AM-18002, a derivative of natural anmindenol A, enhances radiosensitivity in mouse breast cancer cells.

Natural anmindenol A isolated from the marine-derived bacteria Streptomyces sp. caused potent inhibition of inducible nitric oxide synthase without any significant cytotoxicity. This compound consists of a structurally unique 3,10-dialkylbenzofulvene skeleton. We previously synthesized and screened the novel derivatives of anmindenol A and identified AM-18002, an anmindenol A derivative, as a promising anticancer agent. The combination of AM-18002 and ionizing radiation (IR) improved anticancer effects, which were exerted by promoting apoptosis and inhibiting the proliferation of FM3A mouse breast cancer cells. AM-18002 increased the production of reactive oxygen species (ROS) and was more effective in inducing DNA damage. AM-18002 treatment was found to inhibit the expansion of myeloid-derived suppressor cells (MDSC), cancer cell migration and invasion, and STAT3 phosphorylation. The AM-18002 and IR combination synergistically induced cancer cell death, and AM-18002 acted as a potent anticancer agent by increasing ROS generation and blocking MDSC-mediated STAT3 activation in breast cancer cells.

Training efficacy of robotic duct-to-mucosa pancreaticojejunostomy simulation using silicone models for surgical fellows.

Purpose: In the era of minimally invasive surgery (MIS), robotic pancreatoduodenectomy (PD) is actively performed, and clinical fellows need to thoroughly prepare for MIS-PD during the training process. Although pancreaticojejunostomy (PJ) is a difficult anastomosis that requires repeated practice, there are obstacles preventing its practice that concerns patient safety and limited time in the actual operating room. This study evaluated the efficacy of simulation-based training of robotic duct-to-mucosa PJ using pancreatic and intestinal silicone models using a scoring system. Methods: Three pancreatobiliary clinical fellows who had never performed a real robotic PJ participated in this study. Each trainee, who was well acquainted with master's video created by a senor surgeon, performed the robotic PJ procedures 9 times, and 3 independent pancreatobiliary surgeons assessed the videos and analyzed the scores using a blind method. Results: The mean robotic PJ times for the 3 trainees were 42.8 and 29.1 minutes for the first and 9th videos, respectively. The mean score was 13.8 (range, 6-17) for the first video and 17.7 (range, 15-19) for the 9th video. When comparing earlier and later attempts, the PJ time decreased significantly (2,201.67 seconds vs. 2,045.50 seconds, P = 0.007), whereas test scores increased significantly (total score 14.22 vs. 16.89, P = 0.011). Conclusion: This robotic education system will help pancreatobiliary trainees overcome the learning curves efficiently and quickly without raising ethical concerns associated with animal models or direct practice with human subjects. This will be of practical assistance to trainees preparing for MIS-PD.

Breast cancer malignancy is governed by regulation of the macroH2A2/TM4SF1 axis, the AKT/NF-κB pathway, and elevated MMP13 expression.

The histone variant, macroH2A (mH2A) influences gene expression through epigenetic regulation. Tumor suppressive function of mH2A isoforms has been reported in various cancer types, but few studies have investigated the functional role of mH2A2 in breast cancer pathophysiology. This study aimed to determine the significance of mH2A2 in breast cancer development and progression by exploring its downstream regulatory mechanisms. Knockdown of mH2A2 facilitated the migration and invasion of breast cancer cells, whereas its overexpression exhibited the opposite effect. In vivo experiments revealed that augmenting mH2A2 expression reduced tumor growth and lung metastasis. Microarray analysis showed that TM4SF1 emerged as a likely target linked to mH2A2 owing to its significant suppression in breast cancer cell lines where mH2A2 was overexpressed among the genes that exhibited over twofold upregulation upon mH2A2 knockdown. Suppressing TM4SF1 reduced the migration, invasion, tumor growth, and metastasis of breast cancer cells in vitro and in vivo. TM4SF1 depletion reversed the increased aggressiveness triggered by mH2A2 knockdown, suggesting a close interplay between mH2A2 and TM4SF1. Our findings also highlight the role of the mH2A2/TM4SF1 axis in activating the AKT/NF-κB pathway. Consequently, activated NF-κB signaling leads to increased expression and secretion of MMP13, a potent promoter of metastasis. In summary, we propose that the orchestrated regulation of the mH2A2/TM4SF1 axis in conjunction with the AKT/NF-κB pathway and the subsequent elevation in MMP13 expression constitute pivotal factors governing the malignancy of breast cancer.

