Prognostic model for resected borderline and locally advanced pancreatic cancer after neoadjuvant chemotherapy.

BACKGROUND: The current AJCC 8th has been reported to have a poor ability to predict the prognosis in patients with resected borderline resectable pancreatic cancer and locally advanced pancreatic cancer following neoadjuvant chemotherapy. This study was aimed to develop an improved prognostic model by incorporating pathology and parameters of biologic response (BR). MATERIALS METHODS: A retrospective cohort study was conducted including patients who underwent curative-intent surgery following chemotherapy. We developed a modified ypT staging system and incorporated the BR, involving normalization of carbohydrate antigen 19-9 and reduction in the maximum standardized uptake value simultaneously after chemotherapy. The prognostic performance of the current pathologic system, modified pathologic system, and newly developed system incorporating pathology and BR were compared. RESULTS: In this study, 171 patients underwent surgery following chemotherapy. The modified T stage, which unified ypT2 and ypT3, demonstrated improved prognostic performance than the current staging system (area under the curve: 0.706 vs. 0.661). Biologic unresponsiveness was an independent prognostic factor for worse survival (hazard ratio 2.31, 95% confidence interval 1.50-3.55, P<0.001). The modified pathology with BR system demonstrated the highest discriminative ability in predicting 5-year overall survival than the current pathologic system (area under the curve: 0.785 vs. 0.661, P=0.010) and modified pathologic staging system (area under the curve: 0.785 vs. 0.706, P=0.002). CONCLUSIONS: The prognostic model, incorporating modified ypT staging and elevated carbohydrate antigen 19-9 levels and maximum standardized uptake value simultaneously, demonstrated improved results in predicting oncologic outcomes for patients who underwent surgery following neoadjuvant chemotherapy.

Clinical impact of pancreatic invasion in T1-stage distal bile duct cancer and prognostic factors associated with long-term survival: A multicenter study.

BACKGROUND/PURPOSE: The eighth edition of the AJCC staging system introduced a shift in the staging of distal bile duct cancer (DBC), emphasizing the depth of invasion over adjacent organ invasion. This study aimed to evaluate the clinical impact of pancreatic invasion in pT1-stage DBC and identify prognostic factors for long-term survival. METHODS: This multicenter retrospective analysis encompassed DBC patients who underwent pancreaticoduodenectomy between 2009 and 2019 in six Korean tertiary centers, specifically those with final pathology confirming AJCC eighth edition T1 stage and intrapancreatic bile duct tumor origin. Primary endpoints were five-year recurrence-free survival (RFS) and overall survival (OS). Secondary objectives included the identification of prognostic determinants. RESULTS: This study involved 287 patients, comprising 190 without and 97 with pancreatic invasion. Pancreatic invasion did not significantly influence five-year OS and RFS rates (OS: without pancreatic invasion 69.9% vs. with pancreatic invasion 54.1%, p = .25; RFS: 56.3% vs. 55.4%, p = .97). Multivariate analysis highlighted male gender, age, lymphovascular invasion, and N stage as significant OS determinants. Notably, male gender, ampulla of Vater invasion, lymphovascular invasion, and N1 stage were also associated with RFS. CONCLUSIONS: In pT1 DBC, pancreatic invasion demonstrates no substantial impact on long-term prognosis, in accordance with the depth-based paradigm of the eighth edition AJCC staging system. The prognostic factors influencing OS were identified as male gender, age, lymphovascular invasion, and nodal metastasis.

Computed tomography-based vascular burden index as a predictor of vascular resection and pathological vascular invasion in pancreatic cancer with neo-adjuvant chemotherapy.

BACKGROUND: Determination of vessel resection in patients with pancreatectomy after neo-adjuvant chemotherapy remains controversial. The recently introduced computed tomography-based vascular burden index presents a potential solution to this challenge. This study aimed to evaluate the model performance for the prediction of vascular resection and pathological invasion. METHODS: Patients who underwent surgery after neo-adjuvant chemotherapy were included. Two independent reviewers measured the vascular tumour burden index around the adjacent artery (AVBI), and vein (VVBI). The area under the curve was compared to assess the predictive capacity of vascular burden index values and their changes for vascular resection and pathological vascular invasion. RESULTS: Among 252 patients, 179 and 73 had borderline resectable and locally advanced pancreatic cancer, respectively. Concurrent vessel resection and pathological vascular invasion were observed in 121 (48.0 %) and 42 (16.6 %) patients, respectively. In all patients, the VVBI (area under the curve: 0.872) and AVBI (0.911) after neo-adjuvant therapy significantly predicted vessel resection. In patients with vascular resection, the VVBI after neo-adjuvant chemotherapy (0.752) and delta value of the AVBI (0.706) demonstrated better performance for predicting pathological invasion of the resected vein. The regression of the AVBI and VVBI was an independent prognostic factor for survival (hazard ratio: 0.54, 95 % confidence interval: 0.34-0.85; P = 0.009) CONCLUSIONS: Regressed VVBI on serial computed tomography scans is useful for predicting vein resection and pathological venous invasion before surgery. The delta value of the AVBI may therefore be helpful for predicting pathological arterial invasion after neo-adjuvant chemotherapy.

