A Retrospective Cohort Study on the Association between Red Cell Distribution Width and All-Cause Mortality of Patients with Cholecystitis at ICU Admission.

BACKGROUND: Elevated red cell distribution width (RDW) has been reported to be associated with mortality in some critically ill patient populations. The aim of this article is to investigate the relationship between RDW and in-hospital mortality and short- and long-term mortality of patients with cholecystitis. METHOD: We conducted a retrospective cohort study in which data from all 702 patients extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database were used. Receiver operating characteristic (ROC) curves were constructed to evaluate the prognostic predictive value of RDW for in-hospital mortality and short- (i.e., 30-day and 90-day) and long-term (i.e., 180-day, 1-year, 3-year, and 5-year) mortality. We converted RDW into a categorical variable according to quintiles as less than or equal to 13.9%, 14.0-14.8%, 14.9-15.8%, and 15.9-17.2% and more than 17.2%. The Kaplan-Meier (K-M) methods and log-rank tests were used to compare survival differences among different groups. The relationships between RDW levels and in-hospital mortality were evaluated by univariate and multivariate binary logistic regression models. Multivariable Cox regression models were built to investigate the association of RDW on the short-term and long-term mortality. RESULT: After adjusting for potential confounders, RDW was positively associated with in-hospital mortality (OR: 1.187, 95% CI [1.049, 1.343]) and short- (i.e., 30-day: HR: 1.183, 95% CI [1.080, 1.295], 90-day: HR: 1.175, 95% CI [1.089, 1.268]) and long-term (i.e., 1-year: HR:1.162, 95% CI [1.089, 1.240]) mortality in critically ill patients with cholecystitis. Similar results were also shown in the secondary outcomes of 180-day, 3-year, and 5-year mortality. RDW had a significant accurate prognostic effect on different endpoints and could improve the prognostic effect of scoring systems. CONCLUSION: High level of RDW is associated with an increased risk of in-hospital mortality and short- and long-term mortality in critically ill patients with cholecystitis. RDW can independently predict the prognosis of patients with cholecystitis.

Exploration of differentially-expressed exosomal mRNAs, lncRNAs and circRNAs from serum samples of gallbladder cancer and xantho-granulomatous cholecystitis patients.

Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have explored the mechanism of GBC, thus far, few molecules have been discovered that can be utilized as specific biomarkers for the early diagnosis and therapeutic treatment of GBC. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry specific information that can define multiple cancer types. The present study investigated the expression profiles of coding (or messenger) ribonucleic acids (mRNAs) and non-coding RNAs (ncRNAs, including long non-coding RNAs [lncRNAs] and circular RNAs [circRNAs]) in plasma-derived exosomes from GBC patients. Using high-throughput RNA sequencing and subsequent bioinformatic analysis, a number of differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in GBC exosomes, compared to their expressions in xantho-granulomatous cholecystitis (XGC) exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were then conducted to investigate the potential functions of these DE RNAs. Furthermore, the interaction networks and competing endogenous RNA networks of these DE RNAs and their target genes were investigated, revealing a complex regulatory network among mRNAs and ncRNAs. In summary, this study demonstrates the diagnostic value of plasma-derived exosomes in GBC and provides a new perspective on the mechanism of GBC.

Diagnostic Value of Inflammatory Factors in Patients with Gallbladder Cancer, Dysplasia, and Cholecystitis.

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.

Roles of Salmonella typhi and Salmonella paratyphi in Gallbladder Cancer Development.

BACKGROUND: Typhoid (Salmonella typhi and paratyphi) carriers and gall bladder cancer (GBC) are endemic in northern India. Results of previous studies about association of typhoid carriers with GBC are inconsistent. We studied antibodies against Salmonella typhi and paratyphi in serum samples of patients with GBC. METHODS: We performed modified Widal test for antibodies against Salmonella typhi (Vi and O) and Salmonella paratyphi (AO and BO) antigens in patients with GBC (n=100), xanthogranulomatous cholecystitis (XGC, n=24), chronic cholecystitis (CC, n=200) and healthy controls (HC, n=200). RESULTS: Serum antibodies against Salmonella were more frequently positive in GBC (22%) and XGC (29%), particularly in males in age ≥50 years (GBC: 47% and XGC: 50%) vs. HC (0) (p <0.01). Vi antibody was more common in GBC (13%, OR:9.8) and XGC (8%, OR:5.9) than HC (2%). O antibody was more common in GBC (8%, OR: 8.6) and XGC (8%, OR: 9.0) than HC (1%). O antibody was also more common in males with GBC (12%) than CC (1%) and HC (1%) (P=0.02 and p <0.001, respectively). AO (6%) and BO (4%) antibodies were detected in GBC, particularly in males, than HC (0), (p <0.01). Salmonella antibodies were more frequent in GBC with GS than those without GS (50% vs. 20%, OR=3.94, P=0.01). CONCLUSIONS: Salmonella carrier state was more common in GBC and XGC, particularly in elderly males than HC. The Vi antibody was more common in GBC and XGC than HC. Salmonella infection was more common in GBC with GS than those without GS.

