Severe chronic diarrhoea caused by hereditary transthyretin amyloidosis.

Amyloidosis includes a heterogeneous group of diseases caused by the extracellular deposition of insoluble fibrillar proteins, leading to multiple organ dysfunction and a poor life expectancy. In the early stages of amyloidosis, gastrointestinal (GI) symptoms are uncommon. We describe a rare case of hereditary transthyretin amyloidosis (ATTRv) with involvement of the heart, nervous system and GI tract. A man in his 60s was hospitalised due to chronic diarrhoea, orthostatic hypotension, malabsorption and weight loss. An organic origin for the diarrhoea was suspected, but the most common causes were ruled out. The review of GI biopsies and an abdominal fat aspirate confirmed the diagnosis of amyloidosis. The diagnosis of ATTRv amyloidosis with GI presentation is challenging, especially in the early stages, and misdiagnosis is common. The recent approval of therapies emphasises the importance of early diagnosis to prevent irreversible organ damage.

Relevance of sonographic parameters for inflammatory bowel disease in children.

PURPOSE: Intestinal ultrasound (IUS) is widely used as the first exam in patients with suspected inflammatory bowel disease (IBD). This study investigated the accuracy of several IUS parameters, including increased bowel wall thickening (BWT), in detecting IBD in a paediatric population. METHODS: The study included an unselected series of 113 patients aged 2-18 years (mean age 10.8 years, 65 male), referred for recurrent abdominal pain or altered bowel habits, without known organic diseases, to perform an IUS as first investigation of a diagnostic workup. Patients with full systematic IUS examination, clinical and biochemical exams, and ileocolonoscopy or an uneventful follow-up at least one year follow up were eligible. RESULTS: 23 IBD patients (20.4%; 8 ulcerative colitis, 12 Crohn's disease and 3 indeterminate colitis) were diagnosed. We found that increased BWT > 3 mm (OR 5.4), altered IUS bowel pattern (IUS-BP, OR 9.8) and mesenteric hypertrophy (MH, OR 5.2) accurately identified IBD at the multivariate analysis. IUS-BP, MH and BWT > 3 mm had a sensitivity of 78.3%, 65.2% and 69.6% and a specificity of 93.3%, 92.2% and 96.7%, respectively. The combination of these three alterations increased the specificity up to 100%, whilst decreased sensitivity to 56.5%. CONCLUSION: Among several US parameters suggestive of IBD, the increased BWT, MH and altered echopattern are independent predictors of IBD. The ultrasonographic diagnosis of IBD could be more accurate if relied on combination of different sonographic parameters, than on the sole BWT evaluation.

Ultrasonographic and Functional Features of Symptomatic Uncomplicated Diverticular Disease.

INTRODUCTION: To evaluate the ability of intestinal ultrasound (IUS) in discriminating symptomatic uncomplicated diverticular disease (SUDD) among patients with abdominal symptoms including irritable bowel syndrome (IBS). METHODS: This observational, prospective study included consecutive patients classified into the following categories: (i) SUDD; (ii) IBS; (iii) unclassifiable abdominal symptoms; and (iv) controls, including asymptomatic healthy subjects and diverticulosis. The IUS evaluation of the sigmoid: assessed the presence of diverticula, thickness of the muscularis propria, and IUS-evoked pain, namely the intensity of pain evoked by compression with the ultrasound probe on sigmoid colon compared with an area of the left lower abdominal quadrant without underlying sigmoid colon. RESULTS: We enrolled 40 patients with SUDD, 20 patients with IBS, 28 patients with unclassifiable abdominal symptoms, 10 healthy controls, and 20 patients with diverticulosis. Patients with SUDD displayed significantly ( P < 0.001) greater muscle thickness (2.25 ± 0.73 mm) compared with patients with IBS (1.66 ± 0.32 mm), patients with unclassifiable abdominal pain, and healthy subjects, but comparable with that of patients with diverticulosis (2.35 ± 0.71 mm). Patients with SUDD showed a greater (not significant) differential pain score than other patients. There was a significant correlation between the thickness of the muscularis propria and the differential pain score only for patients with SUDD ( r = 0.460; P : 0.01). Sigmoid diverticula were detected by colonoscopy in 40 patients (42.4%) and by IUS with a sensitivity of 96.0% and a specificity of 98.5%. DISCUSSION: IUS could represent a useful diagnostic tool for SUDD, potentially useful in characterizing the disease and appropriately address the therapeutic approach.

