Search

Objective: Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention., Design: We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc. Further molecular mechanism was demonstrated with in vitro and in vivo studies., Results: The cell atlas unveiled an altered immune landscape across different pathological states of gallbladder diseases. GBC featured a more suppressive immune microenvironment with distinct T-cell proliferation patterns and macrophage attributions in different GBC subtypes. Notably, mutual exclusivity between stromal and immune cells was identified and remarkable stromal ecosystem (SC) heterogeneity during GBC progression was unveiled. Specifically, SC1 demonstrated active interaction between Fibro-iCAF and Endo-Tip cells, correlating with poor prognosis. Moreover, epithelium genetic variations within adenocarcinoma (AC) indicated an evolutionary similarity between adenoma and AC. Importantly, our study identified elevated olfactomedin 4 (OLFM4) in epithelial cells as a central player in GBC progression. OLFM4 was related to T-cell malfunction and tumour-associated macrophage infiltration, leading to a worse prognosis in GBC. Further investigations revealed that OLFM4 upregulated programmed death-ligand 1 (PD-L1) expression through the MAPK-AP1 axis, facilitating tumour cell immune evasion., Conclusion: These findings offer a valuable resource for understanding the pathogenesis of gallbladder diseases and indicate OLFM4 as a potential biomarker and therapeutic target for GBC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the thickness of each layer of the gallbladder wall with different diseases in dogs., Sample: 72 gallbladders., Methods: Retrospective study of dogs that underwent cholecystectomy. Histopathological specimens of the gallbladders were reviewed. Histopathological diagnosis was made as gallbladder mucocele or cholecystitis, and cholecystitis was further categorized into chronic cholecystitis, acute-on-chronic cholecystitis, acute cholecystitis, and necrotic cholecystitis. The thickness of each layer of the gallbladder wall was measured., Results: 22 dogs were diagnosed with gallbladder mucocele without cholecystitis, 24 with gallbladder mucocele and cholecystitis, 20 with only cholecystitis, and 6 as normal. Histopathological subclassification of cholecystitis in 44 gallbladders led to diagnosis of chronic cholecystitis in 21 gallbladders, acute-on-chronic cholecystitis in 10 gallbladders, acute cholecystitis in 6 gallbladders, and necrotic cholecystitis in 7 gallbladders. The thickness of the entire wall of the gallbladder (P < .0001) and the thickness of the mucosa (P < .0001) and subserosa (P < .0001) were affected by the different disease processes., Clinical Relevance: Layers of the gallbladder wall were affected by diseases present in the gallbladder. It resulted in a difference in the thickness of the wall of the gallbladder among the gallbladder diseases in this study. Histopathological changes should be taken into consideration before surgery while deciding what technique to use to perform a cholecystectomy.

Background: The aim of this study was to establish features of inflammation in histologically normal gallbladders with gallstones and compare the expression of inflammatory markers in acutely and chronically inflamed gallbladders., Methods: Immunohistochemistry was performed on formalin-fixed paraffin-embedded gallbladders for tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R, and substance p in three groups: Group I (n = 60) chronic cholecystitis, Group II (n = 57) acute cholecystitis and Group III (n = 45) histologically normal gallbladders with gallstones. Expression was quantified using the H-scoring system., Results: Median, interquartile range expression of mucosal IL-2R in Groups I (2.65, 0.87-7.97) and II (12.30, 6.15-25.55) was significantly increased compared with group III (0.40, 0.10-1.35, p < 0.05). Submucosal IL-2R expression in Groups I (2.0, 1.12-4.95) and II (10.0, 5.95-14.30) was also significantly increased compared with Group III (0.50, 0.15-1.05, p < 0.05). There was no difference in the lymphoid cell IL-6 expression between Groups I (5.95, 1.60-18.15), II (6.10, 1.1-36.15) and III (8.30, 2.60-26.35, p > 0.05). Epithelial IL-6 expression of Group III (8.3, 2.6-26.3) was significantly increased compared with group I (0.5, 0-10.2, p < 0.05) as was epithelial TNF-α expression in Group III (85.0, 70.50-92.0) compared with Groups I (72.50, 45.25.0-85.50, p < 0.05) and II (61.0, 30.0-92.0, p < 0.05). Lymphoid cell Substance P expression in Groups I (1.90, 1.32-2.65) and II (5.62, 2.50-20.8) was significantly increased compared with Group III (1.0,1.0-1.30, p < 0.05). Epithelial cell expression of Substance P in Group III (121.7, 94.6-167.8) was significantly increased compared with Groups I (75.7, 50.6-105.3, p < 0.05) and II (78.9, 43.5-118.5, p < 0.05)., Conclusion: Histologically normal gallbladders with gallstones exhibited features of inflammation on immunohistochemistry., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

The relationship between Helicobacter pylori infection and gallbladder diseases, particularly cholecystitis and gallbladder polyps, remains unclear. This study aimed to investigate the presence of H. pylori in gallbladder tissues and its potential role in gallbladder pathologies, as well as to examine the expression of chemokines CXCL2 and CXCL5 in these conditions., Material and Methods: A total of 137 laparoscopically excised gallbladders were analysed through histological examination, PCR for H. pylori-specific DNA, and quantitative real-time PCR for CXCL2 and CXCL5 gene expression. The study cohort included patients with acute calculous cholecystitis, chronic calculous cholecystitis, and gallbladder polyps., Results: H. pylori was detected in 30.7% of cases by histological methods and 42.3% by PCR. Elevated expression of CXCL2 and CXCL5 was observed in 62% and 57.7% of cases, respectively, with a higher prevalence in acute cholecystitis compared to chronic conditions. However, no statistically significant association was found between H. pylori presence and the forms of cholecystitis, as well as between H. pylori presence and chemokine expression in gallbladder., Conclusions: The study did not establish a direct link between the presence of H. pylori infection and forms of gallbladder pathologies. The findings suggest that other factors other than H. pylori may contribute to the upregulation of CXCL2 and CXCL5 in gallbladder diseases. Further research is needed to elucidate the complex interactions between H. pylori, chemokines, and gallbladder pathologies.

