Prospective Comparison of [18F]FDG and [18F]AIF-FAPI-74 PET/CT in the Evaluation of Potentially Resectable Pancreatic Ductal Adenocarcinoma.

PURPOSE: Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in clinical staging is unclear, PET/CT detecting fibroblast-activation protein (FAP) expression has recently received considerable attention for detecting various tumors, including PDAC, with high sensitivity. We explored the efficacy of [18F]FDG and [18F]AIF-FAPI-74 PET/CT in the initial evaluation of potentially resectable PDAC. PROCEDURES: Between 2021 and 2022, twenty participants with newly diagnosed potentially resectable PDAC were enrolled. After the initial evaluation with pancreatic CT, [18F]FDG PET/CT, and [18F]AIF-FAPI-74 PET/CT, treatment strategies were determined considering the participant's general status, clinical staging, and resectability. Pathological information from the surgical specimens was only available in 17 participants who underwent curative-intent surgery. Head-to-head comparisons of quantitative radiotracer uptake and diagnostic performance were performed among imaging modalities. RESULTS: [18F]AIF-FAPI-74 PET/CT showed a significantly higher maximum standardized uptake value than [18F]FDG PET/CT did in evaluating primary pancreatic lesions (median [interquartile range]; 12.6 [10.7-13.7] vs. 6.3 [4.8-9.2]; P < 0.001). In contrast, [18F]AIF-FAPI-74 PET/CT showed a significantly lower mean standardized uptake value than [18F]FDG PET/CT did in evaluating background organ (median [interquartile range]) 0.8 [0.7-0.9] vs. 2.6 [2.3-2.7]; P < 0.001). In addition, the sensitivity of [18F]AIF-FAPI-74 PET/CT in detecting metastatic lymph nodes was higher than that of [18F]FDG PET/CT (50.0% vs. 0.0%; P = 0.026). CONCLUSION: This study demonstrated that [18F]AIF-FAPI-74 PET/CT could improve the clinical staging of potentially resectable PDAC.

Perioperative outcomes of robot-assisted pancreatoduodenectomy (PD) and totally laparoscopic PD after overcoming learning curves with comparison of oncologic outcomes between open PD and minimally invasive PD.

Backgrounds/Aims: Minimally invasive pancreatoduodenectomy (MIPD), such as totally laparoscopic pancreatoduodenectomy (TLPD) or robot-assisted pancreatoduodenectomy (RAPD), is increasingly performed worldwide. This study aimed to compare the perioperative outcomes of TLPD and RAPD, and compare the oncologic outcomes between MIPD and open pancreatoduodenectomy (OPD) for malignant disease. Methods: This retrospective study was conducted at two hospitals that followed similar oncological surgical principles, including the extent of resection. RAPD was performed at Seoul National University Hospital, and TLPD at Seoul National University Bundang Hospital. Patient demographics, perioperative outcomes, and oncological outcomes were analyzed. Propensity score matching (PSM) analysis was performed to compare oncologic outcomes between MIPD and OPD. Results: Between 2015 and 2020, 332 RAPD and 178 TLPD were performed. The rates of Clavian-Dindo grade ≥ 3 complications (19.3% vs. 20.2%, p = 0.816), clinically relevant postoperative pancreatic fistula (9.9% vs. 11.8%, p = 0.647), and open conversions (6.6% vs. 10.5%, p = 0.163) were comparable between the two groups. The mean operation time (341 minutes vs. 414 minutes, p < 0.001) and postoperative hospital stay were shorter in the RAPD group (11 days vs. 14 days, p = 0.034). After PSM, the 5-year overall survival rate was comparable between MIPD and OPD for overall malignant disease (58.4% vs. 55.5%, p = 0.180). Conclusions: Both RAPD and TLPD are safe and feasible, and MIPD has clinical outcomes that are comparable to those of OPD. Although RAPD exhibits some advantages, its perioperative outcomes are similar to those associated with TLPD. A surgical method may be selected based on the convenience of surgical movements, medical costs, and operator experience.

Natural History of the Remnant Pancreatic Duct after Pancreatoduodenectomy for Non-Invasive Intraductal Papillary Mucinous Neoplasm: Results from an International Consortium.

