor prior abdominal surgery. Hence, each patient should individually be evaluated for a minimally invasive approach regardless of a history of previous operations.

Robotic-assisted pancreatic surgery in the elderly patient: experiences from a high-volume centre.

BACKGROUND: Robotic-assisted pancreatic surgery (RPS) has fundamentally developed over the past few years. For subgroups, e.g. elderly patients, applicability and safety of RPS still needs to be defined. Given prognosticated demographic developments, we aim to assess the role of RPS based on preoperative, operative and postoperative parameters. METHODS: We included 129 patients undergoing RPS at our institution between 2017 and 2020. Eleven patients required conversion to open surgery and were excluded from further analysis. We divided patients into two groups; ≥ 70 years old (Group 1; n = 32) and < 70 years old (Group 2; n = 86) at time of resection. RESULTS: Most preoperative characteristics were similar in both groups. However, number of patients with previous abdominal surgery was significantly higher in patients ≥ 70 years old (78% vs 37%, p < 0.0001). Operative characteristics did not significantly differ between both groups. Although patients ≥ 70 years old stayed significantly longer at ICU (1.8 vs 0.9 days; p = 0.037), length of hospital stay and postoperative morbidity were equivalent between the groups. CONCLUSION: RPS is safe and feasible in elderly patients and shows non-inferiority when compared with younger patients. However, prospectively collected data is needed to define the role of RPS in elderly patients accurately. Trial registration Clinical Trial Register: Deutschen Register Klinischer Studien (DRKS; German Clinical Trials Register). Clinical Registration Number: DRKS00017229 (retrospectively registered, Date of Registration: 2019/07/19, Date of First Enrollment: 2017/10/18).

Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma-Who Will Benefit from a Secondary Resection?

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2-22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.

Favourable long-term survival of patients with esophageal cancer treated with extended transhiatal esophagectomy combined with en bloc lymphadenectomy: results from a retrospective observational cohort study.

BACKGROUND: Although considered complex and challenging, esophagectomy remains the best potentially curable treatment option for resectable esophageal and esophagogastric junction (AEG) carcinomas. The optimal surgical approach and technique as well as the extent of lymphadenectomy, particularly regarding quality of life and short- and long-term outcomes, are still a matter of debate. To lower perioperative morbidity, we combined the advantages of a one-cavity approach with extended lymph node dissection (usually achieved by only a two-cavity approach) and developed a modified single-cavity transhiatal approach for esophagectomy. METHODS: The aim of this study was to evaluate the outcome of an extended transhiatal esophageal resection with radical bilateral mediastinal en bloc lymphadenectomy (eTHE). A prospective database of 166 patients with resectable cancers of the esophagus (including adenocarcinomas of the AEG types I and II) were analyzed. Patients were treated between 2001 and 2017 with eTHE at a tertiary care university center. Relevant patient characteristics and outcome parameters were collected and analyzed. The primary endpoint was 5-year overall survival. Secondary outcomes included short-term morbidity, mortality, radicalness of en bloc resection and oncologic efficacy. RESULTS: The overall survival rates at 1, 3 and 5 years were 84, 70, and 61.0%, respectively. The in-hospital mortality rate after eTHE was 1.2%. Complications with a Clavien-Dindo score of III/IV occurred in 31 cases (18.6%). A total of 25 patients (15.1%) had a major pulmonary complication. The median hospital stay was 17 days (interquartile range (IQR) 12). Most patients (n = 144; 86.7%) received neoadjuvant treatment. The median number of lymph nodes resected was 25 (IQR 17). The R0 resection rate was 97%. CONCLUSION: In patients with esophageal cancer, eTHE without thoracotomy resulted in excellent long-term survival, an above average number of resected lymph nodes and an acceptable postoperative morbidity and mortality.

[Teaching and Training in Robot-assisted Surgery]. / Teaching und Training in der robotergestützten Chirurgie.

The development and proliferation of robot-assisted surgery has greatly extended the field of minimally invasive surgery. Thus, this necessitates the development of adequate training programs to prepare surgeons for the operating room of the future. Transferring established and proven methods of training and assessment in aviation could help robotic training programs become more effective, efficient and safer. Simulation is a safe and cost-effective way of training and in addition may improve operating room performance. Proctoring and flying doctor models are established concepts, especially for advanced training. This review summarises current developments in robotic surgical training and teaching and may help to start a controversial discussion.

Postoperative acute necrotizing pancreatitis of the pancreatic remnant (POANP): a new definition of severe pancreatitis following pancreaticoduodenectomy.

