Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

The Role of Pretreatment Serum Interleukin 6 in Predicting Short-Term Mortality in Patients with Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77 advanced PDAC patients via ELISA, the research determined optimal cutoff values for IL-6 and the IL-6:sIL-6Rα ratio using receiver operating characteristic curve analysis, which then facilitated the division of patients into low and high IL-6 groups, showing significantly different survival outcomes. Notably, high IL-6 levels correlated with adverse features such as poorly differentiated histology, higher tumor burden, and low albumin levels, indicating a stronger likelihood of poorer prognosis. With a median follow-up of 9.28 months, patients with lower IL-6 levels experienced markedly better median overall survival and progression-free survival than those with higher levels, underscoring IL-6's role in predicting disease prognosis. Multivariate analysis further confirmed IL-6 levels, alongside older age, and elevated neutrophil-to-lymphocyte ratio, as predictors of worse outcomes, suggesting that IL-6 could be a critical biomarker for tailoring treatment strategies in advanced PDAC, warranting further investigation into its role in systemic inflammation and the tumor microenvironment.

Accuracy of preoperative T2 gallbladder tumor localization and the adequate surgical resection.

INTRODUCTION: The agreement between the radiologic and histopathologic tumor locations in T2 gallbladder cancer is critical. There is no consensus regarding the extent of curative resection by tumor locations. METHODS: Between January 2010 and December 2019, a consecutive series of 118 patients with pathological T2 gallbladder cancer who underwent surgery were retrospectively analyzed in terms of the accordance between radiologic and histopathologic tumor locations, the extents of hepatic resection and the numbers of harvested lymph nodes. Radical resection was defined as liver resection with harvesting of at least four lymph nodes. RESULTS: The accuracy of preoperative tumor localization was only 68%. After radical resection, the 5-year overall survival (OS) was 59.4%; after nonradical resection, the figure was 46.1% (p = 0.092). In subanalyses, the 5-year OS was marginally better for patients who underwent liver resection or from whom at least four lymph nodes were harvested than those who did not undergo liver resection or from whom three or fewer lymph nodes were harvested (58.2% vs. 39.4%, p = 0.072; 59.9% vs. 50.0%, p = 0.072, respectively). In patients with peritoneal side tumor, the 5-year OSs of those who did and did not undergo liver resection were 67% and 41.2%, respectively (p = 0.028). In multivariate analysis, perineural invasion and radical resection were independently prognostic of OS. CONCLUSION: The accuracy of preoperative tumor localization was 68%. Hepatic resection, lymph node dissection harvesting of at least four lymph nodes are required for curative resection for gallbladder cancer, regardless of tumor location.

Pioneering PGC-1α-boosted secretome: a novel approach to combating liver fibrosis.

Purpose: Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. Methods: Upon achieving a cellular confluence of 70%-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models. Results: In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec-treated group, along with reduced collagen type 1A expression (a profibrogenic marker). Conclusion: These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

The Usefulness of High-Magnification Loupe for Reducing Biliary Complications After Liver Transplantation.

BACKGROUND: Despite advances in surgical techniques, biliary complications are still considered to be a technical "Achilles' heel" of liver transplantation (LT). The purpose of this study was to evaluate the effect of loupe magnification in reducing biliary complications after LT. MATERIALS AND METHODS: From April 2017 to February 2022, LT was performed on 307 patients in our center. Among them, except for 3 patients who underwent hepaticojejunostomy, 304 adult patients with LT were enrolled. They were divided into 3 groups according to the loupe magnification: 2.5 times (×2.5 group, n = 105), 3.5 times (×3.5 group, n = 95), and 5.0 times (×5.0 group, n = 105). RESULTS: Biliary complications occurred in 63 (20.7%) patients. Anastomosis site leakage occurred in 37 patients (12.2%), and stricture occurred in 52 patients (17.1%). Anastomosis site leakage occurred in 15 patients (14.3%) in the ×2.5 group, 15 patients (16.0%) in the ×3.5 group, and 7 patients (6.7%) in the ×5.0 group (P = .097). Biliary stricture occurred in 26 patients (24.8%) in the ×2.5 group, 15 patients (16.0%) in the ×3.5 group, and 11 patients (10.5%) in the ×5.0 group (P = .021). Total biliary complications occurred in 31 patients (29.5%) in the ×2.5 group, 19 patients in the ×3.5 group (20.2%), and 13 patients in the ×5.0 group (12.4%) (P = .009). CONCLUSION: The use of a high magnification loupe can reduce biliary complications in liver transplantation. Further large-scale analyses of clinical data or randomized controlled trials are required to support this study.

