Primary lack of response and secondary loss of response (LOR) are major obstacles to the use of anti-tumor necrosis factor (TNF)-based therapies in patients with rheumatoid arthritis or inflammatory ...bowel disease. Here, we review the mechanisms and methods for predicting LOR and the currently used methods for overcoming the ineffectiveness of anti-TNFs. The complex functions of TNF and anti-TNF antibodies, which can promote both pro- or anti-inflammatory actions, and the factors that affect the induction of immune tolerance to their effects are presented. The lack of rules and the continuous dynamics of the immune processes partly underlie the unpredictability of the response to anti-TNFs. Variability is inherent to biological systems, including immune processes, and intra/inter-patient variability has been described in the response to drugs. This variability is viewed as a compensatory adaptation mechanism of the immune system in response to drugs and may contribute to treatment LOR. Dose reductions and drug holidays have been tested in patients treated with anti-TNFs. Regular dose-based regimens may be incompatible with physiological variability, further contributing to treatment inefficacy. We present the concept of overcoming immune system adaptation to anti-TNFs by introducing patient-tailored patterns of variability to treatment regimens.
Background
Choledocholithiasis is a commonly encountered disease that is associated with various clinical presentations ranging from mild form of biliary colic to severe life-threatening acute ...cholangitis. Recently, peri-ampullary diverticulum (PAD) has been linked to the development of biliary diseases; however, data regarding its association with the development of acute cholangitis in the setting of choledocholithiasis are scarce.
Aims
We aimed to identify predictors, specifically PAD, for the development of acute cholangitis in patients with choledocholithiasis.
Methods
We performed a retrospective cross-sectional study of all patients admitted to Galilee Medical Center from 1 January 2010 to 31 December 2019 with different clinical presentations of documented choledocholithiasis including cholangitis, biliary pancreatitis, and biliary colic with abnormal liver enzymes.
Results
Overall, 651 patients were included in the final analysis. Among them, 88 patients (13.5%) had choledocholithiasis associated with acute cholangitis (group A), as compared to 563 patients (86.5%) without acute cholangitis (group B). The average ages in groups A and B were 77.8 ± 13.6 and 62.4 ± 20.4 years, respectively (
P
< 0.0001). The rate of PAD was significantly higher in group A as compared to group B (35.2% vs. 19%,
P
= 0.0002). However, the rate of smoking, chronic liver diseases, hemolytic anemia, and post-cholecystectomy status were not different between the groups (
P
= 0.3,
P
= 0.3,
P
= 0.2, and
P
= 0.3), respectively. On univariate analysis, age (OR 1.05,
P
< 0.0001) and PAD (OR 2.32,
P
= 0.0006) were significantly associated with acute cholangitis. On multivariate logistic regression analysis, the effects of age and PAD were preserved (OR 1.05, 95% CI 1.03–1.07,
P
< 0.0001 and OR 1.64, 95% CI 1.02–2.72,
P
= 0.049), respectively.
Conclusion
PAD showed a significant association with the development of acute cholangitis among patients with choledocholithiasis. Identification of gallbladder and biliary stones in patients with PAD is of paramount importance since early diagnosis and treatment might prevent further life-threatening complications.
Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality. The principal treatment is surgical resection or liver transplantation, depending on whether the patient is a ...suitable transplant candidate. However, in most patients with HCC the diagnosis is often late, thereby excluding the patients from definitive surgical resection. Medical treatment includes sorafenib, which is the most commonly used systemic therapy; although, it has been shown to only minimally impact patient survival by several months. Chemotherapy and radiotherapy are generally ineffective. Due to the poor prognosis of patients with HCC, newer treatments are needed with several being in development, either in pre-clinical or clinical studies. In this review article, we provide an update on the current and future medical and surgical management of HCC.
Background
Dominant stricture (DS) is a main cause of complication among patients with Primary Sclerosing Cholangitis (PSC). Endoscopic treatment options include dilation and plastic stenting, each ...with its own benefits and drawbacks.
Aims
The aim of the current study is to assess the safety and efficacy of fully-covered metal stent (FCMS) in these patients.
Methods
A retrospective study of PSC patients with refractory DS, defined as strictures resistance to conventional therapy (balloon dilatation, plastic biliary stent insertion or both) and who underwent FCMS insertion for 3 months were included. The primary outcome was defined as clinical and laboratory improvement, while secondary outcomes were DS resolution upon stent removal and cholangiographic DS recurrence at 12-months after FCMS extraction.
Results
Twenty patients were enrolled from January 2016 through January 2020. Improvement in weakness and pruritus were seen in 80% and 35%, 75% and 65%, 75% and 35% of patients at 1–3 and 6 months following FCMS removal, respectively. Similarly, consistent improvement in all liver enzymes and total bilirubin were seen in up to 6 month following stent removal. Only one patient (5%) needed premature FCMS removal due to cholangitis 1 week after stent placement and 2 cases (10%) of stent related pancreatitis were encountered. At 3-months all remaining stents were softly removed. Cholangiographic DS resolution was demonstrated in 13 patients (65%) after stent removal at 3-months, and DS recurred in 4 patients (4/13 = 30.7%) at 12-months following stent removal. Notably, only proximal biliary DS location showed a trend for DS recurrence (OR 28.6,
P
= 0.06).
Conclusion
Temporary 3 months duration FCMS was feasible, safe and effective treatment option among patients with PSC related refractory DS.