Downregulation of complement factor H attenuates the stemness of MDA­MB­231 breast cancer cells via modulation of the ERK and p38 signaling pathways.

The complement system is a powerful innate immune system deployed in the immediate response to pathogens and cancer cells. Complement factor H (CFH), one of the regulators involved in the complement cascade, can interrupt the death of target cells. Certain types of cancer, such as breast cancer, can adopt an aggressive phenotype, such as breast cancer stem cells (BCSCs), through enhancement of the defense system against complement attack by amplifying various complement regulators. However, little is known about the association between CFH and BCSCs. In the present study, the roles of CFH in the CSC characteristics and radioresistance of MDA-MB-231 human breast cancer cells were investigated. CFH knockdown in MDA-MB-231 cells decreased the viability of the cells upon complement cascade activation. Notably, CFH knockdown also decreased cell survival and suppressed mammosphere formation, cell migration and cell invasion by attenuating radioresistance. Additionally, CFH knockdown further enhanced irradiation-induced apoptosis through G2/M cell cycle arrest. It was also discovered that CFH knockdown attenuated the aggressive phenotypes of cancer cells by regulating CSC-associated gene expression. Finally, by microarray analysis, it was found that the expression of erythrocyte membrane protein band 4.1-like 3 (EPB41L3) was markedly increased following CFH knockdown. EPB41L3 inhibited ERK and activated the p38 MAPK signaling pathway. Taken together, these results indicated that CFH knockdown attenuated CSC properties and radioresistance in human breast cancer cells via controlling MAPK signaling and through upregulation of the tumor suppressor, EPB41L3.

Clinical outcome of surgical resection for multifocal T2-T3 hepatocellular carcinoma up to 3 nodules: a comparative analysis with a single nodule.

BACKGROUND/AIMS: Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases. METHODS: Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated. RESULTS: All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038). CONCLUSIONS: Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules.

A single-center experience of over 300 cases of single-incision robotic cholecystectomy comparing the da Vinci SP with the Si/Xi systems.

Minimally invasive surgery is usually more beneficial than open surgeries in various fields of surgery. With the newly developed Single-Port (SP) robotic surgical system, even single-site surgery has become easier to access. We compared single-incision robotic cholecystectomy between the Si/Xi and SP systems. This retrospective single-center study enrolled patients who underwent single-incision robotic cholecystectomy between July 2014 and July 2021. The clinical outcomes of the da Vinci Si/Xi and SP systems were compared. In total, 334 patients underwent single-incision robotic cholecystectomy (118 Si/Xi vs. 216 SP). The SP group had more chronic or acute cholecystitis than the Si/Xi group did. There was more bile spillage in the Si/Xi group during the surgery. The total operative and docking times were significantly shorter in the SP group. There was no difference in the postoperative outcomes. The SP system is safe and feasible regarding comparable postoperative complication rates and is more convenient regarding docking and techniques.

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Incidence of bactibilia and related factors in patients who undergo cholecystectomy.

Purpose: In general, bile is normally sterile. However, there are reports bactibilia may occur in certain instances, though the causal factors are unclear. We analyzed possible preoperative predictors of bactibilia upon cholecystectomy. Methods: Bile samples were collected during cholecystectomies from November 2018 to November 2019. A total of 428 open or laparoscopic cholecystectomies were performed. Preoperative, intraoperative, and postoperative variables were compared between the culture-positive and culture-negative groups. Results: One hundred fifty-seven patients (36.7%) were culture-positive. Gram-negative bacteria (95 [61.0%]) were more common. Escherichia coli (38 [40.0%]) and Enterobacter (22 [23.2%]) were the most common species. In univariate analysis, age of ≥70 years (P < 0.001), male sex (P < 0.001), high American Society of Anesthesiologists physical status grades (P = 0.001), diabetes mellitus (P = 0.002), jaundice (P = 0.007), high Tokyo Guideline grades (P = 0.008), percutaneous transhepatic gallbladder drainage (PTGBD; P < 0.001), endoscopic retrograde cholangiopancreatography (ERCP; P < 0.001) were identified as a risk factors for bactibilia. In multivariate analysis, age of ≥70 years (hazard ratio [HR], 2.874; 95% confidence interval [CI], 1.769-4.670; P = 0.001), ERCP (HR, 9.001; 95% CI, 4.833-16.75; P < 0.001), and PTGBD (HR, 2.866; 95% CI, 1.440-4.901; P = 0.002) were independent risk factors for bactibilia. Conclusion: Among patients who underwent cholecystectomy, those who were elderly, symptomatic, and underwent preoperative drainage were more likely to have bactibilia. In such cases, surgeons should take care to prevent bile leakage during surgery and consider administering appropriate antibiotics.