Effects of Livact Granule on Liver Function Recovery After Donor Right Hemi-Hepatectomy.

BACKGROUND: Living donor liver transplantation (LDLT) is currently widespread due to organ shortage. Because LDLT is a high-risk surgery for the donor, donor safety becomes an important issue. In adult LDLT, right lobe grafts are usually used, posing a greater risk to the donor than a left lobe. Reports have demonstrated that branched-chain amino acids help patients recover after hepatectomy. This study aimed to evaluate the effect of Livact granule on donor safety and recovery. METHODS: From January 2016 to December 2021, LDLT was performed on 258 patients at our center. Among them, 148 were in the non-Livact group, and 110 were in the Livact group. Six of 110 patients in the Livact group stopped taking the granules due to nausea and vomiting, leaving 104 patients in the Livact group to be analyzed. Various preoperative and postoperative factors were evaluated to assess donor safety and recovery. RESULTS: In the non-Livact group, the mean donor age was 35.8; in the Livact group, it was 40. There were no differences between the 2 groups in preoperative liver function tests and no difference in future liver remnant or steatosis. There was no difference in total bilirubin level between the 2 groups at 5 days postoperatively; however, in the Livact group, the prothrombin time international normalized ratio was lower, and albumin was higher. The days taken for total bilirubin to normalize were the same in both groups, but fewer days were needed for Livact to realize an international normalized ratio. More patients in the non-Livact group were discharged with the Jackson-Pratt drain because the drainage did not decrease. CONCLUSIONS: In donor right hepatectomy patients, taking Livact granules and branched-chain amino acids helps donor recovery. For donor safety, administration of Livact granules during the perioperative period should be considered.

Proposal of a Network System to Solve the Problem of Small Volume in Liver Transplantation; Catholic Medical Center Network.

INTRODUCTION: Liver transplantation (LT) is a complex and demanding procedure associated with significant perioperative challenges and risks. Concerns have arisen regarding LT outcomes in low-volume centers. We implemented an integrated training and surgical team network to address these concerns within the Catholic Medical Center (CMC) network. This study presents a comprehensive review of our 9-year LT experience within the CMC medical network. METHOD: A retrospective study of LT procedures conducted between January 2013 and August 2021 in 6 CMC-affiliated hospitals was performed. One center was categorized as a high-volume center, conducting over 60 cases annually, and the remaining 5 were considered small-volume centers. The primary endpoints assessed were 1-year and 5-year survival rates. RESULTS: A total of 793 LTs were performed during the study period. The high-volume center performed 411 living donor LT (LDLT) cases and 127 deceased donor LT (DDLT) cases. Also, 146 LDLT cases and 109 DDLT cases were performed in 5 small-volume centers. One-year and 5-year patient survival for LDLT recipients was 88.3% and 78.8% in the high-volume center and 85.6% and 80.6% in the low-volume center. Five-year survival was not significantly different in small-volume centers (P = .903). For DDLT recipients, 1-year and 5-year patient survival was 80.3% and 70.6% in the high-volume center and 76.1% and 67.6% in the low-volume center. In DDLT cases, 5-year survival was not significantly different in small-volume centers (P = .445). CONCLUSION: In conclusion, comparable outcomes for liver transplantation can be obtained in a small-volume center with a high level of integrated training systems and networks.

Hepatic artery protection using a polyglycolic acid sheet during pancreaticoduodenectomy: A multicenter study.

