Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis.

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm2, p <0.001). Conclusions: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased. Impact and implications: There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop.

Spontaneous portosystemic shunt embolization in liver transplant recipients with recurrent hepatic encephalopathy.

INTRODUCTION AND OBJECTIVES: Spontaneous portosystemic shunts (SPSS) are a common cause of recurrent hepatic encephalopathy (HE). Shunt occlusion is an effective and safe procedure when performed in patients with cirrhosis and preserved liver function. We aimed to describe our experience with SPSS embolization after liver transplantation (LT). PATIENTS: We identified five patients who underwent SPSS embolization after LT. Clinical, biochemical and technical procedure data were collected. RESULTS: At presentation, all patients had developed graft cirrhosis and HE after LT. Median Model for End-stage Liver Disease (MELD) at embolization was 9 (range 7-12), median Child-Pugh was 8 (range 7-9). Splenorenal and mesocaval shunt were the most frequent types of SPSS found. Three patients have been completely free of HE. Of the two patients who had HE recurrence after embolization, one patient had two episodes of HE which was controlled well with medications. The other patient required three embolizations because of recurrent HE. Median follow-up was 4.4 years (range 1.0-5.0) and MELD score at last follow up was 13 (range 10-18) and median Child-Pugh score B, 7 points (range 5-12). CONCLUSIONS: SPSS can be considered as a cause of HE after LT. SPSS embolization is feasible and safe in LT recipients.

Spontaneous portosystemic shunts in liver cirrhosis: new approaches to an old problem.

Portal hypertension is the main consequence of liver cirrhosis, leading to severe complications such as variceal hemorrhage, ascites or hepatic encephalopathy. As an attempt to decompress the portal venous system, portal flow is derived into the systemic venous system through spontaneous portosystemic shunts (SPSSs), bypassing the liver. In this review, we aim to provide an overview of the published reports in relation to the prevalence and physiopathology behind the appearance of SPSS in liver cirrhosis, as well as the complications derived from its formation and its management. The role of SPSS embolization is specifically discussed, as SPSSs have been assessed as a therapeutic target, mainly for patients with recurrent/persistent hepatic encephalopathy and preserved liver function. Furthermore, different aspects of the role of SPSS in liver transplantation, as well as in candidates for transjugular intrahepatic portosystemic shunt are reviewed. In these settings, SPSS occlusion has been proposed to minimize possible deleterious effects, but results are so far inconclusive.

Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumor (GIST) initiation and evolution is commonly framed by KIT/PDGFRA oncogenic activation, and in later stages by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Thus, circulating tumor (ct)DNA determination is expected to be an informative non-invasive dynamic biomarker in GIST patients. METHODS: We performed amplicon-based next-generation sequencing (NGS) across 60 clinically relevant genes in 37 plasma samples from 18 GIST patients collected prospectively. ctDNA alterations were compared with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) and cross-validated with droplet digital PCR (ddPCR). RESULTS: We were able to identify cfDNA mutations in five out of 18 patients had detectable in at least one timepoint. Overall, NGS sensitivity for detection of cell-free (cf)DNA mutations in plasma was 28.6%, showing high concordance with ddPCR confirmation. We found that GIST had relatively low ctDNA shedding, and mutations were at low allele frequencies. ctDNA was detected only in GIST patients with advanced disease after imatinib failure, predicting tumor dynamics in serial monitoring. KIT secondary mutations were the only mechanism of resistance found across 10 imatinib-resistant GIST patients progressing to sunitinib or regorafenib. CONCLUSIONS: ctDNA evaluation with amplicon-based NGS detects KIT primary and secondary mutations in metastatic GIST patients, particularly after imatinib progression. GIST exhibits low ctDNA shedding, but ctDNA monitoring, when positive, reflects tumor dynamics.

Abdominothoracic mechanisms of functional abdominal distension and correction by biofeedback.

