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Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.
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Background/Aims@#Gastrointestinal (GI) bezoars are relatively rare diseases with clinical characteristics and treatment modalities that depend on the location of the bezoars. This study evaluated the clinical characteristics and treatment outcomes in patients with GI bezoars. @*Methods@#Seventy-five patients diagnosed with GI bezoars were enrolled in this study. Data were collected on the demographic and clinical characteristics and the characteristics of the bezoars, such as type, size, location, treatment modality, and clinical outcomes. @*Results@#Among the 75 patients (mean age 71.2 years, 38 males), 32 (42.6%) had a history of intra-abdominal surgery. Hypertension (43%) and diabetes (30%) were common morbidities. The common location of the bezoars was the stomach in 33 (44%) and the small intestine in 33 (44%). Non-surgical management, including adequate hydration, chemical dissolution, and endoscopic removal, was successful in 2/2 patients with esophageal bezoars, 26/33 patients with gastric bezoars, 7/9 patients with duodenal bezoars, and 20/33 patients with small intestinal bezoars. The remaining patients had undergone surgical management. @*Conclusions@#The management of GI bezoars requires multidisciplinary approaches, including the appropriate correction of fluid and electrolyte imbalances, chemical dissolution, and endoscopic and surgical treatments. (Korean J Gastroenterol 2023;81:253-258)
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Transarterial chemoembolization (TACE) is a widely used hepatocellular carcinoma (HCC) treatment. Some cases of supraumbilical skin rash after TACE in patients with HCC have been reported. To the best of the authors’ knowledge, there are no reports on atypical, generalized rashes caused by doxorubicin systemic absorption after TACE. This paper presents the case of a 64-year-old male with HCC who developed generalized macules and patches one day after a successful TACE procedure. A histology examination of a skin biopsy of a dark reddish patch on the knee revealed severe interface dermatitis. He was treated with a topical steroid, and all skin rashes improved within a week with no side effects. This report presents this rare case with a literature review on skin rash after TACE.
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Background@#The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. @*Results@#K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. @*Conclusion@#Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
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Purpose@#We assessed the association between the results of tear film-based matrix metalloproteinases 9 (MMP-9) immunoassay and the diagnosis of patients who visited an oculoplastic outpatient clinic. @*Methods@#We conducted a retrospective analysis of the MMP-9 immunoassay results in 1,703 eyes from 1,703 patients who presented with ocular discomfort at an oculoplastic outpatient clinic. The MMP-9 immunoassay results were analyzed in correlation with the final oculoplastic diagnosis of the patients. @*Results@#In total, 1,126 of 1,533 eyes demonstrated positive expression of MMP-9. No statistically significant differences were observed in MMP-9 expression based on sex (p = 0.107) and age (p = 0.510). Furthermore, 120 of 169 eyes with thyroid eye disease (71.0%, p < 0.001), 145 of 161 eyes with nasolacrimal duct obstruction (90.1%, p < 0.001), 282 of 375 eyes with nasolacrimal duct stenosis (75.2%, p < 0.001), 190 of 238 eyes with entropion (79.8%, p < 0.001), 19 of 23 eyes with ectropion (82.6%, p < 0.001), and 370 of 567 eyes with dry eye syndrome (65.3%, p < 0.001) exhibited positive MMP-9 expression. @*Conclusions@#The MMP-9 immunoassay is a noninvasive, convenient, and rapid test that evaluates ocular surface inflammation. Most patients with oculoplastic diseases exhibit positive MMP-9 expression. These findings provide valuable information for guiding diagnostic and management decisions in patients with oculoplastic conditions.
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Although hepatocellular carcinoma (HCC) is associated with a poor prognosis, management of early-stage HCC is often successful with highly efficacious treatment modalities such as liver transplantation, surgical resection, and radiofrequency ablation. However, unfavorable clinical outcomes have been observed under certain circumstances, even after efficient treatment. Factors that predict unsuitable results after treatment include tumor markers, inflammatory markers, imaging findings reflecting tumor biology, specific outcome indicators for each treatment modality, liver functional reserve, and the technical feasibility of the treatment modalities. Various strategies may overcome these challenges, including the application of reinforced treatment indication criteria with predictive markers reflecting tumor biology, compensation for technical issues with up-to-date technologies, modification of treatment modalities, downstaging with locoregional therapies (such as transarterial chemotherapy or radiotherapy), and recently introduced combination immunotherapies. In this review, we discuss the challenges to achieving optimal outcomes in the management of early-stage HCC and suggest strategies to overcome these obstacles.