BACKGROUND: Postpancreatectomy hemorrhage (PPH) is the most feared complication after pancreaticoduodenectomy (PD). The most common cause is erosion of the gastroduodenal artery stump. Preventive measures have been previously reported, but a consensus is lacking. The aim of this study was to analyze the preventive effect of reinforcing the hepatic artery using a polyglycolic acid (PGA) sheet during PD. METHODS: A multicenter retrospective study was performed, collecting data from three tertiary hospitals in Korea. Patients receiving PD from January 2016 to December 2021 were included. The primary endpoint was rate of PPH from the hepatic artery. Arterial reinforcement (AR) was performed by wrapping the artery with Neoveil (Gunze Ltd) and applying fibrin glue. The perioperative data of patients who did not receive AR were compared with data of those who received AR. RESULTS: A total of 904 patients were analyzed. The rate of PPH from the hepatic artery was significantly lower in the AR group. (3.5% vs 0.7%, p = .002) In patients with CR-POPF, the 90 day mortality rate of the AR group was less than half that of the non-AR group (7.2% vs 3.5%, p = .455) Risk factor analysis showed CR-POPF to be an independent risk factor for PPH. Arterial reinforcement was shown to be a strong protective factor for PPH (OR 0.20, 95% CI: 0.05-0.72, p = .014). CONCLUSIONS: AR of the hepatic artery using Neoveil and fibrin glue is a simple method that greatly reduces the rate of PPH after PD.

Histologic subtype-based evaluation of recurrence and survival outcomes in patients with adenocarcinoma of the ampulla of Vater.

Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3-49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04-3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11-3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19-9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23-4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.

What we should consider to facilitate recovery of the hematological profile in all patients after pancreaticoduodenectomy: the role of preoperative intravenous iron treatment.

BACKGROUND: In pancreaticoduodenectomy (PD), the duodenum and upper jejunum responsible for iron absorption are removed, which can lead to massive hemorrhage during surgery and cause iron deficiency anemia after PD. The aim of this study was to evaluate overall changes in hematologic profiles of patients who underwent pancreaticoduodenectomy. Effect of preoperative intravenous iron treatment on recovery of anemia after surgery was also investigated. METHODS: From March 2021 to December 2021, patients who underwent curative PD at our institution due to periampullary lesions were enrolled. They were divided into two groups according to whether or not iron was administered before surgery. In the IV iron group, all patients had been routinely administered with 1000 mg of ferric carboxymaltose intravenously once about 3-7 days before the operation day. Contrarily, patients in the control group did not receive intravenous iron before PD. Changes in hematological profile were measured preoperatively and at 5, 14, and 30 days postoperatively. Clinical results of the two groups were compared and analyzed. Additionally, a subgroup analysis was performed for selected non-anemic patients who had preoperative hemoglobin level of 12.0 g/dl or higher to compare changes in hematologic profiles between the two groups. RESULTS: Thirty patients of the IV iron group and 34 patients of the control group were analyzed. Although no difference was observed in postoperative complications or mortality, hemoglobin and iron levels were recovered significantly faster at two weeks postoperatively in the IV iron group than in the control group. Iron levels were significantly higher in the IV iron group throughout the postoperative period. In subgroup analysis conducted for non-anemic patients, hemoglobin levels were recovered significantly faster and maintained higher in the IV iron group throughout the postoperative period, although baseline levels of hemoglobin were similar between the two groups. In addition, the length of intensive care unit stay was significantly shorter in the IV iron group than in the control group. CONCLUSIONS: Preoperative intravenous iron treatment might be effective in facilitating recovery of hematologic profiles of patients during the recovery period after PD regardless of the presence of preoperative anemia, thus preventing postoperative iron deficiency anemia.

The role of natural killer cell activity as a milestone in oncologic outcome after curative resection of pancreatic adenocarcinoma.

BACKGROUND: The objective of this study was to investigate differences in oncologic outcomes of patients with pancreas cancer according to natural killer cell activity (NKA). METHODS: A total of 118 patients who underwent curative resection for primary pancreas cancer in two hospitals were analyzed. NKA change pattern was analyzed. Difference in disease-free survival or overall survival was investigated by dividing subjects into two groups based on a normal NKA value for each period. RESULTS: NKA value decreased after surgery compared to the value measured at admission. It recovered to normal levels at 5 weeks postoperatively. The low NKA (less than 250 pg/mL) group at admission, 5 weeks postoperatively, and before 1st chemotherapy had significantly poorer disease-free survival than the normal NKA group. In multivariate analysis, NKA values less than 250 pg/mL at admission (odds ratio = 2.267, p = 0.023) and N 1 or N2 category (odds ratio = 2.478, p = 0.023) were significant factors associated with recurrence after curative resection. CONCLUSIONS: NKA in patients with pancreatic cancer demonstrated noticeable changes after surgery. Immunologically predisposed patients with a low NKA value had a high risk of early recurrence and a poor prognosis, although pancreatic cancer was surgically removed.