Complications of a severe autoimmune hemolytic anemia crisis: transfusional iron overload and gangrenous cholecystitis.

BACKGROUND: Evans syndrome is a rare autoimmune disorder that is defined by the simultaneous or sequential presence of two or more cytopenias without an obvious underlying precipitating cause. Evans syndrome usually follows a chronic relapsing and remitting course and is quite rare, making it difficult to evaluate in clinical studies. CASE REPORT: A 66-year-old male patient with a 17-year history of Evans syndrome presented with fulminant autoimmune hemolytic anemia (AIHA). He presented with a markedly elevated C-reactive protein (CRP; 46 mg/L [normal, 0-5 mg/L]) before onset of a decrease in hemoglobin. He required the transfusion of 20 units of red blood cells while awaiting response to aggressive immunosuppressive therapy including high-dose corticosteroids, intravenous immunoglobin therapy, and rituximab. He achieved a complete hematologic response. RESULTS: His postdischarge course was complicated by acute cholecystitis requiring laparoscopic cholecystectomy. In addition, his transfusional iron overload requiring 16 phlebotomies to reduce his ferritin level from 4933 µg/L to 326 µg/L, with phlebotomies ongoing every 2 weeks to achieve a ferritin level of less than 100 µg/L. CONCLUSION: Neither transfusional iron overload nor acute cholecystitis are well-recognized complications of a severe episode of AIHA. An elevated CRP has been recently recognized as an important prognostic marker in patients with immune thrombocytopenic purpura and this case suggests a need to evaluate its utility in AIHA.

The diagnostic role of circulating inflammation-based biomarker in gallbladder carcinoma.

AIM: To investigate the diagnostic roles of circulating inflammatory biomarkers in gallbladder carcinoma (GBC). PATIENTS & METHODS: Circulating inflammatory cell count, fibrinogen, albumin, carcinoembryonic antigen (CEA) and CA199 were measured, neutrophil-to-lymphocyte ratio (NLR), dNLR, PLR, LMR and Alb-to-fib (AFR) were calculated in 306 GBC patients, 306 healthy and 305 benign controls. The reciever operating characteristic curve was used to determine diagnostic accuracy of them. RESULTS: The area under curves of combined AFR, dNLR and lymphocyte were 0.943 and 0.985 for diagnosis of GBC from healthy and polyp controls, area under curve of combined AFR, CEA and CA199 was 0.90 for diagnosis of GBC from the cholecystitis patients. CONCLUSION: Circulating AFR combined with lymphocyte and dNLR or CEA and CA199 could effectively distinguish GBC from the healthy and benign controls.

Risk factors for an additional port in single-incision laparoscopic cholecystectomy in patients with cholecystitis.

Although single-incision laparoscopic cholecystectomy is now widely performed in patients with cholecystitis, some cases require an additional port to complete the procedure. In this study, we focused on risk factor of additional port in this surgery. We performed single-incision cholecystectomy in 75 patients with acute cholecystitis or after cholecystitis between 2010 and 2014 at Gunma University Hospital. Surgical indications followed the TG13 guidelines. Our standard procedure for single-incision cholecystectomy routinely uses two needlescopic devices. We used logistic regression analysis to identify the risk factors associated with use of an additional full-size port (5 or 10 mm). Surgical outcome was acceptable without biliary injury. Nine patients (12.0%) required an additional port, and one patient (1.3%) required conversion to open cholecystectomy because of severe adhesions around the cystic duct and common bile duct. In multivariate analysis, high C-reactive protein (CRP) values (>7.0 mg/dl) during cholecystitis attacks were significantly correlated with the need for an additional port (P = 0.009), with a sensitivity of 55.6%, specificity of 98.5%, and accuracy of 93.3%. This study indicated that the severe inflammation indicated by high CRP values during cholecystitis attacks predicts the need for an additional port. J. Med. Invest. 64: 245-249, August, 2017.