Extranodal extension influences prognosis in pancreatic body/tail cancer: A retrospective cohort study.

BACKGROUND/PURPOSE: Extranodal extension (ENE) is an established prognostic factor in various malignancies, affecting survival in pancreatic head cancer (PHC). However, its significance in pancreatic body/tail cancer (PBTC) remains unclear. Therefore, we aimed to investigate the impact of ENE on PTBC prognosis. METHODS: We analyzed data collected from electronic medical records of patients with PBTC who underwent distal pancreatectomy at a single center between January 2011 and December 2015. The patients were categorized based on ENE presence and prognostic implications were evaluated using Kaplan-Meier survival curves and Cox proportional hazards model. RESULTS: PBTC cases involving lymph node (LN) metastasis and ENE exhibited significantly lower disease-free (DFS) and overall survival (OS) rates compared to cases without LN metastasis or ENE (median DFS; N0, 23 months; LN+/ENE-, 10 months; LN+/ENE+, 5 months; p < .001). No statistically significant difference was observed in DFS and OS rates between patients with N1/N2 in the group without ENE and those with ENE+. Multivariate analysis confirmed ENE as a significant adverse prognostic factor. CONCLUSIONS: ENE significantly predicts poor prognosis in PBTC, particularly in cases with nodal metastasis. The current cancer staging system for PBTC should incorporate ENE status. Moreover, different staging systems should be considered for PHC and PBTC.

Clinical Outcomes of Surgery After Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma.

Purpose: Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy. Materials and Methods: We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020. Results: Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates and postoperative pancreatic fistula rates (Grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC. Conclusion: Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.

Comparison of the different versions of NCCN guidelines for predicting margin-negative resection of pancreatic cancer in patients undergoing upfront surgery.

OBJECTIVES: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. METHODS: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. RESULTS: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). CONCLUSION: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.

Perioperative textbook outcomes of minimally invasive pancreatoduodenectomy: a multicenter retrospective cohort analysis in a Korean minimally invasive pancreatic surgery registry.

BACKGROUND: The aim of this study is to investigate the perioperative composite textbook outcomes of pancreatic surgery after minimally invasive pancreatoduodenectomy (MIPD). MATERIALS AND METHODS: The cohort study was conducted across 10 institutions and included 1552 patients who underwent MIPD registered with the Korean Study Group on Minimally Invasive Pancreatic Surgery between May 2007 and April 2020. We analyzed perioperative textbook outcomes of pancreatic surgery after MIPD. Subgroup analyses were performed to assess outcomes based on the hospital volume of MIPD. RESULTS: Among all patients, 21.8% underwent robotic pancreatoduodenectomy. High-volume centers (performing >20 MIPD/year) performed 88.1% of the procedures. The incidence of clinically relevant postoperative pancreatic fistula was 11.5%. Severe complications (Clavien-Dindo grade ≥IIIa) occurred in 15.1% of the cases. The 90-day mortality rate was 0.8%. The mean hospital stay was 13.7 days. Textbook outcomes of pancreatic surgery success were achieved in 60.4% of patients, with higher rates observed in high-volume centers than in low-volume centers (62.2% vs. 44.7%, P <0.001). High-volume centers exhibited significantly lower conversion rates (5.4% vs. 12.5%, P =0.001), lower 90-day mortality (0.5% vs. 2.7%, P =0.001), and lower 90-day readmission rates (4.5% vs. 9.6%, P =0.006) than those low-volume centers. CONCLUSION: MIPD could be performed safely with permissible perioperative outcomes, including textbook outcomes of pancreatic surgery, particularly in experienced centers. The findings of this study provided valuable insights for guiding surgical treatment decisions in periampullary disease.

Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer.