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Cervical disc arthroplasty (CDA) has become more widespread and diverges from the conventional technique used in anterior cervical fusion for cervical degenerative disc disease. As arthroplasty has become a popular treatment option, few complications have been reported in the literature. These include subsidence, expulsion, posterior avulsion fractures, heterotopic ossification, and osteolysis. One of the critical complications is osteolysis, but current studies on this subject are limited in terms of not elucidating the incidence, etiology, and consequences. The authors present two cases, who presented with clinical signs of gradually worsening myelopathy induced by posterior vertebral body osteolysis, 2 years after CDA. Subsequently, the patient underwent posterior decompression and fusion without prosthesis removal. Postoperatively, the clinical symptoms gradually resolved, with no severe deficits. The present rare cases highlight the osteolysis that occurs after CDA, which can cause cervical myelopathy, and suggest spine surgeons to be alert to this fatal complication.
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Background@#As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. @*Results@#In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. @*Conclusions@#This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.
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Background/Aims@#As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. @*Methods@#Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. @*Results@#Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. @*Conclusions@#In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4cm in size, are asymptomatic and lack worrisome features on preoperative images.
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Gastrointestinal stromal tumors (GISTs) are not uncommon and often cause gastrointestinal bleeding. GISTs occurring in the small intestine are occasionally difficult to identify by endoscopy and CT. In this case, the patient underwent CT three times before surgery, and the lesion was found to be located in a different area of the abdominal cavity on each CT scan. Moreover, the lesion was missed in the first two CT images because it was difficult to distinguish it from the nearby collapsed small intestine. The lesion was eventually detected through angiography; however, the correct diagnosis and treatment were delayed for 3 years because it was mistaken for a vascular malformation, which is the most common cause of obscure GI bleeding in elderly patients. This report emphasizes the need for interventional radiologists to be updated and vigilant of the angiographic features of GISTs to make an accurate diagnosis and establish a management strategy.
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Unilateral vocal cord palsy (UVCP) is frequently observed in patients with stroke. This study aimed to evaluate the association between objective dysphonia severity and the classification of UVCP in patients with stroke by objectively and quantitatively measuring their phonetic function. We recruited patients with UVCP diagnosed using laryngoscopy after stroke.Subgroups were divided according to UVCP type, and the dysphonia severity index (DSI) and maximum phonation time (MPT) were measured to objectively evaluate dysphonia. The DSI and MPT were compared between subgroups using analysis of variance with Tukey’s honest significant difference post hoc test. In total, 103 patients with stroke and UVCP were recruited. We found that a higher UVCP severity possibly had to do with lower DSI and MPT values. We objectively confirmed that phonetic function was worse in patients with stroke with higher UVCP severity, and the DSI and MPT tests can be helpful in determining the severity and need for additional evaluation.
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Purpose@#This study aimed to evaluate the feasibility of surgeon-performed percutaneous transhepatic gallbladder drainage (PTGBD). @*Methods@#Patients treated with PTGBD for acute cholecystitis (AC), performed by surgeons at Chosun University Hospital for 12 months between March 2017 and February 2018, were enrolled retrospectively, into the S-PTGBD group (n = 134). Patients with PTGBD performed by interventional radiologists for 12 months, 6 months before March 2017, and after February 2018, were included in the X-PTGBD group (n = 107). In addition to the basic characteristics of the patients, severity of AC, comorbidities, intervals from hospital admission to the PTGBDs, procedural times, technical success rates, intention-to-treat rates, and complication rates were evaluated and compared. @*Results@#Except for the patient’s age (older in S-PTGBD), there were no differences in the patient’s basic profiles, including the severity of the AC and comorbidities. Although the procedural times were significantly shorter in the X-PTGBD group (18.13 minutes vs. 11.39 minutes), effectiveness indicators such as the technical success rates and intention-totreat rates and safety, such as the major complication rates in the S-PTGBD group, were comparable with those in the X-PTGBD group. The intervals between hospital admissions and PTGBDs were shorter in the S-PTGBD group, although this difference disappeared in the high-risk group. Effectiveness and safety in the high-risk group were also comparable between the groups. @*Conclusion@#The PTGBDs performed by surgeons are as effective and safe as those performed by interventional radiologists with faster implementation of PTGBD.
