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Background: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established., Methods: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis., Results: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3., Conclusion: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The role of laparoscopic radical cholecystectomy (LRC) in the surgical management of T2 gallbladder carcinoma (GBC) is still controversial.The medical records of patients with T2 GBC treated with radical cholecystectomy were retrospectively reviewed. In this study, we compare the short- and long-term oncologic outcomes, using propensity score matching analysis, of patients with T2 GBC who underwent LRC and open radical cholecystectomy (ORC).Among 183 patients, 86 were selected by propensity score matching (LRC = 43 and ORC = 43). The ORC group underwent more extensive surgery (liver resections and extended lymph node dissections [ELND]) than the LRC group. The LRC group had less operative blood loss, shorter length of hospital stay, fewer complications, and had the earlier start of adjuvant chemotherapy. There was no significant difference between the laparoscopic and open surgery groups in terms of 5-year overall survival rate (64.6% vs 80.4%, P = .214) and disease-free survival rate (77.1% vs 82.2%, P = .641). A subgroup analyses showed that liver resection and ELND had no survival advantage compared to no liver resection and regional lymph node dissection, respectively.Our LRC approach is safe and effective, with long-term survival comparable to that of ORC.

Background: We designed a clinical application of glucose to lymphocyte ratio (GLR) as it might be a sensitive parameter to determine the glucose metabolism and behavior of the cancer (i.e., its aggressiveness), and the immunologic status of a patient with cancer. Thus, we investigated the association of GLR with the overall survival (OS) and disease-free survival (DFS) of patients with T2 gallbladder (GB) cancer after curative-intent surgery., Methods: The medical records of patients with T2 GB cancer who underwent surgery were retrospectively reviewed. The clinicopathologic characteristics, preoperative complete blood counts, fasting blood glucose, albumin, cholesterol, and follow-up information were collected., Results: A total of 197 patients were included in the study. In multivariate analysis, high GLR (>69.3) was associated with poor OS (HR = 15.249, 95% CI: 4.090-56.849, P = 0.0001) along with R1 status (HR = 1.755, 95% CI: 0.033-0.910, P = 0.033), >3 metastatic lymph nodes (HR = 2.809, 95% CI: 1.403-5.625; P = 0.004), and lymphovascular invasion (HR = 8.041, 95% CI: 2.881-22.442; P = 0.0001). Moreover, high GLR (HR = 3.666, 95% CI: 1.145-11.737, P = 0.029), adjuvant chemotherapy (HR = 6.306, 95% CI: 1.921-20.699; P = 0.002), lymphovascular invasion (HR = 5.464, 95% CI: 1.783-16.746; P = 0.003), and high-grade tumor (HR = 2.143, 95% CI: 1.042-4.407; P = 0.038) were independently associated with DFS., Conclusions: Preoperative GLR is an independent predictor of OS and DFS in T2 GB cancer. Further studies are required to validate these findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Despite the increasing number of reports on the favorable outcomes of laparoscopic surgery for gallbladder cancer (GBC), there is no consensus regarding this surgical procedure., Objective: The study aimed to develop a consensus statement on the application of laparoscopic surgery for GBC based on expert opinions., Methods: A consensus meeting among experts was held on September 10, 2016, in Seoul, Korea., Results: Early concerns regarding port site/peritoneal metastasis after laparoscopic surgery have been abated by improved preoperative recognition of GBC and careful manipulation to avoid bile spillage. There is no evidence that laparoscopic surgery is associated with decreased survival compared with open surgery in patients with early-stage GBC if definitive resection during/after laparoscopic cholecystectomy is performed. Although experience with laparoscopic extended cholecystectomy for GBC has been limited to a few experts, the postoperative and survival outcomes were similar between laparoscopic and open surgeries. Laparoscopic reoperation for postoperatively diagnosed GBC is technically challenging, but its feasibility has been demonstrated by a few experts., Conclusions: Laparoscopic surgery for GBC is still in the early phase of the adoption curve, and more evidence is required to assess this procedure., (© 2018 S. Karger AG, Basel.)

