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.

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.

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.

Systematic review on surveillance for non-resected branch-duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The management of branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) varies in existing guidelines. This study investigated the optimal surveillance protocol and safe discontinuation of surveillance considering natural history in non-resected IPMN, by systematically reviewing the published literature. METHODS: This review was guided by PRISMA. Research questions were framed in PICO format "CQ1-1: Is size criteria helpful to determine surveillance period? CQ1-2: How often should surveillance be carried out? CQ1-3: When should surveillance be discontinued? CQ1-4: Is nomogram predicting malignancy useful during surveillance?". PubMed was searched from January-April 2022. RESULTS: The search generated 2373 citations. After screening, 83 articles were included. Among them, 33 studies were identified for CQ1-1, 19 for CQ1-2, 26 for CQ1-3 and 12 for CQ1-4. Cysts <1.5 or 2 cm without worrisome features (WF) were described as more indolent, and most studies advised an initial period of surveillance. The median growth rate of cysts <2 cm ranged from 0.23 to 0.6 mm/year. Patients with cysts <2 cm showing no morphological changes and no WF after 5-years of surveillance have minimal malignancy risk of 0-2%. Two nomograms created with over 1000 patients had AUCs of around 0.8 and appear to be feasible in a real-world practice. CONCLUSIONS: For patients with suspected BD-IPMN <2 cm and no other WF, less frequent surveillance is recommended. Surveillance may be discontinued for cysts that remain stable during 5-year surveillance, with consideration of patient condition and life expectancy. With this updated surveillance strategy, patients with non-worrisome BD-IPMN should expect more streamlined management and decreased healthcare utilization.

Examining neoadjuvant treatment candidates in resectable pancreatic cancer based on tumor-vessel interactions and CA 19-9 levels: a retrospective cohort study.

INTRODUCTION: The applicability of neoadjuvant treatment (NAT) for resectable pancreatic ductal adenocarcinoma (PDAC) has arisen, however, high-level evidence is lacking. This study aimed to explore patient subgroups with high-risk resectable PDAC for selecting candidates who may benefit from NAT. METHODS: The 1132 patients with resectable or borderline resectable PDAC who underwent surgery between 2007 and 2021 were retrospectively reviewed. Patients with resectable PDAC without contact of major vessels (R-no contact) ( n =651), with contact of portal vein or superior mesenteric vein (PV/SMV) ≤180° (R-contact) ( n =306), and borderline resectable PDAC without arterial involvement (BR-V) ( n =175) were analyzed. RESULTS: The mean age was 64.3±9.8 years, and 647 patients (57.2%) were male. The median follow-up was 26 months in the entire cohort. Patients with resectable PDAC without vascular contact had the most improved overall survival (OS) (median; 31.5 months). OS did not significantly differ between NAT and upfront surgery in the entire resectable PDAC cohort. However, in R-contact group, NAT showed significantly improved OS compared to upfront surgery (33 vs. 23 months). Neoadjuvant FOLFIRINOX was showed a better OS than gemcitabine-based regimens in patients who underwent NAT (34 vs. 24 months). NAT was associated with a better survival in the patients with CA 19-9 level ≥150 U/ml, only when the tumor has PV/SMV contact in resectable disease (40 vs. 19 months, P =0.001). CONCLUSIONS: NAT can be considered as an effective treatment in patients with resectable PDAC, particularly when the tumor is in contact with PV/SMV and CA 19-9 ≥150 U/ml.

