Characteristics of Liver Disease in 100 Individuals With Joubert Syndrome Prospectively Evaluated at a Single Center.

BACKGROUND AND AIMS: Joubert Syndrome (JS) is a rare, inherited, ciliopathy defined by cerebellar and brainstem malformations and is variably associated with liver, kidney, and ocular dysfunction. This study characterizes the hepatic findings in JS and identifies factors associated with probable portal hypertension. METHODS: Hundred individuals with JS were prospectively evaluated at the National Institutes of Health Clinical Center. Laboratory tests, imaging, and DNA sequencing were performed. Patients were stratified based on the spleen length/patient height ratio as a marker of splenomegaly, used as a surrogate for probable portal hypertension. RESULTS: Forty-three patients (43%) had liver involvement based on elevated liver enzymes and/or liver hyperechogenicity and/or splenomegaly. None of the patients had macroscopic liver cysts or bile duct dilatation. Based on the spleen length/patient height ratio, 13 patients were stratified into a probable portal hypertension group. We observed significant elevations in alkaline phosphatase (269 vs 169 U/L, P ≤ 0.001), alanine aminotransferase (92 vs 42 U/L, P = 0.004), aspartate aminotransferase (77 vs 40 U/L, P = 0.002), and gamma-glutamyl transferase (226 vs 51 U/L, P ≤ 0.001) in the probable portal hypertension group. Platelets were lower in the probable portal hypertension cohort (229 vs 299 × 10 cells/µL, P = 0.008), whereas synthetic function was intact in both groups. Probable portal hypertension was also more prevalent in patients with kidney disease (P = 0.001) and colobomas (P = 0.02), as well as mutations in the TMEM67 gene (P = 0.001). CONCLUSIONS: In JS, probable portal hypertension is associated with abnormal hepatic enzymes, as well as presence of kidney disease, coloboma, and/or mutation in TMEM67. These findings may allow early identification of JS patients who have or are more likely to develop liver disease.

Gastrointestinal Manifestations of STAT3-Deficient Hyper-IgE Syndrome.

OBJECTIVE: STAT 3 deficiency (autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)) is a primary immunodeficiency disorder with multi-organ involvement caused by dominant negative signal transducer and activator of transcription gene 3 (STAT3) mutations. We sought to describe the gastrointestinal (GI) manifestations of this disease. METHODS: Seventy subjects aged five to 60 years with a molecular diagnosis of AD-HIES were evaluated at the National Institutes of Health (NIH). Data collection involved a GI symptom questionnaire and retrospective chart review. RESULTS: In our cohort of 70 subjects, we found that 60% had GI symptoms (42/70). The most common manifestations were gastroesophageal reflux disease (GERD) observed in 41%, dysphagia in 31%, and abdominal pain in 24%. The most serious complications were food impaction in 13% and colonic perforation in 6%. Diffuse esophageal wall thickening in 74%, solid stool in the right colon in 50% (12/24), and hiatal hernia in 26% were the most prevalent radiologic findings. Esophagogastroduodenoscopy (EGD) demonstrated esophageal tortuosity in 35% (8/23), esophageal ulceration in 17% (4/23), esophageal strictures requiring dilation in 9% (2/23), and gastric ulceration in 17% (4/23). Esophageal eosinophilic infiltration was an unexpected histologic finding seen in 65% (11/17). CONCLUSION: The majority of AD-HIES subjects develop GI manifestations as part of their disease. Most notable are the symptoms and radiologic findings of GI dysmotility, as well as significant eosinophilic infiltration, concerning for a secondary eosinophilic esophagitis. These findings suggest that the STAT3 pathway may be implicated in a new mechanism for the pathogenesis of several GI disorders.

Outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts by using combined endoprosthesis and a nasocystic drain.

