Near complete remission of an inoperable pancreatic acinar cell carcinoma after BRAF-/MEK-inhibitor treatment-A case report and review of the literature.

INTRODUCTION: Pancreatic acinar cell carcinomas are rare malignant neoplasms. High-quality evidence about the best treatment strategy is lacking. We present the case of a 52-year-old male with a BRAFV600E -mutated PACC who experienced a complete remission after chemotherapy with BRAF-/MEK-inhibitors. CASE: The patient presented with upper abdomen pain, night sweat, and weight loss. CT scan showed a pancreatic tumor extending from the pancreas head to body. Histological workup identified an acinar cell carcinoma. As the tumor was inoperable, chemotherapy with FOFIRNIOX was initiated and initially showed a slight regression of disease. The regimen had to be discontinued due to severe side effects. Molecular analysis identified a BRAFV600E mutation, so the patient was started on BRAF- and MEK-inhibitors (dabrafenib/trametinib). After 16 months, CT scans showed a near complete remission with a markedly improved overall health. DISCUSSION: Studies suggest that up to one-fourth of PACCs carry a BRAF mutation and might therefore be susceptible to a BRAF-/MEK-inhibitor therapy. This offers a new therapeutic pathway to treat this rare but malignant neoplasm.

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS).

OBJECTIVE: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. SUMMARY BACKGROUND DATA: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. METHODS: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. RESULTS: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. CONCLUSIONS: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.

Surgical Outcome After Distal Pancreatectomy With and Without Portomesenteric Venous Resection in Patients with Pancreatic Adenocarcinoma: A Transatlantic Evaluation of Patients in North America, Germany, Sweden, and The Netherlands (GAPASURG).

BACKGROUND: Pancreatic adenocarcinoma located in the pancreatic body might require a portomesenteric venous resection (PVR), but data regarding surgical risks after distal pancreatectomy (DP) with PVR are sparse. Insight into additional surgical risks of DP-PVR could support preoperative counseling and intraoperative decision making. This study aimed to provide insight into the surgical outcome of DP-PVR, including its potential risk elevation over standard DP. METHODS: We conducted a retrospective, multicenter study including all patients with pancreatic adenocarcinoma who underwent DP ± PVR (2018-2020), registered in four audits for pancreatic surgery from North America, Germany, Sweden, and The Netherlands. Patients who underwent concomitant arterial and/or multivisceral resection(s) were excluded. Predictors for in-hospital/30-day major morbidity and mortality were investigated by logistic regression, correcting for each audit. RESULTS: Overall, 2924 patients after DP were included, of whom 241 patients (8.2%) underwent DP-PVR. Rates of major morbidity (24% vs. 18%; p = 0.024) and post-pancreatectomy hemorrhage grade B/C (10% vs. 3%; p = 0.041) were higher after DP-PVR compared with standard DP. Mortality after DP-PVR and standard DP did not differ significantly (2% vs. 1%; p = 0.542). Predictors for major morbidity were PVR (odds ratio [OR] 1.500, 95% confidence interval [CI] 1.086-2.071) and conversion from minimally invasive to open surgery (OR 1.420, 95% CI 1.032-1.970). Predictors for mortality were higher age (OR 1.087, 95% CI 1.045-1.132), chronic obstructive pulmonary disease (OR 4.167, 95% CI 1.852-9.374), and conversion from minimally invasive to open surgery (OR 2.919, 95% CI 1.197-7.118), whereas concomitant PVR was not associated with mortality. CONCLUSIONS: PVR during DP for pancreatic adenocarcinoma in the pancreatic body is associated with increased morbidity, but can be performed safely in terms of mortality.

Patient-reported outcomes at three months after pancreatic surgery for benign and malignant diseases - A prospective observational study.