Long-Term Outcome of Proximal Gastrectomy for Upper-Third Advanced Gastric and Siewert Type II Esophagogastric Junction Cancer Compared With Total Gastrectomy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate the oncologic long-term safety of proximal gastrectomy for upper-third advanced gastric cancer (AGC) and Siewert type II esophagogastric junction (EGJ) cancer. METHODS: The study enrolled patients who underwent proximal gastrectomy (PG) or total gastrectomy (TG) with standard lymph node (LN) dissection for pathologically proven upper-third AGC and EGJ cancers between January 2007 and December 2018. Propensity score-matching with a 1:1 ratio was performed to reduce the influence of confounding variables such as age, sex, tumor size, T stage, N stage, and tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis was performed to analyze oncologic outcome. The prognostic factors of recurrence-free survival (RFS) were analyzed using the Cox proportional hazard analysis. RESULTS: Of the 713 enrolled patients in this study, 60 received PG and 653 received TG. Propensity score-matching yielded 60 patients for each group. The overall survival rates were 61.7 % in the PG group and 68.3 % in the TG group (p = 0.676). The RFS was 86.7 % in the PG group and 83.3 % in the TG group (p = 0.634). The PG group showed eight recurrences (1 anastomosis site, 1 paraaortic LN, 1 liver, 1 spleen, 1 lung, 1 splenic hilar LN, and 2 remnant stomachs). In the multivariate analysis, the operation method was not identified as a prognostic factor of tumor recurrence. CONCLUSION: The patients who underwent PG had a long-term oncologic outcome similar to that for the patients who underwent TG for upper-third AGC and EGJ cancer.

Optimal Surveillance Interval of Branch Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas.

Importance: Despite the increasing prevalence of intraductal papillary mucinous neoplasm (IPMN), data on the growth and malignant conversion rates based on long-term surveillance cohorts are limited. Many international guidelines recommend surveillance for benign lesions, but the optimal interval and duration are unclear. Objective: To determine the optimal surveillance protocol for IPMN and propose which patients may be exempted from surveillance. Design, Setting, and Participants: This large-scale, international cohort study examined data of 3825 patients with IPMN treated at 5 tertiary pancreatic centers. Included were patients with branch duct (BD) IPMN who underwent surveillance or surgery between January 1, 1988, and December 31, 2020. After a thorough review, 3656 patients were included in the analytic sample. Changes in cyst size, worrisome features or high-risk stigmata, and malignant conversion rates were assessed. Patients who underwent surveillance over 5 years were compared to suggest discontinuation of surveillance protocol. Clinical data collection began in January 1, 2021, and the mean (SD) follow-up duration was 84 (47.7) months. The data analysis was performed from May 2, 2022, through September 14, 2022. Exposure: The patients with BD-IPMN were followed up based on International Association of Pancreatology guidelines. Patients with suspicious malignant neoplasms during surveillance underwent surgical resection. Main Outcome and Measures: The main outcome of this study was the optimal follow-up interval and duration of BD-IPMN surveillance. The association among cyst size, growth rate, and progression was examined using descriptive statistics. Results: Of the 3656 patients with BD-IPMN in the analytic sample (1973 [54.0%] female; mean [SD] age, 63.7 [10.2] years), 172 (4.7%) were confirmed to have malignant lesions through surgery. Considering cyst growth, the time to develop worrisome features, and malignant conversion, a 1.5-, 1-, and 0.5-year surveillance interval could be optimal for cysts smaller than 20 mm, 20 to 30 mm, and 30 mm, respectively, after initial short-term (6-month) follow-up. Patients with cysts smaller than 20 mm, no worrisome features, and no growth during 5-year surveillance did not show malignant conversion after 5 years of follow-up and had time to progression of greater than 10 years. Conclusions: These findings suggest that BD-IPMN surveillance may depend on the size of the cyst and morphologic changes at the initial 6-month follow-up. For patients with small cysts (ie, <20 mm) with no morphologic changes during the initial 5-year surveillance period, surveillance may be discontinued for those unfit for surgery or who have a limited life expectancy of 10 years or less.

Efficacy of local treatment for isolated liver metastasis after pancreatectomy in pancreatic ductal adenocarcinoma: A propensity score-matched analysis.

BACKGROUND: Although attempts of local treatment for isolated liver recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) have increased, the efficacy remains unclear. Therefore, we aimed to evaluate the effect of local treatment for recurrent liver lesions after pancreatectomy on the survival of patients with PDAC. METHODS: Patients who were diagnosed with isolated liver recurrence after pancreatectomy at a high-volume center were included. We classified these patients based on the treatment options after recurrence and performed propensity score matching to minimize confounding. RESULTS: Median with interquartile range survival after recurrence was significantly longer for patients who underwent local treatment for recurrent liver lesions plus chemotherapy (22.0 [17.0-29.0] months) than those treated with chemotherapy alone (13.0 [7.0-21.0] months, p = .027). In multivariate analysis, not only local treatment for recurrent liver lesions plus chemotherapy (hazard ratio [95% confidence interval], 0.55 [0.32-0.94]; p = .030) but also indicators for systemically controlled tumor such as late recurrence (0.57 [0.35-0.92]; p = .021), chemotherapy for ≥6 months (0.25 [0.15-0.42]; p < .001), and disease control by chemotherapy (0.36 [0.22-0.60]; p < .001) were identified as favorable prognostic factors. CONCLUSIONS: PDAC patients with stable recurrent liver lesions should be considered a candidate for local treatment.