Background: Ultrasound is an integral part of evaluating for acute cholecystitis and choledocholithiasis in pediatric patients. Finding the common bile duct (CBD), a structure which is normally <4 mm in children, can be very challenging., Objective: The primary objective of this study was to determine the prevalence of isolated sonographic CBD dilation in pediatric patients with acute cholecystitis and/or choledocholithiasis without laboratory abnormalities or pathologic findings on radiology based biliary ultrasound, apart from cholelithiasis., Methods: We conducted a retrospective chart review of patients ≤21-years-old, at a single free-standing tertiary care children's hospital, who received a biliary ultrasound in the radiology department (RADUS) from September 2005 to February 2020. We identified patients who had a diagnosis of acute cholecystitis and/or choledocholithiasis on RADUS. Based on prior studies, a positive ultrasound was defined as having gallbladder wall thickening (GWT), pericholecystic fluid (PCF), or sonographic Murphy's sign (SMS). The final diagnosis was confirmed using the gold standard, cholecystectomy pathology diagnosis for patients with cholecystitis and endoscopic retrograde cholangiopancreatography (ERCP) diagnosis for patients with choledocholithiasis. Ultrasound data and contemporaneous laboratory values were collected., Results: 180 patients met inclusion criteria. For the study population, 97 (53.9%) had a positive ultrasound, 127 patients (70.6%) had a dilated CBD, and 170 (94.4%) had at least one abnormal laboratory finding. Within the study population there were 76 patients (42.3%) with acute cholecystitis, 55 patients (30.5%) with choledocholithiasis, and 49 patients (27.2%) with acute cholecystitis and choledocholithiasis. Of the 127 patients with a dilated CBD, 80 (62.9%) had a normal ultrasound, apart from cholelithiasis. In this group of 80, 78 patients (97.5%) had at least one abnormal laboratory finding. Thus, for the entire study population, isolated CBD dilation without a positive ultrasound or laboratory abnormalities occurred in 2 patients (1.1%). Of note, these 2 patients had an ultrasound diagnosis of choledocholithiasis., Conclusion: The prevalence of isolated sonographic CBD dilation in pediatric patients with cholecystitis and/or choledocholithiasis was 1.1%. Thus, biliary ultrasound without CBD measurement is unlikely to result in missed cholecystitis and/or choledocholithiasis if the biliary ultrasound does not demonstrate GWT, PCF, SMS, or choledocholithiasis, and the patient has normal laboratory values., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Both xanthogranulomatous cholecystitis (XGC) and IgG4-related cholecystitis (IgG4-CC) are rare chronic fibroinflammatory tumefactive diseases of the gallbladder, which cause a strong confusion with resectable malignancy in view of their mass forming tendency with extension into the liver. We aim to study the histopathologic features of xanthogranulomatous cholecystitis with regard to IgG4-related cholecystitis in extended cholecystectomy specimens., Methods and Results: Sixty cases of extended cholecystectomy with liver wedge resection, diagnosed as XGC on histopathology from January 2018 to December 2021 were retrieved from the archives. Representative sections were reviewed by two pathologists independently. Immunohistochemistry was performed for IgG4 and IgG4/IgG was derived. The cases were dichotomized in two groups on the basis of IgG4 positive plasma cells. Six cases with >50 IgG4 positive plasma cells had storiform fibrosis, IgG4/IgG ratio >0.40 and extra-cholecystic extension. Of these, 50 % had obliterative phlebitis and 66.7 % had perineural plasma cell wrapping., Conclusions: A small subset of XGC cases (~10 %) had morphologic overlap with IgG4-CC, but should not be overcalled as the diagnosis of IgG4-RD requires an integrative approach based on clinical, serologic and imaging criteria and not solely on histopathology., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The timing of cholecystectomy during acute cholecystitis (AC) is controversial, especially whether it is advisable to perform in patients with duration of symptoms between 3 and 10 days. The purpose of this study is to define clearly the sequential evolution of histological changes following symptoms onset to guide recommendations regarding timing of cholecystectomy., Methods: We identified patients with AC (2005-2018) who had cholecystectomy within 10 days of symptom onset of a first attack of AC. Histologic features of gallbladder injury including cellular and exudative inflammatory response to injury were determined on blinded pathologic slides., Results: One hundred and forty-nine patients were divided into three groups; early-who underwent cholecystectomy 1-3 days after symptom-onset, intermediate-4-6 days, and late-7-10 days. Key features of injury were necrosis and hemorrhage. A subgroup of patients in the early phase developed severe necrosis and hemorrhage of an extent associated with difficult cholecystectomy. Large spikes in extent of necrosis and hemorrhage occurred at 7-10 days. Major inflammatory responses to injury were eosinophilic and lymphocytic infiltration and early fibrosis., Conclusions: Severe necrosis may develop rapidly and be present in the early period after symptom onset of AC. Cholecystectomy may be reasonable in some patients but by day 7-10, severe necrosis and hemorrhage may be expected to be present in most patients., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objective: Aim: The study aimed to investigate some parameters of functional status of central and intracardiac haemodynamics in women with thyroid hyperplasia and acalculous cholecystitis., Patients and Methods: Materials and Methods: Functional changes of haemodynamic status in women with thyroid hyperplasia and acalculous cholecystitis were investigated. All data are obtained through general and special clinical methods, standard and special laboratory methods of examination, physiological, biochemical and statistical methods. Parameters of central and intracardiac haemodynamics have been recorded by the method of two-dimensional M-mode echocardiography in the echo chamber "Toshiba-140" (Japan) at the resting state., Results: Results: An increase in heart rate (by 45.6%) was observed in patients, which led to decreased duration of cardiac cycle and ejection time. Statistically significant (p<0.05, 11.7% on average) increase in total peripheral vascular resistance was indicated. Dynamics of changes of parameters of central and intracardiac haemodynamics indicates different parallel existing pathways of secondary disturbances in the part of cardiovascular system. A significant increase in peripheral vascular resistance associated with decreased elasticity (increased vascular rigidity) of the arteries is the element of concentric type of left ventricular hypertrophy. The increase in volume in the absence of vasospastic reactions and increasing venous tone is an element of eccentric hypertrophy., Conclusion: Conclusions: It is possible to talk about the presence of systolic dysfunction in patients, which, however, is predominantly of functional character. The revealed specific changes in homeostatic haemodynamic characteristics in the women's body with thyroid hyperplasia and acalculous cholecystitis require the development of new, more effective and preferably drug-free (due to liver pathology and detoxification dysfunction) approaches to medical treatment of such patients.