BACKGROUND: Little is known about the prognostic significance of pancreatic duct (PD) dilation following pancreatoduodenectomy for intraductal papillary mucinous neoplasms (IPMN). Although PD dilation is typically the hallmark radiographic feature of IPMN, other causes of PD dilation exist, including anastomotic stricture, pancreatitis, senescence, and postsurgical passive dilation. Therefore, PD dilation after pancreatoduodenectomy for IPMN represents a diagnostic and management dilemma. The purpose of this study was to evaluate the significance of PD dilation after pancreatoduodenectomy for noninvasive IPMN. METHODS: All patients who underwent pancreatoduodenectomy for noninvasive IPMN at nine pancreatic academic centers between 2013 and 2018 were included. Variables were entered prospectively into institutional databases and retrospectively reviewed for the purpose of this study. Dilation of the PD remnant was defined as a duct diameter of ≥5 mm, according to international guidelines. RESULTS: Four-hundred and eighty-one patients were included in this study. The mean age of the patients was 66 years (range 30-90). Patients were surveilled for a median of 4.5 (+/-2.3; max 10.6) years. During follow-up, 132 patients (27.4%) developed PD dilation in the remnant tissue after a median of 3.3 years. Multivariable analysis demonstrated that older age at the time of pancreatoduodenectomy (P=0.01) and longer surveillance duration (P=0.002) were predictors of PD dilation. Interestingly, neither the pathological IPMN subtype (branch-duct vs. main duct/mixed, P=0.96) nor the preoperative PD diameter (P=0.14) was associated with an increased risk of PD dilation in the remnant. During follow-up, IPMN recurrence was suspected in the remaining 72 patients (18.4%), solely because of ductal dilation on cross-sectional imaging in 97% (70/72). Completion pancreatectomy was performed in only 16 patients (3.3%), of whom only four (0.8%) had invasive carcinoma. Three of these four patients had high-grade dysplasia in the original pancreatoduodenectomy specimen, whereas only one had a low-grade dysplastic lesion initially. On multivariable analysis, no variable was predictive of IPMN recurrence in the remnant. CONCLUSIONS: New main duct dilation in the pancreatic remnant after pancreatoduodenectomy for IPMN is common, occurring in 27% of the patients. The duration of surveillance is the main factor associated with remnant PD dilation, suggesting that this is likely a physiologic phenomenon. Although recurrence of IPMN in the remnant is often suspected, only 0.8% of patients develop an invasive carcinoma in the pancreatic remnant requiring completion pancreatectomy.

Diagnostic Performance of Surgical Indication for Branch-duct or Mixed-type Intraductal Papillary Mucinous Neoplasms of the Revised International Association of Pancreatology (IAP) 2023 Guidelines.

OBJECTIVE: To evaluate the diagnostic performance of surgical indications of the revised International Association of Pancreatology (IAP) 2023 guidelines compared to the IAP 2017 and European 2018 guidelines. SUMMARY BACKGROUND DATA: The revised IAP guidelines for surgical indications for branch duct (BD) intraductal papillary mucinous neoplasms (IPMN) include the presence of at least two worrisome features without mandatory endoscopic ultrasound. METHODS: Among 663 patients who underwent resection for pathologically confirmed IPMN in a tertiary hospital between 2013 and 2023, 556 patients with BD or mixed-type IPMN were retrospectively reviewed. Diagnostic performances of the three guidelines for predicting high-grade dysplasia or IPMN with invasive carcinoma were compared. The primary outcome was the malignancy rate. Clinicopathological and radiological imaging data were analyzed. RESULTS: A total of 540, 451, and 490 patients met the surgical indications of the IAP, 2017, 2023, and European guidelines, respectively. Malignant IPMN was observed in 229 (41.2%) patients (high-grade dysplasia, n=99; invasive carcinoma, n=130). Surgical indication by the IAP 2023 guidelines showed higher specificity (29.1 vs. 4.9%, P<0.001), positive predictive value (48.6 vs. 42.4%, P=0.031), and accuracy (55.5 vs. 44.1%, P<0.001) than the IAP 2017 guidelines. It also had higher specificity than the European guidelines (18.7%, P=0.024). The IAP 2023 guidelines showed a superior AUC of surgical indication (0.623 vs. 0.582 for the European guidelines, P<0.001; and 0.524 for the IAP guidelines, P=0.008). CONCLUSIONS: The IAP 2023 guidelines showed better malignancy prediction than the IAP 2017 and European guidelines, potentially reducing unnecessary surgeries.

A review of ergonomic positions to improve musculoskeletal distress in hepatobiliary pancreatic surgeons according to open, laparoscopic, and robotic surgeries.

