Laparoscopic Cholecystectomy in the Time of Coronavirus: A Level-1 Trauma Center's Experience.

INTRODUCTION: Laparoscopic cholecystectomy (LC), one of the most common surgical procedures performed in the U.S., offers a window into the effects of the COVID-19 pandemic on routine surgical care. The purpose of our study was to analyze the effects of the COVID-19 pandemic at a Level-1 trauma center on the performance rate of non-elective LC over time. METHODS: A retrospective chart review from July 2019 to December 2020 identified all non-elective LC cases performed at a level-1 trauma center. Patients were categorized into 4 temporal phases along the course of the pandemic based on statewide incidence data on COVID-19: pre-pandemic, peak 1, recovery, and peak 2. We compared the phases based on demographic information and outcomes. RESULTS: In total, 176 patients were reviewed. The performance rate in cases/day varied as follows: pre-pandemic .61, 1st peak .34, recovery .44, and 2nd peak .53. The complication rate was highest in the 2nd peak (16%) (P < .05). Compared to the pre-pandemic period, the intra-pandemic period had a higher incidence of complicated gallbladder disease (P < .05). In the non-elderly subgroup, complicated gallbladder disease was significantly more prevalent in the intra-pandemic period compared to the pre-pandemic period (25% vs 10%, P < .05). CONCLUSIONS: Our data suggests a learning curve throughout the course of the pandemic, reflecting a stepwise increase in the performance rate of LC. The higher incidence of complicated gallbladder disease in the intra-pandemic period may imply patient hesitancy to seek routine surgical care, especially among younger patients.

Efficacy and safety of direct peroral cholangioscopy using a new multibending ultra-slim endoscope for the management of biliary diseases.

BACKGROUND/PURPOSE: Compared with currently available duodenoscopy-assisted systems, direct peroral cholangioscopy (DPOC) using an ultra-slim endoscope is limited by technical difficulties. The multibending (MB) ultra-slim endoscope was introduced as a dedicated cholangioscope for DPOC to challenge the technical problem. We retrospectively analyzed the clinical utility of DPOC using an MB endoscope with free-hand insertion into the bile duct in patients with biliary diseases. METHODS: A total of 145 patients who underwent DPOC using an MB endoscope were analyzed. The primary outcome was the technical success rate of DPOC using the free-hand insertion of the MB endoscope. The secondary outcomes were the technical success rates of DPOC-guided diagnostic and therapeutic interventions, the diagnostic accuracy of DPOC-guided target biopsy, and adverse events related to DPOC. RESULTS: Free-hand biliary insertion of a MB endoscope for DPOC was technically successful in 133 patients (91.7%). DPOC-guided target biopsy was successful in 36 of 38 patients (94.7%) and had a diagnostic accuracy of 91.7% (95% confidence interval, 82.6-100). Sixty-nine therapeutic interventions were performed; technical success was achieved in 65 (94.2%). No severe adverse events were observed. CONCLUSIONS: The MB ultra-slim endoscope was technically effective to perform a DPOC including various diagnosis and therapeutic interventions without device assistance. MB endoscope is considered to contribute to expanding a role of DPOC in diagnosis and treatment of diverse biliary tract diseases.

Maternal smoking during pregnancy is risk factor for gallbladder disease in offspring during adulthood: a prospective study from UK Biobank.

INTRODUCTION AND OBJECTIVES: Gallbladder disease is a common disease with high prevalence. Majority of gallbladder disease is due to gallstone. Though genetics are believed to play a role in its pathogenesis, the contribution of environmental pressures in early life to the development of this disease in adulthood has not been ever investigated. This study aimed to clarify the risk of maternal smoking exposure in association with gallbladder disease in adulthood. The interaction of maternal smoking and own smoking during adulthood on this association was studied as well. PATIENTS AND METHODS: A total of 286,731 eligible participants from the UK Biobank population-based cohort were included. Multivariable Cox regression analysis were used to examine the HR and 95% CI with adjustment for covariates. RESULT: During a median of 8.8 years follow-up, 7110 incident cases of gallbladder disease including 6800 (95.6%) gallstone were identified. Maternal smoking was associated with increased risk of incident total gallbladder disease (HR = 1.13; 95%CI: 1.06 - 1.21; P = 0.0002) as well as gallstones (HR = 1.13; 95%CI: 1.06 -1.21; P = 0.0003) in adulthood. Compared with those who were neither exposed to maternal smoking nor own smoking, subjects adherence to no smoking during adulthood but having maternal smoking exposure still had increased risk of total gallbladder disease (HR = 1.21; 95%CI: 1.1-1.34, P=0.0001) and gallstones (HR = 1.21; 95%CI: 1.1-1.35, P=0.0001). CONCLUSION: The present study using large prospective cohort data from UK Biobank, for the first time, demonstrated maternal smoking exposure bringing elevated risk of incident total gallbladder disease/gallstone in adulthood.