BACKGROUND: The presence of debris within a pseudocyst may impair success of endoscopic drainage. OBJECTIVE: To compare the clinical outcomes and adverse-event rates of EUS-guided pseudocyst drainage with and without a nasocystic drain for the management of pancreatic pseudocysts with viscous solid debris-laden fluid. DESIGN: Retrospective study. SETTING: Single, tertiary-care referral center. PATIENTS: Consecutive patients with pancreatic pseudocysts managed by EUS-guided drainage: those with solid debris who underwent drainage via nasocystic drains alongside stents (n = 63) and those with solid debris who underwent drainage via transmural stents only (n = 24). INTERVENTION: Drainage via nasocystic drains alongside stents or drainage via transmural stents only. MAIN OUTCOME MEASUREMENTS: The primary outcomes were short-term success and long-term success of the procedures. The secondary outcomes were procedure-related adverse events and reintervention. RESULTS: The patients with viscous solid debris-laden fluid whose pseudocysts were drained by both stents and nasocystic tubes had a 3 times greater short-term success rate compared with those who had drainage by stents alone (P = .03). On 12-month follow-up, complete resolution of pseudocysts with debris drained via stents alone was less (58%) compared with those with debris who underwent drainage via nasocystic drains alongside stents (79%; P = .059). The rate of stent occlusion was higher in cysts with debris drained by stents alone (33%) compared with those drained via nasocystic drains alongside stents (13%; P = .03). LIMITATIONS: Retrospective design; limited sample size. CONCLUSION: In patients with pseudocysts with viscous debris-laden fluid, EUS-guided drainage by using a combination of a nasocystic drain and transmural stents improves clinical outcomes and lowers the stent occlusion rate compared with those who underwent drainage via stents alone.

Enteral stents for the management of malignant colorectal obstruction.

Colorectal cancer (CRC) is the 3rd most common cancer in the United States with more than 10000 new cases diagnosed annually. Approximately 20% of patients with CRC will have distant metastasis at time of diagnosis, making them poor candidates for primary surgical resection. Similarly, 8%-25% of patients with CRC will present with bowel obstruction and will require palliative therapy. Emergent surgical decompression has a high mortality and morbidity, and often leads to a colostomy which impairs the patient's quality of life. In the last decade, there has been an increasing use of colonic stents for palliative therapy to relieve malignant colonic obstruction. Colonic stents have been shown to be effective and safe to treat obstruction from CRC, and are now the therapy of choice in this scenario. In the setting of an acute bowel obstruction in patients with potentially resectable colon cancer, stents may be used to delay surgery and thus allow for decompression, adequate bowel preparation, and optimization of the patient's condition for curative surgical intervention. An overall complication rate (major and minor) of up to 25% has been associated with the procedure. Long term failure of stents may result from stent migration and tumor ingrowth. In the majority of cases, repeat stenting or surgical intervention can successfully overcome these adverse effects.

Role of endoscopic ultrasonography in the evaluation of extrahepatic cholangiocarcinoma.

Cholangiocarcinoma is a malignancy that arises from biliary epithelium and is associated with a poor prognosis. Accurate preopera-tive diagnosis and staging of cholangiocarcinoma continues to remain difficult. Endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly performed procedure for cholangiocarcinoma and can provide a tissue diagnosis through brush cytology of the bile duct. However, the sensitivity of biliary brush cytology to diagnose cholangiocarcinoma may be as low as 30%. Endoscopic ultrasound (EUS) is a diagnostic modality which may overcome the limitations of other imaging and biopsy techniques in this setting. EUS can complement the role of ERCP and provide a tissue diagnosis through fine needle aspiration (FNA) and staging through ultrasound imaging. There is currently a paucity of data about the exact role of EUS for the diagnosis of cholan-giocarcinoma in patients with indeterminate extrahepatic biliary strictures. Although multiple studies have shown that EUS is more accurate than ERCP and radiologic imaging for identifying a biliary mass and diagnosing cholangiocarcinoma, the sensitivities are variable. More importantly, the incidence of false negative results is not negligible, though the specificity is close to 100%. There is also controversy regarding the role of EUS-FNA, since even though this may increase diagnosis, it can also lead to tumor seeding.

Primary tumor volume is an important predictor of clinical outcomes among patients with locally advanced squamous cell cancer of the head and neck treated with definitive chemoradiotherapy.

PURPOSE: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. METHODS AND MATERIALS: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. RESULTS: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm(3), and patients with a tumor volume <35 cm(3) had a significantly better prognosis than those with a tumor volume >35 cm(3) at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm(3) had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm(3) larger than tumors without locoregional failure (p = .028) and 27.1-cm(3) larger than tumors that recurred as distant metastases (p = .020). CONCLUSION: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.