BACKGROUND/OBJECTIVES: Pancreatic surgery may have a long-lasting effect on patients' health status and quality of life (QoL). We aim to evaluate patient-reported outcomes (PRO) 3 months after pancreatic surgery. METHODS: Patients scheduled for pancreatic surgery were enrolled in a prospective trial at five German centers. Patients completed PRO questionnaires (EQ-5D-5L, EORTC QLQ-PAN26, patient-reported happiness, and HADS-D), we report the first follow-up 3 months after surgery as an interim analysis. Statistical testing was performed using R software. RESULTS: From 2019 to 2022 203 patients were enrolled, a three-month follow-up questionnaire was available in 135 (65.5 %). 77 (57.9 %) underwent surgery for malignant disease. Patient-reported health status (EQ-5D-5L) was impaired in 4/5 dimensions (mobility, self-care, usual activities, pain, discomfort) for patients with malignant and 3/5 dimensions (mobility, self-care, usual activities) for patients with benign disease 3 months after surgery (p < 0.05). Patients with malignant disease reported an increase in depressive symptoms, patients with benign disease had a decrease in anxiety symptoms (HADS-D; depression: 5.00 vs 6.51, p = 0.002; anxiety: 8.04 vs. 6.34, p = 0.030). Regarding pancreatic-disease-specific symptoms (EORTC-QLQ-PAN26), patients with malignant disease reported increased problems with taste, weight loss, weakness in arms and legs, dry mouth, body image and troubling side effects at three months. Patients with benign disease indicated more weakness in arms and legs, troubling side effects but less future worries at three months. CONCLUSION: Patient-reported outcomes of patients undergoing pancreatic surgery for benign vs. malignant disease show important differences. Patients with malignant tumors report more severely decreased quality of life 3 months postoperatively than patients with benign tumors.

Transatlantic differences in the use and outcome of minimally invasive pancreatoduodenectomy: an international multi-registry analysis.

BACKGROUND: Minimally invasive pancreatoduodenectomy (MIPD) has emerged as an alternative to open pancreatoduodenectomy (OPD). However, the extent of variation in the use and outcomes of MIPD in relation to OPD among countries is unclear as international studies using registry data are lacking. This study aimed to investigate the use, patient selection, and outcomes of MIPD and OPD in four transatlantic audits for pancreatic surgery. METHODS: A post hoc comparative analysis including consecutive patients after MIPD and OPD from four nationwide and multicenter pancreatic surgery audits from North America, Germany, the Netherlands, and Sweden (2014-2020). Patient factors related to MIPD were identified using multivariable logistic regression. Outcome analyses excluded the Swedish audit because < 100 MIPD were performed during the studied period. RESULTS: Overall, 44,076 patients who underwent pancreatoduodenectomy were included (29,107 North America, 7586 Germany, 4970 the Netherlands, and 2413 Sweden), including 3328 MIPD procedures (8%). The use of MIPD varied widely among countries (absolute largest difference [ALD] 17%, p < 0.001): 7% North America, 4% Germany, 17% the Netherlands, and 0.1% Sweden. Over time, the use of MIPD increased in North America and the Netherlands (p < 0.001), mostly driven by robotic MIPD, but not in Germany (p = 0.297). Patient factors predicting the use of MIPD included country, later year of operation, better performance status, high POPF-risk score, no vascular resection, and non-malignant indication. Conversion rates were higher in laparoscopic MIPD (range 28-45%), compared to robotic MIPD (range 9-37%). In-hospital/30-day mortality differed among North America, Germany, and the Netherlands; MIPD (2%, 7%, 4%; ALD 5%, p < 0.001) and OPD (2%, 5%, 3%; ALD 3%, p < 0.001), similar to major morbidity; MIPD (25%, 42%, 38%, ALD 17%, p < 0.001) and OPD (25%, 31%, 30%, ALD 6%, p < 0.001), respectively. CONCLUSIONS: Considerable differences were found in the use and outcome, including conversion and mortality rates, of MIPD and OPD among four transatlantic audits for pancreatic surgery. Our findings highlight the need for international collaboration to optimize treatment standards and patient outcome.

Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial.

BACKGROUND: Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery. METHODS: The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021. RESULTS: For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45). CONCLUSIONS: Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.

International survey on opinions and use of robot-assisted and laparoscopic minimally invasive pancreatic surgery: 5-year follow up.