Left liver graft in adult-to-adult living donor liver transplantation with an optimal portal flow modulation strategy to overcome the small-for-size syndrome - A retrospective cohort study.

BACKGROUND: Adult-to-adult living donor liver transplantation (LDLT) is a notable type of liver transplantation. Several centers prefer the right liver graft (RLG) over the left liver graft (LLG) for better recovery of recipients. We compared the outcomes of donors and recipients between LDLT using LLGs and RLGs. MATERIALS AND METHODS: The study cohort comprised of 25 patients in the LLG group and 93 in the RLG group. When both hemiliver grafts met the selection criteria, an LLG was preferred. When portal flow (≥300 ml/min/100gLW) and hepatic venous pressure gradient (≥10 mmHg) were increased, intraoperative splenic artery ligation was performed for portal modulation. Postoperatively, somatostatin was administered when small-for-size syndrome (SFSS) was highly suspected. RESULTS: The graft-to-recipient weight ratio was lower in the LLG group than in the RLG group. There was no significant complication above Clavien-Dindo grade IIIA in donors. Regarding recipient outcomes, SFSS occurred in four (16.0%) patients in the LLG group and three (3.2%) in the RLG group (P = 0.036). Splenic artery ligation was frequently performed in the LLG group than the RLG group (5 [20.0%] vs. 12 [12.9%], P = 0.035) and 5 patients received intravenous continuous somatostatin for 7 (5-12) days. SFSS-related hospital mortality did not occur. There was no significant difference in the short-term and long-term outcomes between the groups. CONCLUSION: This study demonstrates the comparable outcomes of donors and recipients between the LLG and RLG groups although with a higher risk of SFSS that needs high experience to avoid severe complications and graft loss. We expect LLG to be used more actively in adult-to-adult LDLT with portal flow modulation strategies to overcome fatal SFSS.

Prevalence and clinical significance of pancreatic cystic lesions in immunosuppressed patients following solid organ transplantation.

Background: Pancreatic cystic lesions (PCLs) are occasionally found in solid organ transplant (SOT) recipients. In such recipients, the risk of cancer is increased due to immunosuppressive therapy. This study investigated the prevalence of PCLs and described their clinical course in immunosuppressed patients following SOT. Methods: The presence of PCLs in a retrospective cohort of 805 consecutive SOT recipients from 2009 to 2019 was examined. The characteristics of PCLs were compared using initial and follow-up imaging, where available. These results were compared to an age- and sex-matched immunocompetent control group monitored for at least 12 months. Results: PCLs were present in 15 of 805 SOT patients (seven liver and eight kidney transplantations). The median diameter of the largest lesion was 20 mm (range, 0.2-60 mm) and 60% of lesions were benign. During follow-up imaging, the cyst size remained stable in 46.7%, increased in 13.3%, and decreased in 40.0% of the SOT group. Significantly more of the SOT patients showed PCL size reductions (P=0.007). Among SOT patients diagnosed with intraductal papillary mucinous neoplasms (6/15), worrisome features were noted in one patient at the time of cyst diagnosis. Differences in the development of worrisome features between the study and control groups were not statistically significant. Conclusions: The malignant transformation of PCLs in SOT recipients is rare and most such PCLs can be managed conservatively. The presence of a PCL should therefore not affect transplant eligibility.

Impact of surgery on survival outcomes for Bismuth type IV Klatskin tumors.