Laparoscopic Heller Myotomy and Dor Fundoplication for the Treatment of Esophageal Achalasia After Sleeve Gastrectomy-a Video Vignette.

PURPOSE: Esophageal dysmotility and disorders of the lower esophageal sphincter are well documented in morbidly obese patients. Esophageal achalasia has been reported in up to 1% of obese patients but the development of such esophageal motility disorder after laparoscopic sleeve gastrectomy (LSG) is extremely rare. The purpose of this video was to demonstrate the management of a type II esophageal achalasia diagnosed in a 46-year-old female patient 4-year after LSG. MATERIALS AND METHODS: An intraoperative video has been anonymized and edited to demonstrate the feasibility of laparoscopic Heller myotomy and anterior Dor fundoplication on the mentioned patient. RESULTS: The operation started with the section of the perigastric adhesions. Proceeding in a clockwise direction, the esophagogastric junction, the anterior esophageal wall, and the His angle were freed. A residual slightly dilated fundus was found and isolated. After mobilization of the distal esophagus and identification of the anterior vagus nerve, a "hockey stick" myotomy was carried out for 6 cm on the esophagus and for 2 cm on the gastric side. An anterior Dor fundoplication was fashioned using the residual gastric fundus. CONCLUSION: Esophageal achalasia in patients that previously underwent LSG is exceptional but should always be suspected in case of pathognomonic symptoms onset. In tertiary referral centers, laparoscopic Heller myotomy and, if technically feasible, an anterior Dor fundoplication seem safe and effective to relieve gastroesophageal outflow obstruction and prevent gastroesophageal reflux.

Totally laparoscopic, multi-stage, restorative proctocolectomy for inflammatory bowel diseases. A prospective study on safety, efficacy and long-term results.

BACKGROUND: Laparoscopic ileo-pouch-anal anastomosis (IPAA) has been reported as having low morbidity and several advantages. AIMS: To evaluate safety, efficacy and long-term results of laparoscopic IPAA, performed in elective or emergency settings, in consecutive unselected IBD patients. METHODS: All the patients received totally laparoscopic 2-stage (proctocolectomy and IPAA - stoma closure) or 3-stage (colectomy - proctectomy and IPAA - stoma closure) procedure according to their presentation. RESULTS: From July 2007 to July 2016, 160 patients entered the study. 50.6% underwent a 3-stage procedure and 49.4% a 2-stage procedure. Mortality and morbidity were 0.6% and 24.6%. Conversion rate was 3.75%. 8.7% septic complications were associated with steroids and Infliximab treatment (p = 0.0001). 3-stage patients were younger (p = 0.0001), with shorter disease duration (p = 0.0001), minor ASA scores of 2 and 3 (p = 0.0007), lower inflammatory index and better nutritional status (p = 0.003 and 0.0001), fewer Clavien-Dindo's grade II complications (p = .0001), reduced rates of readmission and reoperation at 90 days (p = 0.03), and shorter hospitalization (p = .0001), but with similar pouch and IPAA leakage, compared to 2-stage patients. 8 years pouch failure and definitive ileostomy were 5.1% and 3.7%. CONCLUSION: A totally laparoscopic approach is safe and feasible, with very low mortality and morbidity rates and very low conversion rate, even in multi-stage procedures and high-risk patients.

Intestinal gas and liver steatosis: a casual association? A prospective multicentre assessment.