In Neoadjuvant FOLFIRINOX Chemotherapy for Pancreatic Ductal Adenocarcinoma, Which Response is the More Reliable Indicator for Prognosis, Radiologic or Biochemical?

BACKGROUND: In this era of increasing neoadjuvant chemotherapy, methods for evaluating responses to neoadjuvant chemotherapy are still diverse among institutions. Additionally, the efficacy of adjuvant chemotherapy for patients undergoing neoadjuvant chemotherapy remains unclear. Therefore, this retrospective study was performed to evaluate the effectiveness of methods for assessing response to neoadjuvant chemotherapy and the need for adjuvant chemotherapy in treating patients with non-metastatic pancreatic ductal adenocarcinoma. METHODS: The study identified 150 patients who underwent neoadjuvant FOLFIRINOX chemotherapy followed by curative-intent pancreatectomy. The patients were stratified by biochemical response based on the normalization of carbohydrate antigen 19-9 and by radiologic response based on size change at imaging. RESULTS: The patients were classified into the following three groups based on their response to neoadjuvant chemotherapy and prognosis: biochemical responders (BR+), radiology-only responders (BR-/RR+), and non-responders (BR-/RR-). The 3-year overall survival rate was higher for BR+ (71.0%) than for BR-/RR+ (53.6%) or BR-/RR- (33.1%) (P < 0.001). Response to neoadjuvant chemotherapy also was identified as a significant risk factor for recurrence in a comparison between BR-/RR+ and BR+ (hazard ratio [HR], 2.15; 95% confidence interval [CI] 1.19-3.88; P = 0.011) and BR-/RR- (HR, 3.82; 95% CI 2.41-6.08; P < 0.001). Additionally, regardless of the response to neoadjuvant chemotherapy, patients who completed adjuvant chemotherapy had a significantly higher 3-year overall survival rate than those who did not. CONCLUSIONS: This response evaluation criterion for neoadjuvant chemotherapy is feasible and can significantly predict prognosis. Additionally, completion of adjuvant chemotherapy could be helpful to patients who undergo neoadjuvant chemotherapy regardless of their response to neoadjuvant chemotherapy.

Inadequacy of the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system for invasive carcinoma associated with premalignant lesions in the pancreas: an analysis using the National Cancer Database.

BACKGROUND: Invasive carcinomas arising from premalignant lesions are currently staged by the same criteria as conventional pancreatic ductal adenocarcinoma. METHODS: Clinicopathologic information and survival data were extracted through a thorough search of histology codes from National Cancer Database (2006-2016). A total of 723 patients with invasive intraductal papillary mucinous neoplasm and mucinous cystic neoplasm were analyzed. RESULTS: The median age was 67 years, and 351 patients (48.5%) were male. There were 212 (29.3%), 232 (32.1%), 272 (37.6%), and 7 (1.0%) patients with T1, T2, T3, and T4 classification. Extrapancreatic extension (EPE) was present in 284 (39.3%). Age (HR = 1.504, 95% CI 1.196-1.891), R1 or R2 resection (HR = 1.585, 95% CI 1.175-2.140), and EPE (HR = 1.598, 95% CI 1.209-2.113) were independent prognostic factors for overall survival. Size criteria did not significantly affect survival. The median survival was 115.9 months for patients without EPE, compared to 34.2 months for those with EPE. EPE discriminated survival better than tumor size. DISCUSSION: The T classification of the eighth edition AJCC staging system is not adequate for invasive carcinomas associated with premalignant lesions of the pancreas. They merit a separate, dedicated staging system that uses appropriate prognostic factors.

Oncologic safety of robotic extended cholecystectomy for gallbladder cancer.