Masquerade: an unusual presentation of gall bladder perforation as umbilical fistula.

A 75-year-old woman presented with intermittent abdominal pain and distention for 2 months, followed by purulent discharge from the umbilicus for ten days. She was evaluated and diagnosed to have perforation of the gall bladder leading to formation of an anterior abdominal wall abscess which presented as an umbilical fistula. She underwent laparoscopic cholecystectomy along with lay open of abscess in the falciform ligament and curettage of the umbilical fistula tract. She had an uneventful postoperative recovery.

Fasting gallbladder volume is increased in patients with Parkinson's disease.

INTRODUCTION: Autonomic denervation in patients with Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) could impede gallbladder function leading to increased fasting gallbladder volume (fGBV) and higher risk of gallstones. We aimed to determine fGBV in patients with PD, iRBD, and healthy controls (HCs). METHODS: We included 189 subjects; 100 patients with PD, 21 with iRBD, and 68 HCs. fGBV was determined from abdominal CT scans, and radiopaque gallstone frequency was evaluated. RESULTS: Median fGBV was 35.7 ml in patients with PD, 31.8 ml in iRBD, and 27.8 ml in HCs (Kruskal-Wallis test: P = 0.0055). Post-tests adjusted for multiple comparison revealed a significant group difference between patients with PD and HCs (P = 0.0038). In the PD group, 23% had enlarged fGBV (cut-off at mean + 2 x standard deviation (SD) in the HC group). No difference in fGBV was observed between iRBD and the other two groups. The total prevalence of gallstones was 6.4% with no differences between the three groups. CONCLUSION: Almost a quarter of patients with PD in our cohort exhibited increased fGBV. This study illuminates a potentially overlooked topic in PD research and calls for more studies on biliary dysfunction.

Synchronous gallbladder metastasis of renal cell carcinoma presenting as a gallbladder polyp: A case report.

RATIONALE: Gallbladder polyps are common in the general population, but gallbladder metastasis of renal cell carcinoma (RCC) is very rare. In a patient with RCC diagnosed with a small gallbladder polyp that does not meet the traditional size criteria, the surgeon faces a dilemma of whether cholecystectomy should be performed given the possibility of metastasis. PATIENT CONCERNS: A 55-year-old man who had received a left nephrectomy for RCC presented with a gallbladder polyp that was noted at the time of the nephrectomy. Imaging showed the maximum diameter of the polyp had increased from 5 mm to 24 mm in the 40 months after the initial diagnosis. DIAGNOSIS: Pathological and immunohistology findings confirmed the gallbladder polyp as a metastasis of clear-cell RCC. INTERVENTIONS: : We performed a laparoscopic cholecystectomy. OUTCOMES: Even though the synchronous solitary gallbladder metastasis was left untreated and a cholecystectomy was not performed over the 40 months, no metastasis occurred in other sites. The patient is free from disease 10 months after the cholecystectomy. LESSONS: Solitary gallbladder metastasis of RCC may have more favorable outcomes than typical metastases. Although gallbladder metastasis of RCC occur rarely, it can occur, and any changes in gallbladder polyps in RCC patients should be managed under a strong suspicion of metastasis.

Congenital Glucagon-like Peptide-1 Deficiency in the Pathogenesis of Protracted Diarrhea in Mitchell-Riley Syndrome.

