Surgical resection for large hepatocellular carcinoma and those beyond BCLC: systematic review with proposed management algorithm.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for the sixth most common cancer and ranks third in mortality worldwide with inhomogeneity in terms of resection for advanced-stage disease. METHODS: A systematic review of published literature using the PubMed, Medline, and Google Scholar databases from 1995 to 2020 was conducted to identify studies that reported outcomes of resection for solitary HCC > 10 cm, BCLC B/C, and multinodular HCC. Our aim was to assess overall survival for resection, identify poor prognostic factors, and to compare it to trans-arterial chemotherapy (TACE) where data was available. RESULTS: Eighty-nine articles were included after a complete database search in the systematic review as per our predefined criteria. Analysis revealed a 5-year overall survival of 33.5% for resection of HCC > 10 cm, 41.7% for BCLC B, 23.3% for BCLC C, and 36.6% for multinodular HCC. Peri-operative mortality ranged from 0 to 6.9%. Studies comparing resection versus TACE for BCLC B/C had a survival of 40% versus 17%, respectively. CONCLUSION: Our systematic review justifies hepatic resection wherever feasible for hepatocellular carcinomas > 10 cm, BCLC B, BCLC C, and multinodular tumors. In addition, we identified and proposed an algorithm with five poor prognostic criteria in this group of patients who may benefit from adjuvant TACE.

Role of neomycin polymyxin sulfate solution bladder wash for prevention of catheter associated urinary tract infection in traumatic brain injury patient admitted to Intensive Care Unit: A prospective randomized study.

BACKGROUND: Catheter - associated urinary tract infection (CAUTI) remains a critical threat for patients in intensive care unit especially in traumatic brain injury patients with low Glasgow coma score (GCS). Almost all patients in ICU receive antibiotic either prophylactic or therapeutic based on local antibiogram of particular ICU or hospital. For prophylaxis, systemic antibiotics are used. It will be helpful to avoid systemic side effects by introducing antibiotics locally through bladder irrigation. The indwelling urinary catheter is an essential part of modern medical care. AIMS AND OBJECTIVES: The primary objective was to study the effect of Neomycin and Polymyxin sulphate solution for bladder wash on CAUTI in traumatic brain injury patients. The secondary objectives was to study the various organisms causing CAUTI and their antibiotic sensitivity and resistance pattern. MATERIALS AND METHODS: This was a prospective randomized controlled study performed on 100 patients who met the inclusion criteria at the trauma intensive care unit of Banaras Hindu University between September and February 2016. The patients were randomized into two groups - one was the study group which received Neomycin and Polymyxin Sulphate solution bladder wash, while the other was the control group that received Normal saline bladder wash. Urine samples were collected at certain days and sent for culture and sensitivity. RESULTS: There was significant reduction in the incidence of CAUTI in neomycin/polymyxin test group in comparison to normal saline irrigated control group. Out of 50 patients in test group 8 patients and in control group 26 patients was identified as CAUTI positive and they were statistically significant. In our study pseudomonas aeruginosa (51%) was the commonest isolated pathogen. CONCLUSIONS: Neomycin and Polymyxin Sulphate bladder wash was effective in preventing CAUTI. It can thus decrease the antibiotic usage thereby preventing the emergence of antibiotic resistance.

Percutaneous ultrasonography-guided nephroscopic evacuation of hydatid cyst in posterior segment of liver.

Hydatid disease commonly affects liver and treatment of choice is surgery. Ultrasound examination is helpful to diagnose, classify and plan management of the cyst. Surgical treatment is done using a conventional open technique or minimal access technique. We report our experience of using ultrasound-guided percutaneous nephroscopic approach to treat liver hydatid cyst.

Association of ORMDL3 with rhinovirus-induced endoplasmic reticulum stress and type I Interferon responses in human leucocytes.

BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodelling and hyperresponsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN)-regulated chemokine CXCL10. OBJECTIVE: The purpose of this study was to determine the relationship between ORMDL3 and rhinovirus-induced ER stress and type I IFN in human leucocytes. METHODS: ER stress was monitored by measuring HSPA5, CHOP and spliced XBP1 gene expression, and type I IFN by measuring IFNB1 (IFN-ß) and CXCL10 expression in human cell lines and primary leucocytes following treatment with rhinovirus. Requirements for cell contact and specific cell type in ORMDL3 induction were examined by transwell assay and depletion experiments, respectively. Finally, the effects of 17q21 genotype on the expression of ORMDL3, IFNB1 and ER stress genes were assessed. RESULTS: THP-1 monocytes overexpressing ORMDL3 responded to rhinovirus with increased IFNB1 and HSPA5. Rhinovirus-induced ORMDL3 expression in primary leucocytes required cell-cell contact, and induction was suppressed by plasmacytoid dendritic cell depletion. The degree of rhinovirus-induced ORMDL3, HSPA5 and IFNB1 expression varied by leucocyte type and 17q21 genotype, with the highest expression of these genes in the asthma-associated genotype. CONCLUSIONS AND CLINICAL RELEVANCE: Multiple lines of evidence support an association between higher ORMDL3 and increased rhinovirus-induced HSPA5 and type I IFN gene expression. These associations with ORMDL3 are cell type specific, with the most significant 17q21 genotype effects on ORMDL3 expression and HSPA5 induction evident in B cells. Together, these findings have implications for how the interaction of increased ORMDL3 and rhinovirus may predispose to asthma.

Evaluation of Glycemia Control Achieved by Glargine and Lispro Versus Detemir and Aspart Insulin Regimes in Type 2 Diabetics Undergoing Surgery.

There is paucity of scientific literature regarding the clinical outcome of long lasting basal insulin and rapid acting mealtime insulin regimes in surgical situations although employed in non-surgical situations. This study has evaluated the clinical outcome of two subcutaneous split-mixed Glargine+Lispro and Detemir+Aspart insulin regimes in type 2 diabetics undergoing surgery.

Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations.

BACKGROUND: Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood. OBJECTIVE: The aim of this analysis was to determine whether cytokine patterns in patients with colds could identify risks for subsequent asthma exacerbations. METHODS: We analysed cytokine levels in nasal lavage fluid (NLF) in 59 subjects (46 with asthma) with acute upper respiratory symptoms and after symptomatic resolution. Analyte choice was based on potential relevance to asthma exacerbations: antiviral (IFN-α, IFN-ß, IFN-γ, IFN-λ1, IP-10, TRAIL), cell recruiting (G-CSF, IL-1ß, IL-8, MCP-1, MCP-3, TNF-α), polarizing (CXCL13, IL-10, IL-13, IL-17, TSLP), and injury remodelling (fibronectin, IL-33, MMP-9, VEGF). RESULTS: The overall cytokine response induced during viral infections was not different between asthmatic and non-asthmatic individuals for a wide array of cytokines. However, mean levels of VEGF, TNF-α and IL-1ß were 1.7-, 5.1- and 4.7-fold higher in samples from asthma subjects who exacerbated in the first 3 weeks of the cold compared with those who did not exacerbate (P = 0.006, 0.01, 0.048, respectively). Using receiver operating characteristic curve-defined thresholds, high VEGF and TNF-α levels predicted a shorter time-to-exacerbation after NLF sampling (25% exacerbation rate: 3 vs. 45 days, and 3 vs. 26 days; P = 0.03, 0.04, respectively). CONCLUSION AND CLINICAL RELEVANCE: Although they produce similar cytokine responses to viral infection as non-asthmatics, asthmatics with higher levels of VEGF and TNF-α in NLF obtained during acute cold phases predicted subsequent asthma exacerbations in this cohort of patients with mild-to-moderate disease. In the future, stratifying the risk of an asthma exacerbation by cytokine profile may aid the targeting of personalized treatment and intervention strategies.

Interferon gene expression in sputum cells correlates with the Asthma Index Score during virus-induced exacerbations.