Abstract Background Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal ...Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS. Methods A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts. Results Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3–11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19–18.84), and age (OR 1, 95% CI 1.01–1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57–83.33, OR 16.3, 95% CI 3.02–88.08). Conclusion MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause.
fatty pancreas (FP) is an old observation, but a new disease with clinical implications and several associated comorbid conditions, ranging from mild to life-threatening diseases. Herein, we aimed to ...assess the association between FP and pancreatic cancer (PC) development.
we performed a retrospective cross-sectional study including all patients who underwent endoscopic ultrasound (EUS) for hepatobiliary indications. The study cohort was divided into patients with and without PC. Univariate and multivariate analysis were used to assess the association of several parameters with PC.
overall, 519 patients were included in the study. Of them, 48 had PC (PC group), and 471 did not (non-PC group). In univariate analysis, age (OR 1.04, 95% CI 1.01-1.07,
= 0.004), congestive heart failure (CHF) (OR 3.89, 95% CI 1.72-8.79,
= 0.001), ischemic heart disease (IHD) (OR 3.36, 95% CI 1.59-7.05,
= 0.001), hypertension (OR 2.42, 95% CI 1.33-4.41,
= 0.004) and fatty pancreas (FP) (OR 2.62, 95% CI 1.23-5.57,
= 0.01) were significantly associated with PC. In multivariate logistic regression analysis, only FP kept its association (OR 2.35, 95% CI 1.04-5.33,
= 0.04).
FP was significantly associated with PC. A follow-up plan should be considered for individuals with FP.
Abstract
Gastro-esophageal reflux disease (GERD) can cause erosive esophagitis (EE) and compromise the quality of life (QoL). We examined differences in symptom severity and QoL according to EE ...severity grade. A follow-up study was conducted among GERD patients at the Nazareth Hospital in Israel. Patients underwent a baseline gastroscopy in 2014–2020 during which the EE grade was determined using the Los Angeles classification. Follow-up telephone interviews were conducted during 2019–2020 with a mean time interval of 18.9 months (SD = 14.9) after the baseline gastroscopy to assess GERD symptoms using the Reflux disease questionnaire (RDQ) and QoL using the GERD QoL questionnaire. The patients were interviewed in their native language (Arabic or Hebrew). Overall, 149 (66.4% males) patients were included; 50 had EE grades C/D and 99 had grades A/B. The mean age at baseline and follow-up was 44.6 years (SD = 15.1) and 46.2 years (SD = 14.9), respectively. Cronbach’s alpha was 0.928 and 0.855 for the RDQ and QoL questionnaires, respectively. Patients with EE C/D grades had more severe symptoms than patients with EE A/B grades (
P
= 0.05), especially in regurgitation scores (
P
= 0.03). Females had more severe symptoms (overall) than males (adjusted OR = 2.34; 95% CI 1.12–4.90). Patients with the more severe esophagitis EE C/D group (adjusted OR = 1.98; 95% CI 0.93–4.24) and those who used PPIs treatment (adjusted OR = 2.19; 95% CI 0.95–5.01) reported more severe GERD symptoms. The number of schooling years was significantly associated with better QoL score (beta coefficient 1.33,
P
= 0.005) but not EE grade or GERD symptoms. Follow-up endoscopy conducted among 22 patients with EE grades C/D showed that 13 (59.1%) of these patients had normal endoscopic findings, 6 patients (27.3%) had a grade A EE, 1 patient (4.5%) had grade B, and 2 (9.1%) remained with grade C EE. The Arabic and Hebrew versions of the RDQ and QoL questionnaires were highly reliable. GERD symptoms severity was more profound among patients with more severe esophagitis. No significant association between EE grade and QoL; this negative result might be due to the improvement in esophagitis endoscopic findings among patients with C/D grade.
Background
Concomitant common bile duct (CBD) stone in the setting of acute calculous cholecystitis (ACC) should be suspected once abnormal liver indices are noticed.
Aim
We aimed to identify ...predictors of CBD stone in patients hospitalized with ACC.
Methods
We performed a retrospective multi-center, case-controlled, study from 1st of January 2016 until the 31th of December 2018. Inclusion criteria included patients with an established diagnosis of ACC based on clinical, laboratory and radiological criteria and who had an endoscopic ultrasound (EUS) for suspected CBD stone. One-hundred and twelve patients were included, of these fifty-three patients (47.3%) were diagnosed with CBD stone by EUS.
Results
In univariate analysis, Age
(
OR 1.038,
P
= 0.001), total bilirubin (mg/dl) (OR 1.429,
P
= 0.02) and CBD width (mm) by US (OR 1.314,
P
= 0.01) were statistically significant in predicting CBD stone and remained significant in multivariate regression analysis. We developed a diagnostic score that included these three parameters, with assignment of weights for each variable according to the coefficient estimate. A low cut-off score of 0 was associated with sensitivity of 100% for CBD stone, whereas a high cut-off score of 3 was associated with sensitivity of 10% and specificity of 96.6% with a positive predictive value of 67% (ROC of 0.7558). We validated this score with an independent cohort (ROC of 0.7416) with a sensitivity of 46.6%, a specificity of 91.5% and a PPV of 87.1%.
Conclusion
We recommend incorporating this score as an aid for stratifying patients with ACC into low or high probability for concomitant CBD stone.
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