CONTEXT: Mitchell-Riley syndrome due to RFX6 gene mutations is characterized by neonatal diabetes and protracted diarrhea. The RFX6 gene encodes a transcription factor involved in enteroendocrine cell differentiation required for beta-cell maturation. In contrast to the pathway by which RFX6 mutations leads to diabetes, the mechanisms underlying protracted diarrhea are unknown. OBJECTIVE: To assess whether glucagon-like peptide-1 (GLP-1) was involved in the pathogenesis of Mitchell-Riley syndrome protracted diarrhea. METHODS: Two case report descriptions. in a tertiary pediatric hospital. "Off-label" treatment with liraglutide. We describe 2 children diagnosed with Mitchell-Riley syndrome, presenting neonatal diabetes and protracted diarrhea. Both patients had nearly undetectable GLP-1 plasma levels and absence of GLP-1 immunostaining in distal intestine and rectum. The main outcome was to evaluate whether GLP-1 analogue therapy could improve Mitchell-Riley syndrome protracted diarrhea. RESULTS: "Off-label" liraglutide treatment, licensed for type 2 diabetes treatment in children, was started as rescue therapy for protracted intractable diarrhea resulting in rapid improvement during the course of 12 months. CONCLUSION: Congenital GLP-1 deficiency was identified in patients with Mitchell-Riley syndrome. The favorable response to liraglutide further supports GLP-1 involvement in the pathogenesis of protracted diarrhea and its potential therapeutic use.

Unusual case of cholecystocolonic fistula secondary to megabowel.

Cholecystocolonic fistula with associated idiopathic megabowel (megacolon and megarectum) is a rare presentation as acute large bowel obstruction. Frequently presenting with chronic constipation, acute bowel obstruction is rarely encountered in the presence of concomitant cholecystocolonic fistula. This presents diagnostic and management difficulties with no consensus on appropriate surgical approach. This case highlights the outcomes following emergency total colectomy and subtotal cholecystectomy as a single-stage procedure for a 68-year-old man presenting with cholecystocolonic fistula secondary to idiopathic megabowel as acute large bowel obstruction.

Fistulization between liver hydatid cyst and gallbladder. A case report and review of the literature.

The most serious complications of liver hydatid cyst disease are fistulization into biliary tract, compression of adjacent vascular structures, anaphylactic reaction, and perforation. Fistulization between liver hydatid cyst and gallbladder tract is an extremely rare complication with only a few cases reported so far. Herein, we aimed to report a 43-year-old man who was diagnosed as having a cholecysto-hydatid cyst fistula. The patient presented to emergency department with signs and symptoms of cholangitis. His biochemical tests revealed elevated AST, ALT, GGT, and bilirubin levels. The radiological examinations (CT, MRCP) revealed a lesion consistent with hydatid cyst (Hydatid cyst ELISA IgG +) with an approximate size of 90*65 mm, which was posterolateral to the gallbladder and fistulized into the latter. In order to relieve pressure within the biliary tract, ERCP with sphincterotomy was performed. He was taken to the operating room a few days later. After draping sponges soaked with 3% NaCl onto the surgical field, near-total pericystectomy + omentopexy + cholecystectomy + common bile duct exploration + T-tube drainage were performed. Bile duct opening to the posterior wall of the cyst was sutured with a prolene suture. Albendazole treatment was started on first postoperative day. After taking a cholangiogram on 21st postoperative day, the T-tube was removed without any complication. In conclusion, cholecysto-hydatid cyst fistula is an extremely rare complication of hydatid cyst disease even in endemic regions. The gold standard for the diagnosis is the combined use of characteristics of clinical presentation, biochemical parameters, and radiological studies. Treatment plan is designed on the basis of the relationship of a fistulized cyst with other bile ducts. KEY WORD: Cholecysto-Hydatid Cyst Fistula, Gallbladder, Hydatid Cyst, Liver.

Disseminated Tuberculosis with Cholecystitis in a Patient after Cord Blood Transplantation.

The incidence of an active tuberculosis infection after allogeneic hematopoietic cell transplantation is high. We herein report the case of a patient with acute myeloid leukemia after cord blood transplantation (CBT). On day 36 after CBT, the patient developed fever, and a computed tomography scan on day 36 showed mild thickening of the wall of the gallbladder. Subsequently, a sputum specimen and a blood culture returned positive for the growth of Mycobacterium tuberculosis. After 2 months of administering combination therapy, both the symptoms and gallbladder findings improved. We therefore describe a case of disseminated tuberculosis with the gallbladder mimicking acute cholecystitis in a CBT recipient.

Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model.

