A case of idiopathic portal hypertension associated with rheumatoid arthritis

A 53-year-old woman who had been diagnosed with rheumatoid arthritis was found to have thrombocytopenia, splenomegaly, and gastric varices. She was diagnosed as having idiopathic portal hypertension on the basis of liver biopsy and angiography. Treatment with prednisolone was not sufficiently effective for thrombocytopenia. After transabdominal devascularization with splenectomy, thrombocytopenia subsided and gastric varices disappeared. In this case, the autoimmune mechanism as well as hypersplenism was suspected of being involved in the mechanism of thrombocytopenia.     

Successful treatment of pure red cell aplasia and autoimmune cytopenia with cyclosporine and prednisolone in a patient with Sjögren’s syndrome

Abstract

A 68-year-old woman was admitted to our hospital with xerophthalmia, xerostomia, leukopenia, and thrombocytopenia. She was diagnosed to have Sjögren’s syndrome and autoimmune cytopenia. After 11 months, she was readmitted with severe anemia and reticulocytopenia. Mild hemolysis was seen, and bone marrow aspirate showed markedly decreased erythropoiesis. An association of pure red cell aplasia (PRCA) and autoimmune hemolytic anemia was diagnosed. After treatment with cyclosporine and prednisolone, her anemia dramatically improved. We discuss the mechanism of PRCA associated with Sjögren’s syndrome.     

Risk stratification for secondary prophylaxis of gastric varices due to portal hypertension

BackgroundGastroesophageal variceal hemorrhage is a common complication associated with portal hypertension. Current guidelines provide well-established recommendations for esophageal varices, while that of gastric varices remain scarce and lack evidential strength. The aim of the study is to identify a feasible risk stratification method based on imaging findings to evaluate patient response to cyanoacrylate injection for the treatment of gastric varices.MethodsA prospective cohort study including patients diagnosed with gastric varices admitted for initial secondary prophylactic treatment for GV was conducted. Routine endoscopic examination and endoscopic ultrasound (EUS) were performed on all subjects to evaluate extraluminal collaterals. All patients with gastric varices were treated uniformly with cyanoacrylate injection. Patients were prospectively followed for at least 12 months and any occurrence of variceal rebleed was recorded.Results102 subjects were enrolled in the study, 66.7% had GOV Type 2, 27.5% had GOV Type 1 and 5.9% had IGV Type 1. During the 12 months follow-up, 33.3% patients experienced variceal rebleed. A risk assessment scoring system was proposed based on endoscopic and EUS findings. A Cox regression analysis demonstrated a significant association between the merited risk score and incidence of variceal rebleed (P < 0.001).ConclusionsPresence of red wales sign, size of varix, and presence of para-gastric vein were all independent risk factors for variceal rebleed after endoscopic therapy for the treatment of gastric varices. Early identification of this subgroup, especially those with higher risk scores, necessitates a change in course of treatment, which can improve prognosis and overall patient outcome.     

Use of the Ultrasonic Microprobe to Evaluate Gastric Varices –Comparison with Endoscopic Color Doppler Ultrasonography–

Abstract: This study was designed to evaluate the usefulness of the ultrasonic microprobe (UMP), as compared with endoscopic color Doppler ultrasonography (ECDUS), in detecting gastric varices in 18 patients. The gastric varices detected were categorized as follows: 14 F₂ type varices, four F₃ type. Among the 18 cases, four had cardiac varices, nine cardiofornical varices, and five fundic varices. UMP was easily performed visually by using an endoscope with a UM-3R (20MHz) probe, inserted via the biopsy channel, and a display unit (Olympus EU-M20). ECDUS was performed using a PENTAX FG-32UA and a FG-36UX, 7.5MHz, convex type. The display monitor was a HITACHI EUB 565. We were able to clearly delineate the vessel images of gastric varices in all 18 patients using UMP. Although the overall features of the peri-gastric collateral veins could not be discerned with UMP, the color flow images of gastric varices and peri-gastric collateral veins were clearly visualized in all 18 patients using ECDUS. It was thus possible to determine blood flow direction using ECDUS. We found the use of UMP to be advantageous in terms of the ease of operation and the excellent view provided of gastric varices. The fact that, due to limited penetration, UMP inadequately delineates the peri-gastric collateral veins was determined to be a major drawback. Therefore, we recommend ECDUS for evaluating overall hemodynamics. It was, however, technically difficult to scan the fundal region because of the characteristics of the ECDUS instrument. Thus, we conclude that detailed evaluation of gastric varix hemodynamics is most successfully accomplished by using UMP in conjunction with ECDUS.     