BACKGROUND: Although laparoscopic cholecystectomy is applicable for the treatment of early gallbladder cancer (GBC), minimally invasive surgery is not widely used for advanced GBC. This is because advanced GBCs necessitate complicated surgical techniques, including lymph node dissection and liver resection. Robotic extended cholecystectomy (REC) is thought to overcome the limitations of laparoscopic surgery, but oncological safety studies are lacking. Therefore, in this study, we aimed to evaluate the oncologic outcomes of REC compared with those of open extended cholecystectomy (OEC). METHODS: A total of 125 patients, who underwent extended cholecystectomy for GBC with tentative T2 or higher stage between 2018 and 2021, were included and stratified by surgical methods. To minimize the confounding factors, 1:1 propensity-score matching was performed between the patients who underwent REC and those who underwent OEC. RESULTS: Regarding short-term outcomes, the REC group showed significantly lower estimated blood loss (382.7 vs. 717.2 mL, P = 0.020) and shorter hospital stay (6.9 vs. 8.5 days, P = 0.042) than the OEC group. In addition, the REC group had significantly lower subjective pain scores than the OEC group from the day of surgery through the 5th postoperative day (P = 0.006). Regarding long-term outcomes, there were no significant differences in the 3-year [5-year] overall survival (OS) and disease-free survival (DFS) rates between the REC group [OS, 92.3% (92.3%); DFS, 84.6% (72.5%)] and the OEC group [OS, 96.8% (96.8%); DFS, 78.2% (78.2%)] (P = 0.807 for OS and 0.991 for DFS). CONCLUSIONS: In this study, REC showed superior short-term outcomes to OEC and no difference in long-term survival outcomes. Additionally, REC was superior to OEC in terms of postoperative pain. Therefore, REC may be a feasible option with early recovery compared with OEC for patients with advanced GBC.

Reconsidering the absence of extrapancreatic extension in T staging for pancreatic adenocarcinoma in the AJCC (8th ed) Staging Manual using the National Cancer Database.

PURPOSE: Although the concept of extrapancreatic extension (EPEx) was removed in the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system, several studies have supported the prognostic significance of EPEx. This study aimed to investigate the significance of EPEx in pancreatic ductal adenocarcinoma (PDAC) using the National Cancer Database (NCDB). METHODS: Data of patients who underwent resection for PDAC between 2006 and 2016 were extracted and analyzed from the NCDB. Cases arising from premalignant lesions, those with metastases, and those treated with neoadjuvant therapy were excluded. RESULTS: Among 37,634 patients, the median overall survival was 23 months and the 5-year survival rate was 22.7%. The EPEx prevalence was the lowest for T1 stage (63.2%) and increased with each T-stage (T2:83.4%, T3:85.8%). The overall survival was better in EPEx-negative patients than in EPEx-positive patients (median 33.7 vs. 21.5 months; p<0.001). When the T-stages were stratified by EPEx, EPEx-positive patients showed worse survival in all T-stages than EPEx-negative patients. Survival was comparable between T1 EPEx-positive and T2 or T3 EPEx-negative patients (p=0.088 and p=0.178, respectively). Furthermore, T2 and T3 EPEx-negative patients had similar survival to each other (p=0.877), and distinctly superior survival compared to T2 and T3 EPEx-positive patients (p<0.001). CONCLUSIONS: EPEx was an important prognostic factor in the overall cohort and in differentiating between T stages. This study strongly suggests that staging systems should reinstate EPEx and apply it to all T-stages, especially in T1, where EPEx was absent in 36% of patients.

The role of local treatment including pancreatectomy for pancreatic ductal adenocarcinoma patients with isolated synchronous liver metastasis: Propensity score-matched analyses.