BACKGROUND: Evidence on the value of minimally invasive pancreatic surgery (MIPS) has been increasing but it is unclear how this has influenced the view of pancreatic surgeons on MIPS. METHODS: An anonymous survey was sent to members of eight international Hepato-Pancreato-Biliary Associations. Outcomes were compared with the 2016 international survey. RESULTS: Overall, 315 surgeons from 47 countries participated. The median volume of pancreatic resections per center was 70 (IQR 40-120). Most surgeons considered minimally invasive distal pancreatectomy (MIDP) superior to open (ODP) (94.6%) and open pancreatoduodenectomy (OPD) superior to minimally invasive (MIPD) (67.9%). Since 2016, there has been an increase in the number of surgeons performing both MIDP (79%-85.7%, p = 0.024) and MIPD (29%-45.7%, p < 0.001), and an increase in the use of the robot-assisted approach for both MIDP (16%-45.6%, p < 0.001) and MIPD (23%-47.9%, p < 0.001). The use of laparoscopy remained stable for MIDP (91% vs. 88.1%, p = 0.245) and decreased for MIPD (51%-36.8%, p = 0.024). CONCLUSION: This survey showed considerable changes of MIPS since 2016 with most surgeons considering MIDP superior to ODP and an increased use of robot-assisted MIPS. Surgeons prefer OPD and therefore the value of MIPD remains to be determined in randomized trials.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma after Curative Resection.

OBJECTIVE: Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). SUMMARY BACKGROUND DATA: DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear. METHODS: Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy. CONCLUSION: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.

Ideal Outcome After Pancreatoduodenectomy: A Transatlantic Evaluation of a Harmonized Composite Outcome Measure.

OBJECTIVE: The aim of this study is to define and assess Ideal Outcome in the national or multicenter registries of North America, Germany, the Netherlands, and Sweden. BACKGROUND: Assessing outcomes after pancreatoduodenectomy among centers and countries requires a broad evaluation that cannot be captured by a single parameter. Previously, 2 composite outcome measures (textbook outcome and optimal pancreatic surgery) for pancreatoduodenectomy have been described from Europe and the United States. These composites were harmonized into ideal outcome (IO). METHODS: This analysis is a transatlantic retrospective study (2018-2020) of patients after pancreatoduodenectomy within the registries from North America, Germany, The Netherlands, and Sweden. After 3 consensus meetings, IO for pancreatoduodenectomy was defined as the absence of all 6 parameters: (1) in-hospital mortality, (2) severe complications-Clavien-Dindo ≥3, (3) postoperative pancreatic fistula-International Study Group of Pancreatic Surgery (ISGPS) grade B/C, (4) reoperation, (5) hospital stay >75th percentile, and (6) readmission. Outcomes were evaluated using relative largest difference (RLD) and absolute largest difference (ALD), and multivariate regression models. RESULTS: Overall, 21,036 patients after pancreatoduodenectomy were included, of whom 11,194 (54%) reached IO. The rate of IO varied between 55% in North America, 53% in Germany, 52% in The Netherlands, and 54% in Sweden (RLD: 1.1, ALD: 3%, P <0.001). Individual components varied with an ALD of 2% length of stay, 4% for in-hospital mortality, 12% severe complications, 10% postoperative pancreatic fistula, 11% reoperation, and 9% readmission. Age, sex, absence of chronic obstructive pulmonary disease, body mass index, performance status, American Society of Anesthesiologists (ASA) score, biliary drainage, absence of vascular resection, and histologic diagnosis were associated with IO. In the subgroup of patients with pancreatic adenocarcinoma, country, and neoadjuvant chemotherapy also was associated with improved IO. CONCLUSIONS: The newly developed composite outcome measure "Ideal Outcome" can be used for auditing and comparing outcomes after pancreatoduodenectomy. The observed differences can be used to guide collaborative initiatives to further improve the outcomes of pancreatic surgery.

Outcomes After Minimally Invasive Versus Open Total Pancreatectomy: A Pan-European Propensity Score Matched Study.

