Genetic Analysis of Multiple Endocrine Neoplasia Type 1 (MEN1) Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands). MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above. METHODS: A 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma) 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1. RESULTS: Genomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion. CONCLUSION: There is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma could be suspected.

Liver Abscess in Advanced Hepatocellular Carcinoma after Sorafenib Treatment / 대한소화기학회지

Hepatocellular carcinoma (HCC) is a critical global health issue and the third most common cause of cancer-related deaths worldwide. The majority of patients who present HCC are already at an advanced stage and their tumors are unresectable. Sorafenib is a multi-kinase inhibitor of the vascular endothelial growth factor pathway and was recently introduced as a therapy for advanced HCC. Furthermore, studies have shown that oral sorafenib has beneficial effects on survival. However, many patients experience diverse side effects, and some of these are severe. Liver abscess development has not been previously documented to be associated with sorafenib administration in HCC. Here, we report the case of a HCC patient that developed a liver abscess while being treated with sorafenib.

Reactivation of Hepatitis B Virus Following Systemic Chemotherapy for Malignant Lymphoma / 대한내과학회지

BACKGROUND/AIMS: Reactivation of hepatitis B virus (HBV) has been reported in HBV surface antigen (HBsAg)-positive patients undergoing chemotherapy, as well as HBsAg-negative patients with antibodies against HBV core antigen (HBcAg) and/or HBsAg (HBsAb). Chemotherapy-including rituximab-has recently been identified as a predictive factor for HBV reactivation in HBsAg-negative patients with malignant lymphoma. The aim of our study was to identify the factors predictive of HBV reactivation after chemotherapy in patients with malignant lymphoma. METHODS: We conducted a retrospective analysis of medical records from patients diagnosed with malignant lymphoma at Gachon University Gil Medical Center in City, County from January 2005 to December 2010. We subsequently determined HBsAg, HBsAb and anti-HBc status in the 196 patients treated with chemotherapy. RESULTS: The mean age of the patients was 57.3 +/- 14.5 years; 56.3% were male. A total of 172 of 196 (88%) patients in the study population were HBsAg (+) prior to chemotherapy. Three patients (3/11, 27.3%) in the HBsAg (+) group had confirmed HBV reactivation after chemotherapy. In addition, 26 of 196 (13%) patients in the study population tested HBcAg (+) positive prior to chemotherapy. One patient (1/15, 6.7%) in the HBsAg (-)/HBcAb (+) group had confirmed HBV reactivation. In the four patients with HBV reactivation, infection was resolved after treatment with 0.5 mg entecavir or 100 mg lamivudine. CONCLUSIONS: Reactivation of HBV after systemic chemotherapy can occur in HBsAg (-) patients. We recommend that malignant lymphoma patients undergoing chemotherapy be screened for HBV infection status, including HBcAg, and followed closely to prevent HBV reactivation.

Should we still use Camitta's criteria for severe aplastic anemia?

BACKGROUND: The criteria by Camitta for diagnosis in severe aplastic anemia (SAA) has been used since 1976. However, there has been no attempt to verify the Camitta's criteria, that the survival in patients with SAA may differ by absolute neutrophil count (ANC), platelet count (PLT), and corrected reticulocyte count (CRC), which are components of the Camitta's criteria. METHODS: 117 SAA patients diagnosed by the Camitta's criteria were analyzed, retrospectively. Univariate and multivariate analyses were used to evaluate the factors affecting overall survival (OS). RESULTS: Response by immunosuppressive therapy (IST) or stem cell transplantation (SCT) significantly affected OS (P=0.001). Therefore, we excluded treatment responders for analysis. Finally, 92 SAA patients including treatment non-responders by IST or SCT and conservative care group were analyzed by using univariate and multivariate analyses. The median age of analyzed patients was 54.5 years. Male to female ratio was 1:1. The median follow-up duration was 74.23 months (range, 54.71-93.74 months). The median ANC, PLT, and CRC were 394/microL, 12,000/microL, and 0.39%, respectively. In multivariate analyses, ANC or =500/microL (P=0.015, HR 2.694, 95% CI: 1.20-6.01) and age (P=0.015, HR 1.022, 95% CI: 1.00-1.04) were the significant factors for OS. CONCLUSION: ANC could be an essential, not an optional criterion for diagnosing SAA. This study suggests the possibility that the Camitta's criteria be modified. Studies in large cohorts are needed to transform the Camitta's criteria.