BACKGROUND: In an era of more effective chemotherapy for pancreatic ductal adenocarcinoma (PDAC), the paradigm of local treatment is changing. However, the efficacy of local treatment in patients with isolated liver metastasis remains unclear. Therefore, we aimed to evaluate the effectiveness of pancreatectomy ± local treatment for metastasis (cytoreductive surgery) in PDAC patients with isolated synchronous liver metastasis. METHODS: In total, 239 patients with isolated liver metastasis were extracted from Seoul National University Hospital (SNUH). For comparison, another 12 637 patients were extracted from the National Cancer Database (NCDB). Propensity score matching was performed to minimize confounding in both cohorts. Survival analyses stratified by the treatment delivered were performed using Kaplan-Meier estimates and log-rank tests. RESULTS: In the SNUH cohort, the median (interquartile range) survival was 20.5 (13.0-42.0) months for patients who underwent cytoreductive surgery plus chemotherapy versus 12.0 (10.0-18.0) months for those who received chemotherapy alone (P < .001). With the NCDB cohort, the median (interquartile range) survival was 15.6 (8.9-31.2) months for patients who underwent cytoreductive surgery plus chemotherapy versus 7.4 (3.4-13.2) months for those who received chemotherapy alone (P < .001). CONCLUSION: Patients with isolated synchronous liver metastasis should be considered for cytoreductive surgery in addition to effective chemotherapy.

Collective review of pancreatic carcinosarcoma, a very rare pancreatic malignancy.

Pancreatic carcinosarcoma is a very rare malignancy with a poor prognosis. Because of these characteristics, a treatment strategy for it has not been established yet. The aim of this study was to establish a therapeutic strategy for pancreatic carcinosarcoma. We reviewed data of a 65-year-old female patient who was diagnosed with pancreatic carcinosarcoma through endoscopic ultrasound-guided fine needle aspiration biopsy before surgery. For literature review, we searched PubMed using terms of "Pancreatic" or "Pancreas" and "carcinosarcoma" or "carcinosarcomatous". The patient received 11 cycles of neoadjuvant treatment with leucovorin, fluorouracil, irinotecan, oxaliplatin and pembrolizumab because the tumor was borderline resectable. She underwent stereotactic ablative body radiotherapy (SABR) with 35 Gy in 5 fractions, followed by robotic pylorus-preserving pancreaticoduodenectomy. After surgery, the patient received adjuvant chemotherapy in the same regimen as before surgery. She is alive without any recurrence. Among 48 patients within 33 available papers, the median survival time was 15 months. The survival rate of patients who received adjuvant chemotherapy tended to be higher than that of those who did not receive adjuvant chemotherapy, although the difference was not statistically significant (median survival, 47 vs. 15 months; p = 0.485). Three patients who received neoadjuvant chemotherapy had a survival period of 13-23.5 months. Surgery with lymphadenectomy, adjuvant therapy, and neoadjuvant therapy are thought to help improve survival outcomes. Modern treatment approaches for conventional pancreatic ductal adenocarcinoma could be applied to pancreatic carcinosarcoma.

Oncological outcome of proximal and middle extrahepatic bile duct cancer according to surgical extent (Is hilar resection oncologically acceptable in proximal and middle extrahepatic bile duct cancer?).

BACKGROUND: For proximal to middle bile duct cancer, it is controversial whether bile duct resection alone is sufficient, or whether hepatic or pancreatic resection should be accompanied by initial planning. This study aimed to determine the optimal surgical extent based on oncological outcomes in patients with proximal to middle bile duct cancer. METHODS: Patients who underwent surgery for proximal to middle extrahepatic bile duct cancer, hilar resection, or combined resection of other organs were included. Clinicopathological characteristics and survival analyses were compared according to operation type. RESULTS: Among 156 patients in total, R0 rate was 56.7% for hilar resection and 82.7% for other organ resection. Although hilar resection was associated with shorter hospital stay and fewer overall complications, operation type did not affect overall survival (p = 0.259) and disease-free-survival (p = 0.774). Overall survival differed according to R status (5YSR 49.8 vs. 27.1%; p = 0.012). CONCLUSION: In proximal to middle extrahepatic bile duct cancer, surgery should be tailored to achieve R0 resection according to the extent of the disease rather than uniformly resecting extensively with other organ resections. Hilar resection could be selected if R0 resection is feasible, considering the lower morbidity with similar long-term survival.