BACKGROUND & AIMS: Excessive intestinal gas and liver steatosis are frequent sonographic findings. Both of these appear to be caused by variations of the gut microflora. We assessed the relationship between ultrasonographic detection of intestinal gas and liver steatosis. METHODS: This study included 204 consecutive patients (99 male; mean age 53.0 ± 15.6 years), who underwent ultrasonography for abdominal complaints or follow-up of benign lesions. Body mass index, biochemical liver markers, sonographic presence of liver steatosis and/or degree of intestinal gas interfering with the examination were collected. Both sonographic findings were assessed based on standardized criteria. The association between liver steatosis and intestinal gas was evaluated by means of univariate and multivariate analyses. RESULTS: Eighty (39.2%) of patients showed moderate to large amounts of gas preventing an accurate evaluation of the liver or pancreas and 90 (44.1%) had liver steatosis. A significant correlation between the degree of intestinal gas and liver steatosis both in obese (r=.603; P<.001) and in nonobese patients (r=.555; P<.001) was found. Univariate analysis showed that intestinal gas, body mass index, aspartate transaminase, alanine transaminase, gamma-GT, age and sex were predictors of liver steatosis; only intestinal gas (OR 7.4; 95% CI 3.4-16.1) and body mass index (OR; 1.4, 95% CI 1.2-1.5), however, were independent predictors at multivariate analysis. The presence of excessive gas was also significantly correlated with liver steatosis coupled with elevated ALT (P = .001). CONCLUSION: This study shows a significant correlation between excessive intestinal gas and liver steatosis. The reasons of this finding and its clinical implications remain to be defined.

Splanchnic Hemodynamics and Intestinal Vascularity in Crohn's Disease: An In Vivo Evaluation Using Doppler and Contrast-Enhanced Ultrasound and Biochemical Parameters.

Crohn's disease (CD) is characterized by inflammation and angiogenesis of affected bowel. We evaluated the correlation among vascularity of intestinal wall in CD, splanchnic hemodynamics, clinical activity and biochemical parameters of inflammation and angiogenesis. Sixteen patients with ileal CD and 10 healthy controls were investigated by means of Doppler ultrasound of the superior mesenteric artery and color Doppler and contrast-enhanced ultrasound of the ileal wall. In parallel, serum levels of vascular endothelial growth factor, tumor necrosis factor-α (TNF-α) and nitric oxide, before and 30 min after a standard meal, were evaluated. In CD patients, there was a significant post-prandial reduction in the resistance index and pulsatility index of the superior mesenteric artery, associated with increased levels of nitric oxide and decreased amounts of TNF-α. A correlation was observed between vascular endothelial growth factor and contrast-enhanced ultrasound parameters of intestinal wall vascularity (r = 0.63-0.71, p < 0.05) and between these parameters and superior mesenteric artery blood flow after fasting (resistance and pulsatility indexes: r = -0.64 and -0.72, p < 0.05). Our results revealed a post-prandial increase in nitric oxide and decrease in TNF-α in CD patients in vivo. They also confirm the role of vascular endothelial growth factor in angiogenesis and in pathologic vascular remodeling of CD and its effect on splanchnic blood flow.

Invasive and noninvasive methods to diagnose portal hypertension and esophageal varices.

Assessing the presence of clinically significant portal hypertension and esophageal varices is clinically important in cirrhosis. The reference standard techniques to assess the presence of portal hypertension and varices are the measurement of the hepatic vein pressure gradient and esophagogastroduodenoscopy, respectively. Some newer methods have shown a good performance, but none has been proven precise enough to replace hepatic vein pressure gradient measurement or esophagogastroduodenoscopy for the diagnosis of portal hypertension or the presence and grade of esophageal varices.

Impact of portal vein thrombosis on the efficacy of endoscopic variceal band ligation.

BACKGROUND: Influence of portal vein thrombosis on efficacy of endoscopic variceal banding in patients with cirrhosis or extrahepatic portal vein obstruction has never been evaluated. Aim of the study was to assess influence of thrombosis on rate and time to eradication in cirrhosis and extrahepatic portal vein obstruction undergoing banding, compared to cirrhotic patients without thrombosis. METHODS: Retrospective analysis of 235 consecutive patients (192 with cirrhosis without thrombosis, 22 cirrhosis and thrombosis and 21 extrahepatic portal vein obstruction) who underwent banding. Banding was performed every 2-3 weeks until eradication; endoscopic follow-up was performed at 1, 3, 6 months, then annually. RESULTS: Eradication was achieved in 233 patients. Median time to eradication in cirrhotic patients with portal vein thrombosis vs. cirrhotic patients without thrombosis was 50.9 days (12-440) vs. 43.4 days (13-489.4); log-rank: 0.04; patients with extrahepatic portal vein obstruction vs. cirrhotic patients without thrombosis 63.9 days (31-321.6) vs. 43.4 days (13.0-489.4); log-rank: 0.008. Thrombosis was shown to be the only risk factor for longer time to eradication. CONCLUSIONS: Portal vein thrombosis per se appears to be the cause of a longer time to achieve eradication of varices but, once eradication is achieved, it does not influence their recurrence.