BACKGROUND: There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. METHODS: Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. RESULTS: Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT was administered in 166 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response [hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.73-5.58, P <0.001] based on cutoff value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels less than 37 IU/l (median survival; 35.5 vs. 20.9 months, P <0.001) and CA19-9 levels at least 37 IU/l (median survival; 34.3 vs. 17.8 months, P =0.03). In patients suspected to be Lewis antigen negative, the predictive performance of MTV was found to be limited ( P =0.84). CONCLUSION: Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.

Deep learning-based prediction of post-pancreaticoduodenectomy pancreatic fistula.

Postoperative pancreatic fistula is a life-threatening complication with an unmet need for accurate prediction. This study was aimed to develop preoperative artificial intelligence-based prediction models. Patients who underwent pancreaticoduodenectomy were enrolled and stratified into model development and validation sets by surgery between 2016 and 2017 or in 2018, respectively. Machine learning models based on clinical and body composition data, and deep learning models based on computed tomographic data, were developed, combined by ensemble voting, and final models were selected comparison with earlier model. Among the 1333 participants (training, n = 881; test, n = 452), postoperative pancreatic fistula occurred in 421 (47.8%) and 134 (31.8%) and clinically relevant postoperative pancreatic fistula occurred in 59 (6.7%) and 27 (6.0%) participants in the training and test datasets, respectively. In the test dataset, the area under the receiver operating curve [AUC (95% confidence interval)] of the selected preoperative model for predicting all and clinically relevant postoperative pancreatic fistula was 0.75 (0.71-0.80) and 0.68 (0.58-0.78). The ensemble model showed better predictive performance than the individual ML and DL models.

Malignant potential of neuroendocrine microtumor of the pancreas harboring high-grade transformation: lesson learned from a patient with von Hippel-Lindau syndrome.

Pancreatic neuroendocrine microtumor (PNEMT) is a neuroendocrine tumor (NET) < 0.5 cm in diameter, and it is considered benign. We report a PNEMT with high-grade transformation (HGT). A man in his 60s with von Hippel-Lindau syndrome underwent surgical resection of a NET. A second sub-centimeter nodule with a nodule-in-nodule pattern was discovered. The 0.4 cm outer nodule contained clear columnar cells with round nuclei and indistinct nucleoli, while the 0.1 cm inner nodule had eosinophilic cells with an increased nuclear to cytoplasmic ratio, vesicular nuclei, and prominent nucleoli. Tumor cells in the outer and inner nodules were synaptophysin and chromogranin positive. Only the inner nodule was p53 positive, while the outer nodule was exclusively positive for carbonic anhydrase 9 and vimentin. The Ki-67 labeling indices for the outer and inner nodules were 2.1% (grade 1) and 44.3% (grade 3), respectively. This nodule was determined to be a PNEMT with HGT. Our findings suggest that a PNEMT may not always be benign and can undergo HGT.

Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Clinical implication of the geometric location (fundal end versus cystic ductal end) of gallbladder cancer.

BACKGROUND: Management of early-stage gallbladder cancer is becoming more important as the rate of early detection is increasing. Although there have been many studies about the clinical implication of the invasion depth or peritoneal/hepatic location of gallbladder cancers, there is no study on the clinical implication of the geometric location of cancer along the longitudinal length of the gallbladder. METHODS: The location of gallbladder cancer was defined as the geometric center of the primary site of a tumour, which lies on the longitudinal diameter of the surgical specimens. We compared the oncologic outcomes following surgery between gallbladder cancers located on the fundal end and those located on the cystic ductal end. We also analysed patients with stage 1 gallbladder cancer who recurred after surgery. RESULTS: A total of 575 patients with gallbladder cancer were included in this study. Patients with gallbladder cancer on the cystic ductal end had significantly lower rates of recurrence-free survival (P = 0.016) and overall survival (P = 0.023) compared to those with gallbladder cancer on the fundal end. Among 90 patients with stage 1 gallbladder cancer, three patients had a recurrence, all of whom had cystic ductal end gallbladder cancer and showed cystic duct invasion or concomitant xanthogranulomatous cholecystitis in permanent pathology. CONCLUSIONS: Gallbladder cancers on the cystic ductal end had worse postoperative oncologic outcomes compared with those on the fundal end.

Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis.

BACKGROUND: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD). METHODS: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70-79 years) and older patients (≥80 years). RESULTS: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65-1.29], p = .596 and OR 1.22 [95% CI: 0.61-2.46], p = .508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (-0.14 days [95% CI: -0.29 to 0.01], p = .071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (-0.28 days [95% CI: -0.62 to 0.05], p = .069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (-0.36 days [95% CI: -0.71 to -0.004], p = .048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group. CONCLUSION: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.