A Case of Balsalazide-Induced Limited Form of Granulomatosis with Polyangiitis with Bronchiolitis Obliterans Organizing Pneumonia-like Variant in Ulcerative Colitis / 결핵및호흡기질환

5-Aminosalicylate agents are the main therapeutic agents for ulcerative colitis. Balsalazide is a prodrug of 5-aminosalicylate and has fewer side effects than the other 5-aminosalicylate agents. Pulmonary complications resembling granulomatosis with polyangiitis in ulcerative colitis are extremely rare. Here, we report a patient with ulcerative colitis on balsalazide presenting respiratory symptoms and multiple pulmonary nodules from a chest radiography that was pathologically diagnosed with a limited form of granulomatosis with polyangiitis with bronchiolitis obliterans organizing pneumonia-like variant. To our knowledge, this is the first report of a balsalazide-induced limited form of granulomatosis with polyangiitis with bronchiolitis obliterans organizing pneumonia-like variant.

Treatment of Hepatocellular Carcinoma with Drug-eluting Beads Chemoembolization and Liver Transplantation / 대한소화기학회지

No abstract available.

Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes / 한국유방암학회지

PURPOSE: The role of first-line trastuzumab-based therapy has been firmly established in patients with human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer. In this trial, we evaluated the efficacy and safety of a vinorelbine and trastuzumab combination chemotherapy in patients who were pretreated with anthracyclines and taxanes. METHODS: Thirty-three patients with HER2 overexpressing metastatic breast cancer, all of whom had previously been treated with anthracyclines and taxanes, were included in this study. The patients were treated with 25 mg/m2 of vinorelbine (over a 15-minute infusion) on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at weekly doses of 2 mg/kg (over 30 minutes). RESULTS: The median age of the patients was 53 years (range, 39-72 years). The overall response rate was 30.3% (10 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the incidence rates of grade > or =3 neutropenia and anemia were 7.2% and 1.0%, respectively. Neutropenic fever was detected in three cycles (1.5%). The non-hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of the patients experienced any serious cardiac toxicity, and no treatment-related deaths occurred. CONCLUSION: These results show that a combination chemotherapy consisting of vinorelbine and trastuzumab is useful in patients with HER2-overexpressing metastatic breast cancer who were pretreated with anthracyclines and taxanes, with a favorable toxicity profile.

A Phase II Study of Modified FOLFOX4 for Colorectal Cancer Patients with Peritoneal Carcinomatosis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin. MATERIALS AND METHODS: CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m2 on day 1, leucovorin 20 mg/m2 followed by 5-fluorouracil (5-FU) via a 400 mg/m2 bolus and a 22 hours continuous infusion of 600 mg/m2 5-FU on days 1-2 at 2-week intervals. RESULTS: Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously. Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death. Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival. CONCLUSION: The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.

Clinical significance of anti-mitochondrial antibodies in a patient with chronic graft-versus-host disease following hematopoietic stem cell transplantation

Recent studies indicate that patients with chronic graft-versus-host disease (GVHD) are not expected to show positivity for anti-mitochondrial antibody (AMA), which is a specific disease marker for primary biliary cirrhosis (PBC). A differential diagnosis between PBC and hepatic involvement of GVHD based on clinical manifestations and pathologic study is difficult because both diseases show similar results. Therefore, the presence of AMA may be important for distinguishing each disease. Here, we report a case of hepatic involvement of chronic GVHD with positive AMA, in which the pathologic findings and initial presentation of clinical findings were compatible with both PBC and chronic GVHD.

A Case of Cardiac Amyloidosis With Diuretic-Refractory Pleural Effusions Treated With Bevacizumab

Cardiac amyloidosis describes a clinical disorder caused by infiltration of abnormal insoluble fibrils in the heart, characterized by progressive heart failure and a grave prognosis. Pleural effusion in cardiac amyloidosis may represent a sign of heart failure, but it can also result from pleural infiltration of amyloid, manifested by recurrent large fluid accumulations. Recently, the role of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of refractory pleural effusion. We report a case of a 53 year-old female patient with cardiac amyloidosis who presented with recurrent accumulation of large pleural effusions. She was initially treated with high dose loop diuretics, but the pleural effusion persisted, with the daily amount of drainage averaging 1 L/day. Accumulation of pleural fluid did not subside after 3 cycles of melphalan/prednisolone therapy. After the introduction of bevacizumab, an anti-VEGF antibody, the amount of pleural effusion decreased significantly. Efficacy of anti-VEGF therapy for refractory pleural effusions needs to be defined through further studies.