BACKGROUND: The majority of asthma exacerbations are related to viral respiratory infections. Some, but not all, previous studies have reported that low interferon responses in patients with asthma increase the risk for virus-induced exacerbations. OBJECTIVE: We sought to determine the relationship between lower airway inflammatory biomarkers, specifically interferon gene expression, and the severity or presence of an exacerbation in asthmatics experiencing a naturally occurring viral infection. METHODS: Sputum samples were analysed from subjects in an asthma exacerbation study who experienced a confirmed viral infection. Subjects were monitored for daily symptoms, medication use and peak expiratory flow rate until baseline. Sputum samples were assessed for cell counts and gene expression. RESULTS: Interferon gamma expression was significantly greater in patients with asthma exacerbations compared to non-exacerbating patients (P = 0.002). IFN-α1, IFN-ß1 and IFN-γ mRNA levels correlated with the peak Asthma Index (r = 0.58, P < 0.001; r = 0.57, P = 0.001; and r = 0.51, P = 0.004, respectively). Additionally, IL-13, IL-10 and eosinophil major basic protein mRNA levels were greater in patients with asthma exacerbations compared to non-exacerbating patients (P = 0.03, P = 0.06 and P = 0.02, respectively), and IL-13 mRNA correlated with the peak Asthma Index (P = 0.006). CONCLUSIONS: Our findings indicate that asthma exacerbations are associated with increased rather than decreased expression of interferons early in the course of infection. These findings raise the possibility that excessive virus-induced interferon production during acute infections can contribute to airway inflammation and exacerbations of asthma.

Modulation of ethanol toxicity by Asian ginseng (Panax ginseng) in Japanese ricefish (Oryzias latipes) embryogenesis.

Alcohol consumption by women during pregnancy often induces fetal alcohol spectrum disorder (FASD) in children who have serious central nervous system (CNS), cardiovascular, and craniofacial defects. Prevention of FASD, other than women abstaining from alcohol drinking during pregnancy, is not known. A limitation of the use of synthetic anti-alcoholic drugs during pregnancy led us to investigate herbal products. In particular, many plants including Asian ginseng (Panax ginseng) have therapeutic potential for the treatment of alcoholism. We used Japanese ricefish (medaka) (Oryzias latipes), an animal model of FASD, for identifying herbal medicines that can attenuate ethanol toxicity. Fertilized eggs in standard laboratory conditions were exposed to ginseng (PG) root extract (0-2 mg/mL) either 0-2 (group A) or 1-3 (group B) day post fertilization (dpf) followed by maintenance in a clean hatching solution. The calculated IC50 as determined 10 dpf in A and B groups were 355.3±1.12 and 679.7±1.6 µg/mL, respectively. Simultaneous exposure of embryos in sub-lethal concentrations of PG (50-200 µg/mL) and ethanol (300 mM) for 48 h disrupted vessel circulation and enhanced mortality. However, PG (100 µg/mL) may partially protect trabecular cartilage (TC) deformities in the neurocranium in B group embryos induced by ethanol (300 mM). To understand the mechanism, embryonic ethanol concentration was measured at 2 dpf and adh5, adh8, aldh2, aldh9a, catalase, GST, and GR mRNAs were analyzed at 6 dpf. It was observed that although ethanol is able to reduce adh8 and GST mRNA contents, the simultaneous addition of PG was unable to alter ethanol level as well as mRNA contents in these embryos. Therefore, antagonistic effects of PG on ethanol toxicity are mediated by a mechanism which is different from those regulating ethanol metabolism and oxidative stress.

Solitary fibrous tumour of lung.

Fibrous tumours arising entirely within the substance of the lung are rare. We report one such rare case in whom the diagnosis was established after surgical removal.

Correlation of gallstone characteristics with mucosal changes in gall bladder.