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.

Gasless robotic single-port cholecystectomy using the DaVinci SP system: A feasible way to minimise surgical derangement while obtaining critical view of safety.

BACKGROUND: The aim of this study was to present our initial experience of gasless robotic single-port cholecystectomy (RSPC). METHODS: We reviewed 48 patients who underwent gasless RSPC with a da Vinci SP Robotic Surgical System. Demographic data, intra-operative results, and postoperative outcomes were evaluated. RESULTS: Gasless RSPC was successfully performed in 48 of 53 patients. Five patients had conversion to standard pressure pneumoperitoneum due to insufficient surgical space (n = 3), GB perforation (n = 1), or bleeding during surgery (n = 1). The mean whole operation time was 53.6 ± 17.2 min. No patients complained of postoperative shoulder pain or had any postoperative complications. The average hospital stay was 2.1 ± 0.3 days. CONCLUSION: Gasless RSPC is feasible and safe. The unique features of an SP robotic platform allow surgeons to perform safely in an incapacious surgical space. However, this procedure is currently only possible for highly selected patients.

Effects of extremely low-pressure pneumoperitoneum on postoperative recovery after single site robot-assisted cholecystectomy: a randomized controlled trial.

PURPOSE: A robotic platform has enabled extremely low-pressure pneumoperitoneum (ELPP, 4 mmHg) to reduce surgical insults to human physiology during a minimally invasive surgery. The objective of this study was to investigate the effect of ELPP in single-site robotic cholecystectomy (SSRC) on postoperative pain, shoulder pain, and physiological changes during surgery compared to a standard pressure pneumoperitoneum (SPP, 12-14 mmHg). METHODS: A total of 182 patients who underwent an elective cholecystectomy were randomized into an ELPP SSRC group (n = 91) and an SPP SSRC group (n = 91). Postoperative pain was assessed at 6, 12, 24, and 48 h after surgery. The number of patients complaining of shoulder pain was observed. Intraoperative changes of ventilatory parameters were also measured. RESULTS: Postoperative pain scores (p = 0.038, p < 0.001, p < 0.001, and p = 0.015 at 6, 12, 24, and 48 h after surgery, respectively) and the number of patients with shoulder pain (p <0.001) were significantly lower in the ELPP SSRC group than in the SPP SSRC group. Intraoperative changes in peak inspiratory pressure (p < 0.001), plateau pressure (p < 0.001), EtCO2 (p < 0.001), and lung compliance (p < 0.001) were also less in the ELPP SSRC group. CONCLUSION: The ELPP during robotic cholecystectomy could significantly relieve postoperative pain and shoulder pain. In addition, the ELPP can reduce changes in lung compliance during surgery and the demand for postoperative analgesics, thereby improving the quality of life of patients during early stages of postoperative rehabilitation.

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma.

BACKGROUND: Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater (AoV) carcinoma is limited. AIM: To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival (DFS) rates than cases of observation following curative surgery. METHODS: We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival (OS) in patients with stage IB-III AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes. RESULTS: Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio (HR) = 2.24, P = 0.046], advanced tumor stage (HR = 1.85, P = 0.030), and vascular invasion (HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group (HR = 0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant (HR = 0.58, P = 0.098). CONCLUSION: Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.

Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer.

BACKGROUND: Interactions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC. METHODS: Exosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model. RESULTS: The median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17-18.3) and 6.36 months (95% CI, 3.27-9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35-1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166). CONCLUSIONS: The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.

The effectiveness of extremely low-pressure pneumoperitoneum on pain reduction after robot-assisted cholecystectomy.

