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.

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.

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.

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.

Thoracic epidural catheterization leading to delayed transient neurological symptoms with normal imaging findings.

Paraparesis after epidural catheterization is rare but may be multifactorial. We report a case of temporary paraparesis in a 32-year-old female patient after thoracic epidural catheterization performed analgesia. A 16 G epidural needle was introduced at the T(7)-T(8) interspace but as frank blood came through, it was withdrawn and was reinserted at the T(8)-T(9) interspace. An 18 G epidural catheter was introduced and 10 ml of 0.125% bupivacaine with buprenorphine 150 mcg was given. Further top-ups were given for 48 h on complain of pain. There was an episode of hypotension after giving the epidural drug but later on the patient remained haemodynamically stable. On the fourth post-operative day, the patient reported paraparesis with heaviness and tingling sensation in both lower extremities. MRI was normal with no evidence of spinal cord compression, oedema, haematoma or abscess. The patient improved gradually within a period of 3 days. The possible causes of delayed onset of neurological symptoms are discussed.

Adenolipoma of the thyroid gland.

Thyrolipoma or adenolipoma of the thyroid gland is defined as a thyroid adenoma containing mature fat tissue. It is a rare encapsulated lesion. A case of a 35-year-old female presenting with swelling in the neck that was diagnosed as adenolipoma is described because of its extreme rarity.

Testicular granulosa cell tumor, adult type.

Granulosa cell tumor (GCT) of the adult type is a rare and slow-growing neoplasm in the testis. This tumor may be associated with endocrine manifestations and resemble classic GCT of the ovary morphologically. It has a potential for distant metastasis or recurrence late in the clinical course. We report a case of granulose cell tumor of the testis, adult type.

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.

Heat shock response and protein degradation: regulation of HSF2 by the ubiquitin-proteasome pathway.

Mammalian cells coexpress a family of heat shock factors (HSFs) whose activities are regulated by diverse stress conditions to coordinate the inducible expression of heat shock genes. Distinct from HSF1, which is expressed ubiquitously and activated by heat shock and other stresses that result in the appearance of nonnative proteins, the stress signal for HSF2 has not been identified. HSF2 activity has been associated with development and differentiation, and the activation properties of HSF2 have been characterized in hemin-treated human K562 erythroleukemia cells. Here, we demonstrate that a stress signal for HSF2 activation occurs when the ubiquitin-proteasome pathway is inhibited. HSF2 DNA-binding activity is induced upon exposure of mammalian cells to the proteasome inhibitors hemin, MG132, and lactacystin, and in the mouse ts85 cell line, which carries a temperature sensitivity mutation in the ubiquitin-activating enzyme (E1) upon shift to the nonpermissive temperature. HSF2 is labile, and its activation requires both continued protein synthesis and reduced degradation. The downstream effect of HSF2 activation by proteasome inhibitors is the induction of the same set of heat shock genes that are induced during heat shock by HSF1, thus revealing that HSF2 affords the cell with a novel heat shock gene-regulatory mechanism to respond to changes in the protein-degradative machinery.

Stress-specific activation and repression of heat shock factors 1 and 2.

Vertebrate cells express a family of heat shock transcription factors (HSF1 to HSF4) that coordinate the inducible regulation of heat shock genes in response to diverse signals. HSF1 is potent and activated rapidly though transiently by heat shock, whereas HSF2 is a less active transcriptional regulator but can retain its DNA binding properties for extended periods. Consequently, the differential activation of HSF1 and HSF2 by various stresses may be critical for cells to survive repeated and diverse stress challenges and to provide a mechanism for more precise regulation of heat shock gene expression. Here we show, using a novel DNA binding and detection assay, that HSF1 and HSF2 are coactivated to different levels in response to a range of conditions that cause cell stress. Above a low basal activity of both HSFs, heat shock preferentially activates HSF1, whereas the amino acid analogue azetidine or the proteasome inhibitor MG132 coactivates both HSFs to different levels and hemin preferentially induces HSF2. Unexpectedly, we also found that heat shock has dramatic adverse effects on HSF2 that lead to its reversible inactivation coincident with relocalization from the nucleus. The reversible inactivation of HSF2 is specific to heat shock and does not occur with other stressors or in cells expressing high levels of heat shock proteins. These results reveal that HSF2 activity is negatively regulated by heat and suggest a role for heat shock proteins in the positive regulation of HSF2.

Type-2 diabetes related intermediate phenotypic traits in north Indian diabetics.