The aims of this retrospective study were to characterise the epidemiological, clinical, histopathological, and microbiological findings as well as surgical outcomes in dogs admitted to a specialist veterinary hospital in Hong Kong for surgical management of gallbladder mucocoele (GBM). Inclusion criteria were cases with histopathological diagnosis of GBM and accompanying abdominal imaging, serum biochemistry, bile culture, and liver biopsy histology results. Fifty-six cases met the inclusion criteria. The median age at diagnosis was 12 years (range, 5-16 years). Miniature or toy pure-breed dogs were most commonly affected, including Poodles, Pomeranians, Schnauzers, Bichon frises and Chihuahuas. However, no breed was over-represented compared with their expected proportions among annual hospital admissions. Histological evidence of cholecystitis was present in 84% of cases, including acute cholecystitis in 18%, chronic cholecystitis in 37.5%, acute on chronic cholecystitis in 28% and acute with necrosis in 6%. The most common liver lesions were cholestasis in 64%, along with portal fibrosis in 55%, oedema in 50% and bile duct hyperplasia in 50%. Bile culture was positive in 29.6% of cases. Escherichia coli and Enterobacter species were most commonly isolated. Stentrophomonas maltophili was cultured from one case. Of the 16 cases where bacteria were isolated from bile culture, 94% had evidence of chronic cholecystitis and 81% had evidence of cholangiohepatitis. Fifty dogs (89.3%) survived to discharge including 5/5 dogs with ruptured gallbladders. Of 34 dogs with follow-up data, 21/34 (61.8%) were still alive 12 months later. Gallbladder mucocoeles were frequently associated with both acute and chronic inflammation. High survival rates to discharge were achieved., Competing Interests: Conflict of interest statement None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Cholecystectomy in patients with hematologic malignancies remains poorly understood., Methods: We retrospectively evaluated patients with hematologic malignancies who underwent cholecystectomy at a single institution., Results: Of 313 patients who presented for evaluation of abdominal pain, 64 underwent cholecystectomy for acute cholecystitis (34.4%), gangrenous cholecystitis (21.9%), chronic cholecystitis (23.4%), and cholelithiasis (20%). Most had a history of hematopoietic cell transplantation (62.5%) and/or immunosuppressive medication within 30 days of consultation (82.8%). Ultrasound had a 39% false-negative rate for acute nongangrenous cholecystitis. Operative time was 92 ± 39 min, 7 were performed open, 10 had intraoperative transfusions, and 4 had grade 3+ complications. Intraoperative transfusion was associated with increased postoperative length of stay (p = 0.03). Open procedure, operative time, estimated blood loss, intraoperative transfusion, and complications were not associated with timing of surgery., Conclusions: Patients with hematologic malignancies can safely undergo cholecystectomy. Length of postoperative stay for inpatients is associated with intraoperative blood transfusion., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To summarize the value of multislice spiral CT (MSCT) in the differential diagnosis of thick-wall gallbladder carcinoma (TWGC) and chronic cholecystitis (CC), the clinical data of 36 patients with TWGC and 60 patients with chronic cholecystitis who were treated in our hospital from January 2017 to May 2021 were retrospectively analyzed, and the CT image features and diagnostic accuracy of the patients were summarized. Compared with the CC group, the proportions of disruption of gallbladder mucosa line, blurred gallbladder outline, high obstruction of biliary tract, lymphomegaly, adjacent invasion, peritoneal effusion, wall nodules, and the gallbladder wall thickness in the TWGC group were higher, with statistical significance ( P < 0.05). Thirty-four patients with TWGC and 62 patients with chronic cholecystitis were diagnosed by MSCT. The sensitivity and specificity of MSCT in diagnosing TWGC were 86.11% and 95.00%, respectively. The positive likelihood ratio was 17.222 and the negative likelihood ratio was 0.1462. The positive prediction rate was 91.18%, the negative prediction rate was 91.94%, and the correct rate was 91.67%. MSCT can show the characteristic difference between TWGC and chronic cholecystitis, which can be used for differential diagnosis., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Hua Han and Jun Han.)

Aim: To identify sonographic signs of cholecystitis that correlate with surgical outcomes., Materials and Methods: Three hundred and thirty-three consecutive patients who underwent cholecystectomy between 22/06/2014 and 1/3/2016 and underwent abdominal ultrasound (US) within 7 days of surgery were included. Individual US signs, including gallstones, gallbladder distention, wall thickening, pericholecystic fluid, and abscess, were graded by two radiologists, 1 and 2. Outcomes included operative duration (OD), drain placement, partial cholecystectomy, conversion from laparoscopic to open cholecystectomy, surgical pathology, bile leak, infection, and 30-day readmission. US signs and outcomes were analysed using analysis of variance, chi-square test, or odds ratios (OR)., Results: Radiologist 1 reported 141/333 and radiologist 2 reported 128/333 patients showed gallbladder distention. For the subset with OD, radiologist 1 reported 140/320 and radiologist 2 reported 126/320 patients showed gallbladder distention. Distention was predictive of increased OD (radiologist 1, +23.2 minutes, p<0.0001; radiologist 2, +19.4 minutes, p=0.0003). Cases with gallbladder distention were more likely to have surgical drain placement (OR= 2.60; 95% confidence interval [CI]: 1.12-6.08, p=0.027 radiologist 1; OR=2.59; 95% CI: 1.13-5.95, p=0.025 radiologist 2). Wall thickening was present in 126/333 patients reported by radiologist 1 and 120/333 by radiologist 2. Cases with wall thickening were more likely to have drain placement (OR=2.66; 95% CI: 1.16-6.13, p=0.021 radiologist 1; OR=3.49; 95% CI: 1.49-8.16, p=0.004 radiologist 2). For the subset with OD, wall thickening was present for 121/320 reported by radiologist 1 and 116/320 by radiologist 2 and predicted longer OD (radiologist 1, +15.9 minutes, p=0.0033; radiologist 2, +13.3 minutes, p=0.0143)., Conclusion: Gallbladder distention and wall thickening on US correlate with prolonged OD and surgical drain placement in patients with cholecystitis., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Dysregulation in Wnt/β-catenin signaling has been associated with the initiation and metastasis of cancer cells. Transcription factor 4 (TCF4) (also named as transcription factor 7-like 2) is a key transcriptional factor of the Wnt signaling pathway, which, when interact with β-catenin activates Wnt genes which plays an essential role in tumor development. The expression pattern and clinical significance of TCF4 in gallbladder cancer (GBC) are not yet established., Aims: This study was performed to assess the expression pattern of TCF4 in GBC tissue and attempted to correlate its expression with different clinicopathological parameters., Materials and Methods: The study was conducted on 33 surgically resected specimens of gallbladder carcinoma (GBC) and 12 cases of chronic cholecystitis (CC) as control, which had been confirmed from histology. The expression of TCF4 was performed by the reverse transcription polymerase chain reaction and immunohistochemistry., Results: Relative mRNA expression levels of β-catenin and TCF4 in GBC tissues were significantly (P < 0.05) higher than in CC samples. TCF4 protein expression was observed in 81.82% (27/33) GBC cases. Specifically, among GBC samples, 21.21% (7/33) was graded as strongly positive, 60.61% (20/33) graded as moderately positive, whereas 18.18% (6/33) graded as negative. All 12 CC samples graded as negative. Overall, TCF4 expression in GBC tissues was statistically significant over CC samples (P < 0.05). Moreover, we observed that TCF4 expression was significantly higher (P < 0.05) in high tumor grades than low grade, higher (P < 0.05) in Stage 2 and Stage 3 than Stage 1., Conclusion: The present study suggests that TCF4 may exert an oncogenic role in the progression of GBC and may serve as a new potential candidate biomarker for tumor progression, and it might be a potential therapeutic target against GBC., Competing Interests: None