Portal vein thrombosis in inflammatory bowel diseases: a single-center case series.

BACKGROUND AND METHODS: Portal vein thrombosis (PVT) has been reported as a complication of IBD in some case reports. We describe the presentation, diagnostic approaches, underlying risks factors and clinical outcome of 8 IBD patients with PVT. CASE-SERIES: The patients presented with partial PVT (4 patients) or portal cavernoma. Five patients had undergone surgery. In 2 patients portal biliopathy was diagnosed after detection of PVT. In 4 patients, the diagnosis of PVT was made while IBD was in remission. Five patients showed at least one risk factor for hypercoagulability: lupus anti-coagulant (one patient), increased von Willebrand factor (2 patients) or homocysteine levels (4 patients). Four patients received anticoagulant therapy for 6 months. None experienced other thrombotic events during a median of 5 years (range 2-8 years). CONCLUSION: PVT is a potential complication of IBD, usually associated with acquired or inherited risks factors for hypercoagulability and with a benign outcome.

The course of esophageal varices in patients with hepatitis C cirrhosis responding to interferon/ribavirin therapy.

BACKGROUND: Gastrointestinal haemorrhage from ruptured esophageal varices (EV) is a significant cause of morbidity and mortality in patients with HCV-related cirrhosis. The risk of developing EV and bleeding is influenced by hepatitis severity, which can be attenuated by successful interferon (IFN) therapy. Our aim was to prospectively assess whether a successful IFN therapy modifies development and/or progression of EV in patients with HCV-related compensated cirrhosis. METHODS: Child-Pugh A patients with either no or small (F1) EV underwent surveillance with repeated endoscopy during and after completion of IFN-based therapy. RESULTS: A total of 127 patients (59 years, 79 males, 65 HCV-1/4 and 17 F1 EV) received weight-based ribavirin (RBV) combined with either IFN-α2b 3 MU three times per week (n=36), weekly pegylated (PEG)-IFN-α2b 1.5 µg/kg (n=68) or weekly PEG-IFN-α2a 180 µg (n=23). Patients were followed-up for 18-108 months after treatment completion with a median endoscopic follow-up of 68 months for the 62 patients with a sustained virological response (SVR) and 57 months for the 65 non-SVR patients (P=0.3). De novo EV developed in 10 (9.1%) patients including 2/57 SVR and 8/53 non-SVR (3.5% versus 15.1%; P=0.047), whereas EV progressed in size in 3 patients, including 1/5 SVR and 2/12 non-SVR (P=0.87). Two non-SVR patients bled from EV and one died. CONCLUSIONS: A successful IFN therapy prevents or delays the de novo onset of EV in patients with compensated cirrhosis due to HCV, but does not abrogate the need for continued endoscopic surveillance.

Schwann cell hamartoma: case report.

BACKGROUND: Colorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening. CASE PRESENTATION: We report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract. CONCLUSION: As recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma.

Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method.