BACKGROUND: Recent studies have suggested acute pancreatitis as a separate pancreatic-specific complication following pancreaticoduodenectomy. However, data on necrotizing pancreatitis of the pancreatic remnant is limited. This study aimed to evaluate parameters of patients undergoing completion pancreatectomy (CP) after initial pancreaticoduodenectomy (PD) and compare those with or without necrosis of the pancreatic remanent. METHODS: Patients who underwent CP following PD between January 2005 and December 2017 were identified from a prospectively collected database. Perioperative parameters were recorded, and patients were divided into those with or without histological evidence of necrosis of the pancreatic remnant. RESULTS: Postoperative acute necrotizing pancreatitis (POANP) was histologically detected in 33 (41%) of 79 patients after CP. Serum CRP levels on POD 2 and the day of revision were significantly higher in the POANP group (p < 0.001 for each). POANP was reflected by higher APACHE II and SOFA scores after PD (P < 0.001 for each). Although patients with POANP had an earlier revision, length of ICU and total hospital stay was prolonged (p < 0.001 for each). POANP was associated with more major complications (Clavien-Dindo ≥ 3) and more often necessitated reoperations within 30 days (p < 0.001 for each). CONCLUSION: Patients requiring CP following PD for POANP have an increased risk of major complications, and longer hospital stay. CRP levels, APACHE II and SOFA score, seem to correlate with the severity and might predict POANP. Universally accepted definitions with a clinically validated grading system of severity for POAP and POANP are needed to facilitate appropriate treatment strategies and enable comparison of future studies.

Analysis of outcomes and predictors of long-term survival following resection for retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPS) include a heterogeneous group of rare malignant tumours, and various treatment algorithms are still controversially discussed until today. The present study aimed to examine postoperative and long-term outcomes after resection of primary RPS. PATIENTS AND METHODS: Clinicopathological data of patients who underwent resection of primary RPS between 2005 and 2015 were assessed, and predictors for overall survival (OS) and disease-free survival (DFS) were identified. RESULTS: Sixty-one patients underwent resection for primary RPS. Postoperative morbidity and mortality rates were 31 and 3%, respectively. After a median follow-up time of 74 months, 5-year OS and DFS rates were 58 and 34%, respectively. Histologic high grade (5-year OS: G1: 92% vs. G2: 54% vs. G3: 43%, P = 0.030) was significantly associated with diminished OS in univariate and multivariate analyses. When assessing DFS, histologic high grade (5-year DFS: G1: 63% vs. G2: 24% vs. G3: 22%, P = 0.013), positive surgical resection margins (5-year DFS: R0: 53% vs. R1: 10% vs. R2: 0%, P = 0.014), and vascular involvement (5-year DFS: yes: 33% vs no: 39%, P = 0.001), were significantly associated with inferior DFS in univariate and multivariate analyses. CONCLUSIONS: High-grade tumours indicated poor OS, while vascular involvement, positive surgical resection margins, and histologic grade are the most important predictors of DFS. Although multimodal treatment strategies are progressively established, surgical resection remains the mainstay in the majority of patients with RPS, even in cases with vascular involvement.

R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.

Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine, and colon. Expansion of these cells requires activation of the receptor Lgr5 by its ligand R-spondin 1 and is likely facilitated by the fact that in healthy adults the stem cells in these organs are highly proliferative. In many other adult organs, such as the liver, proliferating cells are normally not abundant in adulthood. However, upon injury, the liver has a strong regenerative potential that is accompanied by the emergence of Lgr5-positive stem cells; these cells can be isolated and expanded in vitro as organoids. In an effort to isolate stem cells from non-regenerating mouse livers, we discovered that healthy gallbladders are a rich source of stem/progenitor cells that can be propagated in culture as organoids for more than a year. Growth of these organoids was stimulated by R-spondin 1 and noggin, whereas in the absence of these growth factors, the organoids differentiated partially toward the hepatocyte fate. When transplanted under the liver capsule, gallbladder-derived organoids maintained their architecture for 2 weeks. Furthermore, single cells prepared from dissociated organoids and injected into the mesenteric vein populated the liver parenchyma of carbon tetrachloride-treated mice. Human gallbladders were also a source of organoid-forming stem cells. Thus, under specific growth conditions, stem cells can be isolated from healthy gallbladders, expanded almost indefinitely in vitro, and induced to differentiate toward the hepatocyte lineage.