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Purpose@#Several investigations have been performed for a postoperative edema after extraction, but the results have been controversial due to low objectivity or poorly reproducible assessments of the edema. The aim of this study was to suggest a classification and patterns of postoperative edema according to the anatomical division associated with extraction of mandibular third molar as a qualitative evaluation method. @*Methods@#This study was conducted forty-four mandibular third molars extracted and MRI was taken within 48 h after extraction. The postoperative edema space was classified by MRI (one anatomic component—buccinator muscle—and four fascial spaces—supra-periosteum space, buccal space, parapharyngeal space, and lingual space), and evaluated independently by two examiners. The inter-examiner reliability was calculated using Kappa statistics. @*Results@#The evaluation of buccinator muscle edema showed good agreement and the fascial spaces showed constant high agreement. The incidence of postoperative edema was high in the following order: supra-periosteum space (75.00%), buccinator muscle (68.18%), parapharyngeal space (54.55%), buccal space (40.91%), and lingual space (25.00%). @*Conclusion@#Postoperative edema could be assessed clearly by each space, which showed a different tendency between the anatomic and fascial spaces.
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Background@#Angiotensin-converting enzyme 2 facilitates the entry of severe acute respiratory syndrome coronavirus 2 into the human body. We investigated the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with severe coronavirus disease 2019 (COVID-19) outcomes in hypertensive patients. @*Methods@#We identified hypertensive patients with confirmed COVID-19 from the Korean Health Insurance Review and Assessment Service from inception to May 15, 2020. The primary outcome was the composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO), and death from COVID-19. The individual components were evaluated as secondary outcomes. @*Results@#Of 1,374 hypertensive patients with COVID-19, 1,076 (78.3%) and 298 (21.7%) were users and never-users of RAAS inhibitors, respectively. The RAAS inhibitor users were not associated with the risk of the primary outcome (adjusted odds ratio [aOR], 0.72; 95% confidence interval [CI], 0.46 to 1.10). The risk of ICU admission was significantly lower in the users than the never-users (aOR, 0.44; 95% CI, 0.24 to 0.84). The RAAS inhibitors were beneficial only in ICU admissions that did not require IMV (aOR, 0.28; 95% CI, 0.14 to 0.58). The risk of death from COVID-19 was comparable between the groups (aOR, 1.09; 95% CI, 0.64 to 1.85). We could not evaluate the risks of CRRT and ECMO owing to the small number of events. @*Conclusion@#RAAS inhibitor use was not associated with the composite of severe outcomes in the hypertensive patients with COVID-19 but significantly lowered the risk of ICU admission, particularly in patients who did not require IMV.
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Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Signaling pathways that are essential for virus production have potential as therapeutic targets against COVID-19. In this study, we investigated cellular responses in two cell lines, Vero and Calu-3, upon SARS-CoV-2 infection and evaluated the effects of pathway-specific inhibitors on virus production. SARS-CoV-2 infection induced dephosphorylation of STAT1 and STAT3, high virus production, and apoptosis in Vero cells. However, in Calu-3 cells, SARS-CoV-2 infection induced long-lasting phosphorylation of STAT1 and STAT3, low virus production, and no prominent apoptosis. Inhibitors that target STAT3 phosphorylation and dimerization reduced SARS-CoV-2 production in Calu-3 cells, but not in Vero cells. These results suggest a necessity to evaluate cellular consequences upon SARS-CoV-2 infection using various model cell lines to find out more appropriate cells recapitulating relevant responses to SARS-CoV-2 infection in vitro.
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Objectives@#Recent studies have reported that delayed initiation of clozapine can affect clinical response in patients with treatment-resistant schizophrenia (TRS). This study aimed to explore the relationship between delayed initiation of clozapine and acute treatment response. @*Methods@#Sixty-five inpatients with TRS who started clozapine for the first time were included through a retrospective chart review. Acute treatment response was defined as a 30% reduction in the Positive and Negative Syndrome Scale score or a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) at 4 weeks after initiating clozapine. @*Results@#After meeting the TRS criteria, the mean delay for initiating clozapine was approximately 13.8 months. The delay was shorter in patients who showed a better response to clozapine in logistic regression analysis (p=0.037). @*Conclusion@#Our findings suggest that reducing the delay in initiating clozapine increases the effectiveness of clozapine in patients with TRS.
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Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.
