Management of hypersplenism in non-cirrhotic portal hypertension:a surgical series

BACKGROUND:Hypersplenism is commonly seen in patients with non-cirrhotic portal hypertension(NCPH).While a splenectomy alone can effectively relieve the hypersplenism,it does not address the underlying portal hypertension.The present study was undertaken to analyze the impact of shunt and non-shunt operations on the resolution of hypersplenism in patients with NCPH.The relationship of symptomatic hypersplenism,severe hypersplenism and number of peripheral cell line defects to the severity of portal hypertension and outcome was also assessed.METHODS:A retrospective analysis of NCPH patients with hypersplenism managed surgically between 1999 and 2009 at our center was done.Of 252 patients with NCPH,64(45 with extrahepatic portal vein obstruction and 19 with non-cirrhotic portal fibrosis) had hypersplenism and constituted the study group.Statistical analysis was done using GraphPad InStat.Categorical and continuous variables were compared using the chi-square test,ANOVA,and Student’s t test.The MannWhitney U test and Kruskal-Wallis test were used to compare non-parametric variables.RESULTS:The mean age of patients in the study group was 21.81±6.1 years.Hypersplenism was symptomatic in 70.3% with an incidence of spontaneous bleeding at 26.5%,recurrent anemia at 34.4%,and recurrent infection at 29.7%.The mean duration of surgery was 4.16±1.9 hours,intraoperative blood loss was 457±126(50-2000) mL,and postoperative hospital stay 5.5±1.9 days.Following surgery,normalization of hypersplenism occurred in all patients.On long-term followup,none of the patients developed hepatic encephalopathy and 4 had a variceal re-bleeding(2 after a splenectomy alone,1 each after an esophago-gastric devascularization and proximal splenorenal shunt).Patients with severe hypersplenism and those with defects in all three peripheral blood cell lineages were older,had a longer duration of symptoms,and a higher incidence of variceal bleeding and postoperative morbidity.In addition,patients with triple cell line defects had elevated portal pressure(P=0.001),portal biliopathy(P=0.02),portal gastropathy(P=0.005) and intraoperative blood loss(P=0.001).CONCLUSIONS:Hypersplenism is effectively relieved by both shunt and non-shunt operations.A proximal splenorenal shunt not only relieves hypersplenism but also effectively addresses the potential complications of underlying portal hypertension and can be safely performed with good long-term outcome.Patients with hypersplenism who have defects in all three blood cell lineages have significantly elevated portal pressures and are at increased risk of complications of variceal bleeding,portal biliopathy and gastropathy.

A rabbit model of non- cirrhotic portal hypertension by repeated injections of E. coli through indwelling cannulation of the gastrosplenic vein

BACKGROUND: Non-cirrhotic portal hypertension is acommon cause of portal hypertension in developing coun-tries. To understand its etiopathogenesis we developed ananimal model by repeated portal endotoxemia inducedthrough the gastrosplenic vein.METHODS: Twenty-nine rabbits (1.5-2.0 kg) were divid-ed into control (group n = 13) and experimental ( groupn = 16) groups. Heat killed E. coli were injected throughan indwelling cannula into the gastrosplenic vein in pre-sensitized animals. The animals were sacriflced at 1, 3 and6 months.RESULTS: The mean portal pressure in group animalswas significantly (P < 0. 05) higher than in group at 1(17.5 ±3.4 vs 10.4±2.2 mmHg), 3 (17.8±1.3 vs7.2 +3.6mmHg), and 6 (19.8±3.1 vs 10.3±4.8 mmHg) months.Similarly, the mean splenic weight in group was signifi-cantly greater than in group (P <0.05). Histopathologi-cally, the spleen showed medullary congestion, hemosid-rin-laden macrophages and mild fibrosis. Histologically,the liver had normal parenchyma with mild portal lympho-cytic infiltrates and kupffer cell hyperplasia. No significantanomalies were detected by liver function tests.CONCLUSIONS: The rabbit model showed significantsplenomegaly with a persistent increase in portal pressureand mild fibrosis without hepatic parenchymal injury, quiteakin to non-cirrhotic portal fibrosis as seen in humans. Re-current intra-abdominal infection may play an importantrole in the pathogenesis of non-cirrhotic portal fibrosis.

Upgrading the definition of early gastric cancer: better staging means more appropriate treatment

Since Murakami defined early gastric cancer(EGC) as a "carcinoma limited to the gastric mucosa and/or submucosa regardless of the lymph node status", several authors have focused on the most influential histopathological parameters for predicting the development of lymph node metastases by considering the lymph node status as an important prognostic factor. A few authors have also considered the depth of invasion as one of the keys to explaining the existence of subgroups of patients affected by EGC with poor prognoses. In any case, EGC is still considered an initial phase of tumor progression with good prognosis. The introduction of modern endoscopic devices has allowed a precise diagnosis of early lesions, which can lead to improved definitions of tumors that can be radically treated with endoscopic mucosal resection or endoscopic submucosal dissection(ESD). Given the widespread use of these techniques, the Japanese Gastric Cancer Association( JGCA) identified in 2011 the standard criteria that should exclude the presence of lymph node metastases. At that time, EGCs with nodal involvement should have been asserted as no longer fitting the definition of an early tumor. Some authors have also demonstrated that the morphological growth pattern of a tumor, according to Kodama's classification, is one of the most important prognostic factors, thereby suggesting the need to report it in histopathological drafts. Notwithstanding the acquired knowledge regarding the clinical behavior of EGC, Murakami's definition is still being used. This definition needs to be upgraded according to the modern staging of the disease so that the appropriate treatment would be selected.