Gallbladder carcinoma is an uncommon malignancy with an overall 5-year survival of less than 5%. Gallbladder carcinoma has been strongly linked with cholelithiasis and chronic inflammation. Case reports and series have described cholecystitis with acute (neutrophilic) inflammation in association with gallbladder carcinoma, although a clear relationship to patient outcome has not been established. Our series included 8 cases of gallbladder carcinoma with high tumor-associated neutrophils (>25 per high power field) that were associated with shorter patient survival (Cox regression coefficient 6.2, p = 0.004) than age- and stage-matched controls. High tumor-associated neutrophils were not associated with gallbladder rupture/perforation or increased bacterial load measured by 16S PCR. Neutrophilic inflammation with gallbladder carcinoma correlates to shorter survival, independent of patient age and stage of carcinoma. The findings suggest that the degree of neutrophilic inflammation may have prognostic significance in specimens from patients with gallbladder carcinoma after cholecystectomy. Further studies with larger case numbers are needed to confirm and generalize these findings., (Copyright © 2021. Published by Elsevier Inc.)

An important article was published, whicht evaluated statistically significant associations (p < 0.05) using the odds ratio (OR), in the first issue of volume 113 of this journal. The study evaluated a relationship between C-reactive protein levels (CRP > 100) and the histological diagnosis of gangrenous acute cholecystitis in patients who underwent cholecystectomy (OR = 3.1).

Background: Xanthogranulomatous cholecystitis (XGC) is an extremely rare entity. Due to XGC's clinical and radiological resemblance to gallbladder carcinoma (GBC), intraoperative frozen section during cholecystectomy is often performed to exclude the diagnosis of GBC. Our study is aiming to find a noninvasive indicator of XGC. To our knowledge, this is the largest XGC cohort ever studied., Methods: This study retrospectively collected clinical characteristics, serological tests, and imaging features of 150 GBC patients and 90 XGC patients. The diagnosis of these 150 GBC patients and 90 XGC patients was based on intraoperative frozen section histopathology. T-test was utilized to compare differences between XGC and GBC. Receiver operating characteristic (ROC) curve was conducted and the area under the curve (AUC) was managed to evaluate the validity., Results: The carcinoembryonic antigen (CEA) level in blood tests was significantly elevated in GBC patients than in XGC patients (p = 0.007). The presence of submucosal hypo-attenuated nodules (80% in XGC, 16% in GBC, p < 0.001), low density border (60% in XGC, 21% in GBC, p = 0.001), and nodular thickening in the bottom of the gallbladder with calcification (70% in XGC, 37% in GBC, p = 0.004) is significantly associated with XGC patients, whereas massive hilar infiltration (0% in XGC, 21% in GBC, p < 0.001), multiple lymph nodes in the hilar area (10% in XGC, 72% in GBC, p = 0.001), and gallbladder mucosal line continuity (50% in XGC, 95% in GBC, p = 0.002) are highly associated with GBC patients. The ROC curve was performed and the gallbladder mucosal line continuity (AUC = 0.708) and the AUC of low density border around the occupation (AUC = 0.654) showed a good prediction of XGC., Conclusions: Gallbladder mucosal line continuity and low density border around the occupation presented good indication value for the diagnosis of XGC. Our study proposed a noninvasive differential diagnosis method for XGC and GBC., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Anecdotal evidence suggests that community infection control measures during the COVID-19 outbreak have modified the number and natural history of acute surgical inflammatory processes (ASIP-appendicitis, cholecystitis, diverticulitis and perianal abscesses) admissions. This study aims to evaluate the impact of the COVID-19 pandemic on the presentation and treatment ASIP and quantify the effect of COVID-19 infection on the outcomes of ASIP patients. This was a multicentre, comparative study, whereby ASIP cases from 2019, 2020 and 2021 (March 14th to May 2nd) were analyzed. Data regarding patient and disease characteristics as well as outcomes, were collected from sixteen centres in Madrid, and one in Seville (Spain). The number of patients treated for ASIP in 2019 was 822 compared to 521 in 2020 and 835 in 2021. This 1/3rd reduction occurs mainly in patients with mild cases, while the number of severe cases was similar. Surgical standards suffered a step back during the first wave: Lower laparoscopic approach and longer length of stay. We also found a more conservative approach to the patients this year, non-justified by clinical circumstances. Luckily these standards improved again in 2021. The positive COVID-19 status itself did not have a direct impact on mortality. Strikingly, none of the 33 surgically treated COVID positive patients during both years died postoperatively. This is an interesting finding which, if confirmed through future research with a larger sample size of COVID-19 positive patients, can expedite the recovery phase of acute surgical services., (© 2021. The Author(s).)

Background: Subtotal cholecystectomy is a "damage control" or "bailout procedure" that is used in difficult gallbladder cases when severe inflammation distorts the local anatomy resulting in increased risk in damage to surrounding structures. Subtotal cholecystectomy rates increased nationally over the past decade. We aimed to determine provider experience and patient factors associated with the performance of subtotal cholecystectomies., Methods: All cholecystectomies from 2016 to 2019 were reviewed. Patient demographics, laboratory values, imaging, preoperative diagnosis, surgical technique (fenestrating vs. reconstituting), and years of attending and resident experience were collected. Multivariable regression analysis was performed to evaluate for factors that increase the likelihood of subtotal cholecystectomy., Results: Of 916 cholecystectomies, 86 were subtotal. The likelihood of subtotal cholecystectomy did not increase based on attending experience of ≤5 vs. > 5 years (odds ratio (OR) .66, P = .09). Older age (adjusted odds ratio (aOR) 1.23, P = .03), male sex (aOR 2.59, P < .01), white blood cells (WBC) above 10.3 (aOR 2.02, P = .02), and preoperative diagnosis of acute on chronic cholecystitis (aOR 5.47, P < .01) were associated with increased likelihood of subtotal cholecystectomy., Discussion: Older age, male sex, WBC above 10.3, and preoperative diagnosis of acute on chronic cholecystitis were associated with the increased likelihood of subtotal cholecystectomies. The performance of subtotal cholecystectomy was not impacted by attending years of experience. In cases of severe gallbladder pathology, this technique is being used as an operative strategy among all surgeon levels.