Background: Favorable outcomes of laparoscopic surgery for gallbladder cancer (GBC) have been reported; yet consensus on the indications and surgical techniques for laparoscopic surgery for GBC is lacking., Objective: To evaluate the current status of laparoscopic surgery for GBC by analyzing the results of a survey of experts and by reviewing the relevant published literature., Methods: Before an expert meeting was held on September 10, 2016 in Seoul, Korea, an international survey was undertaken of expert surgeons in the field of GBC surgery., Results: The majority of surgeons who responded agreed that laparoscopic surgery has an acceptable role for suspicious or early GBC, and that laparoscopic extended cholecystectomy has a value comparable to that of open surgery in selected patients with GBC. However, the selection criteria for laparoscopic surgery for overt GBC and the details of the surgical techniques varied among surgeons., Conclusions: This survey and literature review revealed that laparoscopic surgery for GBC is performed in highly selected cases. However, the favorable outcomes in the published reports and the positive view of experienced surgeons for this operative procedure suggest a high likelihood that laparoscopic surgery will be more frequently performed for GBC in the future., (© 2018 S. Karger AG, Basel.)

Background: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer., Methods: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club., Results: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis., Conclusion: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis., Competing Interests: Disclosure: The authors have no potential conflicts of interest to disclose.

Background: The aim of this study was to investigate the clinical features and clinical outcomes of T1 gallbladder (GB) cancer and to determine an appropriate surgical strategy for T1 GB cancer., Methods: A nationwide multicenter study, in which 16 University Hospitals in Korea participated, was performed from 1995 to 2004. A total of 258 patients, 117 patients with T1a and 141 patients with T1b disease were enrolled. Clinicopathologic findings and long-term follow-up results were analyzed after a consensus meeting of the Korean Pancreas Surgery Club was held., Results: Simple cholecystectomy was performed in 95 patients (81.2 %) with T1a tumor and in 89 patients (63.1 %) with T1b tumor (p < 0.01). Lymph node metastasis was observed in 2.9 % of T1a patients and in 9.9 % of T1b patients (p = 0.391). A significant difference in 5-year disease-specific survival (DSS) rates was observed between T1a and T1b patients (96.4 vs 84.8 %, respectively, p = 0.03). However, no significant 5-year DSS rate difference was observed between those who underwent simple cholecystectomy or extended cholecystectomy, regardless of whether lymph node dissection was performed or whether lymph node metastasis was present. There was no significant difference in recurrence-free survival between simple cholecystectomy and extended cholecystectomy., Conclusions: There was no superiority of extended cholecystectomy over simple cholecystectomy in the aspect of survival and recurrence especially in T1b gallbladder cancer. Furthermore, the effectiveness of regional lymphadenectomy for treatment purpose remains questionable. Therefore, simple cholecystectomy could be recommended as a surgical strategy of T1 gallbladder cancer.

Objectives: The aim of this study was to evaluate the outcome of adjuvant therapy on the overall survival (OS) and disease-free survival (DFS) after curative resection (RO) of patients with TNM stage II gallbladder (GB) cancer., Methods: A total of 160 patients who had received curative resection (RO) between January 2000 and December 2009 were retrospectively reviewed. Among 61 stage II GB cancer patients, 43 received adjuvant therapy, while 18 others received surgery alone. The median follow-up period was 27.3 months (range 2.2-98.9 months)., Results: OS was not significantly different among the adjuvant therapies (p = 0.180), but DFS was (p = 0.033). The 3-year OS and DFS from surgery alone, adjuvant chemotherapy, adjuvant radiotherapy, and adjuvant concurrent chemo-radiotherapy were 64, 78, 36 and 36%, and 56, 69, 14 and 47%, respectively. Overall, the chemotherapy group had a better prognosis, although there were no significant differences., Conclusions: The data from this study do not provide evidence that adjuvant therapy is an effective treatment option for curative resected GB cancer. A large randomized controlled study is necessary to confirm the efficacy of adjuvant therapy. Newer adjuvant studies should be focused on gemcitabine-based chemotherapy or chemo-radiotherapy with molecular-based target agents., (Copyright © 2010 S. Karger AG, Basel.)

Background: Gallbladder carcinoma is a relatively rare malignancy with a poor prognosis. We have often encountered patients in whom the course of their disease differed substantially from what would be predicted based on their clinical staging, which highlights the needs to consider additional predictive factors. Gallbladder carcinoma occurs more frequently in women than men, yet expression of the estrogen receptor (ER) and progesterone (PR) have not been studied. We applied an immunohistochemical stain to examine the expression of ER(alpha), ER(beta), and PR in radically resected gallbladder carcinoma., Material and Methods: We immunohistochemically investigated 30 specimens of gallbladder adenocarcinoma tissues using ER(alpha), ER(beta), and PR antibodies., Results: Adenocarcinoma of gallbladder is negative for both ER(alpha) and PR. However, 22 of 30 cases (73.3%) were confirmed positive for ER(beta), which was significantly correlated with tumor differentiation. Five-year survival rates of ER(beta) positive and negative patients were 53.3% and 31.1%, respectively (P = 0.034). In multivariate analysis, only a low proportion score of ER(beta) status was a statistically significant factor (P = 0.033)., Conclusions: Evaluation of ER(beta) expression in gallbladder carcinoma may be an important factor in identifying a poor prognostic group of gallbladder carcinoma.