Safe and successful endoscopic initial treatment and long-term eradication of gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2-cyanoacrylate) injection

Abstract

Objective. Optimal endoscopic treatment of gastric varices is still not standardized nowadays. Actively bleeding varices may prohibit a successful endoscopic injection therapy of Histoacryl® (N-butyl-2-cyanoacrylate). Since 2006, we have treated gastric varices by standardized endoscopic ultrasound (EUS) guided Histoacryl injection therapy without severe adverse events. Material and methods. We present a large single-center cohort over 7 years with a standardized EUS-guided sclerotherapy of all patients with gastric varices. Application was controlled by fluoroscopy to immediately detect any glue embolization. Only perforating veins located within the gastric wall were treated. In the follow up, we repeated this treatment until varices were eradicated. Results. Utmost patients (36 of 40) were treated during or within 24 h of active bleeding. About 32.5% of patients were treated while visible bleeding. Histoacryl injection was always technically successful and only two patients suffered a minor complication. Acute bleeding was stopped in all patients. About 15% (6 of 40) of patients needed an alternative rescue treatment in the longer course. Three patients got a transjugular portosystemic shunt and another three underwent an orthotopic liver transplantation. Mean long-term survival of 60 months was excellent. Conclusion. Active bleeding of gastric varices can be treated successfully without the necessity of gastric rinsing with EUS-guided injection of Histoacryl.     

An Application of Endoscopic Color Doppler Ultrasonography (ECDUS) in the Diagnosis of Hemodynamics of Gastric Varices,and the Therapeutic Effect of Endoscopic Therapy

Abstract: We studied 14 patients using endoscopic color Doppler ultrasonography (ECDUS) to evaluate the hemodynamics of gastric varices, and evaluated the endoscopic therapeutic effects on gastric varices in 8 patients. Three patients had F₃ type gastric varices and eleven had F₂. The ECDUS was performed with a PENTAX FG-32UA (7.5MHz, convex type) and a HITACHI EUB 565 was used as a display machine. The intramural blood flow in the gastric varices and inflows from the extra-gastric wall were clearly observed with the ECDUS in all 14 patients. The extramural blood flow (gastro or spleno-renal shunts) was detected in 9 of 14 patients. The velocity of the intramural flow in tumorous type varices (F₃) was higher than in the nodular or flat elevated type (Fa). Next, we evaluated the therapeutic effects on gastric varices of the ECDUS. The successful disappearance of intramural blood flow was observed in 6 of 8 patients who had this endoscopic therapy. In two of the 8 patients, there was not enough therapeutic effect on the intramural blood flow. The extramural blood flow, however, did not change before or after endoscopic therapy with the ECDUS. Therefore, we concluded that ECDUS is a very useful modality for the diagnosis of hemodynamics and to evaluate the therapeutic effects on gastric varices.     

The long-term outcome of patients with bleeding gastric varices after balloon-occluded retrograde transvenous obliteration

Background The purpose of our study was to evaluate the long-term outcome and complications of balloon-occluded retrograde transvenous obliteration (B-RTO) in patients with hemorrhage from gastric fundal varices. Methods Thirty-four consecutive patients with bleeding from gastric varices who were treated with B-RTO were enrolled in this study between December 1994 and September 2005 (urgent cases, n = 12; elective cases, n = 22). The long-term outcome, complications, and various liver functions were evaluated. Results Complete obliteration was achieved in 31 of 34 (91%) patients with an acute bleeding episode. In one of the remaining patients, there was a technical failure, and the other two had only partial obliteration. The two patients with partial obliteration did not obtain hemostasis. Thus, the rate of hemostasis was 94% (31/33). Gastric varices disappeared in all patients with complete obliteration during the treatment. The rate of gastric variceal eradication was 91%. Variceal rebleeding from esophageal varices occurred in three patients. The rate of rebleeding was 10% (3/31). Rebleeding from gastric varices was not observed after complete obliteration. None of the patients showed worsening of their Child-Pugh score. Although the 5-year cumulative worsening rate of esophageal varices was 52%, neither portal hypertensive gastropathy nor ectopic varices were observed. The patients with worsening esophageal varices were successfully treated with an endoscopic procedure. The 5-year survival rate was 68%. Conclusions B-RTO is useful for treatment of bleeding gastric varices, achieving high eradication of gastric varices, a low rebleeding rate, and a fairly good prognosis with improved hepatic function.     