BACKGROUND: Bismuth-Corlette type IV Klatskin tumors have conventionally been considered unresectable. This retrospective study aimed to demonstrate the survival improvement of patients with type IV Klatskin tumors when resected and suggest possible radiological features for R0 resectability. METHODS: Data on type IV Klatskin tumors diagnosed between 2008 and 2019 were reviewed retrospectively. Patients with distant metastasis, concomitant other cancers at the initial state, extensive vascular invasions, poor liver function, and poor general condition were excluded. The survival outcomes of patients and radiologic parameters of bile duct tumors were compared between the curative resection (R0, 1 resection) and non-resection groups. RESULTS: The demographic findings of patients with curative resection (n = 48) and non-resection (n = 111) were comparable. Both were potentially resectable in the initial state. The postoperative morbidity was 22.9% and the 90-day mortality 4.2%. There was a significant difference in the median survival among the curative-intended resection, palliative treatment, and supportive care groups (35, 16, and 12 months, respectively; P < 0.001). DISCUSSION: In patients with type IV Klatskin tumor without extensive tumor invasion into adjacent tissues, including major vessels, surgical resection can be considered for better survival. CLINICAL REGISTRATION NUMBER: IRB No. 2009-100-1157.

Single-port robot plus one port (SP + 1) distal pancreatectomy using the new da Vinci SP system.

PURPOSE: Single-incision laparoscopic distal pancreatectomy has not been widely applied due to technical challenges and increased operative risks. The newly released da Vinci SP system has been introduced to overcome these limitations and offer improvements for established robotic single-site procedures. We report our experience of robotic single port plus one port distal pancreatectomy using the da Vinci SP system. METHODS: We performed robotic distal pancreatectomy in three patients using the da Vinci SP surgical system with one additional port used for applying the energy device and stapling. Technical and clinical feasibility were examined. RESULTS: The mean age and body mass index were 70.7 years and 27.8 kg/m2, respectively. The mean operation time was 215 min. The estimated blood loss was less than 500 mL. All patients underwent combined splenectomy. The postoperative course of all patients was uneventful. CONCLUSION: Robotic distal pancreatectomy using the da Vinci SP system is safe and feasible, with acceptable perioperative outcomes.

In vivo study for the hemostatic efficacy and foreign body reaction of a new powder-type polysaccharide hemostatic agent.

PURPOSE: Various hemostatic agents have been introduced in therapy as postoperative bleeding is a poor prognostic factor for postoperative outcomes. These products can be divided into those that directly promote the hemostatic cascade and those that physically form a barrier by absorbing blood. The latter, powder-type hemostatic agents have the advantages of being inexpensive and more absorbable with less foreign body reactions (FBRs) and are applicable to a relatively wide area. This study was conducted to verify the safety and efficacy of a newly invented polysaccharide product (OOZFIX, Theracion Biomedical), which improves blood absorption and hemostatic effects. METHODS: Two separate animal experiments were performed. The first evaluated FBRs histologically at 3 days, 2 weeks, and 4 weeks, after implantation of OOZFIX in rats, and the second compared hemostatic performance of OOZFIX and Arista AH (Bard) in the porcine liver punch biopsy model. RESULTS: We found minimal FBRs in the 3-day group and no reactions in both the 2-week and 4-week groups after implantation of hemostatic agents. The time to hemostasis of OOZFIX was not significantly different from that of Arista AH (median [interquartile range]: 9 [6-10] minutes vs. 8 [6-10] minutes, respectively; P = 0.522). When comparing the serial bleeding grade tendency, there was no statistical difference between OOZFIX and Arista AH (P = 0.656). CONCLUSION: OOZFIX caused a minimal FBR that disappeared within 2 weeks in vivo, and its hemostatic performance was comparable with that of an existing agent, Arista AH. Further clinical studies are required in the future.

Comparison of oncologic outcomes of extrahepatic cholangiocarcinoma according to tumor location: perihilar cholangiocarcinoma versus distal bile duct cancer.

PURPOSE: Extrahepatic cholangiocarcinoma is distinguished into perihilar cholangiocarcinoma (PHC) and distal bile duct cancer (DBC). The studies for each subtype have been conducted separately. This study compared oncological outcomes between PHC and DBC. METHODS: From 2001 to 2017, patients who underwent surgery at Seoul National University Hospital for PHC or DBC were enrolled. T stage was reclassified for tumor extent as 'confined to' or 'beyond' the bile duct (BD). In survival analysis, stage matching was performed based on tumor extent and lymph node (LN) metastasis. RESULTS: There were 680 patients enrolled: 295 with PHC and 385 with DBC. The R0 resection rate was higher in DBC (77.3% vs. 89.9%, P = 0.001). Tumors confined to BD were more common in PHC (61.7% vs. 37.7%, P = 0.001). The 5-year survival rate (5YSR) was higher in DBC patients (30.8% vs. 47.8%, P = 0.001). After stage matching, DBC patients showed better 5YSR for tumors confined to BD/LN(-) (47.1% vs. 64.3%), confined to BD/LN(+) (22.0% vs. 35.0%), beyond BD/LN(-) (21.9% vs. 49.8%), and beyond BD/LN(+) (9.6% vs. 26.9%). The overall recurrence rate was higher in PHC (59.7% vs. 51.9%, P = 0.045), with no difference in the recurrence types between two groups. Radiation therapy was effective for patients with advanced stage disease (5YSR: 35.8% vs. 29.5%, P = 0.022); adjuvant chemotherapy was effective for patients receiving R1 resection (5YSR: 37.3% vs. 13.2%, P = 0.040). CONCLUSION: Differences were identified in oncological outcomes between PHC and DBC, including pathologic findings and survival outcomes.