Comparison of Surgical Outcomes of Laparoscopic and Robotic Surgery in Adult Choledochal Cysts.

Background: Minimally invasive surgery (MIS) for cyst excision and Roux-en-Y hepaticojejunostomy (HJ) is widely performed for adult choledochal cysts. Few articles compared the robotic and laparoscopic approaches for choledochal cysts. Methods: Between 2014 and 2022, 157 patients who underwent MIS for choledochal cysts were retrospectively analyzed. Perioperative outcomes of patients who underwent totally robotic surgery, robot-assisted surgery, and laparoscopic surgery were compared, respectively. Also, postoperative outcomes of patients with robotic reconstruction and laparoscopic reconstruction during HJ were compared. Results: Perioperative outcomes were comparable between robotic and laparoscopic groups. The suturing technique for the anterior and posterior walls of the HJ differed significantly between the robotic and laparoscopic reconstruction groups (P = .001). However, there were no significant differences in postoperative outcomes, including total complications (P = .304), major complications (P = .411), and postoperative interventions (P = .411), between the two groups. Conclusions: The robotic and laparoscopic approaches for adult choledochal cysts have comparable surgical outcomes. In the MIS era, robotic surgery could be an alternative surgical option for adult choledochal cysts.

Evaluation of postoperative outcomes of minimally invasive distal pancreatectomy for left-sided pancreatic tumors based on the modified frailty index: a retrospective cohort study.

BACKGROUND: This study compared the postoperative outcomes of minimally invasive distal pancreatectomy (MIDP) for left-sided pancreatic tumors based on the modified frailty index (mFI). MATERIALS AND METHODS: This retrospective study included 2212 patients who underwent MIDP for left-sided pancreatic tumors between 2005 and 2019. Postoperative outcomes, including complications (morbidity and mortality), were analyzed using mFI, and the participants were divided into two groups: frail ( n =79) and nonfrail ( n =2133). A subanalysis of 495 MIDPs for pancreatic ductal adenocarcinoma was conducted to compare oncological outcomes. RESULTS: Clinically relevant postoperative pancreatic fistula was significantly higher in the frail group than in the nonfrail group. A significant between-group difference was observed in overall complications with Clavien-Dindo classification grade ≥III. Furthermore, the proportion of all complications before readmission was higher in the frail group than in the nonfrail group. Among all readmitted patients, the frail group had a higher number of grade ≥IV patients requiring ICU treatment. The frail group's 90-day mortality was 1.3%; the difference was statistically significant (nonfrail: 0.3%, P =0.021). In the univariate and multivariate logistic regression analyses, mFI ≥0.27 (odds ratio 3.231, 95% CI: 1.889-5.523, P <0.001), extended pancreatectomy, BMI ≥30 kg/m 2 , male sex, and malignancy were risk factors for Clavien-Dindo classification grade ≥III. CONCLUSION: mFI is a potential preoperative tool for predicting severe postoperative complications, including mortality, in patients who have undergone MIDP for left-sided tumors.

15-Year Experience of Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer-A Korean Nationwide Investigation.

BACKGROUND: As systemic treatment for pancreatic cancer advances, distal pancreatectomy with celiac axis resection (DP-CAR) has been considered a curative-intent surgical option for advanced pancreatic cancer. This study aimed to review the surgical and oncologic outcomes of patients undergoing DP-CAR based on Korean nationwide data. METHODS: We collected the data of patients who underwent DP-CAR for pancreatic cancer between 2007 and 2021 at seven major hospitals in Korea. The clinicopathological characteristics, postoperative complications, and data on the survival of the patients were retrospectively reviewed. Logistic regression analysis was performed to identify risk factors for postoperative complications and survival. RESULTS: A total of 75 patients, consisting mainly of borderline resectable (n = 32) or locally advanced (n = 30) pancreatic cancer, were included in the analysis. Forty-two (56.0%) patients underwent neoadjuvant treatment (NAT). Twenty (26.7%) patients experienced Clavien-Dindo grade ≥ 3 complications, including four patients with ischemic gastropathy, two with hepatic ischemia, and two procedure-related mortalities. Neoadjuvant chemotherapy increased the risk of postoperative complications (p = 0.028). The median recurrence-free and overall survival were 7 and 19 months, with a 5-year survival rate of 13% and 24%, respectively. In the NAT group, a decrease in CA 19-9 and the post-NAT maximum standardized uptake value (SUVmax) in positron emission tomography were associated with survival after surgical resection. CONCLUSIONS: Despite the possibility of major complications, DP-CAR could be a feasible option for achieving curative resection with fair survival outcomes in patients with borderline resectable or locally advanced pancreatic cancer. Further studies investigating the safety of the procedure and identifying proper surgical candidates with potential survival gains are necessary.

