Ayako Moriyama

Triple-negative Breast Cancer and Poly(ADP-ribose) Polymerase Inhibitors

Recent gene profiling studies have identified at least 5 major subtypes of breast cancer, including normal type, luminal A type, luminal B type, human epidermal growth factor receptor (HER)-2 positive type, and basal-like type. Triple-negative breast cancer (TNBC), showing no or low expressions of estrogen receptor (ER), progesterone receptor (PgR), and HER2, considered important clinical biomarkers, accounts for 10% to 20% of all breast cancers. Hormonal therapy and molecular targeted therapy are not indicated for the management of TNBC, resulting in poor outcomes. Because TNBC lacks clear-cut therapeutic targets, effective treatment strategies remain to be established. However, TNBC is known to share similar biologic characteristics with basal-like type breast cancer and is often accompanied by loss of functional BRCA, a gene-modifying enzyme. Breast cancer with BRCA1 or BRCA2 mutations is accompanied by activation of the enzyme poly(ADP-ribose) polymerase (PARP). PARP, a DNA base-excision repair enzyme, is known to play a central role in gene repair, along with BRCA. Because some breast cancers with BRCA1 or BRCA2 mutations are TNBC, the suppression of PARP has attracted attention as a new treatment strategy for TNBC. In this article, we review the clinical characteristics of TNBC, discuss problems in treatment, and briefly summarize the international development status of PARP inhibitors.

Intersigmoid hernia: Report of a case

A 28-year-old man with no previous history of abdominal surgery presented at a local hospital with abdominal pain. He was diagnosed to have an intestinal obstruction and was treated conservatively. However, the symptoms persisted, and he was thereafter referred to this hospital. Plain abdominal radiographs demonstrated small-bowel gas. A computed tomographic scan of the abdomen disclosed wall thickening of an edematous, fluid-filled ileum. An exploratory laparotomy was performed to determine the cause of the intestinal obstruction. The ileum had herniated into the intersigmoid fossa, 100 cm proximal to the ileocecal valve, and the patient was diagnosed to have an intersigmoid hernia. Since the incarcerated portion of the small bowel was viable, reduction of the hernia and closure of the defect in the sigmoid mesocolon were performed. The postoperative course was uneventful. A sigmoid mesocolon hernia is an uncommon condition. This report presents a case of intersigmoid hernia and a review of 60 cases of sigmoid mesocolon hernia reported in Japan.

Tumor-like growth of giant inflammatory polyposis in a patient with ulcerative colitis.

We report a unique case of giant obstructing inflammatory polyposis associated with ulcerative colitis (UC). A 25-year-old Japanese man with an UC history of 2 years and 6 months was referred to our institution because of diarrhea and melena. His computed tomography scan showed marked dilation of the transverse and descending colon; therefore, we performed total colectomy. Macroscopic evaluation of the excised specimen indicated constricting lesions with giant polyposis in the transverse and descending colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregular ulcers. Histologic evaluation of the excised specimen indicated transmural inflammation with a thickened proper muscular layer overlaid with inflammatory polyposis. Based on these data, a diagnosis of giant inflammatory polyposis should be considered in patients who have had UC. Although giant inflammatory polyposis is considered benign, surgical treatment may be indicated to avoid serious complications.

Fournier's gangrene progressing from the buttocks to the scrotum following a perianal abscess

We describe a case of gas-producing infection following a perianal abscess. A 61-year-old man was admitted to our hospital complaining of perineal pain and was found to have a perianal abscess. He was diabetic but had not received treatment for the disease. Although the perianal abscess was drained and antibiotic treatment started, severe swelling of the scrotum, with crepitation, redness, and partial necrosis progressed rapidly. Computed tomography revealed subcutaneous gas formation in the scrotum. A culture study revealed Clostridium, Enterococcus, and numerous other types of bacteria. The patient was diagnosed with Fournier’s gangrene caused by infection with Clostridium in combination with other species of bacteria. The infection was refractory to drainage and antibiotic therapy. Thus, repeated extensive debridement of all necrotic tissue in the scrotum was required until healthy granulation was present in the wound. Our case shows that, in patients with Fournier’s gangrene caused by infection with Clostridium in combination with other species of bacteria, the mainstay of treatment should be open drainage and aggressive surgical debridement of all necrotic tissue, followed by broadspectrum antibiotic therapy.

Efficacy and tolerability of oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of folfox therapy in colorectal cancer patients.

196 Background: The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients. METHODS This was a single-center retrospective study of 64 CRC patients who underwent FOLFOX therapy at the Toho University Sakura Medical Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group), whereas the additional 35 patients (non-OXY group) were not given oxycodone during the FOLFOX treatment course. The incidence and severity of OIPN and the number of FOLFOX cycles were measured and compared between the two groups. Neurological toxicities were assessed according to the Common Terminology Criteria for Advanced Events, version 3.0. RESULTS All study patients had OIPN. Most patients experienced grade 1 or 2 sensory neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non-OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy, whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY and non-OXY groups were 13 (range, 6-46) and 7 (range, 2-18), respectively (P < 0.05). The median cumulative oxaliplatin doses were 1072.3 mg/m2 (range, 408.7-3385.3 mg/m2) in the OXY group and 483.0 mg/m2 (range 76.2-1414.1 mg/m2) in the non-OXY group (P < 0.05). CONCLUSIONS Our findings indicate that CR oxycodone might attenuate the severity of OIPN and extend the use of FOLFOX therapy.