Quantification of Circulating Free DNA as a Diagnostic Marker in Gall Bladder Cancer.

Gall bladder Carcinoma (GBC) is the fifth most common cancer of the digestive tract and frequently diagnosed in late stage of disease. Estimation of circulating free DNA (cfDNA) in serum has been applied as a "liquid biopsy" in several deep seated malignancies. Its value in diagnosis of gall bladder carcinoma has not been studied. The present study was designed to assess the role of cfDNA in the diagnosis of GBC and correlate levels with the TNM stage. Serum was collected from 34 patients with GBC and 39 age and sex matched controls including 22 cholecystitis and 17 healthy individuals. Serum cfDNA levels were measured through quantitative polymerase chain reaction (qPCR) by amplification of ß-globin gene. Performance of the assay was calculated through the receiver operating characteristic (ROC) curve. The cfDNA level was significantly lower in healthy controls and cholecystitis (89.32 ± 59.76 ng/ml, 174.21 ± 99.93 ng/ml) compared to GBC (1245.91 ± 892.46 ng/ml, p = <0.001). The cfDNA level was significantly associated with TNM stage, lymph node involvement and jaundice (0.002, 0.027, and 0.041, respectively). Area under curve of ROC analysis for cancer group versus healthy and cholecystitis group was 1.00 and 0.983 with sensitivity of 100 %, 88.24 % and specificity of 100 % respectively. Quantitative analysis of cfDNA may distinguish cholecystitis and gall bladder carcinoma and may serve as new diagnostic, noninvasive marker adjunct to imaging for the diagnosis of GBC.

[Persistent elevation of Ca 19-9 and an unexpected finding. A case report]. / Elevación persistente de Ca 19-9 y un hallazgo inesperado. Reporte de un caso.

BACKGROUND: Tumour markers are substances produced by the tumour itself, or by the host in response to a tumour. These markers could be measured either in the blood or in body secretions. One of the most common tumour markers used in gastrointestinal diseases is Ca 19-9. It is the marker most used for pancreatic cancer, but can be elevated in many benign processes. Thus, it is not a specific marker. CLINICAL CASE: The case is presented of a male patient with 4 years of moderate abdominal pain, weight loss, and persistent elevation of Ca 19-9. After an extensive work-up, renal and hepatic cysts were found, as well as steatosis and, apparently, a gallbladder polyp. With these findings and the persistent elevation of Ca 19-9, it was decided to operate the patient. An exploratory laparoscopy was performed showing multiple, yellowish nodular lesions all over the hepatic surface suggestive of metastases, as well as simple hepatic cysts. Pathology reported biliary hamartomas, steatosis, and chronic cholecystitis. After 2years of follow up, although there is no evidence of malignant neoplasia, there is still an elevation of Ca 19-9. CONCLUSION: The persistent elevation of Ca 19-9 is probably due to the presence of multiple benign diseases such as steatosis, urolithiasis, hepatic and renal cysts, and cholecystitis. An algorithm is needed for healthy patients with elevated levels of Ca 19-9 marker, in order to lower costs, avoid misdiagnoses, and improve management.

1H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation.

OBJECTIVE AND DESIGN: We present in this article 1H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC). MATERIAL/METHODS: Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). 1H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation. Receiver operating curve (ROC) and pathway analysis on NMR data were also carried out to validate the findings. RESULTS: Serum metabolites such as glutamine, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), alanine, branch chained amino acids (BCAA), histidine and tyrosine were found to be depleted whereas formate, lactate, 1,2-propanediol were found to be elevated in CC. Metabolic pathways associated with metabolite alteration have also been reported. CONCLUSIONS: NMR has been established for disease diagnosis along with identification of metabolic pattern recognition in biofluids. Gallstones cause inflammation of the gallbladder in the form of CC. Inflammation plays a major role in causation of gall bladder cancer and leads the way to malignancy. Metabolic analysis of CC may lead to early diagnosis of disease and its progression to gallbladder cancer.