Hepatobiliary disease causes significant morbidity in people with cystic fibrosis (CF), yet this problem remains understudied. We previously found that newborn CF pigs have microgallbladders with significant luminal obstruction in the absence of infection and consistent inflammation. In this study, we sought to better understand the early pathogenesis of CF pig gallbladder disease. We hypothesized that loss of CFTR would impair gallbladder epithelium anion/liquid secretion and increase mucin production. CFTR was expressed apically in non-CF pig gallbladder epithelium but was absent in CF. CF pig gallbladders lacked cAMP-stimulated anion transport. Using a novel gallbladder epithelial organoid model, we found that Cl- or HCO3- was sufficient for non-CF organoid swelling. This response was absent for non-CF organoids in Cl-/HCO3--free conditions and in CF. Single-cell RNA-sequencing revealed a single epithelial cell type in non-CF gallbladders that coexpressed CFTR, MUC5AC, and MUC5B. Despite CF gallbladders having increased luminal MUC5AC and MUC5B accumulation, there was no significant difference in the epithelial expression of gel-forming mucins between non-CF and CF pig gallbladders. In conclusion, these data suggest that loss of CFTR-mediated anion transport and fluid secretion contribute to microgallbladder development and luminal mucus accumulation in CF.

Association between the non-HDL-cholesterol-to-HDL-cholesterol ratio and the risk of gallbladder polyp formation among men: a retrospective cohort study.

BACKGROUND: Dyslipidaemia and male sex are associated with gallbladder polyp (GBP) formation. However, the potential relation between the non-high-density lipoprotein-cholesterol-to-high-density lipoprotein-cholesterol (non-HDL-c/HDL-c) ratio and GBPs in men is unclear. METHODS: A total of 1866 eligible subjects were selected for this retrospective cohort study from Wuhan Union Hospital between April 1, 2013, and November 30, 2014. Clinical and laboratory data of subjects were collected. Patients with GBPs or cholecystectomy at baseline, with missing data for baseline lipid profiles, following abdominal ultrasonography or taking lipid-lowering drugs were excluded. The patients were divided into five groups based on their non-HDL-c/HDL-c ratios, and descriptive analyses of the baseline data were performed. A Cox proportional hazards model was applied to estimate the relationship between the non-HDL-c/HDL-c ratio and GBPs. RESULTS: After a median follow-up of 1 year, 7.34% (n = 137) of the subjects developed GBPs. Compared with subjects without GBPs, those who developed GBPs after follow-up had significantly higher triglyceride (TG) levels and non-HDL-c/HDL-c ratios. The prevalence of GBPs showed a linearity increment with age, peaked in the 30-39 years group, 40-49 years group and 50-59 years group, and then declined slightly. The results of univariate analysis showed that the non-HDL-c/HDL-c ratio (hazard ratio (HR) = 1.29, 95% confidence interval (CI), 1.05-1.60, P = 0.0159) was positively correlated with GBPs. In the fully adjusted Cox regression model, the HRs were 2.24 for quintile 2 (95% CI: 1.13-4.44, P = 0.0203), 1.50 for quintile 3 (95% CI: 0.73-3.10, P = 0.269), 2.52 for quintile 4 (95% CI: 1.26-5.01, P = 0.0087) and 2.13 for quintile 5 (95% CI: 1.04-4.37, P = 0.0397). No interaction was found among the subgroups. CONCLUSIONS: A higher non-HDL-c/HDL-c ratio is independently related to a higher risk of GBP formation in Chinese men. Further research is needed to investigate whether this association exists in different regions and races.

Incidence of and risk factors for late cholecystectomy in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Gallbladder disease and need for cholecystectomy are common and significant contributors to patient morbidity and healthcare costs. Childhood cancer survivors are at elevated risk for developing cholelithiasis. However, their incidence of and risk factors for late (>5 years from diagnosis) cholecystectomy have not been studied. METHODS: A total of 25,549 survivors (median age at diagnosis 6.9 years, range 0-21.0; current age 30.7 years, range 5.6-65.9) diagnosed between 1970 and 1999 and 5037 siblings were queried for self-reported cholecystectomy occurring five or more years from primary cancer diagnosis. Piecewise exponential models evaluated associations between cancer treatment exposures and late cholecystectomy. RESULTS: Over a median follow-up period of 21.9 and 26.0 years, respectively, 789 survivors and 168 siblings underwent late cholecystectomy (cumulative incidence 7.2%, 95% confidence interval [CI] = 6.5-7.8% and 6.6%, 95% CI = 5.4-7.6%, respectively; rate ratio [RR] = 1.3, 95% CI = 1.1-1.5). Compared with siblings, survivors of acute lymphoblastic leukaemia (RR = 1.4, 95% CI = 1.2-1.8), soft tissue sarcoma (RR = 1.4, 95% CI = 1.0-1.8) and bone cancer (RR = 1.3, 95% CI = 1.0-1.8) were at the greatest risk. In addition to attained age, female sex and increasing body mass index, exposure to high-dose (≥750 mg/m2) platinum chemotherapy (RR = 2.6, 95% CI = 1.5-4.5), vinca alkaloid chemotherapy (RR = 1.4, 95% CI = 1.1-1.8) or total body irradiation (TBI; RR = 2.2, 95% CI = 1.2-4.2) were each associated with late cholecystectomy. CONCLUSIONS: Independent of traditional risk factors for gallbladder disease, exposure to high-dose platinum chemotherapy, vinca alkaloid chemotherapy or TBI increased risk for late cholecystectomy. These findings should inform current long-term follow-up guidelines and education regarding risk for late cholecystectomy.