UNLABELLED: Patients with cirrhosis possess an imbalance in procoagulant versus anticoagulant activity due to increased factor VIII and decreased protein C. This imbalance can be detected by thrombin-generation assays performed in the presence/absence of thrombomodulin (predicate assay) that are not readily available in clinical laboratories. We sought to assess this hypercoagulability with a simpler thrombin-generation assay performed in the presence/absence of Protac, a snake venom that activates protein C in a manner similar to thrombomodulin (new assay). We analyzed blood from 105 patients with cirrhosis and 105 healthy subjects (controls). Results for the predicate-assay or the new-assay were expressed as ratio (with:without thrombomodulin) or as Protac-induced coagulation inhibition (PICI%). By definition, high ratios or low PICI% translate into hypercoagulability. The median(range) PICI% was lower in patients (74% [31%-97%]) than controls (93% [72%-99%]; P < 0.001), indicating that patients with cirrhosis are resistant to the action of Protac. This resistance resulted in greater plasma hypercoagulability in patients who were Child class C than those who were A or B. The hypercoagulability of Child C cirrhosis (63% [31%-92%]) was similar to that observed for patients with factor V Leiden (69% [15%-80%]; P = 0.59). The PICI% values were correlated with the levels of protein C (rho = 0.728, P < 0.001) or factor VIII (rho = -0.517, P < 0.001). Finally, the PICI% values were correlated with the predicate assay (rho = -0.580, P < 0.001). CONCLUSION: The hypercoagulability of plasma from patients with cirrhosis can be detected with the new assay, which compares favorably with the other markers of hypercoagulability (i.e., high factor VIII and low protein C) and with the predicate-assay based on thrombin-generation with/without thrombomodulin. Advantages of the new assay over the predicate assay are easy performance and standardized results. Prospective trials are needed to ascertain whether it is useful to predict thrombosis in patients with cirrhosis.

High levels of factor VIII and risk of extra-hepatic portal vein obstruction.

BACKGROUND/AIMS: High levels of coagulation factor VIII are a risk factor for lower-limb deep vein thrombosis (DVT). Their role in extra-hepatic portal vein obstruction (EHPVO) is not established. METHODS: Factor VIII was measured in 85 patients with EHPVO (primary in 58 and complicating liver cirrhosis in 27), in 200 with lower-limb DVT, in 108 with liver cirrhosis without thrombosis and in 200 healthy controls. RESULTS: Factor VIII levels were significantly higher in patients with primary EHPVO (138 IU/dL, range 86-366), EHPVO and cirrhosis (147 IU/dL, 95-242), lower-limb DVT (140 IU/dL, 64-400) and cirrhosis alone (160 IU/dL, 43-446) than in controls (112 IU/dL, 62-250, p<0.001). When factor VIII exceeded 129 IU/dL (66th percentile), the odds ratios were 10.5 (95%CI 3.3-33.4) for primary EHPVO, 6.0 (1.2-30.7) for EHPVO and cirrhosis, 5.0 (2.6-9.4) for lower-limb DVT. After exclusion of the effect of the acute phase reaction, the odds ratio for primary EHPVO was 4.2 (0.8-22.7), and was 8.7 (0.9-80.5) after exclusion also of patients with chronic myeloproliferative disorders. CONCLUSIONS: High factor VIII levels are independently associated with an increased risk for EHPVO. The risk of EHPVO increased with increasing factor VIII levels and was only partially dependent on the acute phase reaction.

The coagulopathy of cirrhosis assessed by thromboelastometry and its correlation with conventional coagulation parameters.

BACKGROUND: Thromboelastometry allows continuous registration of the blood viscoelastic changes upon activation by cephaline or tissue-factor plus calcium-chloride. The technique is used as a near-patient-testing device to guide transfusion in cardiac surgery or liver transplantation and less to investigate hemostasis in acquired or congenital coagulopathies. AIMS: (i) Review of the coagulopathy associated with cirrhosis and (ii) report on its investigation by thromboelastometry in comparison with conventional coagulation parameters. METHODS: We investigated citrated blood samples from 51 adult cirrhotics for the following thromboelastometry parameters: coagulation-time (CT), clot-formation-time (CFT), maximum-clot-firmness (MCF). RESULTS: Relatively few patients [14/51(27%)] were identified as abnormal by CT; in contrast, a greater proportion were identified by the CFT [41/51(80%)] or MCF [39/51(76%)]. CFT and MCF were correlated with the platelet-count, antithrombin and fibrinogen. Prothrombin time (PT) was correlated with CFT and MCF. None of the coagulation parameters were correlated with CT. The correlation of the Child-Pugh-score (taken as index of severity) versus MCF or PT was -0.457(p < 0.001) or 0.484(p < 0.001), suggesting MCF as a suitable prognostic index. CFT and MCF, but not CT obtained ROC curves that were useful to distinguish patients from healthy individuals. CONCLUSIONS: Thromboelastometry, currently used to assist liver transplantation is also suitable for investigating stable cirrhosis. CFT and MCF are the most interesting parameters to be considered for future clinical studies needed to assess their value as measures of bleeding-risk and prognosis in this category of patients.