Outcomes of Distal Pancreatectomy With Celiac Axis Resection for Pancreatic Cancer.

OBJECTIVES: This study aimed to show the clinical and oncologic outcomes of distal pancreatectomy with celiac axis resection (DP-CAR) from a high-volume single center and analyze them from diverse perspectives. METHODS: Forty-eight patients with pancreatic body and tail cancer with celiac axis involvement who underwent DP-CAR were included in the study. The primary outcome was morbidity and 90-day mortality, and the secondary outcome was overall survival and disease-free survival. RESULTS: Morbidity (Clavien-Dindo classification grade ≥3) occurred in 12 patients (25.0%). Thirteen patients (27.1%) had pancreatic fistula grade B and 3 patients (6.3%) had delayed gastric emptying. The 90-day mortality was 2.1% (n = 1). The median overall survival was 25.5 months (interquartile range, 12.3-37.5 months) and median disease-free survival was 7.5 months (interquartile range, 4.0-17.0 months). During the follow-up period, 29.2% of participants survived for up to 3 years and 6.3% survived for up to 5 years. CONCLUSIONS: Despite its associated morbidity and mortality, DP-CAR should be considered as the only therapeutic option for pancreatic body and tail cancer with celiac axis involvement when carried out on carefully selected patients performed by a highly experienced group.

Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection.

PURPOSE: There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). MATERIALS AND METHODS: Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. RESULTS: Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. CONCLUSION: Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial.

BACKGROUND AND AIMS: The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node-positive extrahepatic cholangiocarcinoma. APPROACH AND RESULTS: Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 on days 1 and 8) or capecitabine (1250 mg/m2 twice daily on days 1-14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1. Between July 2017 and November 2020, 101 patients (50 in the GemCis and 51 in the capecitabine group) were included in the intention-to-treat population. Perihilar and distal bile ducts were the primary sites in 45 (44.6%) and 56 (55.4%) patients, respectively, and 32 (31.7%) had R1 resections. Median (1-sided 90% CI) follow-up duration was 33.4 (30.5-35.8) months. In the GemCis and capecitabine group, 2-year disease-free survival rates were 38.5% (29.5%-47.4%) and 25.1% (17.4%-33.5%) [HR=0.96 (CI, 0.71-1.30), p=0.430], and median overall survival was 35.7 months (29.5-not estimated) and 35.7 months (30.9-not estimated) [HR=1.08 (CI, 0.71-1.64), 1-sided p=0.404], respectively. Grade 3-4 adverse events occurred in 42 (84.0%) and 8 patients (16.0%) in the GemCis and capecitabine groups, respectively. No treatment-related deaths were reported. CONCLUSIONS: In resected lymph node-positive extrahepatic cholangiocarcinoma, adjuvant GemCis did not improve survival outcomes compared with capecitabine.

Prognostic significance of extranodal extension of nodal metastasis in adenocarcinoma of the ampulla of Vater.

Although nodal metastasis (NM) is an important prognostic factor of ampullary adenocarcinoma, the prognostic implication of extranodal extension (ENE) is not well characterized. NM with ENE status was investigated in 279 surgically resected ampullary adenocarcinoma patients and compared with other clinicopathologic factors, including overall survival (OS) and recurrence-free survival (RFS). Expression of epithelial-mesenchymal transition (EMT) markers, including E-cadherin, Twist, and Snail, was assessed in a subset of the cohort. NM was observed in 94 cases (33.7%), of which ENE was observed in 32 cases (34%). NM with ENE was more frequently associated with tumors with poor differentiation than NM without ENE (P = .017). The 5-year OS and RFS rates of patients with NM and ENE was significantly worse (13.0% and 6.3%) than those with NM without ENE (37.7% and 21.4%) and those without NM (57.6% and 50.2%, respectively; P < .001). When pN category was matched, the OS and RFS was worse in patients with ENE than in those without ENE (P < .05). Moreover, the expression of E-cadherin and Twist was significantly different between NM areas with and without ENE (all, P < .001). Since ENE was associated with poorly differentiated ampullary adenocarcinomas and showed different expression of EMT markers, EMT could be a possible mechanism of ENE. Ampullary adenocarcinoma patients with ENE had worse OS and RFS than those without ENE. Therefore, evaluation of ENE can provide additional survival information for patients with surgically resected ampullary carcinoma.