Background: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis., Methods: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants., Results: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions., Conclusion: We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella , in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Introduction: Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory disease of the gallbladder (GB). XGC surgery is a difficult process due to its clinical, radiological, and intraoperative findings. In this study, our aim is to show the difficulties of XGC surgery and to find out if laparoscopic surgery is a sufficient procedure. Materials and Methods: Histological findings of 3339 cholecystectomy patients, who were operated between January 2015 and January 2020, were retrospectively reviewed. Age, gender, radiological results, clinical features, intraoperative findings, and surgical management of the patients with XGC were recorded. Results: XGC was observed in 70 patients (2.09%). The average age was 53.75. M:F ratio was 1.2. In radiological examinations, gallstones were found in 94.2% of the patients and GB wall thickness (≥3 mm) was increased in 58.5% of the patients. Around 45.7% of the patients came to the clinic with chronic cholecystitis and 32.9% with acute cholecystitis. In the intraoperative period, adhesions were observed in 80% and increase in GB wall thickness was observed in 77.1% of the patients. The operation started laparoscopically in 66 patients. In 14 patients (21.2%), it was converted to open surgery usually due to insufficient dissection of Calot's triangle. Gallbladder carcinoma (GBC) was suspected in 6 patients, but none of them had malignancy in frozen sections or histology. Conclusions: XGC surgery is difficult due to its radiological, clinical, and intraoperative features and mimicking GBC. It can be converted to open cholecystectomy due to difficulties in laparoscopic dissection. However, since conversion cholecystectomy rates are reasonable, laparoscopic surgery is recommended in patients with suspected XGC.

Despite significant advances in understanding the role of the immune response in Opisthorchis viverrini-associated carcinogenesis, little is known about how infection induces gall bladder disease. This study investigated whether mast cells are activated in cholecystitis associated with O. viverrini, gall bladder specimens from ninety-two patients who had undergone cholecystectomy at the Khon Kaen Regional Hospital, Khon Kaen, Thailand. Two representative sections from the body of fresh gall bladder tissue were fixed in Carnoy's solution and embedded in paraffin wax. The paraffin sections were stained for mast cells and IgE plasma cells by the double histochemical and immunohistochemical method. The cells in the epithelium, lamina propria, muscular layer, and subserosa were counted and expressed as cells per square millimeter. The gall bladder bile was examined for the presence of O. viverrini eggs. Significantly higher mean mast cell numbers were found in the lamina propria (221.41 ± 16.01 vs 116.97 ± 14.61 cells per mm 2 ; P < 0.005) of egg positive compared to egg negative groups, respectively. No comparable differences in mast cell number were observed in other layers. IgE plasma cells were rarely seen. The results suggest that mast cell hyperplasia occurs during cholecystitis in association with opisthorchiasis and may play a role in the pathogenesis of the disease.

Background: Involving pre-sampled patients with cholecystitis, dysplasia, and adenocarcinoma, the present study aimed to compare the neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), platelet/lymphocyte (PLR) ratios, and plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) values and to determine their prognostic importance., Methods: The present study involved 187 cholecystectomy specimens that were diagnosed as cholecystitis, dysplasia, and adenocarcinoma. Preoperative neutrophil, monocyte, lymphocyte, and platelet counts, NLR, MLR, and PLR ratios, and PCT, MPV, and PDW levels of the same patient groups were retrospectively recorded., Results: In the present study, the cut-off values for dysplasia of NLR, PLR, and MLR were found as 1.61, 81.45, and .19, whereas those for cancer of NLR, PLR, and MLR were 2.65, 182.69, and .35, respectively. The NLR, PLR, and MLR values of the chronic cholecystitis and chronic calculous cholecystitis groups were statistically significantly lower than those of the chronic active calculous cholecystitis group ( P < .01). The NLR and MLR values of the non-cancer and non-dysplasia groups were statistically lower than those of the cancer and dysplasia groups ( P < .05)., Conclusion: According to the results of the present study, using additional imaging methods, acute-phase cholecystitis can be distinguished using preoperative neutrophil and monocyte counts, and NLR, PLR, and MLR cut-off values can be used to distinguish dysplasia, which is the antecedent of gallbladder cancer. It is thought that this might provide patients with an advantage in terms of early treatment and survival.

Context.: Follicular cholecystitis (FC) is a poorly characterized entity., Objective.: To determine its frequency/clinicopathologic associations., Design.: A total of 2550 cholecystectomy specimens were examined. Two hundred three of these were consecutive routine cholecystectomies submitted entirely for microscopic examination to determine the relative frequency of incidental pathologies in gallbladders (GBs). The remainder had representative sampling. Underlying conditions were nonobstructive pathologies (1270 nonspecific cholecystitis), obstructive (62 distal biliary tract tumors, 35 primary sclerosing cholangitis, and 31 autoimmune pancreatitis), and neoplastic (n = 949). FC was defined as 3 distinct lymphoid follicles (LFs)/centimeter., Results.: In the GBs totally submitted for microscopic examination, the true frequency of FC was found to be 2.5% (5/203), and in the representatively sampled group, it was 1.9%, with similar frequencies in nonobstructive, obstructive, and neoplastic cases (2.3%, 3.1%, and 1.3%, respectively, P = .77). When the 39 FC in nonneoplastic GBs contrasted with ordinary chronic cholecystitis, they were associated with older age (68 vs 49 years, P < .0001), similar gallstone frequency (68 vs 81%), female/male ratio (2.7 vs 2.6), and wall thickness (4 mm for both). None had lymphoma/parasites/ Salmonella infection. Of 17 cases who had undergone gastric biopsy, 5 had chronic gastritis (2 with Helicobacter pylori ). Microscopically, the LFs were the main inflammatory process often with minimal intervening inflammation. IgG4-positive plasma cell density was low (<10/high-power field) in 21/24(87.5%) cases., Conclusions.: Follicular cholecystitis is seen in 2% of cholecystectomies, typically in significantly older patients, suggesting a deranged immune response. A third of the patients reveal biopsy-proven gastritis. FC does not seem to be associated with autoimmunity, lymphoma, or obstructive pathologies.

Background: Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery., Case Presentation: A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder., Conclusions: Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.