Parallel Analysis of Pre- and Postoperative Circulating Tumor DNA and Matched Tumor Tissues in Resectable Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for early tumor detection and minimal residual disease (MRD) assessment in early-stage cancer, but quantifying minute amounts of ctDNA is challenging and well-designed studies on ctDNA in early-stage cancer are still lacking. Here, we adapted a sensitive next-generation sequencing (NGS) technology and performed parallel analysis of pre- and postoperative ctDNA and matched tumor tissues in a prospective cohort of patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: In total, 70 consecutive patients undergoing curative resection for resectable PDAC were enrolled. We performed integrated digital error suppression-enhanced cancer personalized profiling by deep sequencing NGS of triple-matched samples (pre/postoperative plasma cell-free DNA [cfDNA], tumor tissue, and genomic DNA) targeting 77 genes. RESULTS: Preoperative ctDNA was detected in 37.7% of the evaluable patients, with a median variant allele frequency of 0.09%. Twelve additional oncogenic mutations were detected exclusively in preoperative ctDNA but not in tissue. When quantitative concentrations of ctDNA were estimated in haploid genome equivalents per milliliter (hGE/mL), the risk of early recurrence was high in patients with postoperative ctDNA >1 hGE/mL. cfDNA variants from 24.5% of patients had features compatible with clonal hematopoiesis. CONCLUSIONS: An optimized NGS approach might add value beyond tissue analysis through the highly sensitive detection of minute amounts of ctDNA in resectable PDAC. Postoperative ctDNA concentration could be a tool for MRD assessment. Moreover, parallel analyses of matched tissues and leukocytes might be required to accurately detect clinically relevant ctDNA.

Oncologic Benefits of Neoadjuvant Treatment versus Upfront Surgery in Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant treatment (NAT) followed by surgery is the primary treatment for borderline resectable pancreatic cancer (BRPC). However, there is limited high-level evidence supporting the efficacy of NAT in BRPC. PubMed was searched to identify studies that compared the survival between BRPC patients who underwent NAT and those who underwent upfront surgery (UFS). The overall survival (OS) was compared using intention-to-treat (ITT) analysis. A total of 1204 publications were identified, and 19 publications with 21 data sets (2906 patients; NAT, 1516; UFS, 1390) were analyzed. Two randomized controlled trials and two prospective studies were included. Thirteen studies performed an ITT analysis, while six presented the data of resected patients. The NAT group had significantly better OS than the UFS group in the ITT analyses (HR: 0.63, 95% CI = 0.53-0.76) and resected patients (HR: 0.68, 95% CI = 0.60-0.78). Neoadjuvant chemotherapy with gemcitabine or S-1 and FOLFIRINOX improved the survival outcomes. Among the resected patients, the R0 resection and node-negativity rates were significantly higher in the NAT group. NAT improved the OS, R0 resection rate, and node-negativity rate compared with UFS. Standardizing treatment regimens based on high-quality evidence is fundamental for developing an optimal protocol.

Can Surgical Resection of Metastatic Lesions Be Beneficial to Pancreatic Ductal Adenocarcinoma Patients with Isolated Lung Metastasis?

In the era of effective chemotherapy on pancreatic ductal adenocarcinoma (PDAC) with distant metastasis, data on the effects of metastatectomy are lacking. So, we investigated the effect of metastatectomy on survival after metastasis in PDAC patients with isolated lung metastasis. This retrospective study analyzed 1342 patients who were histologically diagnosed with PDAC with distant metastasis from January 2007 to December 2018, of which 83 patients had isolated pulmonary metastasis. Additionally, 4263 patients were extracted from the National Cancer Database (NCDB) and analyzed. Log-rank test and Kaplan−Meier survival analysis were used to analyze survival after metastasis. The five-year survival rate was significantly higher in patients who underwent pulmonary metastatectomy than in those who received only chemotherapy or supportive treatment (60.6% vs. 6.2% vs. 0.0%, p < 0.001). A similar trend was observed in the NCDB (two-year survival rate, 27.4% vs. 15.8% vs. 4.7%, p < 0.001). In the multivariate analysis, lung lesion multiplicity (hazard ratio (HR) = 2.004, p = 0.017), metastatectomy (HR = 0.278, p = 0.036), chemotherapy (HR = 0.434, p = 0.024), and chemotherapy cycles (HR = 0.300, p < 0.001) had significant effects on survival. Metastatectomy with primary pancreatic lesions is recommended with effective chemotherapy in PDAC patients with isolated lung metastasis.