BACKGROUND: The robot-assisted cholecystectomy could provide a sufficient surgical field with the extremely low-pressure pneumoperitoneum (ELPP; 4 mmHg) by the robot arm lifting the abdominal wall upward. This study aimed to investigate the effect of ELPP on the postoperative outcomes in benign gallbladder disease. METHODS: A retrospective study was designed to compare the postoperative pain in addition with operation time, estimated blood loss, length of hospital stay, and complication of three types of cholecystectomy for benign gallbladder disease: 75 ELPP single site robot-assisted cholecystectomy (SSRC), 114 standard-pressure pneumoperitoneum (SPP) SSRC and 110 SPP conventional laparoscopic cholecystectomy (CLC). RESULTS: There was no difference in whole operation time between ELPP SSRC and SPP SSRC group (p = 0.159). Postoperative pain score was significantly less in ELPP SSRC group as compared to SPP SSRC or SPP CLC group at 6, 12, and 24 h postoperatively (p = 0.004, p = 0.004, and p = 0.013 respectively). The incidence of shoulder pain was also significantly lower in ELPP SSRC group (p < 0.001). The rate of postoperative complication and length of stay were not different among the three groups. CONCLUSIONS: This study shows that ELPP technique using robot is feasible without increasing postoperative complications in the process of cholecystectomy and the use of the ELPP can reduce postoperative pain and shoulder pain compared to the use of the SPP.

Clinical significance of preoperative antibiotic use in mild to moderate acute inflammatory gallbladder disease: A randomized controlled trial.

BACKGROUND: Many patients receive empirical antibiotics for the prevention of postoperative infectious complications following cholecystectomy due to acute cholecystitis (AC). The purpose of this study was to investigate the clinical significance of preoperative antibiotics in mild to moderate AC patients undergoing emergency laparoscopic cholecystectomy. METHODS: This was a double-blind, placebo-controlled, randomized study. Patients with AC eligible for emergency laparoscopic cholecystectomy were randomly assigned to an antibiotic or a placebo group. Clinical outcomes including infectious complications were reviewed. RESULTS: An imputed per-protocol analysis of 234 patients showed that the postoperative infection rate was 8.6% (10 of 116 patients) in the antibiotic group and 7.6% (9 of 118 patients) in the placebo group (absolute difference, 1%; 95% CI: -8.1% to 6.1%; P = .815). Based on a noninferiority margin of 10%, the lack of preoperative antibiotic treatment was not associated with worse clinical outcomes than antibiotic treatment. Surgical site infection was the most common complication among the infectious complications, and there was no significant difference between the two groups (7.8% in the antibiotic group vs 7.6%, in the placebo group, P = .53). CONCLUSIONS: The absence of prophylactic antibiotics has no significant impact on the incidence of infectious complications in mild to moderated AC.

Gallbladder polyps growth rate is an independent risk factor for neoplastic polyps.

BACKGROUND: The size of gallbladder (GB) polyps is a representative risk factor for neoplastic polyps. However, whether growth rate during follow-up is associated with neoplastic polyps remains unclear. METHODS: From 2009 to 2019, a cohort of patients with GB polyps who underwent cholecystectomy was enrolled. We included only patients who underwent at least two abdominal ultrasonography procedures at least 6 months apart prior to cholecystectomy. Performance and optimal cutoff value of polyp growth rate for predicting neoplastic polyps were estimated using receiver operating characteristic (ROC) analysis. In addition to growth rate, several other variables considered suitable for predicting neoplastic polyps were also investigated. A nomogram was created to predict neoplastic polyps. RESULTS: A total of 239 patients with neoplastic polyps (n = 27, 11.3%) and non-neoplastic polyps (n = 212, 88.7%) were included. The median follow-up period was 28.5 months. The area under the ROC curve (AUROC) of polyp growth rate for neoplastic polyps was 0.66 (95% confidence interval, 0.59-0.72). The growth rate cutoff value for prediction of neoplastic polyps was 3 mm/year (sensitivity, 37.0%; specificity, 86.3%). Multivariate analysis identified several factors predicting neoplastic polyps: polyp size ≥10 mm (odds ratio [OR], 3.74, p = 0.041), solitary polyp (OR, 3.92, p = 0.004), and polyp growth rate ≥ 3 mm/year (OR, 2.75, p = 0.031). The AUROC of the nomogram using these three significant factors in multivariate analysis was 0.71. CONCLUSION: GB polyps with a growth rate of over 3 mm per year on ultrasonography during follow-up should be considered a risk factor for neoplastic polyps.