A randomized trial of a 4- vs 12-week daily interferon dose regimen combined with ribavirin in treatment of patients with chronic hepatitis C

BACKGROUND: Standard combination-therapy of ribavi- rin with alternate day interferon (IFN) in patients with chronic hepatitis C ( CHC) has been reported to achieve 30%-55% sustained viral response. Early reduction of viral load by daily dosage of IFN could enhance viral clearance. However, the duration of daily dosage protocol and the likely side-effects have not been well studied. We compared the efficacy and safety of a 4- vs 12-week daily IFN dosage in patients with CHC. METHODS: Fifty-nine, histologically proven CHC patients having ALT levels >1.5 ×ULN were divided randomly into 2 groups, group I was given IFN 3 MIU daily for 4 weeks, followed by tiw up to 12 months and group was given IFN 3 MIU daily for 12 weeks, followed by tiw up to 12 months. Ribavirin was given in a dose of 800-1200 mg/d for 12 months. RESULTS: Fifty-two of the 59 patients (group group completed the study. The pretreatment vari- ables and the prevalence of HCV genotype 1 were compara- ble between the groups. Nine patients (29%) in group and 6 (25%) in group had stage 3, 4 fibrosis. At the end of 4, 12, 24 and 52 weeks, HCV RNA negativity was ob- served in 27%, 54%, 65% and 71% in group I and 38%, 54%, 71% and 75% in group respectively (P =ns). Four of the eight (50%) patients with genotype 1 and 30 (69.8%) of 43 patients with genotype non-1 responded to therapy (P =ns). Sustained viral response was achieved in 61% and 71% in groups respectively. None of the variables predicted non-response precisely. No serious adverse effects were observed and they were comparable between the two groups. CONCLUSION: Daily IFN dosage with ribavirin is safe and can achieve response in up to 65% patients. Since the effica- cy of a 4-week daily dosage of IFN is comparable to a 12- week schedule, we recommend the former regimen.

Pleomorphic hepatocellular carcinoma following consumption of hypericum perforatum in alcoholic cirrhosis

Hepatocellular carcinoma (HCC) often develops in patients with underlying liver disease, yet HCC with syncytial giant cells (SGCs) is extremely rare. Herein, we report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during his regular checkup presented with marked elevation of alpha-fetoprotein. Clinical examination and imaging analyses revealed a tumor-like lesion in segment 4 of the liver, which was removed by limited wedge resection. Histological analysis by hematoxylin and eosin staining indicated pleomorphic and atypical nodules, with some SGCs, embedded within the boundaries of the neoplastic lesion. The adjacent liver parenchyma showed microvesicular steatosis, pericellular fibrosis, and moderate hemosiderin accumulation (grade 2, as determined by Prussian blue iron stain) in hepatocytes and Kupffer cells but no copper accumulation (as determined by orcein stain). Immunohistochemical analysis showed hepatocyte antigen-positive staining for the neoplastic cells and SGCs. The diagnosis was made for cirrhosis-related HCC with SGCs. The previous reports of pleomorphic HCC have featured osteoclast-like (i.e., mesenchymal type) giant cells, making this case of epithelial type giant cells very rare. The patient&#x02019;s 6-month history of hypericum perforatum/St John&#x02019;s wort self-medication may have prompted the cirrhosis or HCC progression or the unusual SGC manifestation.

Serous pancreatic neoplasia, data and review

AIM To describe the imaging features of serous neoplasms of the pancreas using ultrasound, endoscopic ultrasound, computed tomography and magnetic resonance imaging.METHODS This multicenter international collaboration enhances a literature review to date, reporting features of 287 histologically confirmed cases of serous pancreatic cystic neoplasms(SPN). RESULTS Female predominance is seen with most SPN presenting asymptomatically in the 5th through 7th decade. Mean lesion size was 38.7 mm, 98% were single, 44.2% cystic, 46% mixed cystic and solid, and 94% hypoechoic on B-mode ultrasound. Vascular patterns and contrast-enhancement profiles are described as hypervascular and hyperenhancing.CONCLUSION The described ultrasound features can aid differentiation of SPN from other neoplastic lesions under most circumstances.

Primary biliary cirrhosis in India

BACKGROUND: Primary biliary cirrhosis (PBC) is a rare cause of chronic liver disease in India. We analyzed the clinical, biochemical, serological and histological features of patients with PBC for over a 10-year period. METHODS: PBC was diagnosed by the presence of raised level of serum alkaline phosphatase (ALP), anti-mitochondrial antibody (AMA) positivity (1:40 dilution), and/or diagnostic liver histology. RESULTS:Fifteen female patients with mean age of 46.5±11 years were studied. Pruritis (80%) followed by jaundice (67%), skin changes (pigmentation, coarsening, xanthelesma and vitiligo) (67%) and fatigue (60%) were common symptoms. The mean duration of the symptoms was 3.5± 5.4 years (3 months to 20 years). Dryness of eyes was observed in only 2 patients. Hepatomegaly was noted in 87% of the patients and ascites at presentation in 40%. Mean levels of bilirubin and albumin at the time of diagnosis were 3.4±3.3 mg/dl and 3.5±0.8 g/dl, respectively. The level of serum ALP ranged from 54 to 2400 IU/L, with a median being 552 IU/L (2×ULN). In all the 15 patients with AMA positive, 8(53%) were also positive for either anti-nuclear or anti-smooth muscle antibodies. Two patients presented with persistently elevated SAP after an acute hepatitic illness. Liver biopsy was available in 13 patients, diagnostic of PBC Ⅱ & Ⅲ(8) and with evidence of cirrhosis (5). Associated autoimmune disorders were observed in 5 patients (33%). The mean time for follow-up was 26±21 months (1 to 87 months). In 4 deaths, 3 were due to liver related causes. CONCLUSION: PBC is a rare cause of chronic liver disease in India. PBC in India, unlike in the West, presents late, often with features of cirrhosis and decompensation.