Successful management of thrombocytopenia by partial splenic embolization in patients with advanced gastric cancer and invasion of the splenic vein: Case reports

Rationale:Hypersplenism causes thrombocytopenia, which may lead to the reduction or discontinuation of chemotherapy. Partial splenic embolization (PSE) is an effective treatment for thrombocytopenia associated with hypersplenism. However, there have been no reports of patients with gastric cancer who have resumed and continued chemotherapy after PSE for splenic hypersplenism associated with tumor infiltration.Here, we report two cases in which we performed PSE for hypersplenism associated with gastric cancer that had invaded the splenic vein. Chemotherapy was continued in both cases.Patient concerns:Both patients developed thrombocytopenia with splenomegaly due to advanced gastric cancer that required discontinuation of chemotherapy.Diagnosis:Upper gastrointestinal endoscopy and computed tomography showed advanced gastric cancer with invasion of the splenic vein and splenomegaly. Both patients developed thrombocytopenia.Interventions:Patients were treated with PSE.Outcomes:PSE produced an increase in thrombocyte count, and chemotherapy could be resumed.Lessons:PSE seems to be a useful treatment for thrombocytopenia with splenomegaly associated with advanced gastric cancer and may allow continuation of chemotherapy.     

Segmental portal hypertension in mixed connective tissue disease

Abstract

A 64-year-old Japanese woman was diagnosed with mixed connective tissue disease based on the clinical evidence; myositis with infiltration of CD45RO⁺ T cells and histiocytes, interstitial pneumonia, isolated high titer of anti-U1RNP antibody and hypocomplementemia. Endoscopic examination revealed gastric varices due to isolated splenic vein obstruction. Antiphospholipid antibody, antilymphocyte antibody, anti-U1RNP antibody and miscellaneous pathogens from the intestines were possible causes for obstruction of the splenic vein.     

Preliminary study of magnetically controlled capsule gastroscopy for diagnosing superficial gastric neoplasia

BackgroundMagnetically controlled capsule gastroscopy (MCCG) is a newly developed non-invasive method designed for gastric examination. Although favorable diagnostic accuracy has been reported, there is little if any data about its ability to diagnose gastric cancer.AimsTo compare the detectability of superficial gastric neoplasia by MCCG and gastroscopy.MethodsThis study was a self-controlled comparison study. Ten subjects diagnosed with superficial gastric neoplasia and scheduled to undergo endoscopic submucosal dissection (ESD) at a tertiary hospital were prospectively invited for an MCCG examination. The diagnostic agreement of MCCG, ESD and pathology were compared, including location, size and endoscopic appearance of the lesions.ResultsOf the 10 enrolled patients, 6 were confirmed as having early gastric cancer/high-grade intraepithelial neoplasia, 2 gastric low-grade intraepithelial neoplasia (LGIN), 1 tubular adenoma with LGIN and 1 neuroendocrine tumor. The per-patient and per-lesion sensitivities of MCCG for superficial gastric neoplasia detection were 100% and 91.7%. Location and size of the lesions were compared favorably to gastroscopy whilst one cardiac lesion was missed. Endoscopic appearances of these lesions observed on MCCG and EGD demonstrated good consistency. No adverse events were observed.ConclusionWith good gastric preparation and careful examination of stomach, MCCG is able to detect superficial gastric neoplasms.     