Advances in surgical ergonomics are essential for the performance, health, and career longevity of surgeons. Many surgeons experience work-related musculoskeletal disorders (WMSDs) resulting from various surgical modalities, including open, laparoscopic, and robotic surgeries. To prevent WMSDs, individual differences may exist depending on the surgical method; however, the key is to maintain a neutral posture, and avoid static postures. This review aims to summarize the concepts of ergonomics and WMSDs; identify the ergonomic challenges of open, laparoscopic, and robotic surgeries; and discuss ergonomic recommendations to improve them.

Clinical outcomes of preservation versus resection of portal/superior mesenteric vein during pancreaticoduodenectomy in pancreatic cancer patients who respond to neoadjuvant treatment: A retrospective cohort study.

BACKGROUND: R0 rates have increased as neoadjuvant treatment (NAT) has become the primary treatment for pancreatic ductal adenocarcinoma (PDAC) with venous involvement, suggesting a decrease in venous tumor infiltration. The aim of this study was to investigate the clinical outcomes of preserving the portal/superior mesenteric vein (PV/SMV) during pancreaticoduodenectomy (PD) in PDAC patients who underwent NAT. MATERIAL AND METHODS: The 113 patients with resectable and borderline resectable PDAC with venous involvement who responded to NAT and underwent curative PD between 2012 and 2022 were retrospectively reviewed. RESULTS: Among the 113 patients, PV/SMV preservation (PVP) was performed in 68 patients (60.2%), and PV/SMV resection (PVR) was performed in 45 patients (39.8%). There was no significant difference in the R0 rate, 5-year overall survival (OS) and recurrence-free survival between the two groups. PV/SMV stenosis within 3 months after surgery was more common in the PVR group than in the PVP group (1.5% versus 22.2%; P < 0.001), and 5-year PV/SMV stenosis-free survival was significantly higher in the PVP group than in the PVR group (76.5% versus 53.4%; P=0.014). Multivariate analysis showed that gemcitabine-based neoadjuvant chemotherapy was associated with poor OS. PVR, clinically relevant postoperative pancreatic fistula, and locoregional recurrence were independent risk factors for PV/SMV stenosis. CONCLUSION: The PVP group had similar oncologic outcomes and better vessel-functional outcomes than the PVR group. Therefore, if dissection is possible and there is a high likelihood of achieving R0 resection after NAT, routine PVR may be unnecessary in PDAC patients with venous involvement.

Development of a Fit-For-Purpose Multi-Marker Panel for Early Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from a lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for the discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating the analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, the throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from the early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In the discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including a short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

Interobserver Variability in the International Study Group for Pancreas Surgery (ISGPS)-Defined Complications After Pancreatoduodenectomy: An International Cross-Sectional Multicenter Study.

OBJECTIVE: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others. SUMMARY BACKGROUND DATA: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking. METHODS: International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored six standardized case vignettes. This variability and the 'within centers' variability were calculated for twofold scoring (no complication/grade A vs grade B/C) and threefold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula (POPF), post-pancreatoduodenectomy hemorrhage (PPH), chyle leak (CL), bile leak (BL), and delayed gastric emptying (DGE). Interobserver variability is presented with Gwet's AC-1 measure for agreement. RESULTS: Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for twofold scoring was 68% (95%-CI: 55%-81%, AC1 score: moderate agreement) and for threefold scoring 55% (49%-62%, AC1 score: fair agreement). The mean 'within centers' agreement for twofold scoring was 84% (80%-87%, AC1 score; substantial agreement). CONCLUSION: The interobserver variability for the ISGPS defined complications of pancreatoduodenectomy was too high even though the 'within centers' agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability.

Learning curve stratified outcomes after robotic pancreatoduodenectomy: International multicenter experience.

