Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment.

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.

Development of hypertension within 2 weeks of initiation of sorafenib for advanced hepatocellular carcinoma is a predictor of efficacy.

BACKGROUND: Sorafenib is an agent that inhibits vascular endothelial growth factor and is associated with onset or worsening of hypertension in some patients. We conducted a retrospective analysis of whether the development of hypertension during sorafenib treatment of advanced hepatocellular carcinoma could be a predictor of anti-cancer efficacy. METHODS: The study included 38 patients with advanced hepatocellular carcinoma who had received sorafenib for at least 1 month between January 2010 and December 2012. A retrospective analysis of the efficacy of sorafenib was conducted by dividing the patients into two groups-a hypertension group, presenting with grade 2 or higher hypertension according to the Common Terminology Criteria for Adverse Events (CTCTE) version 4.0; and a non-hypertension group, which included all other patients. This study evaluated the occurrence of hypertension within 2 weeks of initiation of therapy in order to avoid any treatment duration bias. Images were evaluated using the modified Response Evaluation Criteria in Solid Tumors. The response rate, time to progression, and overall survival were assessed. RESULTS: Twenty-two patients (58 %) developed grade 2 or higher hypertension within 2 weeks of initiation of therapy. The response rate was significantly higher in the hypertension group. Median time to progression was 153 days in the hypertension group versus 50.5 days in the non-hypertension group, which was significantly longer in the hypertension group. Moreover, median overall survival was 1,329 days in the hypertension group versus 302 days in the non-hypertension group, which was significantly longer in the hypertension group. CONCLUSIONS: Hypertension within 2 weeks of initiation of therapy may be a predictor of the anti-cancer efficacy of sorafenib when used for the treatment of advanced hepatocellular carcinoma.

Extensive portal and mesenteric vein thrombosis in a young man with Klinefelter's syndrome.

Klinefelter's syndrome (KS) is a unique physical condition characterized by tall stature, eunuchoid body proportions, gynecomastia, and azoospermia, in addition to an extra X chromosome. In contrast to the original description, symptoms or physical findings can be extremely varied. KS is the most common chromosomal disorder, with an incidence of 1 in 500 males and is also the most commonly undiagnosed chromosomal disorder. Here, we present the case of a 26-year-old man with KS, who visited our hospital with complaints of abdominal pain and fever. On a routine physical examination, he did not differ from a normal karyotype male. Computed tomography showed extensive portal and mesenteric vein thrombosis (PMVT). It is well known that KS is frequently associated with venous thrombosis, but KS with PMVT has rarely been reported. Approximately one-third of PMVT is idiopathic, but this case suggests the possibility that undiagnosed KS is one of the causes of PMVT, as some individuals with KS are not easily distinguishable from those with the normal karyotype.

Irinotecan as the key chemotherapeutic agent in second-line treatment of metastatic gastric cancer after failure of first-line S-1 or S-1/CDDP therapy.

BACKGROUND: S-1, an oral fluoropyrimidine, is one of the standard chemotherapeutic agents for the treatment of metastatic gastric cancer(MGC). However, the most effective second-line regimen after failure of treatment with first-line agents such as S-1 is yet to be determined. The aim of this study was to investigate the various second-line chemotherapy regimens in MGC patients. METHODS: We retrospectively studied patients with MGC who received second-line treatment after failure of the first-line S-1 or S-1/cisplatin treatment. The overall survival times with each second-line regimen were determined using the Kaplan-Meier method, and the effect on overall survival was analyzed using Cox regression analysis. RESULTS: The median survival time for all patients was 14. 2 months(95% confidence interval(CI): 12. 88-15. 43 months)with a 1-year survival rate of 60. 4%. Kaplan-Meier analysis revealed that the second-line regimens containing irinotecan significantly improved the median survival time as compared to regimens without irinotecan(median survival time: 16. 5 and 13. 8 months, respectively). Cox regression analysis showed that irinotecan-containing regimens were associated with improved overall survival(hazard ratio: 0. 165; 95% CI: 0. 041-0. 665). CONCLUSION: The use of irinotecan-containing regimens as second-line chemotherapy after failure of first-line S-1 therapy may be beneficial for MGC patients.

Anorectal melanoma with a KIT-activating mutation, which is a target for tyrosine kinase inhibitor.

Recent advances in our understanding of the genetic mutations associated with melanoma have led to the classification of distinct melanoma subtypes. A number of reports have consistently demonstrated that mucosal and acral melanomas more commonly harbor KIT-activating mutations than do other subtypes. Success in treating gastrointestinal stromal tumors with imatinib has led to speculation that KIT-mutated melanoma might also be effectively managed using this approach. A 78-year-old woman presented with a 4-month history of rectal bleeding. A colonoscopy revealed a black polypoid mass, 30 mm in diameter, originating near the dentate line, and a biopsy revealed malignant melanoma. Computed tomography showed multiple liver and lung metastases. A KIT mutation analysis showed the L576P mutation in exon 11. The patient did not want to undergo chemotherapy including a tyrosine-kinase inhibitor, so palliative radiotherapy for rectal symptoms was performed, but the patient died 4 months later due to disease progression. We describe the first case of anorectal melanoma with a KIT-activating mutation in Japan and summarize findings from the literature regarding the efficacy of KIT kinase inhibitors on this melanoma subtype.

[Effectiveness and safety of chemoradiation in a community-based population of patients with esophageal cancer].