BACKGROUND & AIMS: In patients with functional gut disorders, abdominal distension has been associated with descent of the diaphragm and protrusion of the anterior abdominal wall. We investigated mechanisms of abdominal distension in these patients. METHODS: We performed a prospective study of 45 patients (42 women, 24-71 years old) with functional intestinal disorders (27 with irritable bowel syndrome with constipation, 15 with functional bloating, and 3 with irritable bowel syndrome with alternating bowel habits) and discrete episodes of visible abdominal distension. Subjects were assessed by abdominothoracic computed tomography (n = 39) and electromyography (EMG) of the abdominothoracic wall (n = 32) during basal conditions (without abdominal distension) and during episodes of severe abdominal distension. Fifteen patients received a median of 2 sessions (range, 1-3 sessions) of EMG-guided, respiratory-targeted biofeedback treatment; 11 received 1 control session before treatment. RESULTS: Episodes of abdominal distension were associated with diaphragm contraction (19% ± 3% increase in EMG score and 12 ± 2 mm descent; P < .001 vs basal values) and intercostal contraction (14% ± 3% increase in EMG scores and 6 ± 1 mm increase in thoracic antero-posterior diameter; P < .001 vs basal values). They were also associated with increases in lung volume (501 ± 93 mL; P < .001 vs basal value) and anterior abdominal wall protrusion (32 ± 3 mm increase in girth; P < .001 vs basal). Biofeedback treatment, but not control sessions, reduced the activity of the intercostal muscles (by 19% ± 2%) and the diaphragm (by 18% ± 4%), activated the internal oblique muscles (by 52% ± 13%), and reduced girth (by 25 ± 3 mm) (P ≤ .009 vs pretreatment for all). CONCLUSIONS: In patients with functional gut disorders, abdominal distension is a behavioral response that involves activity of the abdominothoracic wall. This distension can be reduced with EMG-guided, respiratory-targeted biofeedback therapy.

Small bowel obstruction secondary to internal hernia through a defect of the broad ligament: preoperative multi-detector CT diagnosis.

We report a case of small bowel obstruction secondary to internal hernia through a defect in the broad ligament diagnosed by MDCT and confirmed at surgery. The CT findings that allow the diagnosis of this very rare cause of SBO are presented here.

Usefulness of computed tomography performed immediately after excretory urography in patients with delayed opacification or dilated upper urinary tract of unknown cause.

PURPOSE: To evaluate the diagnostic value of computed tomography (CT) performed immediately after excretory urography (EU) in patients with delayed renal opacification or dilated upper urinary system with nonconclusive diagnosis after EU. MATERIALS AND METHODS: CT was performed immediately after EU in 39 patients with delayed opacification or dilated upper urinary system of unknown cause, without additional intravenous contrast administration for the CT study. We classified EU + CT findings as benign or malignant causes and we compared our results with the final diagnosis. RESULTS: The combination of EU + CT correctly diagnosed 38 out of the 39 cases with a sensitivity of 97%. Correct diagnosis was established in all malignant cases (n = 17) but one benign case consistent with blood clots in the upper urinary tract was incorrectly diagnosed as a multicentric urothelial carcinoma. Sensitivity, specificity, and accuracy for the diagnosis of the underlying cause with EU + CT was 100%, 95%, and 97%, respectively. The final diagnoses were: urothelial carcinoma (n = 10), stone disease (n = 10), bladder tumor (n = 4), benign post-treatment ureteral stenosis (n = 4), ureteral invasion (n = 3), benign bladder disease (n = 2), urinary tract infections (n = 2), crossing vessels (n = 1), ureteropelvic junction obstruction (n = 1), retrocaval ureter (n = 1), and blood clots in the upper urinary tract due to bleeding renal metastasis from lung cancer (n = 1). CONCLUSION: Combined EU and CT study allowed correct diagnosis of the underlying cause of delayed excretion or upper urinary tract dilatation in 97% of cases. The combination of EU and CT provides diagnosis reducing time and radiation.

Successful embolization of a spontaneous mesocaval shunt using the Amplatzer Vascular Plug II.

A 48-year-old man with alcoholic liver cirrhosis and hepatic encephalopathy was found to have a large, spontaneous mesocaval shunt. The shunt was successfully occluded with the use of an Amplatzer Vascular Plug. To our knowledge, this is the first report of the use of this device to embolize a mesocaval shunt involving the superior mesenteric vein.

Abdominal distention results from caudo-ventral redistribution of contents.