Asian Indians are known to be at a higher risk of developing T2DM, but the underlying genetic factor in this population is still not well understood. T2DM is a complex genetic trait and assessment of disease related intermediate phenotypic traits is an important initial step towards any systematic genomic study. Therefore, in the present study we have assessed diabetes related intermediate phenotypic traits of insulin secretion and insulin resistance in the patients belonging to this population. The study included 157 T2DM patients of either sex ranging in age from 45-80 years and 84 non-diabetic subjects with no family history of diabetes, ranging in age from 45 to 75 years served as controls. Intermediate phenotypic traits studied were BMI, W: H ratio, fasting free fatty acid level and Insulin resistance and secretion. Diabetics were found to have significantly higher W: H ratio (p<0.001), FFA (p<0.001) and HOMA-R (p<0.001) as compared to non-diabetics. However, there was no significant difference in their BMI and HOMA-ß. There was a positive correlation between FFA level and HOMA-R among diabetics, but not among controls. These findings suggest that in abdominal obesity FFA mediated insulin resistance is an important causative factor underlying T2DM in this population. Moreover, comparable HOMA-ß in diabetics reflects compensatory insulin hyper secretion in these subjects. There is a need to examine relative contribution and precise nature of genetic factor in their tendency for central obesity, free fatty acidemia and insulin resistance.

Adrenal angiomyolipoma: A rare entity.

Angiomyolipoma is apparently a part of a family of neoplasms that derive from perivascular epitheloid cells. It is a rare mesenchymal tumor, usually found in the kidney. Extrarenal angiomyolipoma is uncommon and the most common extrarenal site is the liver. Only two cases of adrenal angiomyolipoma are reported in English literature. Authors wish to add one more case to world literature. Because of its large size and symptomatic presentation of extremely rare tumor merits documentation.

Acute renal failure in the intensive care unit.

BACKGROUND: Acute renal failure (ARF) in the intensive care unit (ICU) is associated with high mortality. A thorough understanding of the clinical spectrum of the disease is needed in order to devise methods to improve the final outcome due to this problem. AIMS AND OBJECTIVES: The aim of the present study was to analyze the clinical spectrum, causes, risk and prognostic factors and final outcome of ARF in the setting of ICU. METHOD: This prospective study involved patients admitted to ICU during the period between September 2003 to January 2005 (17 months). Patients who developed ARF during the ICU stay were included in the study. The clinical and laboratory data were collected at admission and then on daily basis. Data recorded included; patient characteristics, underlying medical conditions responsible for ICU admission, dialytic status, need for ventilation, total duration of ICU stay, APACHE-III score and final outcome, and these data were analyzed for predicting survival using univariate and multivariate analysis. RESULTS: Twelve hundred and fifteen (1215) patients were admitted to ICU from September 2003 to January, 2005 and 46 (3.79%) patients developed ARF after admission to ICU. Mean age of patients was 44.9 +/- 17 years and 56.5% were males. Comorbidity was seen in 24 (52%) patients; hypertension (34.7%), diabetes mellitus (28.3%), coronary artery disease (30.4%) and chronic kidney disease (13%). ARF had developed complicating medical and surgical conditions in 33 (71.7%) and 11 (23.7%) patients respectively. The etiology of ARF was multifactorial and included; hypotension (71.74%), volume depletion (17.4%), nephrotoxic drugs (67.39%), and sepsis (69.5%). Multiple organ system failure (MOSF) was noted in 63% of cases and dialysis was required in 25 (54.3%) patients. Mortality occurred in 63% of patients. MOSF and sepsis were found to be significant adverse prognostic factors when multiple logistic regression analysis was done. CONCLUSIONS: ARF was seen in 3.79% of cases in our ICU and associated with poor prognosis. Presence of sepsis, MOSF, higher APACHE--III scores and ventilation need were correlated with higher mortality in ARF patients in the intensive care unit.

Detecting role of apoptosis in mediating cyclophosphamide induced teratogenesis in vitro.

Programmed cell death (apoptosis) refers to a specific type of cell death under stringent genetic control. Even a slight alteration in this process leads to malformations characterized by birth defects. Based on the above hypothesis we deduced that apoptosis plays an important role in mediating the teratogenicity of cyclophosphamide in vitro. The present study was undertaken to see whether this phenomenon holds true or not. In this study, 11-day-old rat embryos were cultured for 24 hours with various concentrations of CP (i.e. 0, 5, 10 and 100 mug/ml culture). After culturing for 24 hours, embryos exposed to 10 and 100 mug/mL culture of CP were found having both malformations and growth retardation. Exposure to CP at 5 mug/mL culture did not show significant effect on embryonic development. Parallel to this, flow cytometric analysis (cell cycle and annexin V binding) and DNA fragmentation assay were also carried out followed by quantitation by 3'-OH labeling of cultured embryos to evaluate CP-induced apoptosis. All the results were found to be dose-dependant, and the data suggested that apoptosis is involved in mediating the teratogenicity of CP in vitro.

Cystic lymphangioma of the spleen--a case report.

Splenic cystic lymphangioma is a very rare condition. It occurs commonly in children in whom it is often an incidental imaging finding. In the absence of histologic confirmation, it usually mimics hydatid disease and other cystic vascular proliferations of the spleen. We present a case of cystic lymphangioma of the spleen in 15 years old female.

Extraskeletal chondroma of the hand--a case report.

Extraskeletal chondroma is a rare entity. A fairly benign condition, it is usually seen in adults. It presents as an enlarging mass, most commonly in the hand. Local excision is the treatment of choice. We present a case of extraskeletal chondroma of hand in a 12 year male child. Its variable histological appearance not infrequently leads to a mistaken diagnosis of chondrosarcoma.