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.

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.

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 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 were administered in 167 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 (HR 3.11, 95% CI 1.73-5.58, P <0.001) based on cut-off value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels <37 IU/L (median survival; 35.5 vs. 20.9 mo, P <0.001) and CA19-9 levels ≥37 IU/L (median survival; 34.3 vs. 17.8 mo, P =0.03). In patients suspected to be Lewis antigen negative, 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.

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.

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.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

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.

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.

Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA.

Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX.

PURPOSE: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. RESULTS: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). CONCLUSION: Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Laparoscopic versus open pancreaticoduodenectomy with major vein resection for pancreatic head cancer.

BACKGROUND/PURPOSE: Laparoscopic pancreaticoduodenectomy (PD) with major vein resection is a challenging procedure. Herein, we evaluated the feasibility and safety of laparoscopic vein resection in pancreatic head cancer with portal vein/superior mesenteric vein (PV/SMV) invasion, and compared the survival rate following laparoscopic surgery with that following open surgery. METHODS: We retrospectively reviewed the electronic medical records of all patients with pancreatic head cancer who underwent surgery performed by a single surgeon from January 2015 to December 2017. Kaplan-Meier curves were plotted to compare the disease-free survival, while Cox-proportional hazard models were used to analyze prognostic factors for survival. RESULTS: Among 76 patients, 63 underwent open PD and 13 underwent laparoscopic PD with PV/SMV resection. There was no significant difference in the rate of complications, including portal vein stenosis and portal vein thrombus, recurrence of tumors, or pathological outcomes after surgery between the groups. There was also no significant difference in disease-free survival (p = .803) between the two groups. Additionally, the surgical method was not an independent prognostic factor for disease-free survival. CONCLUSIONS: Laparoscopic PD with major vein resection can be feasibly performed in select patients with abutment and focal narrowing of the PV/SMV in pancreatic head cancer.

Robotic versus laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: A propensity score-matched analysis.

BACKGROUND: Minimally invasive surgery is becoming increasingly popular in the field of pancreatic surgery. However, there are few studies of robotic distal pancreatectomy (RDP) for pancreatic ductal adenocarcinoma (PDAC). This study aimed to investigate the efficacy and feasibility of RDP for PDAC. METHODS: Patients who underwent RDP or laparoscopic distal pancreatectomy (LDP) for PDAC between January 2015 and September 2020 were reviewed. Propensity score matching analyses were performed. RESULTS: Of the 335 patients included in the study, 24 underwent RDP and 311 underwent LDP. A total of 21 RDP patients were matched 1:1 with LDP patients. RDP was associated with longer operative time (209.7 vs. 163.2 min; P = 0.003), lower open conversion rate (0% vs. 4.8%; P < 0.001), higher cost (15 722 vs. 12 699 dollars; P = 0.003), and a higher rate of achievement of an R0 resection margin (90.5% vs. 61.9%; P = 0.042). However, postoperative pancreatic fistula grade B or C showed no significant inter-group difference (9.5% vs. 9.5%). The median disease-free survival (34.5 vs. 17.3 months; P = 0.588) and overall survival (37.7 vs. 21.9 months; P = 0.171) were comparable between the groups. CONCLUSIONS: RDP is associated with longer operative time, a higher cost of surgery, and a higher likelihood of achieving R0 margins than LDP.

Extranodal extension influences prognosis in pancreatic head cancer: A retrospective cohort study.

BACKGROUND: Extranodal extension (ENE) is an established prognostic factor in several gastrointestinal cancers. However, the prognostic impact remains unclear. Here, we investigated the prognostic implications of ENE in patients with surgically resected pancreatic cancer. METHODS: We retrospectively reviewed 476 surgically resected pancreatic head cancer patients who consecutively underwent upfront pancreaticoduodenectomy for pathologically confirmed pancreatic ductal adenocarcinoma between January 2009 and December 2013. We compared the disease-free survival (DFS) rates of the patients according to ENE status. RESULTS: Among the 476 patients, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; LN+/ENE-, 7 months; LN+/ENE+, 6 months; P < .001). In addition, even in the same N stage, patients with ENE had lower DFS rates than those without ENE (N0, 13 months; N1/ENE- 8 months; N1/ENE+, 7 months; N2/ENE-, 7 months; N2/ENE+, 4 months, P < .001). However, there was no significant difference in survival rates between patients in the N1/ENE+ group and those in the N2/ENE- group. Additionally, ENE was an independent prognostic factor for pancreatic cancer. CONCLUSIONS: Extranodal extension significantly predicted a poor prognosis among patients with pancreatic head cancer, especially those with nodal metastasis. Therefore, ENE should be considered a prognostic factor in future editions of the staging system.

Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study.

BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255). CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Mixed adenoneuroendocrine carcinoma of the ampulla of Vater: Three case reports and a literature review.

Mixed adenoneuroendocrine carcinoma is defined as a tumor with a mixture of adenocarcinoma components and neuroendocrine neoplasm components. Each of these two components of mixed adenoneuroendocrine carcinoma accounts for at least 30% of all tumors. Mixed adenoneuroendocrine carcinoma might be located in the ampulla of Vater, a very rare location compared to other organs. Thus, its treatment and prognosis plans have not been established yet. We report three cases of mixed adenoneuroendocrine carcinoma occurring in the ampulla of Vater. Each patient had a different clinical course. In general, difficulty in preoperative diagnosis, risk of early recurrence, and poor disease course were main hallmarks of mixed adenoneuroendocrine carcinoma arising from the ampulla of Vater. However, one patient in this case report survived although she did not receive adjuvant chemotherapy due to her old age. Therefore, it is important to establish a careful treatment strategy for mixed adenoneuroendocrine carcinoma arising from the ampulla of Vater.

Effect of resection margin status on recurrence pattern and survival in distal pancreatectomy for left-sided pancreatic ductal adenocarcinoma.

BACKGROUND: The association of resection margin status with recurrence and survival after pancreatectomy for pancreas ductal adenocarcinoma (PDAC) remains controversial. The aim of this study was to identify the effect of R1 resection on recurrence pattern and survival after distal pancreatectomy for left-sided PDAC. METHODS: Patients who underwent distal pancreatectomy for PDAC at two high-volume institutions between January 2010 and December 2017 were retrospectively reviewed. Perioperative characteristics, pathological outcomes, recurrence pattern, and survival data were collected to compare R0 resection and R1 resection. RESULTS: Among 558 patients who underwent distal pancreatectomy for PDAC, 158 patients (28.3%) showed R1 resection margin. R1 patients were associated with large tumor size (3.3 cm vs. 3.7 cm, p = .006) and lower number of positive lymph nodes (1.3 vs. 2.0, p = .001). Median overall survival (37.3 months vs. 20.1 months, p < .001) and recurrence-free survival (14.6 months vs. 6.9 months, p < .001) significantly differed between the R0 and R1 groups. Disease recurrence patterns were not statistically different between the two groups (p = .182). Among the recurrence patterns, peritoneal carcinomatosis had the shortest recurrence-free survival (5.6 months, p < .05) and overall survival (13.6 months, p < .05) compared with all other recurrence patterns. CONCLUSIONS: R1 resection margin after distal pancreatectomy was associated with poor survival and early recurrence. There is no significant difference in recurrence pattern between R0 and R1. Among the recurrence patterns, peritoneal carcinomatosis showed the worst prognosis.

Comparison of EUS-guided ablation and surgical resection for nonfunctioning small pancreatic neuroendocrine tumors: a propensity score-matching study.

BACKGROUND AND AIMS: Treatment strategies for small pancreatic neuroendocrine tumors (PNETs) <2 cm in size are still under debate. The feasibility and safety of EUS-guided ethanol ablation (EUS-EA) have been demonstrated. However, sample sizes in previous studies were small with no comparative studies on surgery. Therefore, we aimed to compare the safety and long-term outcomes of EUS-EA with those of surgery for the management of nonfunctioning small PNETs. METHODS: We retrospectively reviewed patients with PNETs who were managed by EUS-EA (from 2011 to 2018) and surgery (from 2000 to 2018) at Asan Medical Center. Propensity score matching (PSM) was performed to increase comparability. The primary outcome was early and late major adverse events (Clavien-Dindo grade ≥III) after treatment. Secondary outcomes were 10-year overall (OS) and disease-specific survival (DSS) rates, length of hospital stay, and development of endocrine pancreatic insufficiency. RESULTS: Of all patients, 97 and 188 patients were included in the EUS-EA and surgery groups, respectively. PSM created 89 matched pairs. EUS-EA was associated with a significantly lower rate of early major adverse events (0% vs 11.2%, P = .003). Late major adverse events occurred more frequently after surgery, with no significant difference between groups (3.4% vs 10.1%, P = .07). Both treatment modalities showed comparable 10-year OS and DSS rates. The length of hospital stay was significantly shorter in the EUS-EA group (4 days vs 14.1 days, P < .001), and endocrine pancreatic insufficiency was less common after EUS-EA than after surgery (33.3% vs 48.6%, P = .121). CONCLUSIONS: EUS-EA had fewer adverse events and a shorter hospital stay with similar OS and DSS rates compared with surgery, suggesting that EUS-EA may be a preferred alternative to surgical resection in selected patients with nonfunctioning small PNETs.