BACKGROUND & AIMS: Abdominal bloating is a frequent symptom in various categories of patients; however, its origin is unclear. Our aim was to establish the mechanisms of abdominal bloating. METHODS: The study evaluated 56 patients whose predominant symptom was abdominal bloating. Of these, 47 (44 female and 3 male; aged 19-74 years) were diagnosed with functional intestinal disorder by Rome II criteria and 9 (7 female and 2 male; aged 18-64 years) were diagnosed with intestinal dysmotility by gastrointestinal manometry. Computed tomographic scans were obtained before (basal level) and during a severe bloating episode. Control scans were also obtained from 12 healthy subjects (11 female and 1 male; aged 19-62 years). Morpho-volumetric differences between basal and severe bloating scans were measured using an original computer analysis program. RESULTS: During severe bloating, patients with dysmotility exhibited anterior wall protrusion (23 +/- 4 mm; P < .001 vs basal) associated with a marked increase in total abdominal volume (1.4 +/- 0.3 L; P = .002 vs basal) and with cephalic displacement of the diaphragm. By contrast, in patients with functional intestinal disorder, total abdominal volume barely increased (0.3 +/- 0.1 L; P < .001 vs dysmotility); in these patients, abdominal distention (14 +/- 2 mm anterior wall protrusion; P < .001 vs basal) was related to diaphragmatic descent (-12 +/- 3 mm; R = -0.62; P < .001). CONCLUSIONS: Abdominal distention might be caused by an increase in intra-abdominal volume or abdomino-phrenic displacement and ventro-caudal redistribution of contents.

Pancreatic metastasis of renal cell carcinoma: multidetector CT findings.

Pancreatic metastasis of renal cell carcinoma is more prevalent than the rates reported in the literature before the development of multidetector computed tomography (MDCT). These lesions are usually asymptomatic and used to be an incidental finding detected on radiological follow-up of these patients. If they are not associated with extrapancreatic involvement, they show an excellent response to surgical treatment. Thus, radiologists should be aware of the radiological characteristics of this condition to allow detection at an early stage. In this article we review the MDCT features of four cases of pancreatic metastasis of renal cell carcinoma to familiarize radiologists with this entity and the most suitable study method for its detection. The main imaging findings observed were hypervascular lesions in arterial phase of biphasic studies, hence the detection of these lesions is performed better during the early phase scanning.

Intestinal gas and bloating: effect of prokinetic stimulation.

BACKGROUND: It is unknown if abdominal bloating is attributable to excess abdominal gas or improved by a prokinetic agent. AIMS: To assess abdominal gas content in functional abdominal bloating and to ascertain the effect of a prokinetic agent on intestinal gas symptoms in these patients. METHODS: In 20 patients, intra-abdominal gas content and symptoms were quantified before and during treatment with pyridostigmine (30 mg/8 hp. o) in this randomized, placebo-controlled, double-blind study. Daily symptoms were quantified for 5 days before and 10 days during treatment, and abdominal gas volume was quantified by CT imaging before and at the fourth day of treatment. A CT scan was also obtained in 10 healthy subjects. RESULTS: Before treatment, the total volume of intestinal gas was similar in patients (112 +/- 18 mL) and in healthy controls (116 +/- 20 mL). The treatment-induced change in total and regional intestinal gas volume was not significantly different between pyridostigmine (-4 +/- 18 mL; mean +/- SEM) and placebo (0 +/- 15 mL). However, pyridostigmine reduced the severity of bloating from 3.3 +/- 0.3 to 2.6 +/- 0.4 (P < 0.05), whereas placebo did not (3.2 +/- 0.3 vs 3.0 +/- 0.4), although the change did not reach statistical difference across groups. CONCLUSION: In patients complaining of functional bloating, the volume and distribution of intestinal gas, measured on nonselected days, is comparable to asymptomatic subjects. Prokinetic stimulation improves bloating sensation without detectable changes in gas content.

[Krukenberg's tumor as the first clinical manifestation of fibrolamellar hepatocarcinoma]. / Tumor de Krukenberg como manifestación inicial de hepatocarcinoma fibrolamelar.

Krukenberg's tumor refers to unilateral or bilateral ovarian metastatic tumors whose origin may be known or unknown. The incidence of this type of tumor is difficult to evaluate but may represent between 3% and 8% of ovarian tumors. In most cases, the primary tumor is identified and is usually digestive (basically gastric or colorectal). There are some references to primary hepatic tumors (gall bladder tumor and hepatocarcinoma) but none to fibrolamellar hepatocarcinoma as the primary tumor. We present the case of a 45-year-old woman who presented with lower hemiabdominal pain and who was diagnosed with Krukenberg's tumor of hepatic origin. Although ovarian involvement in primary digestive tumors is possible, hepatic origin is rare.

[Hepatic angiomyolipoma in two patients infected with hepatitis C virus]. / Angiomiolipoma hepático en dos pacientes con infección por el virus de la hepatitis C.

