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.

Robot-Assisted Versus Laparoscopic Distal Pancreatectomy in Patients with Resectable Pancreatic Cancer: An International, Retrospective, Cohort Study.

BACKGROUND: Robot-assisted distal pancreatectomy (RDP) is increasingly used as an alternative to laparoscopic distal pancreatectomy (LDP) in patients with resectable pancreatic cancer but comparative multicenter studies confirming the safety and efficacy of RDP are lacking. METHODS: An international, multicenter, retrospective, cohort study, including consecutive patients undergoing RDP and LDP for resectable pancreatic cancer in 33 experienced centers from 11 countries (2010-2019). The primary outcome was R0-resection. Secondary outcomes included lymph node yield, major complications, conversion rate, and overall survival. RESULTS: In total, 542 patients after minimally invasive distal pancreatectomy were included: 103 RDP (19%) and 439 LDP (81%). The R0-resection rate was comparable (75.7% RDP vs. 69.3% LDP, p = 0.404). RDP was associated with longer operative time (290 vs. 240 min, p < 0.001), more vascular resections (7.6% vs. 2.7%, p = 0.030), lower conversion rate (4.9% vs. 17.3%, p = 0.001), more major complications (26.2% vs. 16.3%, p = 0.019), improved lymph node yield (18 vs. 16, p = 0.021), and longer hospital stay (10 vs. 8 days, p = 0.001). The 90-day mortality (1.9% vs. 0.7%, p = 0.268) and overall survival (median 28 vs. 31 months, p = 0.599) did not differ significantly between RDP and LDP, respectively. CONCLUSIONS: In selected patients with resectable pancreatic cancer, RDP and LDP provide a comparable R0-resection rate and overall survival in experienced centers. Although the lymph node yield and conversion rate appeared favorable after RDP, LDP was associated with shorter operating time, less major complications, and shorter hospital stay. The specific benefits associated with each approach should be confirmed by multicenter, randomized trials.

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.

Endotypes of intraoperative hypotension during major abdominal surgery: a retrospective machine learning analysis of an observational cohort study.

BACKGROUND: Intraoperative hypotension is associated with myocardial injury, acute kidney injury, and death. In routine practice, specific causes of intraoperative hypotension are often unclear. A more detailed understanding of underlying haemodynamic alterations of intraoperative hypotension may identify specific treatments. We thus aimed to use machine learning - specifically, hierarchical clustering - to identify underlying haemodynamic alterations causing intraoperative hypotension in major abdominal surgery patients. Specifically, we tested the hypothesis that there are distinct endotypes of intraoperative hypotension, which may help refine therapeutic interventions. METHODS: We conducted a secondary analysis of intraoperative haemodynamic measurements from a prospective observational study in 100 patients who had major abdominal surgery under general anaesthesia. We used stroke volume index, heart rate, cardiac index, systemic vascular resistance index, and pulse pressure variation measurements. Intraoperative hypotension was defined as any mean arterial pressure ≤65 mm Hg or a mean arterial pressure between 66 and 75 mm Hg requiring a norepinephrine infusion rate exceeding 0.1 µg kg-1 min-1. To identify endotypes of intraoperative hypotension, we used hierarchical clustering (Ward's method). RESULTS: A total of 615 episodes of intraoperative hypotension occurred in 82 patients (46 [56%] female; median age: 64 [57, 73] yr) who had surgery of a median duration of 270 (195, 335) min. Hierarchical clustering revealed six distinct intraoperative hypotension endotypes. Based on their clinical characteristics, we labelled these endotypes as (1) myocardial depression, (2) bradycardia, (3) vasodilation with cardiac index increase, (4) vasodilation without cardiac index increase, (5) hypovolaemia, and (6) mixed type. CONCLUSION: Hierarchical clustering identified six endotypes of intraoperative hypotension. If validated, considering these intraoperative hypotension endotypes may enable causal treatment of intraoperative hypotension.

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.

Benchmarking of minimally invasive distal pancreatectomy with splenectomy: European multicentre study.

BACKGROUND: Benchmarking is the process to used assess the best achievable results and compare outcomes with that standard. This study aimed to assess best achievable outcomes in minimally invasive distal pancreatectomy with splenectomy (MIDPS). METHODS: This retrospective study included consecutive patients undergoing MIDPS for any indication, between 2003 and 2019, in 31 European centres. Benchmarks of the main clinical outcomes were calculated according to the Achievable Benchmark of Care (ABC™) method. After identifying independent risk factors for severe morbidity and conversion, risk-adjusted ABCs were calculated for each subgroup of patients at risk. RESULTS: A total of 1595 patients were included. The ABC was 2.5 per cent for conversion and 8.4 per cent for severe morbidity. ABC values were 160 min for duration of operation time, 8.3 per cent for POPF, 1.8 per cent for reoperation, and 0 per cent for mortality. Multivariable analysis showed that conversion was associated with male sex (OR 1.48), BMI exceeding 30 kg/m2 (OR 2.42), multivisceral resection (OR 3.04), and laparoscopy (OR 2.24). Increased risk of severe morbidity was associated with ASA fitness grade above II (OR 1.60), multivisceral resection (OR 1.88), and robotic approach (OR 1.87). CONCLUSION: The benchmark values obtained using the ABC method represent optimal outcomes from best achievable care, including low complication rates and zero mortality. These benchmarks should be used to set standards to improve patient outcomes.