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Purpose@#The study aimed to investigate the current status and prognostic factors for overall survival in patients who had undergone pulmonary metastasectomy for colorectal cancer. @*Materials and Methods@#The data of 2,573 patients who had undergone pulmonary metastasectomy after surgery for colorectal cancer between January 2009 and December 2014 were extracted from the Korean National Health Insurance Service claims database. Patient-, colorectal cancer–, pulmonary metastasis–, and hospital-related factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis to identify prognostic factors for overall survival after pulmonary metastasectomy. @*Results@#The mean age of the patients was 60.9±10.5 years; 66.2% and 79.1% of the participants were male and had distally located colorectal cancer, respectively. Wedge resection (71.7%) was the most frequent extent of pulmonary resection; 21.8% of the patients underwent repeated pulmonary metastasectomies; 73% of pulmonary metastasectomy cases were performed in tertiary hospitals; 53.9% of patients were treated in Seoul area; 82% of patients received chemotherapy in conjunction with pulmonary metastasectomy. The median survival duration was 51.8 months. The 3- and 5-year overall survival rates were 67.7% and 39.4%, respectively. In multivariate analysis, female sex, distally located colorectal cancer, pulmonary metastasectomy-only treatment, and high hospital volume (> 10 pulmonary metastasectomy cases/yr) were positive prognostic factors for survival. @*Conclusion@#Pulmonary metastasectomy seemed to provide long-term survival of patients with colorectal cancer. The female sex, presence of distally located colorectal cancer, and performance of pulmonary metastasectomy in high-volume centers were positive prognostic factors for survival.
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Background@#Mouse hepatitis virus (MHV) A59 is a highly infectious pathogen and starts in the respiratory tract and progresses to systemic infection in laboratory mice. The complement system is an important part of the host immune response to viral infection. It is not clear the role of the classical complement pathway in MHV infection. @*Objectives@#The purpose of this study was to determine the importance of the classical pathway in coronavirus pathogenesis by comparing C1qa KO mice and wild-type mice. @*Methods@#We generated a C1qa KO mouse using CRISPR/Cas9 technology and compared the susceptibility to MHV A59 infection between C1qa KO and wild-type mice. Histopathological and immunohistochemical changes, viral loads, and chemokine expressions in both mice were measured. @*Results@#MHV A59-infected C1qa KO mice showed severe histopathological changes, such as hepatocellular necrosis and interstitial pneumonia, compared to MHV A59-infected wildtype mice. Virus copy numbers in the olfactory bulb, liver, and lungs of C1qa KO mice were significantly higher than those of wild-type mice. The increase in viral copy numbers in C1qa KO mice was consistent with the histopathologic changes in organs. These results indicate that C1qa deficiency enhances susceptibility to MHV A59 systemic infection in mice. In addition, this enhanced susceptibility effect is associated with dramatic elevations in spleen IFN-γ, MIP-1 α, and MCP-1 in C1qa KO mice. @*Conclusions@#These data suggest that C1qa deficiency enhances susceptibility to MHV A59 systemic infection, and activation of the classical complement pathway may be important for protecting the host against MHV A59 infection.
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Purpose@#Cholecystectomy is the gold standard treatment for gallbladder disease. As life expectancy increases, awareness of cholecystitis treatment in the elderly changes. The safety and feasibility of cholecystectomy in octogenarians have been proven in many studies. Surgical treatment for cholecystitis should be considered in octogenarians and even nonagenarians. In this study, we aimed to assess the outcomes of cholecystectomy in octogenarians and nonagenarians with acute cholecystitis. @*Methods@#A total of 393 patients aged 80 to 89 years (352 octogenarians) and 90 to 99 years (41 nonagenarians) diagnosed with acute cholecystitis underwent cholecystectomy between March 2012 and June 2020. All patients were classified according to the Tokyo guidelines. The evaluated parameters included demographic data, surgical outcomes, American Society of Anesthesiologists physical status classification, and Tokyo guidelines. @*Results@#All 393 patients were analyzed and divided into two groups according to age; octogenarians (83.57 ± 2.64 years) and nonagenarians (92.98 ± 3.15 years). The survival rate was 97.7% for octogenarians and 97.6% for nonagenarians. Laparoscopic surgery was performed more in both groups (96.8% in octogenarians and 92.7% in nonagenarians) than open surgery (3.2% in octogenarians and 7.3% in nonagenarians). The operation time of the nonagenarian group (74.63 ± 30.83 minutes) was shorter than the octogenarian group (75.85 ± 34.63 minutes). The incidences of postoperative complications in the octogenarian and nonagenarian groups were as follows: pneumonia, 5.7% and 7.3%; bleeding, 1.7% and 2.4%; gastrointestinal symptoms, 6.0% and 2.4%; and bile leakage, 0.6% and 2.4%, respectively. @*Conclusion@#Cholecystectomy is a safe and efficient procedure for the treatment of acute cholecystitis in both octogenarians and nonagenarians.