AIM: The aim of this study is to present our experience with two cases of hepatic angiomyolioma in hepatitis C virus (HCV) positive patients, and to up-date the clinical manage, diagnostic and treatment of this entity. CLINICAL OBSERVATIONS: Both cases were presented in women in their 4-5th decade of life. Clinical presentation was with symptoms in one but incidental in the other. Both were HCV positive. Values of alpha-fetoprotein were normal. Radiological imaging was not diagnostic. Histopathological examination and immunohistochemical findings gave the diagnosis of angiomyolipoma. At time of diagnosis the size of tumours was 4.8 and 8 cm of diameter. Both cases were treated with surgery in order to definetly rule out malignancy. After 6 and 3 years of follow-up, there is no evidence of recurrence. DISCUSSION AND CONCLUSION: The hepatic angiomyolipoma is a rare benign tumour, mimicking other liver tumours. Although no patognomonic features, there are some radiological findings that point out to the diagnosis of angiomy olipoma. Nevertheless, definitive diagnosis is done by his tological and immunohistochemical findings (HMB-45). The hepatic angiomyolipoma consists of varing proportion of three elements, mature fat cells, smooth muscle cells and blood vessels. Although it is a benign tumour, the difficulty in ruling out malignancy, prompted surgical management. It is not described its relation with HCV virus, thus we consider our cases as an coincident finding.

Gas distribution within the human gut: effect of meals.

BACKGROUND AND AIMS: Patients frequently complain of gas symptoms precipitated by meals, but the effect of early digestion on intestinal gas content remains unknown. Our aim was to determine the influence of meals on intestinal gas volume and distribution. METHODS: First, we developed a CT image analysis program, based on independent software modules, to measure gas content within the gut. The system was validated in nine healthy subjects by taking helical abdominal CT scans before and after rectal infusion of known volumes of air (100-400 mL). In 15 healthy subjects, intestinal gas distribution was measured in fast and early postcibal CT scans. The postcibal scan was taken 99 +/- 22 minutes after a 597 +/- 57 kcal meal. RESULTS: The volume of gas infused per rectum was detected with an accuracy of 100.4 +/- 3.0%. During fasting, intestinal gas volume was 94 +/- 7 mL (excluding two extreme outliers). After the meal, gas content within the gut increased by 64.7% (up to 149 +/- 21 mL, P < 0.01 vs fast) and the increment occurred in the colon (59 +/- 9 mL precibal vs 121 +/- 20 mL postcibal, P < 0.001), while other gut compartments remained unchanged. CONCLUSION: Ingestion of a meal activated gas metabolism and increased gas content within the gut. The increment occurred early, presumably prior to colonic fermentation of food substrates and was localized in the distal gut, suggesting that gas had a proximal origin and was propelled caudally.

Oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts.

BACKGROUND/AIMS: Congenital portosystemic shunts are rare abnormalities of liver vasculature that can cause neurological symptoms, probably secondarily to the effects of the metabolism of ammonia in the brain. Our aim was to investigate the relationship between capillary blood ammonia after oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts. METHODS: Neuropsychological tests, oral glutamine challenge and magnetic resonance spectroscopy were performed at baseline and after 6 months of follow-up in three patients with congenital portosystemic shunts. The results were compared to those obtained in a group of six cirrhotic patients with prior episodes of hepatic encephalopathy and healthy controls. RESULTS: Patients with congenital portosystemic shunts exhibited abnormalities of neuropsychological tests, magnetic resonance spectroscopy and a response to the oral glutamine challenge similar to those observed in patients with cirrhosis. The intensity of the rise of brain glutamine was correlated to the area under the curve of ammonia after the oral glutamine challenge (R=0.72). CONCLUSIONS: Neurological manifestations of patients with congenital portosystemic shunts are mediated through similar mechanisms that are involved in the pathogenesis of hepatic encephalopathy. The area under the curve appears to be the better parameter that defines the response to the oral glutamine challenge.

Aortic stenosis: spectrum of diseases depicted at multisection CT.

Aortic stenosis, or narrowing of the aortic lumen, has many causes. It may originate in coarctation or pseudocoarctation of the aorta, midaortic dysplastic syndrome, atherosclerosis, Takayasu arteritis, aortic dissection, or various intraaortic and periaortic diseases or as a result of aortic surgical repair. The impedance of blood flow through the stenotic segment may lead to the development of various collateral arterial pathways, according to the location of stenosis. Aortography is the standard technique for evaluating aortic stenosis; however, helical computed tomography (CT), particularly multisection CT, may provide additional information or in some cases may be used instead of arteriography. Multisection CT can depict the aorta and thoracoabdominal collateral pathways in less than 1 minute and provide high-quality arterial-phase imaging data suitable for multiple two-dimensional and three-dimensional reformations. To produce a useful differential diagnosis, the imaging specialist must be able to recognize the type of stenosis and the configuration of collateral circulatory pathways.