OBJECTIVE: To assess postoperative 90-day outcomes after minimally invasive (laparoscopic/robot-assisted) total pancreatectomy (MITP) in selected patients versus open total pancreatectomy (OTP) among European centers. BACKGROUND: Minimally invasive pancreatic surgery is becoming increasingly popular but data on MITP are scarce and multicenter studies comparing outcomes versus OTP are lacking. It therefore remains unclear if MITP is a valid alternative. METHODS: Multicenter retrospective propensity-score matched study including consecutive adult patients undergoing MITP or OTP for all indications at 16 European centers in 7 countries (2008-2017). Patients after MITP were matched (1:1, caliper 0.02) to OTP controls. Missing data were imputed. The primary outcome was 90-day major morbidity (Clavien-Dindo ≥3a). Secondary outcomes included 90-day mortality, length of hospital stay, and survival. RESULTS: Of 361 patients (99MITP/262 OTP), 70 MITP procedures (50 laparoscopic, 15 robotic, 5 hybrid) could be matched to 70 OTP controls. After matching, MITP was associated with a lower rate of major morbidity (17% MITP vs. 31% OTP, P = 0.022). The 90-day mortality (1.4% MITP vs. 7.1% OTP, P = 0.209) and median hospital stay (17 [IQR 11-24] MITP vs. 12 [10-23] days OTP, P = 0.876) did not differ significantly. Among 81 patients with PDAC, overall survival was 3.7 (IQR 1.7-N/A) versus 0.9 (IQR 0.5-N/ A) years, for MITP versus OTP, which was nonsignificant after stratification by T-stage. CONCLUSION: This international propensity score matched study showed that MITP may be a valuable alternative to OTP in selected patients, given the associated lower rate of major morbidity.

Short-term Outcomes After Spleen-preserving Minimally Invasive Distal Pancreatectomy With or Without Preservation of Splenic Vessels: A Pan-European Retrospective Study in High-volume Centers.

OBJECTIVE: To compare short-term clinical outcomes after Kimura and Warshaw MIDP. BACKGROUND: Spleen preservation during distal pancreatectomy can be achieved by either preservation (Kimura) or resection (Warshaw) of the splenic vessels. Multicenter studies reporting outcomes of Kimura and Warshaw spleen-preserving MIDP are scarce. METHODS: Multicenter retrospective study including consecutive MIDP procedures intended to be spleen-preserving from 29 high-volume centers (≥15 distal pancreatectomies annually) in 8 European countries. Primary outcomes were secondary splenectomy for ischemia and major (Clavien-Dindo grade ≥III) complications. Sensitivity analysis assessed the impact of excluding ("rescue") Warshaw procedures which were performed in centers that typically (>75%) performed Kimura MIDP. RESULTS: Overall, 1095 patients after MIDP were included with successful splenic preservation in 878 patients (80%), including 634 Kimura and 244 Warshaw procedures. Rates of clinically relevant splenic ischemia (0.6% vs 1.6%, P = 0.127) and major complications (11.5% vs 14.4%, P = 0.308) did not differ significantly between Kimura and Warshaw MIDP, respectively. Mortality rates were higher after Warshaw MIDP (0.0% vs 1.2%, P = 0.023), and decreased in the sensitivity analysis (0.0% vs 0.6%, P = 0.052). Kimura MIDP was associated with longer operative time (202 vs 184 minutes, P = 0.033) and less blood loss (100 vs 150 mL, P < 0.001) as compared to Warshaw MIDP. Unplanned splenectomy was associated with a higher conversion rate (20.7% vs 5.0%, P < 0.001). CONCLUSIONS: Kimura and Warshaw spleen-preserving MIDP provide equivalent short-term outcomes with low rates of secondary splenectomy and postoperative morbidity. Further analyses of long-term outcomes are needed.

Robotic Distal Pancreatectomy: A Novel Standard of Care? Benchmark Values for Surgical Outcomes From 16 International Expert Centers.

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series. RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay. CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Panomics reveals patient individuality as the major driver of colorectal cancer progression.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity. METHODS: We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results. RESULTS: Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes. CONCLUSION: Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.

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.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

The impact of intra- and postoperative fluid balance in pancreatic surgery - A retrospective cohort study.

BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the impact of perioperative fluid administration in pancreatic surgery. METHODS: Patients who underwent pancreatic resections were identified from our institution's prospectively maintained database. Fluid balances were recorded intraoperatively and at 24hr postoperatively. Patients were stratified into tertiles of fluid administration (low, medium, high). Adjusted multivariable analysis was performed and outcome measures were postoperative complications. RESULTS: A total of 211 patients were included from 2012 to 2017. Complication rates were POPF(B/C) 19.4%, DGE(B/C) 14.7%, PPH(C) 10.0% and CDC ≥ IIIb 26.1%. In multivariable analysis, high perioperative fluid balance was an independent risk factor associated with POPF (OR = 10.5, 95%CI 2.7-40.7, p = .001), CDC (OR = 2.5, 95%CI 1.2-5.3, p < .002), DGE (OR = 2.3, 95%CI 1.0-5.2, p = .017), PPH (OR = 6.7 95%CI 2.2-20.0, p = .038) and reoperation (OR = 3.1, 95%CI 1.6-6.2, p = .006). In multivariable analysis with intraoperative and postoperative fluid balances as separate predictors, intraoperative (OR = 2,5, 95%CI 1.2-5.5, p = .04) and postoperative fluid balance (OR = 2.5, 95%CI 1.2-5.5, p = .02) were predictors of POPF. Postoperative fluid balance was the only predictor for mortality (OR = 4.5, 95%CI 1.0-18.9, p = .041) and predictor for CDC (OR = 2.0, 95%CI 1.0-4.0, p = .043) and OHS days (OR = 6.9, 95%CI 0.03-13.7, p = .038). CONCLUSIONS: High postoperative fluid balance in particular is associated with postoperative morbidity. Maintaining a fluid-restrictive strategy postoperatively should be recommended for patients undergoing pancreatic surgery.

Long-term functional outcome after tubular laparoscopic sigmoid resection for diverticular disease.

PURPOSE: Sigmoid resection for diverticular disease is a frequent surgical procedure in the Western world. However, long-term bowel function after sigmoid resection has been poorly described in the literature. This study aims to assess the long-term bowel function after tubular sigmoid resection with preservation of inferior mesenteric artery (IMA) for diverticular disease. METHODS: We retrospectively identified patients who underwent sigmoid resection for diverticular disease between 2002 and 2012 at a tertiary referral center in northern Germany. Using well-validated questionnaires, bowel function was assessed for fecal urgency, incontinence, and obstructed defecation. The presence of bowel dysfunction was compared to baseline characteristics and perioperative outcome. RESULTS: Two hundred and thirty-eight patients with a mean age of 59.2 ± 10 years responded to our survey. The follow-up was conducted 117 ± 32 months after surgery. At follow-up, 44 patients (18.5%) had minor LARS (LARS 21-29) and 35 (15.1%) major LARS (LARS ≥ 30-42), 35 patients had moderate-severe incontinence (CCIS ≥ 7), and 2 patients (1%) had overt obstipation (CCOS ≥ 15). The multivariate analysis showed that female gender was the only prognostic factor for long-term incontinence (CCIS ≥ 7), and ASA score was the only preoperative prognostic factor for the presence of major LARS at follow-up. CONCLUSION: Sigmoid resection for diverticular disease can be associated with long-term bowel dysfunction, even with tubular dissection and preservation of IMA. These findings suggest intercolonic mechanisms of developing symptoms of bowel dysfunction after disruption of the colorectal continuity that are so far summarized as "sigmoidectomy syndrome."

Near-infrared fluorescence tattooing: a new approach for endoscopic marking of tumors in minimally invasive colorectal surgery using a persistent near-infrared marker.

INTRODUCTION: Intraoperative accurate localization of tumors in the lower gastrointestinal tract is essential to ensure oncologic radicality. In minimally invasive colon surgery, tactile identification of tumors is challenging due to diminished or absent haptics. In clinical practice, preoperative endoscopic application of a blue dye (ink) to the tumor site has become the standard for marking and identification of tumors in the colon. However, this method has the major limitation that accidental intraperitoneal spillage of the dye can significantly complicate the identification of anatomical structures and surgical planes. In this work, we describe a new approach of NIR fluorescent tattooing using a near-infrared (NIR) fluorescent marker instead of a blue dye (ink) for endoscopic tattooing. METHODS: AFS81x is a newly developed NIR fluorescent marker. In an experimental study with four domestic pigs, the newly developed NIR fluorescent marker (AFS81x) was used for endoscopic tattooing of the colon. 7-12 endoscopic submucosal injections of AFS81x were placed per animal in the colon. On day 0, day 1, and day 10 after endoscopic tattooing with AFS81x, the visualization of the fluorescent markings in the colon was evaluated during laparoscopic surgery by two surgeons and photographically documented. RESULTS: The detection rate of the NIR fluorescent tattoos at day 0, day 1, and day 10 after endoscopic tattooing was 100%. Recognizability of anatomical structures during laparoscopy was not affected in any of the markings, as the markings were not visible in the white light channel of the laparoscope, but only in the NIR channel or in the overlay of the white light and the NIR channel of the laparoscope. The brightness, the sharpness, and size of the endoscopic tattoos did not change significantly on day 1 and day 10, but remained almost identical compared to day 0. CONCLUSION: The new approach of endoscopic NIR fluorescence tattooing using the newly developed NIR fluorescence marker AFS81x enables stable marking of colonic sites over a long period of at least 10 days without compromising the recognizability of anatomical structures and surgical planes in any way.