Novel developments in esophageal vascular disorders.

PURPOSE OF REVIEW: Esophageal variceal bleeding is a life-threatening complication of liver cirrhosis. The aim of this review is to discuss the most important studies published in 2007 concerning diagnosis of esophageal varices, primary and secondary prophylaxis and treatment of variceal bleeding. RECENT FINDINGS: The specific areas reviewed are the noninvasive or minimally invasive diagnosis of oesophageal varices, prevention of the formation of varices and their progression from small to large, prevention of the first variceal hemorrhage, treatment of acute bleeding episodes and prevention of rebleeding, assessment of costs related to prophylaxis and treatment of variceal bleeding. Multidetector computed tomographic esophagography was found to identify the presence and grade the size of esophageal varices. Portal vein thrombosis was found to be an independent predictor of the aggravation of esophageal varices in patients with cirrhosis and hepatocellular carcinoma. The role of hepatic vein pressure gradient measurement in the prediction of decompensation of cirrhosis has been elucidated. SUMMARY: Relevant studies are reviewed on the diagnosis and the natural history of esophageal varices, prevention of their formation and growth, prevention of the first variceal bleed, use of hepatic vein pressure gradient to predict the evolution of portal hypertension and to estimate the response to pharmacological treatment, prediction of bleeding, treatment of variceal bleeding and prevention of rebleeding, and cost strategies.

Diagnosis and therapy of esophageal vascular disorders.

PURPOSE OF REVIEW: The most relevant studies concerning the diagnosis of esophageal varices, primary and secondary prophylaxis and treatment of variceal bleeding published in the last year are reported. RECENT FINDINGS: The specific areas reviewed are those that refer to studies on the noninvasive or minimally invasive diagnosis of the presence of esophageal varices, the prevention of the formation and of the progression of varices from small to large, the prevention of the first variceal haemorrhage, the treatment of the acute bleeding episode, and the prevention of rebleeding. SUMMARY: Relevant studies are reviewed regarding the validation of noninvasive indices for the presence of varices, the use of the esophageal videocapsule to diagnose varices, the comparison of methods to prevent the first variceal haemorrhage, the use of the hepatic vein pressure measurement to monitor the haemodynamic response to beta-blockers, the long-term protection from bleeding by beta-blockers, the use of a double dose of somatostatin to control bleeding, the evaluation of the best endoscopic method to treat variceal bleeding in addition to vasoactive drugs, and the identification of prognostic factors for early and late mortality after a variceal bleed.

Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis.

The diagnosis of an underlying chronic myeloproliferative disorder (CMPD) is often problematic in patients with primary extrahepatic portal vein obstruction (EHPVO) or Budd-Chiari syndrome (BCS); indeed, conventional clinical and hematological parameters usually yield insufficient information. To assess the diagnostic contribution of the gain-of-function mutation V617F of the JAK2 gene, 93 patients with EHPVO or BCS were investigated. JAK2 V617F was identified in 35.6% of 73 patients with EHPVO and in 40% of 20 patients with BCS. Taking the JAK2 mutation as a test with the highest positive predictive value for the diagnosis of CMPD, conventional clinical-hematological parameters had a sensitivity for CMPD lower than 48%. Bone marrow (BM) histology provided a diagnosis of CMPD in 41/74 (55.4%) patients, with a sensitivity of 93.5%. Clonality of hematopoiesis as assessed by granulocyte X-chromosome inactivation was present in 65.1% of 43 informative female patients, with a sensitivity of 86.6%. By resolving the sensitivity bias of the JAK2 mutation with the results of BM histology and clonality assay, CMPD was diagnosed in 53% of patients with EHPVO or BCS. In conclusion, CMPD is the major cause of primary EHPVO or BCS. JAK2 V617F is a very reliable and noninvasive molecular marker for CMPD and should be used as a first test for diagnosis.