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.

The Relation Between Mean Arterial Pressure and Cardiac Index in Major Abdominal Surgery Patients: A Prospective Observational Cohort Study.

BACKGROUND: Cardiac output is an important hemodynamic variable and determines oxygen delivery. In contrast to blood pressure, cardiac output is rarely measured even in high-risk surgical patients, suggesting that clinicians consider blood pressure to be a reasonable indicator of systemic blood flow. However, the relationship depends on constant vascular tone and volume, both of which routinely vary during anesthesia and surgery. We therefore tested the hypothesis that there is no clinically meaningful correlation between mean arterial pressure and cardiac index in major abdominal surgery patients. METHODS: In this prospective observational study, we assessed the relationship between mean arterial pressure and cardiac index in 100 patients having major abdominal surgery under general anesthesia. RESULTS: The pooled within-patient correlation coefficient calculated using meta-analysis methods was r = 0.34 (95% confidence interval, 0.28-0.40). Linear regression using a linear mixed effects model of cardiac index on mean arterial pressure revealed that cardiac index increases by 0.014 L·min-1·m-2 for each 1 mm Hg increase in mean arterial pressure. The 95% Wald confidence interval of this slope was 0.011 to 0.018 L·min-1·m-2·mm Hg-1 and thus within predefined equivalence margins of -0.03 and 0.03 L·min-1·m-2·mm Hg-1, thereby demonstrating lack of clinically meaningful association between mean arterial pressure and cardiac index. CONCLUSIONS: There is no clinically meaningful correlation between mean arterial pressure and cardiac index in patients having major abdominal surgery. Intraoperative blood pressure is thus a poor surrogate for cardiac index.

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.

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.

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.

Correction: Felsenstein M. et al. Perineural Invasion in Pancreatic Ductal Adenocarcinoma (PDAC): A Saboteur of Curative Intended Therapies? J. Clin. Med. 2022, 11, 2367.

In the original publication [...].

Robot-assisted pancreatic surgery-optimized operating procedures: set-up, port placement, surgical steps.

Even in most complex surgical settings, recent advances in minimal-invasive technologies have made the application of robotic-assisted devices more viable. Due to ever increasing experience and expertise, many large international centers now offer robotic-assisted pancreatic surgery as a preferred alternative. In general however, pancreatic operations are still associated with high morbidity and mortality, while robotic-assisted techniques still require significant learning curves. As a prospective post-marketing trial, we have established optimized operating procedures at our clinic. This manuscript intends to publicize our standardized methodology, including pre-operative preparation, surgical set-up as well as the surgeons' step-by-step actions when using pancreatic-assisted robotic surgery. This manuscript is based on our institutional experience as a high-volume pancreas operating center. We introduce novel concepts that should standardize, facilitate and economize the surgical steps in all types of robotic-assisted pancreatic surgery. The "One Fits All" principle enables single port placement irrespective of the pancreatic procedure, while the "Reversed 6-to-6 Approach" offers an optimized manual for pancreatic surgeons using the robotic console. Novel and standardized surgical concepts could guide new centers to establish a robust, efficient and safe robotic-assisted pancreatic surgery program.

Perineural Invasion in Pancreatic Ductal Adenocarcinoma (PDAC): A Saboteur of Curative Intended Therapies?

(1) Background: Perineural invasion (PNI) is a common characteristic of pancreatic ductal adenocarcinoma (PDAC) and is present in most resection margins. We hypothesized that curative pancreatic tumor resection with long-term survival could only be achieved in PNI-negative patients. (2) Material and Methods: A retrospective investigation of PDAC patients who underwent curative-intended surgery during the period 2008 to 2019 was performed at our institution. (3) Results: We identified 571 of 660 (86.5%) resected patients with well-annotated reports and complete datasets. Of those, 531 patients (93%) exhibited tumors with perineural invasion (Pn1), while 40 (7%) were negative for PNI (Pn0). The majority of patients in the Pn1 group presented advanced tumor stage and positive lymph node infiltration. Patients in the Pn0 group showed an improved disease-free and long-term survival compared to the Pn1 group (p < 0.001). Subgroup analysis of all R0-resected patients indicated improved long-term survival and disease-free survival of R0 Pn0 patients when compared to R0 Pn1 patients (p < 0.001). (4) Conclusion: Our study confirmed that Pn0 improves the long-term survival of PDAC-resected cancer patients. Furthermore, PNI significantly challenges the long-term survival of formally curative (R0) resected patients. We provide new insights into the dynamics of PNI in pancreatic cancer patients which are needed to define subgroups of patients for risk stratification and multimodal treatment strategies.

Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival.

(1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution's register of liver allograft recipients (Charité-Universitätsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7-27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0-196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.