G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer.

Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-ß superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation.

Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance.

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN. METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival, and recurrence outcomes according to pathology and margin were analyzed. RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD), 78 had high-grade dysplasia (HGD), and 117 had invasive IPMN. Total 50 patients developed recurrences, with 4 resection margins, 10 remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, P < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, P < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P < 0.001). Carbohydrate antigen 19-9 >37 ( P = 0.003), invasive IPMN ( P < 0.001), and malignant margin ( P = 0.036) were associated with recurrence. CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

Outcomes of 5000 pancreatectomies in Korean single referral center and literature reviews.

BACKGROUND: Pancreatic resection has higher postoperative mortality and morbidity rates than other abdominal operations. Some centers have reported remarkable postoperative outcomes of minimally invasive surgery. This study investigated the chronological trends of pancreatectomies by analyzing a large-scale database. METHODS: The medical records of 5175 patients who underwent pancreatic resection between 1961 and 2019 at a single institution were reviewed. To investigate the chronological change in survival outcomes of periampullary cancer, the survival data of 3,108 patients were analyzed. RESULTS: Patient age and the proportion with pancreatic cancer have increased over time. From 2015 to 2019, pancreatic cancer was the most common cause for resection (35.9%), followed by pancreatic cysts (24.8%) and common bile duct cancer (13.4%). The incidence of postoperative complications tended to decrease over time (26.0% from 2000 to 2004; 20.8% from 2015 to 2019). A comparison of survival outcomes of periampullary malignancies by period revealed that patients with pancreatic cancer significantly improved (5-year survival rate: 14.4% before 2000% vs 15.2% from 2000 to 2009% vs 29.0% after 2009, P < .001). CONCLUSIONS: Postoperative outcomes of pancreatic resection have improved over the past few decades. To improve outcomes in the future, an active multidisciplinary approach and postoperative management are required.

Radiological tumour invasion of splenic artery or vein in patients with pancreatic body or tail adenocarcinoma and effect on recurrence and survival.

BACKGROUND: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. METHODS: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. RESULTS: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9 cm, P = 0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P = 0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P < 0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P = 0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. CONCLUSION: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach.

Conversion surgery for initially unresectable extrahepatic biliary tract cancer.

BACKGROUNDS/AIMS: Surgical resection is the only curative treatment for biliary tract cancers; however, most patients undergo palliative chemotherapy because they are contraindicated for surgery. Conversion surgery, a treatment strategy for downsizing chemotherapy and subsequent surgical resection, is feasible for initially unresectable biliary tract cancers following the introduction of effective chemotherapeutic agents. METHODS: Patients initially diagnosed with unresectable biliary tract cancers, and treated with conversion surgery after palliative chemotherapy between 2013 and 2019, were reviewed retrospectively. RESULTS: Twelve patients underwent conversion surgery after palliative chemotherapy for initially unresectable biliary tract cancers. The final pathological diagnosis included six perihilar cholangiocarcinomas, four distal common bile duct cancers, and two gallbladder cancers. Different chemotherapy regimens were used, but all the patients were treated with gemcitabine at some point during their treatment. The median overall survival was 28 months, which was longer than that of patients treated with isolated palliative chemotherapy in previous studies. CONCLUSIONS: Conversion surgery represents a therapeutic alternative for specific cases of unresectable biliary tract cancers. Palliative chemotherapy for initially unresectable biliary tract cancers is recommended for downsizing the tumor and expanding the indications for surgery. Further studies and clinical trials are required to develop new and effective chemotherapeutic regimens.