Gall stones are one of the major causes of morbidity and mortality all over the world and common health problems throughout in developing countries. Cholecystectomy is one of the most common surgical practices and postoperative analysis of cholecystectomy specimen has a great value since histopathological reports may document some entities with significant clinical significances. Gallbladder carcinomas in cholecystectomy specimens are received in our histopathology laboratory to analyse their clinicopathological features. This was a descriptive study carried out at the histopathology section of the Department of Pathology at our hospital over a period of two years ranging from November 2016 to October 2018. Both intraoperative and postoperative histological examinations of the excised gallbladder facilitated the diagnosis of gallbladder cancer. Surgery-related variables and surgical approaches were evaluated according to the extent of tumor invasion. Twenty five cholecystectomy specimens of the acute and symptomatic chronic cholecystitis patients were analyzed. Standardization of the reporting were examined. Age, gender, presence of gall stone, cholesterolosis, adenomatous hyperplasia, gastric or intestinal metaplasia, dysplasia, histopathological type of gallbladder carcinoma, cellular differentiation, grading, lympho vascular invision, perineural invasion, lymph node invasion, involvement of cystic duct end margin, liver invasion, omental tissue invasion and T.N.M. staging were investigated. Reported rates of histopathological findings were comparable between patients aged twenty six years to seventy six years. Epithelial hyperplasia and metaplasia were found to be related to age. The correlation between cholesterolosis and gender or metaplasia was noted. We suggest that in India and other nations, high incidences of gallbladder carcinoma, all cholecystectomy specimens must be submitted to routine macroscopic and histopathology examination in the laboratory, as this is the only capability through which malignancies can be detected at an early, potentially curable stage. This incidental finding has altered the management and outcome of this dreadful disease.

Objective: to describe the histological findings of the gallbladders of patients undergoing cholecystectomy and to evaluate the presence of factors associated with gallbladder incidental cancer., Methods: we conducted a descriptive, cross-sectional, observational study with 1,278 histopathological exams of gallbladders coming from cholecystectomy for cholelithiasis and of their reports, held from January 2008 to December 2017., Results: the most common pathological finding was chronic cholecystitis, present in 1,251 patients (97.8%), followed by gallbladder cholesterolosis, in 131 (10.2%). Gallbladder cancer was identified in six patients, with a prevalence of 0.5% in this sample. There was a significant association between the presence of cancer and age ≥60 years and wall thickness ≥0.3cm., Conclusion: there was low prevalence of gallbladder cancer in this population, higher occurrence in the elderly and association of the tumor with gallbladder wall thickness.

We present the images of ultrasound, magnetic resonance and histology of a patient with suggestive findings of xanthogranulomatous cholecystitis. Gallbladder cancer cannot be completely ruled out until the histological study of the surgical sample is performed.

Primary epithelial tumors of the gallbladder are rarely reported in animals. In this study, 9 aged pigs (6-12 years old) were histopathologically examined for gallbladder proliferative lesions. At necropsy, a large gallstone occupied the lumen of the gallbladder of 3 pigs. Histopathological examination revealed chronic cholecystitis in all 9 pigs, mucosal hyperplasia in 2 pigs, adenoma in 1 pig, and adenocarcinoma in 2 pigs. Bacilli were detected in the gallbladder lumen of 6 pigs by Warthin-Starry stain. Mucosal hyperplasia, adenoma, and adenocarcinoma were characterized by papillary projections of the mucosa with occasional acinar structures. Tumor invasion of the surrounding tissue was observed in the cases of adenocarcinoma. On Alcian blue and periodic acid-Schiff double-stained sections, the acinar structure of gallbladder mucosa in chronic cholecystitis and mucosal hyperplasia was stained in a mosaic pattern, indicating pyloric gland metaplasia. The results of immunohistochemistry revealed a CD10-positive epithelial brush border and mucin (MUC) 2-positive goblet cells in chronic cholecystitis, adenoma, and adenocarcinomas, indicating intestinal metaplasia. Immunoreactivity of MUC5 AC and cytokeratin 19 was weaker in adenoma and adenocarcinomas compared with the normal and hyperplastic gallbladder mucosa. The number of p53-positive nuclei and the Ki-67 index were higher in adenocarcinomas compared with benign lesions. These results suggest that chronic cholecystitis associated with gallstones and/or bacterial infections may contribute to metaplastic changes and development of gallbladder tumors in aged pigs. Alteration of mucin, cytokeratin, and p53 profiles in gallbladder proliferative lesions in pigs were similar to that in humans, suggesting a common pathogenesis in tumor development.

Background: Laparoscopic subtotal cholecystectomy (LSC) can be employed when extensive fibrosis or inflammation of the cystohepatic triangle prohibits safe dissection of the cystic duct and artery. The purpose of this study was to compare postoperative outcomes in patients with severe cholecystitis who underwent laparoscopic cholecystectomy (LC) or LSC., Methods: In this retrospective study, we compared the postoperative outcomes of patients with severe cholecystitis who underwent LC or LSC between July 2010 and July 2016 at St. Joseph’s Health Centre, Toronto. We further stratified LSC cases on the basis of the extent of gallbladder (GB) dissection and GB remnant closure., Results: A total of 105 patients who underwent LC and 46 who underwent LSC were included in the study. There were 4 bile duct injuries in the LC group and 0 in the LSC group. Bile leaks (relative risk [RR] 3.4, 95% confidence interval [CI] 1.01–11.5) and subphrenic collections (RR 3.1, 95% CI 1.3–8.0) were more common in the LSC group. Overall postoperative morbidity did not differ significantly between the 2 groups. Postoperative endoscopic retrograde cholangiopancreatography (ERCP) (RR 3.2, 95% CI 1.1–9.5) and biliary stent insertion (RR 4.6, 95% CI 1.2–17.5) were more common in the LSC group. Bile leaks appeared to be more prominent with open GB remnants but all cases of leak were successfully managed with ERCP and biliary stenting., Conclusion: LSC may mitigate the risk of bile duct injury when dissection into the cystohepatic triangle is unsafe. There were more bile leaks in patients who underwent LSC; however, they were readily managed with endoscopic stents. Long-term biliary fistulae were not observed. LSC should be considered early as a means of completing difficult cholecystectomies safely without the need for cholecystostomy tube or conversion to laparotomy., Competing Interests: R. Purzner, K. Ho and E. Al-Sukhni declare no competing interests. S. Jayaraman reports receiving consulting fees from Ethicon, Olympus, Ipsen, Baxter, Pendopharm and Pfizer and speaker fees from Ethicon, Olympus, Baxter and Celgene in the last 2 years., (© 2019 Joule Inc. or its licensors)

