Background: Programmed death ligand 1 (PD-L1), a potential target for immune checkpoint inhibitors, has been considered a novel biomarker for prognosis in various solid tumors. However, scant data is available on the role of PD-L1 expression in advanced gallbladder cancer (GBC). The aim of this study is to evaluate prognostic significance of expression of PD-L1 in advanced GBC and provide evidence for PD-L1 targeted therapy in the future. Methods: We investigated the expression of PD-L1 in 192 advanced GBC cases who underwent surgery and were pathologically confirmed as T3 or T4 between 2010 and 2017. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Clinicopathological characteristics and survival data were correlated with PD-L1 expression analyzed at different cut-offs of ≥ 1%, ≥ 10% and ≥ 50% in tumor cells and tumor-infiltrating immune cells. Results: Tumor cells expressed PD-L1 in 47.4% of cases (n = 91), and tumor-infiltrating immune cells expressed PD-L1 in 70.5% of cases (n = 135). The median overall survival (OS) and median progression-free survival (PFS) of patients with PD-L1 positivity in tumor-infiltrating immune cells at a cutoff of 10% was 23.9 and 16.8 months, respectively and significantly better than those of patients with PD-L1 negativity (23.9 vs. 15.7 months, p = 0.023, 16.8 vs. 10.0 months, p = 0.018). In multivariate analysis, simple cholecystectomy, no adjuvant chemotherapy and PD-L1 negativity (negative & < 10% positive) in tumor-infiltrating immune cells were significant poor prognostic factors. Conclusions: Our results showed that PD-L1 expression in tumor-infiltrating immune cells at a cutoff of 10% is an independent significant prognostic factor in advanced GBC patients. Therefore, PD-L1 expression could be a good prognostic marker to guide future immune target-based therapies in GBC. Further large scale study is needed.
Background: Fungal cholecystitis is one of the rarest forms of acute cholecystitis. It is known to occur mainly in elderly, comorbid patients and have a dreadful outcome. Recently, we experienced a case of recurrent acute acalculous cholecystitis caused by Candida in a 80-year-old patient with chronic myeloid leukemia (CML). We report case series of fungal cholecystitis and review the published literature. Methods: We investigated 290 positive bile cultures from 728 patients who underwent PTGBD and 321 positive bile cultures from 931 patients with acute/chronic cholecystitis who underwent laparoscopic cholecystectomy between January 2010 and December 2021. In total 14 patients, fungus has grown in their bile juice, which collected from PTGBD (3 Candida tropicalis; 2 Candida albicans; 1 Candida glabrata and 1 Candida dubliniensis) or intraoperatively during cholecystectomy (3 Candida albicans; 2 Saccharomyces cerevisiae, 1 Candida tropicalis, 1 Cryptococcus laurentii). Results: In 7 patients who underwent elective cholecystectomy, fungus has grown but their clinical course was not eventful, even without antifungal drug. An average age of the other 7 patients with PTGBD was 79 years (range 69-85). In 4 patients, fungus had grown from other site such as urine (3) and blood (1). All patients had several underlying diseases such as malignant tumor (CML, Klatskin tumor, Follicular lymphoma), chronic kidney disease, heart failure, pneumonia, or were in bed-ridden state with poor performance status. Only 2 patients underwent delayed cholecystectomy and were able to recover safely. However, 3 out of the 5 patients who could not undergo surgery passed away due to ongoing sepsis and aggravation of their underlying diseases. Conclusions: Fungal cholecystitis is life threatening complication of critically ill or elderly patients. A high index of suspicion for this fungal pathogen and prompt drainage or cholecystectomy, if possible, with addition of systemic antifungal therapy represent the mainstays of therapy and offer the greatest chance for survival.
Background:Recently, the incidence of gallbladder disease is` increasing and particularly, the number of people who underwent laparoscopic cholecystectomy (LC) has increased in extremely elderly patients, older than 80 years. The purpose of this study is to investigate the safety and efficacy of LC in extremely elderly patients Methods: We retrospectively reviewed a total of 476 elderly (more than 70 years) patients who underwent LC between 2017 and 2021. Perioperative data were compared between octogenarian (n = 134, 28.2%) and younger patients (n = 42, 71.8%). A subgroup undergoing LC for acute cholecystitis (n = 107, 22.4%) was further analyzed. Results: In octogenarian, more patients had ASA scores of 3 or 4 (49.3% vs. 33.9%, p = 0.002) and preoperative PTGBD (30.6% vs. 17.0%, p = 0.001) than younger patients. Significantly more patients were diagnosed as acute cholecystitis (27.6% vs. 17.5%, p = 0.014) and gallbladder cancer (6.0% vs. 2.3%, p = 0.001) in octogenarian. The length of hospital stay was longer (4.8 vs. 6.5 days, p = 0.005), and more patients took care in the intensive care unit immediately after surgery in octogenarian. However, there were no significant differences in operating time, open conversion rate, severe postoperative complication rate, and mortality between two groups. A subgroup analysis for acute cholecystitis showed the same results with the whole group analysis. Multivariate analysis for risk factors on severe complication (more than CD grade 3a) demonstrated existence of preoperative PTGBD (odd ratio: 6.17) and admission via emergency room (3.84) were significant, but age (> 80 compared to 71-80 age) was not significant. Conclusions: Although acute cholecystitis was more common in octagenarians, the postoperative clinical outcome was comparable between octogenarian and younger patients groups. If sufficient preoperative assessment and systematic postoperative management would be performed, LC could be safely performed in extremely elderly patients.
Lecture: Gallbladder cancer (GBC) is the most common biliary tract cancer with very poor prognosis. The majority of patients present with advanced disease but for those with earlier stage disease, surgical resection is the only curative option. Oncologic resection guidelines are based on T stage, extended cholecystectomy, including hepatic resection and lymphadenectomy, recommended for cancers staged greater T2. The value of lymphadenectomy in GBC is thought to be associated with accurate diagnosis, prediction of prognosis and improvement of overall survival. Generally regional lymph nodes, so-called as N1 group lymph nodes are regarded as lymph nodes around hepatoduodenal ligaments and extended regional lymph nodes, so-called as N2 group lymph nodes are regarded as retroportal, posterosuperior pancreaticoduodenal, posteroinferior pancreaticoduodenal, along the common hepatic artery, celiac, superior mesenteric, and interaorticocaval lymph nodes. However, the consensus for extent of lymph node dissection in GBC has not been established yet. Due to various terminologies and definitions having been used, it is very difficult for GBC as a rare malignancy to establish the extent of regional lymph node and extent of lymphadenectomy. To establish proper extent of lymph node dissection, consensus for definition of regional lymph node and further international or multi-institutional prospective study is needed.
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