BACKGROUND AND AIM: Gallstones are known to produce diverse histopathological changes in the gall bladder. Our aim was to correlate various gallstone characteristics (number, size, weight, volume and morphological type) with the type of mucosal response in gall bladder (inflammation, hyperplasia, metaplasia and carcinoma). METHODS: The study was conducted on 330 open cholecystectomy specimens with complete gallstones. The stones were assessed for various parameters i.e. number, size, weight, volume and morphological type. For microscopy, sections were obtained from the fundus, body and neck of the gallbladder. Additional sections were taken from abnormal looking areas. RESULTS: Out of the 330 cases, 194 (59%) had mixed stones, 84 (25%) combined, 30 (9%) pigment and 22 (7%) had cholesterol stones. Number of stones varied from a single calculus in 131 (39.6%) cases, double in 29 (8.8%) and multiple in the remaining 170 (51.6%) cases. Cholecystitis, hyperplasia, metaplasia and carcinoma were more commonly seen with mixed and multiple stones. The average weight of calculi in cholecystitis was 2.551 gm, in hyperplasia 3.619 gm, metaplasia4.549 gm and 17.96 gm in cases with carcinoma. Similarly, average volume of the stone(s) was 2.664 ml in cholecystitis, 3.742 ml in hyperplasia, 4.532 ml in metaplasia and 19.178 ml in carcinoma. The average calculus size (2.147 cm) was found to be maximum in cases with carcinoma, followed by hyperplasia (1.187 cm), metaplasia (1.145 cm) and cholecystitis (1.136 cm). CONCLUSION: As the weight, volume and size of the stone increases the changes in the gall bladder mucosa changes from cholecystitis, hyperplasia, metaplasia, dysplasia, to carcinoma.

The lady with a calcified brain.

The authors present here a case that demonstrates the importance of exclusion of metabolic conditions before giving a diagnosis of Fahr disease. This case also highlights the possibility of exacerbation of hypocalcaemia by antiepileptic agents.

Laparoscopic release of median arcuate ligament.

Median arcuate ligament (MAL) syndrome, also known as the celiac axis compression syndrome, is rare. It is a diagnosis of exclusion, characterised by the clinical triad of postprandial abdominal pain, weight loss and vomiting. Computed tomographic angiography is the gold standard for making the diagnosis of MAL and colour Doppler is essential to confirm the diagnosis. The classic management involves the surgical division of the MAL fibres. We report successful management of two patients diagnosed as MAL syndrome and treated by laparoscopic release of the MAL.

Variable clinical presentations of histoplasmosis: a report of six cases.

Histoplasma is a dimorphic fungus that primarily involves the lungs and the environmental reservoir is soil. It has emerged as an important opportunistic fungal infection in immunocompromised patients. Six cases of histoplasmosis with variable clinical presentations diagnosed either on cytology or histopathology are discussed - three were HIV-positive. The possibility of histoplasmosis should always be borne in mind, especially in immunocompromised patients, as it can have variable clinical presentations.

Donor safety in live-related liver transplantation.

Living donor liver transplantation (LDLT), since its advent in late 1980's and early 1990's, has rapidly increased especially in countries like Japan, Korea and India where cadaveric programmes are not as well established as in the western world. The main advantage of LDLT is the availability of an organ in the elective setting in the course of a progressive liver disease. This is most applicable in patients with Cirrhosis and Hepatocellular carcinoma. LDLT, from the donor's perspective does carry a risk of not only morbidity but mortality. To date the surgical mortality risk is estimated at 0.1% for left lateral donation and 0.5% for right liver donation. Donor mortality has been reported from various centres in India. There are reports of complications like Hepatic artery thrombosis, portal vein thrombosis and especially biliary leaks and strictures occurring at a significantly increased frequency after living as compared to deceased donor liver transplantation. The key to reduce donor morbidity and mortality is meticulous donor selection and thorough donor work up. In the present study we will analyse the factors that contributed to donor mortality and morbidity and prepare a detailed work up plan, intraoperative and post-operative strategy to reduce donor morbidity and mortality.

Isolated tuberculous splenic abscess in an immunocompetent individual.

Tuberculosis (TB) of the spleen is an extremely rare clinical entity particularly among immunocompetent persons. We report a case of isolated tuberculous abscess of spleen in a 13- years- old boy. No primary focus of infection was detected in lungs or any other organ. The patient was treated by splenectomy after a therapeutic failure with standard antituberculous medication.