Background: HER2 is an oncoprotein which is overexpressed in several cancers including breast and stomach. Several studies have shown that HER2 is overexpressed in gallbladder cancer and in precancerous lesions. The present study was undertaken to assess pattern and level of expression of HER2 in metaplasia, dysplasia, and different stages of gallbladder carcinoma, which would determine its suitability as a prognostic biomarker in neoplastic transformation of gallbladder epithelium. The study was also aimed at to find the significance of Ki-67 index in these lesions., Methods and Materials: One hundred and twenty-eight patients who underwent cholecystectomy comprised the study group. Among them, 108 (84.4%) specimens showing metaplasia, dysplasia, and carcinoma on routine histopathology were considered as cases and 20 (15.6%) specimens of chronic cholecystitis having non-metaplastic mucosa were considered as control. Immunohistochemistry (IHC) was performed for HER2 and Ki-67. For HER2 interpretation ASCO/CAP guideline for breast cancer was followed. Chi-square test was used to find out the significance of HER2 expression in dysplasia/metaplasia/carcinoma. The ANOVA and Tukey-Kramer Multiple Comparisons Test were used for determining the association of Ki-67 with malignant transformation., Results and Conclusions: Overexpression of HER2 was observed in 48% (n = 12) of adenocarcinomas, 58% (n = 7) of high-grade dysplasia, 47% (n = 8) of low-grade dysplasia, and 74% (n = 25) of intestinal metaplasia. Ki-67 index increases in a non-linear fashion as the precursor lesions progress toward malignancy. In the future, these markers might be used as a prognostic biomarker for gallbladder carcinoma and its precursor lesions and it might become a valid indication for targeted therapies for gallbladder cancer.

Aim: Thick-walled gallbladder is difficult to characterize on conventional imaging. 18F-FDG PET was used to differentiate benign and malignant wall thickness and compared with histopathology., Methods: Thirty patients with gallbladder (GB) wall thickening (focal > 4 mm and diffuse > 7 mm), underwents uspected on  ultrasound, or CT scan, and underwent 18F-FDG PET. Histopathology of the specimen was compared with imaging findings., Results: The mean age was 48.22 ± 31.33 years with a M:F 1:4 ratio. Twenty patients had diffuse and 10 had focal thickening. On 18F-FDG PET, lesion was benign in 12, malignant in 13, and indeterminate in 5. Histopathology was malignancy in 12; benign in 18-chronic cholecystitis in 11, xanthogranulomatous in 4, IgG4 related in 2, and polyp in 1. The mean GB wall thickness was 7.79 ± 3.59 mm (10.34 malignant and 6.10 in benign, p = 0.001). At a cutoff of 8.5 mm, the sensitivity and specificity of detecting malignancy was 94% and 67%. The mean SUV uptake was 7.46 (benign 4.51, malignant 14.26, p = 0.0102). At a cutoff of 5.95, the sensitivity and specificity of detecting malignancy was 92% and 79%. For 18F-FDG PET, overall sensitivity was 91%, specificity 79%, PPV 77%, NPV 92%, and diagnostic accuracy was 84%., Conclusion: 18F-FDG PET is a reliable method of differentiation between benign and malignant thickening of the gallbladder particularly when wall thickness and SUV value is taken into account.

Biliary tract infection (BTI)-derived sepsis remains a serious problem with significant morbidity and mortality in the modern era of critical care management. Current animal models of BTI have relied mostly on injecting purified bacteria or their toxins into the biliary tract. These models do not fully reflect pathophysiology or disease processes of clinical cholangitis or cholecystitis. In the current study, we developed a novel model of BTI by performing cholecystocolonic anastomosis (CCA) in rabbits and characterized pathophysiologic changes in this model. This model is intended to mimic the clinical process of cholecystocolonic fistula with reflux cholangitis, a severe form of BTI. Adult male rabbits were subjected to BTI-derived sepsis through an anastomosis of the gall bladder to the colon (i.e., CCA). The animals were monitored for 7 days to record survival. In additional groups of animals, various bacterial, hemodynamic, histological and biochemical parameters were measured at 12, 24, 48 and 72 h after CCA. The anastomosis between the gallbladder and the colon required about 5-8 min to finish. The median survival time for rabbits after CCA was 96 h. The positive rates of bacterial culture at 72 h after CCA were 83.3% and 100% in the blood and liver, respectively. The most common microorganism was Escherichia coli followed by Enterococcus. Plasma Tumor Necrosis Factor-α (TNF-α), Lnterleukin-10 (IL-10), Lnterleukin-6 (IL-6), and High-mobility group box 1 protein (HMGB-1) levels were greatly elevated after CCA. The cardiac index and heart rate increased slightly at 12 h after CCA and then continued to decrease. Systemic hypotension developed 48 h after CCA. Histological studies showed reflux cholangitis with acute lung and kidney injury. Cholecystocolonic anastomosis produces polymicrobial sepsis in rabbits, which mimics many aspects of human BTI-derived sepsis. It is reproducible and easy to perform and may serve as an excellent model for future sepsis research.

Aim: The aim of this study was to evaluate the results of laparoscopic cholecystectomy (LC) in patients with xanthogranulomatous cholecystitis (XGC) compared with patients without XGC., Methods: A retrospective study was performed including patients who had undergone elective LC between January 2003 and November 2017. Results of patients with XGC (25) were compared with those of patients without XGC (2181) with respect to operative time, conversion rate, drain use, postoperative complications, and postoperative stay., Results: The mean operative times in patients with and without XGC were 112.8 and 66.3 minutes, respectively (P=0.001). The conversion rate was 36% in patients with XGC and 3.89% in patients without XGC (P=0.001). Drains were used in 76% of patients with XGC and in 24% of patients without XGC (P=0.001). Postoperative complication rate was 16% and 9.9% in patients with and without XGC, respectively (P=0.309). Mean postoperative stays in patients with and without XGC were 4.3 and 2.3 days, respectively (P=0.001)., Conclusions: LC in patients with XGC is associated with significantly longer operative time, higher conversion rate, greater drain use, and longer postoperative stay compared with patients without XGC.