Autoimmune pancreatitis complicated by gastric varices: a report of 3 cases

We present three cases of autoimmune pancreatitis (AIP) complicated by gastric varices. Case 1: A 57-year-old man was diagnosed with AIP complicated by gastric varices and splenic vein obstruction. Splenomegaly was not detected at the time of the diagnosis. The AIP improved using steroid therapy, the splenic vein was reperfused, and the gastric varices disappeared; case 2: A 55-year-old man was diagnosed with AIP complicated by gastric varices, splenic vein obstruction, and splenomegaly. Although the AIP improved using steroid therapy, the gastric varices and splenic vein obstruction did not resolve; case 3: A 68-year-old man was diagnosed with AIP complicated by gastric varices, splenic vein obstruction, and splenomegaly. The gastric varices, splenic vein obstruction, and AIP did not improve using steroid therapy. These three cases suggest that gastric varices or splenic vein obstruction without splenomegaly may be an indication for steroid therapy in patients with AIP because the complications will likely become irreversible over time.     

Turner syndrome associated with acquired von Willebrand disease,primary biliary cirrhosis,and inflammatory bowel disease

We report a unique case of Turner syndrome associated with acquired von Willebrand disease (AvWD), primary biliary cirrhosis (PBC), and inflammatory bowel disease (IBD). During 7 years of close follow-up, the patient presented with multiple major episodes of upper and lower gastrointestinal bleeding caused by different pathogenic mechanisms, such as IBD, AvWD, gastric varices, and thrombocytopenia. AvWD mimicking familial vWD type III on laboratory testing was most probably triggered by autoimmune mechanism associated with PBC. Therapy of PBC with ursodeoxycholic acid (UDCA) resulted in significant decrease of liver enzymes followed by normalization of vWF and FVIII levels. Portosystemic shunt placement with ligation of gastric varices improved hypersplenism and severe thrombocytopenia and led to clinical stability for more than 24 months. The clinicopathological features of these disorders and of the recurrent bleeding episodes are discussed in the text along with a review of the literature.     

Retrospective evaluation of risk factors of postoperative varices after pancreaticoduodenectomy with combined portal vein resection

BackgroundCombined portal vein (PV) resection is performed for pancreatic head cancer to achieve clear resection margins. This can be complicated by the formation of varices due to sinistral portal hypertension after pancreaticoduodenectomy (PD) with combined PV resection. However, clinical strategies to prevent varices formation due to sinistral portal hypertension remain controversial. Moreover, the critical vein among splenic vein (SPV), inferior mesenteric vein, left gastric vein, or middle colonic vein requiring preservation to prevent the development of varices remains unclear.MethodsWe retrospectively analyzed patients with pancreatic cancer who underwent PD with combined PV resection over 18 years at our institution. Varices were evaluated using enhanced computed tomography (CT) and endoscopy. Preoperative types of porto-mesenterico-splenic confluence, venous drainage, and venous resection types were determined by operative records and CT findings.ResultsOf the 108 subjects, the incidence of postoperative varices was observed in 24.1% of cases over 5.6 months. These varices were classified into five types based on location, as pancreaticojejunostomy anastomotic (11.5%), gastrojejunostomy anastomotic (11.5%), esophageal (11.5%), splenic hilar-gastric (23.1%), and right colonic (65.4%) varices. No case of variceal bleeding occurred. Multivariate analysis showed SPV ligation as the greatest risk factor of varices (P < 0.001), with a higher incidence of left-sided varices in patients with all the SPV venous drainage sacrificed (60%) than in the others (16.7%). Therefore, sacrificing all the SPV venous drainage was the only independent risk factor of varices (P = 0.049).ConclusionsPreservation of SPV venous drainage should be considered during SPV ligation to prevent post-PD varices.     