[The influence of sinusoidal modulated currents on the fatty acid composition of plasma and blood erythrocytes in the patients presenting with chronic cholecystitis]. / Vliyanie sinusoidal'nykh modulirovannykh tokov na sostav zhirnykh kislot plazmy i eritrotsitov krovi u patsientov s khronicheskim kholetsistitom.

The objective of the present study was to evaluate the effectiveness of the treatment with sinusoidal modulated currents on lipid metabolism in the patients presenting with chronic cholecystitis in the state of remission. PATIENTS AND METHODS: The study included 25 patients with chronic non-calculosis cholecystitis in phase of remission and 20 healthy subjects (controls). We studied the serum lipid spectrum as well as the fatty acid composition of plasma and blood erythrocytes before and after therapy with sinusoidal modulated currents applied to the right-sided hypochondrium region. RESULTS AND DISCUSSION: The treatment of the patients with chronic cholecystitis in remission with the use of sinusoidal modulated currents produced moderate lipid-modulatory and membranotropic effects mediated through the activation of the processes of lipid metabolism that may result in the depletion of the pool of essential polyunsaturated fatty acids. CONCLUSION: The results of this study give evidence that it is advisable to treat the patients presenting with chronic cholecystitis by sinusoidal modulated currents in the combination with the oral intake of exogenous polyunsaturated fatty acids.

Lipopolysaccharide-pathway proteins are associated with gallbladder cancer among adults in Shanghai, China with mediation by systemic inflammation.

PURPOSE: We examined inflammation as a mediator of associations between bacterial infection markers and gallbladder cancer (GBC). METHODS: Bacterial response proteins (lipopolysaccharide [LPS], soluble cluster of differentiation 14 [sCD14], and LPS-binding protein [LBP]) were measured in 40 GBC cases and 126 gallstone controls with data on 63 serum inflammation markers. The relationships of LPS, LBP, and sCD14 with GBC were examined by logistic regression, which also was used to evaluate whether these associations are influenced by systemic inflammation as measured by a combinatorial inflammation score. RESULTS: The third versus the first tertiles of sCD14 and of LBP were associated with an increased GBC risk (odds ratio [95% confidence interval]: 5.41 [2.00-16.75] for sCD14, and 6.49 [2.24-23.79] for LBP). sCD14 and LBP were strongly associated with inflammation score (above vs. below the median), which itself was associated with a more than 21-fold increased risk of GBC for the third versus first tertiles. Associations between GBC and sCD14 and LBP were markedly attenuated when the inflammation score was included in the model. While LPS was not associated with GBC or inflammation, only 35% of cases and 22% of controls had detectable levels. CONCLUSIONS: These findings suggest that these LPS-pathway proteins are associated with GBC via inflammation-related pathways.

[Serious Coagulation Dysfunction in a Patient with Gallstone-related Cholecystitis Successfully Treated with Vitamin K].

An 85-year-old woman with a diagnosis of choledocholithiasis due to common duct stones gradually developed severe coagulation dysfunction over the course of 27 days after hospitalization. Initial clinical findings were fever, general malaise, and obstructive jaundice. She was treated with fasting, and received cephem antibiotics containing N-methyl-thio-tetrazole. Because the common duct stones were not removed endoscopically, cholecystectomy was scheduled. Coagulation on admission was normal, but gradually became impaired. On the scheduled day of the operation, 27 days after hospitalization, coagulation [both prothrombin time (PT) and activated partial thromboplastin time (APTT)] were severely impaired PT, < 10%; PT-international normalized ratio, 6.29; and APTT, 71.6 s. No other abnormalities were identified. Surgery was postponed and antibiotics were discontinued. Simultaneously, administration of vitamin K was initiated. Six days after starting vitamin K, coagulation dysfunction had resolved and the surgery was safely performed under general anesthesia combined with thoracic epidural anesthesia. Care is warranted regarding coagulation dysfunction due to vitamin K deficiency in patients with hepatobiliary disease treated by fasting and antibiotics.

Use of Liver Function Tests as First-line Diagnostic Tools for Predicting Common Bile Duct Stones in Acute Cholecystitis Patients.