BACKGROUND: Robotic pancreatoduodenectomy is increasingly being implemented worldwide, with good results reported from individual expert centers. However, it is unclear to what extent outcomes will continue to improve during the learning curve, as large international studies are lacking. METHODS: An international retrospective multicenter case series, including consecutive patients after robotic pancreatoduodenectomy from 18 centers in 8 countries in Europe, Asia, and South America until December 31, 2019, was conducted. A cumulative sum analysis was performed to determine the inflection points for the feasibility (operative time and blood loss) and proficiency (postoperative pancreatic fistula grade B/C and major morbidity) learning curves. Outcomes were compared in 3 groups on the basis of the learning curve inflection points. RESULTS: Overall, 2,186 patients after robotic pancreatoduodenectomy were included. The feasibility learning curve was reached after 30-45 robotic pancreatoduodenectomy procedures and the proficiency learning curve after 90 robotic pancreatoduodenectomy procedures. These inflection points created 3 phases, which were associated with major morbidity (24.7%, 23.4%, and 12.3%, P < .001) but not 30-day mortality (2.1%, 2.0%, and 1.5%, P = .670). Other outcomes mostly continued to improve, including median operative time 432, 390, and 300 minutes (P < .0001), conversion 6.0%, 4.7%, and 2.7% (P = .002), bile leakage 7.2%, 4.1%, and 2.4% (P < .001), postpancreatectomy hemorrhage 6.5%, 6.1%, and 1.8% (n = 21) but not R0 resection (pancreatic ductal adenocarcinoma only) 78.5%, 73.9%, and 82.8% (P = .35), and 90-day mortality rate 3.1%, 3.5%, and 2.1% (P = .191). Centers performing >20 robotic pancreatoduodenectomies annually had lower rates of conversion, reoperation, and shorter median operative time as compared with centers performing 10-20 robotic pancreatoduodenectomies annually. CONCLUSION: This international multicenter study demonstrates that most outcomes of robotic pancreatoduodenectomy continued to improve during 3 learning curve phases without a negative effect on 90-day mortality. Randomized studies are needed in high-volume centers that have surpassed the first learning curves, to compare these outcomes with the open approach.

'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer.

BACKGROUND: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. METHOD: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. RESULTS: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. CONCLUSIONS: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.

Early postoperative fever as a predictor of pancreatic fistula after pancreaticoduodenectomy: a single-center retrospective observational study.

BACKGROUND: The connection between early postoperative fever and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy remains unclear. This study aimed to investigate this association and assess the predictive value of early postoperative fever for CR-POPF. METHODS: This retrospective observational study included adult patients who underwent pancreaticoduodenectomy at a tertiary teaching hospital between 2007 and 2019. Patients were categorized into those with early postoperative fever (≥ 38 °C in the first 48 h after surgery) and those without early postoperative fever groups. Weighted logistic regression analysis using stabilized inverse probability of treatment weighting (sIPTW) and multivariable logistic analysis were performed. The c-statistics of the receiver operating characteristic curves were calculated to evaluate the impact on the predictive power of adding early postoperative fever to previously identified predictors of CR-POPF. RESULTS: Of the 1997 patients analyzed, 909 (45.1%) developed early postoperative fever. The overall incidence of CR-POPF among all the patients was 14.3%, with an incidence of 19.5% in the early postoperative fever group and 9.9% in the group without early postoperative fever. Early postoperative fever was significantly associated with a higher risk of CR-POPF after sIPTW (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.34-2.22; P < 0.001) and multivariable logistic regression analysis (adjusted OR, 1.88; 95% CI, 1.42-2.49; P < 0.001). The c-statistics for the models with and without early postoperative fever were 0.76 (95% CI, 0.73-0.79) and 0.75 (95% CI, 0.72-0.78), respectively, showing a significant difference between the two (difference, 0.02; 95% CI, 0.00-0.03; DeLong's test, P = 0.005). CONCLUSIONS: Early postoperative fever is a significant but not highly discriminative predictor of CR-POPF after pancreaticoduodenectomy. However, its widespread occurrence limits its applicability as a predictive marker.

Comparing clinical and genomic features based on the tumor location in patients with resected pancreatic cancer.

BACKGROUND: Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location. METHODS: In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis. RESULTS: Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77-1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers. CONCLUSIONS: We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.

Re-evaluation of risk and oncological outcomes of resection of veins and arteries in the resection of pancreatic cancer.

BACKGROUND: Advances in chemotherapy have led to increasing major vascular resection during pancreatectomy which has been contraindicated due to high morbidity. This study aimed to verify the safety and oncological outcomes of vascular resection during pancreatectomy in the era of neoadjuvant therapy. METHODS: Data from patients who underwent surgery for pancreatic cancer at Seoul National University Hospital between 2001 and 2021 were reviewed. Clinicopathological outcomes were analyzed according vessel resection. A propensity-score-matched (PSM) analysis was performed to evaluate survival outcomes. RESULTS: Of 1596 patients, the proportion of those who underwent vascular resection increased from 9.2% to 23.4% over time divided into 5-year intervals. There were no differences in major complications (15.6% vs. 13.0%; p = .266) and 30-day mortality rate (0.3% vs. 0.6%; p = .837) between the vascular and nonvascular resection groups. After PSM, the vascular resection group demonstrated comparable survival outcome with the nonvascular resection group (5 year-survival-rate 20.4 vs. 23.7%; p = .194). Arterial resection yielded comparable survival outcome with nonvascular resection (5 year-survival-rate 38.1% vs. 23.7%; p = .138). CONCLUSIONS: Appropriate vascular resection-even arterial-is safe and effective in patients carefully selected for radical surgery in the era of neoadjuvant therapy. Further studies are needed to determine the optimal indication and method for vascular resection in patients with pancreatic cancer.