Incidence of the appearance of the red color sign on esophageal varices and its predictive factors: long-term observations of 359 patients with cirrhosis

Purpose. The red color sign observed by endoscopic examination is a reliable predictive factor for variceal bleeding. The aim of this study was to calculate the incidence of the appearance of the red color sign and to evaluate its predictive factors. Methods. Endoscopic examination was repeatedly performed in 359 consecutive patients diagnosed as having liver cirrhosis with or without esophageal varices, during a median follow-up period of 2651 days. Results. The incidence of the appearance of the red color sign on esophageal varices at the end of the tenth year was compared among patients without varices (11.4%), those with small varices (45.4%), and those with mid-size varices (65.0%). The difference was significant (P < 0.0001). The number of varices (P = 0.0010), size of varices (P = 0.0064), platelet count (P = 0.0168), and alpha-fetoprotein level (P = 0.0207) were significantly correlated with the appearance of the red color sign, as estimated by the multivariate Cox hazard model. To exclude the influence of carcinogenesis, observation was stopped when hepatocellular carcinoma was discovered. Additive predictive factors with significance were: number of varices (P = 0.001), size of varices (P = 0.027), and platelet count (P = 0.0315). Conclusions. Endoscopic signs of esophageal varices and platelet count were significant predictors for the appearance of the red color sign. Received: April 3, 2000 / Accepted: December 22, 2000     

Ectopic variceal bleeding after hepatobiliary surgery: A case report

Rationale:Jejunal varices are rare in portal hypertension and are often difficult to diagnose and treat. Herein, we present a case of gastrointestinal bleeding due to jejunal varices after hepatobiliary surgery.Patient concerns:A 69-year-old man presented with recurrent massive gastrointestinal bleeding. He underwent partial right hepatectomy and cholangiojejunostomy 2 years prior to the first onset of bleeding. Two sessions of endoscopic vessel ligation for esophageal varices were performed afterwards, and hematemesis resolved completely, but massive melena still recurred during the following 5 years.Diagnosis:The patient was diagnosed with jejunal varices caused by portal venous stenosis after hepatobiliary surgery.Intervention:Portal venous angioplasty using balloon dilation and stent implantation was performed.Outcomes:After the intervention procedure, the patient did not experience any onset of gastrointestinal bleeding during follow-up.Lessons:Hepatopancreatobiliary could lead to the formation of jejunal varices. The combined use of capsule endoscopy, contrast-enhanced computed tomography, and sometimes portal venography is a promising strategy to search for jejunal varices. Transcatheter angioplasty appears to be a safe and effective method for treatment of jejunal varices in certain appropriate cases.     

Characteristics,prognosis and outcome of patients with oesophageal varices in a university hospital in Sweden 1994–1999

Objective. Patients with liver cirrhosis, portal hypertension and oesophageal varices are known to have high morbidity and mortality. The knowledge of incidence, aetiology and outcome in Sweden in recent years is limited. Material and methods. All patients with oesophageal varices diagnosed for the first time at Sahlgrenska University Hospital during the 6-year period 1994–1999 were retrospectively studied. Information about the aetiology of liver cirrhosis and oesophageal varices, as well as about the proportion of bleeding and non-bleeding varices, endoscopic and pharmacological treatment and outcome, was analyszed. Results. 312 patients were retrieved, 297 with liver cirrhosis (197 diagnosed before first bleeding (P), 92 after bleeding (B) and 8 at autopsy) and 15 with portal vein thrombosis without cirrhosis. Fifty-four percent had alcoholic liver disease. Fifty-five percent in group B and 13% in group P had at least one bleeding episode during follow-up (p<0.001). There was no significant difference in survival between groups B and P. Twenty-six percent of the cirrhotics died of liver failure and 19% from variceal bleeding. In a multivariate analysis, variables predicting mortality were: Child-Pugh class, group B, age and bilirubin levels. Conclusions. Variceal bleeding is still a strong risk factor for recurrent bleeding, but few die from their first bleeding. This concurs with studies indicating declining mortality from variceal bleeding. However, this patient group still has a high mortality from other causes.     