BACKGROUND: Prior studies have examined the use of liver function tests (LFT) for predicting the presence of common bile duct (CBD) stones in chronic cholecystitis (CC) patients. It is currently unclear whether LFT are also useful for predicting CBD stones in patients with acute cholecystitis (AC). METHODS: Of 1059 patients who visited an emergency room with gallbladder-related symptoms between March 2004 and December 2009, 854 patients were analyzed, and were divided into three groups (556 AC patients without CBD stones (AC - CBD), 98 AC patients with CBD stones (AC + CBD), and 200 CC patients without CBD stones). We compared the LFT values at admission and the changes in LFT values over time following admission among the three groups. RESULTS: The LFT values were significantly greater in the AC + CBD group than in the AC - CBD groups. Of all the LFT variables analyzed, γ-glutamyl transpeptidase was the most reliable variable for predicting the presence of CBD stones, with a sensitivity of 80.6 % and a specificity of 75.3 % at the cut-off level of 224 IU/L. The elevated LFT values decreased significantly from the start of the follow-up assessment to before cholecystectomy in the AC - CBD group, but were unchanged before stone removal in the AC + CBD group. CONCLUSION: The LFT values on initial admission and the changes in LFT values over time are reliable predictors of CBD stones in patients with AC.

ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH HYPOTHYROIDISM AND CONCOMITANT CHRONIC CHOLECYSTITIS.

Activity of endothelial dysfunction markers in patients with hypothyroidism and concomitant chronic cholecystitis was investigated. In patients with hypothyroidism and chronic cholecystitis a increased lactate dehydrogenase and alkaline phosphatase activity was observed, accompanied by the manifestation of cholestasis. In this patients increased vascular endothelium growth factor plasma level and endotheliocytes number was detected, attested the accelerated severity of endothelium dysfunction. Inverse correlation between the vascular endothelium growth factor plasma concentration, desquamated endotheliocytes number in peripheral blood and bilirubin level was detected, that points to the protective role of bilirubin in the prevention of the endothelium dysfunction development.

Prognostic importance of pentraxin 3 levels in acute cholesistitis.

BACKGROUND: Cholelithiasis is a frequently encountered problem in developed countries. Gallstone is present in at least 10% of the adults. While 40-60% of people with gallstones manifest an asymptomatic clinical course, in most of the cases with symptomatic cholelithiasis, there is also an asymptomatic period. 20% of the patients with symptomatic gallstones are admitted to emergency services with clinical features of acute cholecystitis. In this study, our aim was to evaluate the diagnostic value of pentraxin 3 on complications and prognosis and also to reduce the morbidity and mortality rates in cases with acute cholecystitis. METHODS: This study was conducted on patients diagnosed with acute calculous cholecystitis and operated on between September 2012 and January 2014, in the Department of General Surgery of Atatürk University Medical Faculty. Forty-five patients with ages above 18, who were clinically and radiologically diagnosed with acute calculous cholecystitis (Group I) and 45 healthy people, older than 18 (Group II) were included into the study. Patients were randomly selected. RESULTS: In our study, although the plasma pentraxin 3 (PTX3) levels were increased in the patient group and also in patients who developed morbidity, this was not statistically significant. PTX3 values were determined to be significantly increased in older patients (p<0.05). Moreover, when the duration of hospital stays were compared, PTX3 was found to be significantly higher in patients hospitalized for longer periods (p<0.05). CONCLUSION: PTX3 levels were found to be elevated in all evaluated parameters in patients with acute cholecystitis. Therefore, PTX3 level may be a valuable indicator in diagnosis and also in predicting prognosis.

[Influence of ursodeoxycholic acid on the immune status of patients with cholesterosis of gall-bladder depending on cholesterol index in blood].

Application of ursodeoxycholic acid in a standard dosage for 3 months provided a positive effect in relation to the indexes of the immune system for patients with the cholesterosis of gall-bladder. It is shown that medicine assists renewal of T-cell immunity, renders positive influence on B-link and renewal of index of immunoregulation can be seen. Reliable increase of specific receptors to CD25, HLA-DR and high level of CD95 testifies about including of the scray reaction of organism under influence of ursodeoxycholic acid on the remaining high indexes of B-cell of immunity. At the initial indexes of lipid spectrum, corresponding to the norm, the efficiency of normalization of immunological changes is more considerable than at the higher level of general cholesterol of serum of blood.