BACKGROUND: In Japan, esophagectomy with three-field lymphadenectomy is the standard therapy for resectable esophageal cancer. However, its outcome is considered unsatisfactory because the 5-year survival rate is less than 50%. Chemoradiotherapy (CRT) is the standard therapy for unresectable esophageal cancer and could also be considered as an option for resectable esophageal cancer. We retrospectively determined the efficacy and safety of CRT for patients with esophageal cancer. METHODS: The study population comprised patients with esophageal cancer who had been treated with CRT between April 2004 and October 2009 in our institute. Acute and late toxicity was assessed with NCI-CTC and RTOG/EORTC late radiation morbidity scoring scheme, respectively. Survival time was calculated using Kaplan-Meier methods. RESULTS: We enrolled 29 consecutive patients and classified them on the basis of clinical staging: stage I, 4 patients; stage II/III, 11 patients; and stage IV, 14 patients. Complete response was achieved in 37.9% and 45.5% of the total study population and the stage II/III group, respectively. The median survival time in these groups was 12.1 months and 15 months, respectively. Grade 3/4 acute toxicities were observed in 62.1% of the patients. Grade 3/4 late toxicities were observed in 12% of the patients. The first failure after CRT was almost locoregional. CONCLUSION: CRT appears to be an effective therapy for esophageal cancer; however, its outcome is not satisfactory. Therefore, it is necessary to evaluate the role of salvage surgery after CRT and new chemotherapeutic agents.

[Primary malignant melanoma of the esophagus--detection of circulating tumor cells].

Primary malignant melanoma of esophagus (PMME) is a rare tumor; therefore, the prognostic factors, predictive factors, and difference in biological behaviors of cutaneous melanoma and primary esophageal squamous cell carcinoma remain uncertain. Although we did not adopt a standard therapeutic strategy, we performed surgical resection, chemotherapy, immunotherapy, and radiotherapy either alone or in combination; all procedures resulted in poor outcomes. A 67-year-old woman presented with a swallowing disorder. An esophagogastroduodenoscopy was performed, leading to diagnosis of PMME. According to the Japanese Classification of Esophageal Cancer, the pathological stage was T1b, ly0, v0, N0, M0, stage I . KIT immunostaining was focally positive. After subtotal esophagectomy, adjuvant chemotherapy was performed, but the malignant melanoma relapsed in the mediastinum and the patient died 10 months after diagnosis. We serially monitored the patient using several new modalities, including PET/CT, metabolites of melanin: 5-S-CD, and circulating tumor cells (CTCs) by reverse transcription-polymerase chain reaction to identify the melanoma-specific gene. To our knowledge, this is the first report of a case in which CTCs in PMME were detected.

[Pulmonary embolism during palliative chemotherapy including cetuximab for metastatic colorectal cancer].

In May 2007, a 48-year-old woman was admitted to our hospital for acute intestinal obstruction, and she was subsequently diagnosed with metastatic colorectal cancer in the sigmoid colon. Jejunum-ileum anastomosis and colostomy were performed as palliative surgery because the locally-advanced primary tumor had involved the ileum and other surrounding organs and formed huge mass. After placement of a central venous port, palliative chemotherapy mFOLFOX6 was commenced. In May 2008, mFOLFOX6 was replaced with FOLFIRI because of progression of both the metastasized and the primary tumors. On November 20, 2008, cetuximab was added to FOLFIRI because of the further disease progression. However, on December 24, 2008, the patient presented with sudden-onset dyspnea. Her blood gas analysis revealed severe hypoxemia and metabolic acidosis, and CT scan showed bilateral pulmonary artery embolism. After intensive treatment, the patient was able to walk under the room-air condition. However, on January 19, 2009, she died of pneumonitis. We believe that this is an interesting case with respect to the relationship between pulmonary embolism and malignancy and may hint at a causal relationship between pulmonary embolism and cetuximab, which is currently uncertain. We report this case herein along with a literature review.

[An autopsied case of thoracic esophageal cancer with polymyositis].

A 47-year-old woman patient who presented with weakness in the proximal parts of the upper and lower limbs and difficulty in swallowing was given a diagnosis of advanced esophageal cancer complicated with polymyositis. Steroid therapy was initiated for the polymyositis, but the CK level remained high. Chemotherapy was then selected as the preferred treatment option for the esophageal cancer, however, the treatment was ineffective and the patient died of respiratory failure. There is currently no consensus on the safety of therapy for malignant carcinoma complicated with collagen diseases, therefore, the selection of treatment modality for the disease must be made with care.

[A case of Giant GIST of the stomach successfully treated with imatinib mesylate neoadjuvant therapy and followed postoperatively].

Since the advent of imatinib mesylate (IM), its clinical efficacy against gastrointestinal stromal tumor (GIST) has been widely acknowledged, and therapeutic strategies for this disease have undergone great changes. We recently experienced a case of giant GIST of the stomach that was successfully treated with IM neoadjuvant therapy prior to surgical resection, but liver metastasis recurred 1 year and 7 months after the operation. The patient was a 65-year-old male who presented at our department with the chief complaints of dizziness, malaise, and fever in April 2002. An abdominal CT revealed a mass with a maximum diameter of 17 cm, as well as a cystic septate mass, 12 cm in diameter, with a thick capsule in the left lobe of the liver. The patient was diagnosed with GIST of the stomach and liver metastasis. Since radical operation was considered difficult at that point, IM (400 mg/day) was started on May 9. The result of treatment was determined to be PR, and radical operation was considered feasible. On March 18, 2003, total gastrectomy and left hepatic lobectomy/S 6 partial lobectomy were performed in the surgery department of our hospital. The postoperative course was favorable and oral administration of IM was resumed soon after the operation. However, the drug was discontinued for financial reasons and a decreased white blood cell count (grade 3) 2 months after the operation. Recurrence in the liver and abdominal wall was found in October 2004, and oral administration of IM was resumed again. Currently, treatment with IM is ongoing. Case reports on the efficacy of IM neoadjuvant therapy are occasionally found in the literature, but there are few reports on its long-term prognosis. We report this case with a discussion of future therapeutic options.