Despite the advances in imaging techniques, most patients can only be diagnosed at advanced stage: The prognosis is very poor. Recent studies showed that aggressive radical resection for advanced gallbladder carcinoma can give an acceptable prognosis. However, recurrence frequently remains the main problem after curative resection of advanced gallbladder carcinoma. The aim of this study was to identify the patterns and risk factors of recurrence after curative resection for stage II gallbladder carcinoma. Between January 1991 and December 2003, 100 patients received radical curative resection for gallbladder carcinoma at Yonsei University Medical Center. Of these, 77 were defined with stage II gallbladder carcinoma according to the Union Internationale Contre Le Cancer classification (sixth edition). Of the 77 patients, 67 were reviewed for the predictors of tumor recurrence. Among the 67 patients, 38 (56.7%) suffered a recurrence. The mean length to the recurrence was 21.1 +/- 26.7 months, with the most common site being the intraabdominal organs: liver and aortocaval lymph nodes. Infiltrating and poorly differentiated types were identified as independent prognostic factors of recurrence after curative resection for stage II gallbladder carcinoma and it suggests that large multicenter randomized control trials are necessary to clarify the role of adjuvant chemotherapy in these patients.

Background/aims: Despite the development in diagnostic tools, gallbladder carcinoma is often diagnosed at an advanced stage. Therefore, early diagnosis and radical resection are most important factors for the prognosis of gallbladder carcinoma. However, prognostic factors after radical resection of gallbladder carcinoma have not been well identified. The aim of this study was to evaluate the prognostic factors of gallbladder carcinoma after curative resection., Methods: We reviewed the records of the 115 patients with gallbladder carcinoma who underwent curative surgery between 1989 and 2004 at Yonsei University Medical Center (YUMC). The relationship between survival and clinicopathological variables was assessed., Results: In 311 patients presenting with gallbladder carcinoma, 195 patients (62.5%) were radically resected. Among 195 patients, 80 patients were excluded because of incomplete clinicopathologic data and unsatisfactory follow-up. The 5 year overall survival rate was 36.0%, and disease free 5 year survival rate was 3.9%. Univariate analysis showed that survival was closely related to gross morphology, depth of tumor invasion, lymph node metastasis and preoperative serum CA19-9 level. Three significant factors identified by multivariate analysis were depth of tumor invasion, gross morphology, and preoperative serum CA19-9 level., Conclusions: Depth of tumor invasion, gross morphology, and preoperative serum CA19-9 level are independent significant prognostic factors of resectable gallbladder carcinoma.

Capecitabine and gemcitabine are used in the treatment of a variety of solid tumors including pancreatic and biliary tract carcinomas. The authors evaluated survival, response, and toxicity associated with using a combination of capecitabine and gemcitabine to treat patients with unresectable or metastatic gallbladder adenocarcinoma (GBC). Eligible patients had histologically- or cytologically-confirmed GBC, no prior systemic therapy with capecitabine or gemcitabine, Karnofsky Performance Status 70%, serum total bilirubin up to three times normal, and measurable disease. Treatment consisted of gemcitabine 1000 mg/m2 IV on Days 1 and 8 concurrent with administration of capecitabine 1000 mg/m2 PO BID on Days 1 through 14, on a 3-week cycle. Tumor response was assessed by the response evaluation criteria in solid tumors (RECIST criteria) and survival was calculated from initiation of CapGem therapy. A total of 24 patients were enrolled. Median age at the time of diagnosis was 62 years (range, 41-78 years). Fourteen patients had undergone prior surgery. Results showed that eight patients achieved partial response (33%) with an additional 10 patients achieving stable disease (42%). The overall median time to disease progression was 6.0 months (95% CI, 3.8-8.1 months) and overall survival was 16 months (95% CI, 13.8-18.3 months). The one-year survival rate was 58%. No Grade 4 toxicity was seen. Transient Grade 3 neutropenia/ thrombocytopenia and manageable nausea, hand-foot syndrome and anorexia were the most common toxicities. Our study shows that CapGem is an active and well-tolerated chemotherapy regimen in patients with advanced GBC.