Predictive genetic profiles for regional lymph node metastasis in primary cutaneous melanoma: a case-matched pilot study.

Melanoma confers an estimated lifetime risk of one in 50 for 2016. Clinicopathologic staging and sentinel lymph node biopsy (SLNB) have been the standard of care for T2 and T3 lesions. Molecular biomarkers identified in the primary lesion suggestive of metastatic potential may offer a more conclusive prognosis of these lesions. Our purpose was to investigate molecular mutations in primary melanoma that were predictive for micrometastasis as defined by a positive sentinel lymph node (SLN) in a case-controlled manner: nine patients with negative SLN and nine with positive SLN. The two cohorts were statistically identical as shown by a t-test for age (P=0.17), race (P=0.18), Breslow depth (P=0.14), Clark level (P=0.33), host response (P=0.17), ulceration (P=0.50), satellite nodules (P=0.17), lymphovascular invasion (P=0.50), and mitotic activity (P=0.09). While no single gene was significantly associated with SLN status, multivariate analysis using classification and regression tree assessment revealed two unique gene profiles that completely represented regional metastases in our cohort as defined by a positive SLN: PIK3CA (+) NRAS (-) and PIK3CA (-) ERBB4 (-) TP53 (+) SMAD4 (-). These profiles were identified in 89% of the patients with positive SLN; none of these profiles were identified in the SLN-negative cohort. We identified two unique gene profiles associated with positive SLN that do not overlap other studies and highlight the genetic complexity that portends the metastatic phenotype in cutaneous melanoma.

FibroSURE and elastography poorly predict the severity of liver fibrosis in Fontan-associated liver disease.

OBJECTIVE: As the population of patients with Fontan circulation surviving into adulthood increases, hepatic cirrhosis has grown to be a significant cause of morbidity and mortality. Early detection of advanced hepatic fibrosis is imperative for proper intervention and consideration for heart or combined heart/liver transplantation. Noninvasive biomarkers and elastography have been evaluated for their diagnostic utility with variable results in the Fontan population. DESIGN: The cohort included 14 patients age 26.4 SD 7.5 who underwent Fontan surgery. All patients were evaluated with FibroSURE, shear wave elastography (SWE), hepatic duplex sonography, and liver biopsy. Liver fibrosis on biopsy was evaluated according to the congestive hepatic fibrosis system. RESULTS: In our cohort, 100% of patients had fibrosis with 36% demonstrating advanced fibrosis. FibroSURE agreed with liver biopsy in only 5 out of 14 cases (36%): underestimating in 7 and overestimating in 2 individuals. SWE agreed with liver biopsy in 0% of cases: overestimating in 10 and underestimating in 4 cases. None of the duplex sonography indices predicted the presence or severity of liver fibrosis. CONCLUSION: This study demonstrates that children who have undergone a Fontan procedure universally develop some hepatic fibrosis and a significant number have advanced fibrosis by adulthood. The FibroSURE blood test, SWE, and hepatic duplex sonography were unable to accurately predict the presence or severity of hepatic fibrosis when compared with liver biopsy. Further studies are needed to investigate novel noninvasive methods and/or biomarkers that can adequately detect advanced hepatic fibrosis before the development of cirrhosis and hepatic decompensation.

Refractory Hepatic Hydrothorax: A Rare Complication of Systemic Sclerosis and Presinusoidal Portal Hypertension.

We report on a rare case of refractory hepatic hydrothorax in an individual with Scleroderma/CREST syndrome and noncirrhotic portal hypertension. Portal pressure measurements revealed a normal transjugular hepatic venous portal pressure gradient, mild pulmonary hypertension, and an unremarkable liver biopsy except for mild sinusoidal dilation. Pulmonary hypertension, cardiac diastolic dysfunction, and chronic kidney disease were determined to be the causes of his refractory pleural effusions and ascites. Over the year, he underwent 50 thoracenteses and 20 paracenteses averaging 10-12 liters/week. Repeat pulmonary evaluation determined his pulmonary pressures to be normal and a secondary review of the "unremarkable" liver biopsy noted mild venous outflow obstruction and possibly Nodular Regenerative Hyperplasia (NRH). Repeat portal pressures indirectly and directly confirmed the existence of presinusoidal portal hypertension that has been associated with NRH. A transjugular intrahepatic portal systemic shunt (TIPS) was placed and he has not required thoracentesis or paracentesis over the past 18 months.

Postmenopausal Deep Infiltrating Endometriosis of the Colon: Rare Location and Novel Medical Therapy.

We report an uncommon case of deep infiltrating endometriosis of the colon presenting as iron deficiency anemia nine years after hysterectomy with bilateral salpingo-oophorectomy. The endometrial implant was found at the hepatic flexure, an exceedingly rare location for endometriosis invasion with no cases distinctly reported in the literature. Additionally, the presentation of gastrointestinal endometriosis as iron deficiency anemia is not well documented in the literature. Instead of surgery, we prescribed a novel medical therapeutic approach using conjugated estrogen-bazedoxifene to antagonize the proliferative effects of estrogen on endometrial tissue. After five months of therapy and repeat colonoscopy, no evidence of endometrial tissue remained in the hepatic flexure.