A Whole-Food-Based Health Product (A-F Betafood®) Improves Gallbladder Function in Humans at Risk of Gallbladder Insufficiency: A Randomized, Placebo-Controlled Clinical Trial.

A-F Betafood® is a whole food-based health product. The product contains phytonutrients and bioactives with antioxidant properties that may support gallbladder and liver function. Herein, we investigated the efficacy of A-F Betafood® on gallbladder and liver function. In this randomized, placebo-controlled, parallel study fifty overweight but otherwise healthy adults received A-F Betafood® or placebo for 12 weeks. Gallbladder function as assessed by gallbladder volume, ejection fraction (GBEF), ejection rate, wall thickness and liver function determined via aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase, and high-sensitivity c-reactive protein analysis at baseline and week 12 were the primary outcomes. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and oxidative stress markers including oxidized low-density lipoprotein, tumor necrosis factor-α, adiponectin and malonyldialdehyde (MDA) were assessed as secondary outcomes. A-F Betafood®-supplementation significantly reduced gallbladder wall thickness (p = 0.049) by 9% compared to placebo from baseline to week 12. The A-F Betafood® group alone had significant improvements in gallbladder volume (32%; p = 0.044) and GBEF (19%; p = 0.047) at week 12. There were no changes in liver function, oxidative stress markers or blood lipid concentrations, though MDA concentrations decreased in both groups. Our findings demonstrate A-F Betafood®-supplementation significantly improves measures of gallbladder function and support healthy gallbladder function in the individuals with gall bladder condition.

Risk factors of gallbladder polyps formation in East Asian population: A meta-analysis and systematic review.

To perform Meta-analysis to identify risk factors associated with gallbladder polyps (GBP) formation in east Asian population. Three English electronic bibliographic databases includes PubMed, Embase and Medline, with reviewed researches from 1986 to 2017. All possible risk factors of GBP formation were recorded. Meta-analyses were performed by Review Manager Software. Pooled odds ratios (OR) or the mean difference (MD) were used to determine risk factors. Sixteen studies and 227021 people were recruited, including 17261 people with GBP and 209760 without GBP. For categorical variables evaluated by OR test., risk factors of GBP formation were male gender (OR, 1.63; 95%CI, 1.42-1.87) and positive HBsAg. GBP formation were not correlated with age <50 years old, hypertension, DM, BMI ≥ 25kg/m2, smoking, drinking, HDL decrease, TC increase, TG increase, fatty liver and GBS. For continuous variables evaluated by MD test, risk factors of GBP formation were DBP (MD, 1.08; 95%CI, 0.15-2.02), mean BMI (MD,0.19; 95%CI,0.02-0.35), waist circumference (MD,1.780; 95%CI, 0.17,3.40), mean LDL (MD,0.89; 95%CI,0.03-1.75), mean HDL (MD,-1.87; 95%CI,-3.21 to -0.52). GBP formation were not correlated with mean age, SBP, mean TC, mean TG, ASL and ALT. In conclusion, risk factors of gallbladder polyp formation included male gender, higher BMI, higher waist circumference, higher DBP, higher LDL, lower HDL and positive HBsAg in east Asian population. GBP formation was not correlated with age, hypertension, DM, smoking, drinking, fatty liver, GBS, TC, TG, SBP, ASL and ALT. The mechanism of Dyslipidemias causing GBP needs deeper study in future.