Surgical treatment for pancreatic cystic lesions-implications from the multi-center and prospective German StuDoQ|Pancreas registry.

PURPOSE: The detection of pancreatic cystic lesions (PCL) causes uncertainty for physicians and patients, and international guidelines are based on low evidence. The extent and perioperative risk of resections of PCL in Germany needs comparison with these guidelines to highlight controversies and derive recommendations. METHODS: Clinical data of 1137 patients who underwent surgery for PCL between 2014 and 2019 were retrieved from the German StuDoQ|Pancreas registry. Relevant features for preoperative evaluation and predictive factors for adverse outcomes were statistically identified. RESULTS: Patients with intraductal papillary mucinous neoplasms (IPMN) represented the largest PCL subgroup (N = 689; 60.6%) while other entities (mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine tumors, pseudocysts) were less frequently resected. Symptoms of pancreatitis were associated with IPMN (OR, 1.8; P = 0.012) and pseudocysts (OR, 4.78; P < 0.001), but likewise lowered the likelihood of MCN (OR, 0.49; P = 0.046) and SCN (OR, 0.15, P = 0.002). A total of 639 (57.2%) patients received endoscopic ultrasound before resection, as recommended by guidelines. Malignancy was histologically confirmed in 137 patients (12.0%), while jaundice (OR, 5.1; P < 0.001) and weight loss (OR, 2.0; P = 0.002) were independent predictors. Most resections were performed by open surgery (N = 847, 74.5%), while distal lesions were in majority treated using minimally invasive approaches (P < 0.001). Severe morbidity was 28.4% (N = 323) and 30d mortality was 2.6% (N = 29). Increased age (P = 0.004), higher BMI (P = 0.002), liver cirrhosis (P < 0.001), and esophageal varices (P = 0.002) were independent risk factors for 30d mortality. CONCLUSION: With respect to unclear findings frequently present in PCL, diagnostic means recommended in guidelines should always be considered in the preoperative phase. The therapy of PCL should be decided upon in the light of patient-specific factors, and the surgical strategy needs to be adapted accordingly.

Use and outcome of minimally invasive pancreatic surgery in the European E-MIPS registry.

BACKGROUND: The European registry for minimally invasive pancreatic surgery (E-MIPS) collects data on laparoscopic and robotic MIPS in low- and high-volume centers across Europe. METHODS: Analysis of the first year (2019) of the E-MIPS registry, including minimally invasive distal pancreatectomy (MIDP) and minimally invasive pancreatoduodenectomy (MIPD). Primary outcome was 90-day mortality. RESULTS: Overall, 959 patients from 54 centers in 15 countries were included, 558 patients underwent MIDP and 401 patients MIPD. Median volume of MIDP was 10 (7-20) and 9 (2-20) for MIPD. Median use of MIDP was 56.0% (IQR 39.0-77.3%) and median use of MIPD 27.7% (IQR 9.7-45.3%). MIDP was mostly performed laparoscopic (401/558, 71.9%) and MIPD mostly robotic (234/401, 58.3%). MIPD was performed in 50/54 (89.3%) centers, of which 15/50 (30.0%) performed ≥20 MIPD annually. This was 30/54 (55.6%) centers and 13/30 (43%) centers for MIPD respectively. Conversion rate was 10.9% for MIDP and 8.4% for MIPD. Overall 90 day mortality was 1.1% (n = 6) for MIDP and 3.7% (n = 15) for MIPD. CONCLUSION: Within the E-MIPS registry, MIDP is performed in about half of all patients, mostly using laparoscopy. MIPD is performed in about a quarter of patients, slightly more often using the robotic approach. A minority of centers met the Miami guideline volume criteria for MIPD.