Emerging role of local treatment in the era of advanced systemic treatment in pancreatic cancer with liver metastasis: A systematic review and meta-analysis.

BACKGROUND: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. METHODS: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model. RESULTS: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73). CONCLUSIONS: Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies.

Correction: Gallbladder polyps: Correlation of size and clinicopathologic characteristics based on updated definitions.

[This corrects the article DOI: 10.1371/journal.pone.0237979.].

Optimal timing of surgery after neoadjuvant treatment in borderline resectable pancreatic cancer.

BACKGROUND: Neoadjuvant treatment (NAT) is standard for borderline resectable pancreatic cancer (BRPC). However, consensus is lacking on the optimal surgical timing for patients with BRPC undergoing NAT. The aim of this study was to investigate the long-term outcomes of patients undergoing NAT for BRPC and suggest optimal resection timing. METHODS: Prospectively collected data for 282 patients with BRPC between January 2007 and December 2019 were retrospectively reviewed. There were 164 patients who underwent NAT followed by surgery, 45 for chemotherapy only, and 73 for upfront surgery. Among them, 150 patients who underwent R0 or R1 resection following NAT were investigated to identify prognostic factors. RESULTS: Patients receiving NAT followed by surgery showed the best survival (median overall survival [OS]; NAT followed by surgery vs. upfront surgery vs. chemotherapy only; 35 vs. 23 vs. 16 months). In the NAT group, 54 (36.0%) patients received less than 3 months of NAT, 68 (45.3%) received ≥3, <6 months, and 28 (18.7%) received longer than 6 months. Patients receiving ≥3 months of NAT showed an improved OS compared to <3 months (median; not reached vs. 27 months). In the FOLFIRINOX group, patients who received more than eight FOLFIRINOX cycles showed a good prognosis (<6 vs. 6-7 vs. ≥8 cycles; median survival, 26 vs. 41 months vs. not-reached). However, >12 cycles did not carry a survival benefit compared to 8-11 cycles. CONCLUSION: The optimal resection timing following NAT is once a patient undergoes at least 3 months of neoadjuvant chemotherapy or at least eight FOLFIRINOX cycles.

Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy: An ISGPS Consensus.

OBJECTIVE: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD). BACKGROUND: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience. METHODS: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSION: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries.

Conversion surgery for initially unresectable locally advanced biliary tract cancer: A multicenter collaborative study conducted in Japan and Korea.

BACKGROUND: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. METHODS: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. RESULTS: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%. CONCLUSIONS: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required.

Association between hypotension during pancreatectomy and development of postoperative diabetes.

CONTEXT: With advancements in long-term survival after pancreatectomy, post-pancreatectomy diabetes has become a concern, and the risk factors are not established yet. Pancreatic islets are susceptible to ischemic damage, though there is a lack of clinical evidence regarding glycemic deterioration. OBJECTIVE: To investigate association between hypotension during pancreatectomy and development of post-pancreatectomy diabetes. DESIGN: In this retrospective, longitudinal cohort study, we enrolled patients without diabetes who underwent distal pancreatectomy or pancreaticoduodenectomy between January 2005 and December 2018, from two referral hospitals in Korea. MAIN OUTCOME MEASURES: Intraoperative hypotension [IOH] was defined as a 20% or greater reduction in systolic blood-pressure. The primary and secondary outcomes were incident diabetes and postoperative Homeostatic Model Assessment [HOMA] indices. RESULTS: We enrolled 1,129 patients (average age, 59 years; 49% men; 35% distal pancreatectomy). IOH occurred in 83% (median duration, 25 minutes; interquartile range [IQR], 5-65). During a median follow-up of 3.9 years, diabetes developed in 284 patients (25%). The cumulative incidence of diabetes was proportional to increases in the duration and depth of IOH (P < 0.001). For the median duration in an IOH when compared to a reference time of 0 minute, the hazard ratio [HR] was 1.48 (95% CI, 1.14-1.92). The effect was pronounced with distal pancreatectomy compared to pancreaticoduodenectomy. Furthermore, the duration of IOH was inversely correlated with 1-year HOMA beta-cell function (P < 0.002), but not with HOMA insulin resistance. CONCLUSIONS: These results support the hypothesis that IOH during pancreatectomy may elevate risk of diabetes by inducing beta cell insufficiency.