Effect of direct-acting antivirals on future occurrence of hepatocellular carcinoma in compensated cirrhotic patients

BackgroundThe achievement of high rates of sustained virological response (SVR) with direct-acting antivirals (DAAs) in hepatitis C virus (HCV) infected patients will reduce decompensating terminal events.AimsTo investigate whether hepatocellular carcinoma (HCC) occurrence could change due to the DAA-induced increase in life-expectancy.MethodsA Markov model was built on clinical data of 494 cirrhotic patients and available literature to estimate probabilities of “death before HCC” and of “HCC occurrence” without and with DAA.ResultsIn comparison to untreated patients, DAA therapy reduced the 20-year mortality before HCC by 21.9% in patients without varices and by 21.5% in those with varices, considering an SVR of 95% and no direct effect on hepatocarcinogenesis. Tumour occurrence increased by 5%–8.2% and the proportion of HCCs diagnosed in compensated stages increased to >98%. If we consider DAA as having “anti-tumoral” effects, the benefit becomes greater, achieving a 20-year survival of 81.5% in patients without varices, and 52.2% in patients with varices. Instead, if we consider DAA as having a “pro-tumoral” effect, then, the increased incidence of HCC nullifies the survival benefits.ConclusionDAAs drastically reduce the mortality caused by the liver function worsening, increasing the proportion of HCCs diagnosed in compensated stages. Knowledge of the DAA effect on hepatocarcinogenesis remains pivotal.     

Portal hemodynamics and clinical outcomes of patients with gastric varices after balloon-occluded retrograde transvenous obliteration

Background

Long-term hemodynamic effects and clinical outcomes after balloon-occluded retrograde transvenous obliteration (B-RTO) remain unclear. The purpose of this study was to evaluate long-term clinical results and effects on portal hemodynamics after B-RTO for the treatment of gastric varices with spontaneous gastrorenal shunt.

Methods

A total of 21 patients with cirrhosis and gastric varices treated by B-RTO were evaluated. The cumulative survival rate was calculated, portal blood flow was measured by Doppler ultrasonography, and liver function was estimated on the basis of Child-Pugh classification before and 1 year after B-RTO.

Results

Gastric varices disappeared or decreased markedly in size in all patients. Overall cumulative survival rates at 1, 3 and 5 years were 90.48, 71.11 and 53.71%, respectively. Portal blood flow increased significantly from 681.9 ± 294.9 to 837.0 ± 279.1 ml/min (P = 0.0125) after B-RTO. Child-Pugh score was not significantly changed (P = 0.755) after obliteration, but serum albumin was elevated significantly from 3.49 ± 0.49 to 3.75 ± 0.53 g/dl (P = 0.0459). The ascites score was significantly increased (P = 0.0455) after B-RTO, but all cases of ascites could be controlled with medication.

Conclusions

Balloon-occluded retrograde transvenous obliteration is a safe and effective treatment for gastric varices with gastrorenal shunt. Portal blood flow and serum albumin parameters are increased, and liver function is unchanged after B-RTO.     

Macrophage coculture enhanced invasion of gastric cancer cells via TGF-β and BMP pathways

Abstract

Objective. Transforming growth factor β (TGF-β) superfamily plays an important role in regulating gastric cancer progression. As previously demonstrated, tumor-associated macrophages (TAMs) promoted the invasion of gastric cancer cells in Matrigel. However, the role of TGF-β superfamily signaling between TAMs and gastric cancer remains unclear. Material and methods. Three-dimensional dynamic migration imaging system was used to detect gastric cancer invasion rate cocultured with macrophages in Matrigel before or after TGF-β receptor 1 or bone morphogenic protein (BMP) receptor 1A and 1B inhibition; real-time RT-PCR was used to quantitatively investigate gene expression (TGF-β1, TGF-β2, BMP4, and BMP7, ADAM9, MMP9, TIMP3, VEGF-A, and VEGF-C). Results. TGF-β1, TGF-β2, BMP4, and BMP7 expressions were increased significantly in macrophages grown with cancer cells as compared to macrophages grown alone. The invasion rate and invasion-related genes expressions of both AGS and Hs-746T gastric cancer cell lines were upregulated by macrophages, although the expression profile was different. Invasion rate and invasion-related genes' expressions of AGS cells cocultured with macrophages were downregulated significantly after TGF-βR1 and BMPR1 inhibition. Conclusions. Macrophages associated with tumor might promote gastric cancer cells invasion though enhancing TGF-β/BMPs signal pathway. Inhibiting TGF-β/BMPs signal between TAMs and gastric cancer cells might provide a new therapeutic method of gastric cancer.