Follicular cholecystitis (FC) is a relatively rare entity with uncertain causal associations. In this study, we aimed to explore different clinicopathologic associations of FC, and to better characterize the entity. A retrospective review of archival hematoxylin and eosin slides and pertinent clinical information was undertaken for all cholecystectomy cases with a rendered diagnosis of "follicular cholecystitis," from 1991 to 2017. Concurrent conventional chronic cholecystitis (CC) and lymphocytic cholecystitis (LC) were documented. Forty-three consecutive patients were confirmed to have FC. The majority of the patients (88.4%) had at least one other histologic association in the gallbladder (LC, CC, or both). Remarkably, functional distal biliary obstruction (from choledocholithiasis, sclerosing cholangitis, distal biliary strictures, or malignancies of the pancreatic head or ampulla) was found in 76.7% of the patients, irrespective of the presence of other concurrent histologic findings. FC associated with CC was relatively more common in females (61%) and strongly associated with cholelithiasis (70%). However, those without CC were predominantly males (70%) and had a significant association with LC (75%). All four cases of FC without any other histologic associations who had clinical information available showed some form of distal biliary obstruction. FC cases without concurrent LC were often associated with CC (74%). FC is strongly associated with extrahepatic biliary obstruction distal to the gallbladder. Therefore, this finding at routine cholecystectomy may warrant further evaluation to rule out a cause for distal biliary tract obstruction. Additionally, it is commonly associated with other concomitant histologic abnormalities in the gallbladder such as CC and/or LC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Gallbladder cancer (GBC) is a fatal condition with dismal prognosis and aggressive local invasiveness; and with uncharacterised molecular pathology relating to non-specific therapeutic modalities. Given the importance of oxidative stress in chronic diseases and carcinogenesis, and the lacunae in literature regarding its role in gallbladder diseases, this study aimed to study the involvement of oxidative stress and deregulation in the base excision repair (BER) pathway in the pathogenesis of gallbladder diseases including GBC. This study involved patients from the North-East Indian population, where the numbers of reported cases are increasing rapidly and alarmingly. Oxidative stress, based on 8-OH-dG levels, was found to be significantly higher in gallbladder anomalies (cholelithiasis [CL] and cholecystitis [CS]) and GBC at the plasma and DNA level, and was associated with GBC severity. The expressions of key BER pathway genes were downregulated in gallbladder anomalies and GBC compared to controls, and in GBC compared to both non-neoplastic controls and gallbladder anomalies. Expression of XRCC1 and hOGG1 was significantly associated with both susceptibility and severity of GBC. The XRCC1 codon280 polymorphism was associated with disease susceptibility; and significantly higher oxidative stress was observed in hOGG1 genotypic variants. The genomes of GBC patients were found to be more hypermethylated compared to controls, with the promoters of XRCC1 and hOGG1 being hypermethylated and, therefore, being silenced. This study underlined the prognostic significance of the oxidative stress marker 8-OH-dG and BER pathway genes, especially hOGG1 and XRCC1, in gallbladder anomalies and GBC, as well as stated their potential for therapeutic targeting.

Background: Previously, our group developed the Parkland grading scale for cholecystitis (PGS) to stratify gallbladder (GB) disease severity that can be determined immediately when performing laparoscopic cholecystectomy (LC). In prior studies, PGS demonstrated excellent interrater reliability and was internally validated as an accurate measure of LC outcomes. Here, we compare PGS against a more complex cholecystitis severity score developed by the national trauma society, American Association for the Surgery of Trauma (AAST), which requires clinical, operative, imaging, and pathologic inputs, as a predictor of LC outcomes., Methods: Eleven acute care surgeons prospectively graded 179 GBs using PGS and filled out a postoperative questionnaire regarding the difficulty of the surgery. Three independent raters retrospectively graded these GBs using PGS from images stored in the electronic medical record. Three additional surgeons then assigned separate AAST scores to each GB. The intraclass correlation coefficient statistic assessed rater reliability for both PGS and AAST. The PGS score and the median AAST score became predictors in separate linear, logistic, and negative binomial regression models to estimate perioperative outcomes., Results: The average intraclass correlation coefficient of PGS and AAST was 0.8647 and 0.8341, respectively. Parkland grading scale for cholecystitis was found to be a superior predictor of increasing operative difficulty (R, 0.566 vs. 0.202), case length (R, 0.217 vs. 0.037), open conversion rates (area under the curve, 0.904 vs. 0.757), and complication rates (area under the curve, 0.7039 vs. 0.6474) defined as retained stone, small-bowel obstruction, wound infection, or postoperative biliary leak. Parkland grading scale for cholecystitis performed similar to AAST in predicting partial cholecystectomy, readmission, bile leak rates, and length of stay., Conclusion: Both PGS and AAST are accurate predictors of LC outcomes. Parkland grading scale for cholecystitis was found to be a superior predictor of subjective operative difficulty, case length, open conversion rates, and complication rates. Parkland grading scale for cholecystitis has the advantage of being a simpler, operative-based scale which can be scored at a single point in time., Level of Evidence: Single institution, retrospective review, level IV.

Objective: Ultrasound (US) evaluation of biliary pathology can be influenced by a variety of factors. This study examines the effect of patient specific factors on the accuracy of sonographic evaluation of gallbladder wall thickness (GBW)., Methods: We performed a retrospective review of all patients who underwent cholecystectomy at a single institution from November 2012 to October 2015. GBW measured on US was compared with pathology results. Results were analyzed in relation to patient specific factors to include BMI, age, presence of diabetes, sex, and urgent versus elective cases., Results: In total 601 patients underwent cholecystectomy, 484 of which had paired preoperative US GBW measurement and postoperative pathologic specimen measurement. No significant difference in accuracy or precision of US measurement of the GBW based on BMI was found. Accuracy was not related to age, sex, urgency, or diabetes. Precision decreased with pathologic thickening, age, male sex, and urgent case performance., Conclusions: US is accurate in measuring GB wall thickness regardless of patient specific factors. A nonsignificant trend exists with decreased precision with pathologic thickening, age, male sex, and urgently performed cases.

Xanthogranulomatous cholecystitis is a rare variant of chronic cholecystitis, which can involve adjacent organs including liver, colon and duodenum mimicking gallbladder cancer. Preoperative and intraoperative differentiation of xanthogranulomatous cholecystitis from gallbladder cancer is often difficult and the final diagnosis is made on histopathology of the resected specimen. We hereby report four cases of xanthogranulomatous chol ec ystitis w hich were misdiagnosed as cases of advanced gallbladder cancer based on presentation and radiological findings and underwent radical resections but the final histopathology was a diagnostic surprise. Xanthogranulomatous cholecystitis is still a diagnostic challenge as no single modality has been helpful to diagnose this entity till date. Radical resection seems justified in patients who present with the features mimicking gallbladder cancer.

Interstitial cells of Cajal (ICC) were first described by Santiago Ramon y Cajal over 100 years ago. They are thought to play an important role in the regulation of gastrointestinal motility. There is increasing evidence that the decline in their number in the gallbladder wall contributes to the formation of concrements. The aim of the study was to determine the exact location of interstitial cells of Cajal in the gallbladder wall in patients with calculous and non-calculous cholecystitis. Sixty-eight patients were examined, of whom 50 were cases of cholelithiasis and 18 were of non-calculous cholecystitis. The technique of immunohistochemistry with the CD117 antibody was used to determine the cells of Cajal, while to distinguish them from mast cells the technique with mast cell tryptase (MCT) was applied. Redistribution of the interstitial cells of Cajal from the muscle membrane to lamina propria of mucous tissue was observed in the cases of cholelithiasis, while in the group of non-calculous cholecystitis most of the ICC was located within the muscle tissue.