Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal cancer patients.

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/m(2) (range, 408.7-3385.3 mg/m(2)) in the OXY group and 483.0 mg/m(2) (range 76.2-1414.1 mg/m(2)) 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.

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.

Regulation of perioperative immunological changes following laparotomy: effects of biological response modifier (BRM) on surgical stress.

Immune responses have been reported to decline following surgical stress, leading to an increased susceptibility to infection or to the growth of tumors. In this study, we report that pre-operative treatment with the biological response modifier (BRM) polysaccharide Kureha (PSK) can inhibit the decline of immunocompetence during the perioperative period. BALB/c mice were laparotomized, the intestinal tracts were exposed to room air for 1.5 h, and then the abdomens were closed. Six hours after the operation, the spleen and serum were collected. The concentrations of IL-6 in the serum and of IFNgamma and IL-4 in the supernatant of splenocyte cultures were measured. In the surgical stress group that received surgical stress and the PSK treatment, the serum IL-6 concentration was significantly elevated in the group with surgical stress. PSK treatment controlled the stress-induced elevation. IFNgamma concentrations were measured in the supernatant of Concanavalin A (Con A) stimulated splenocyte cultures. It was lower in the group with surgical stress than in the cultures derived from the non-treated group. The IFNgamma concentration in the group with surgical stress plus PSK treatment was significantly higher than the level in the group with surgical stress alone. The IL-4 concentration was significantly lower in the surgical stress group than in the control group, however, the concentration tended to be higher in the surgical stress plus PSK treatment group than in the group with surgical stress alone. The IFNgamma/IL-4 ratio in the group with surgical stress was lower than the ratio in the non-treated group. The ratio in the group with surgical stress plus PSK treatment was significantly higher than the ratio in the group with surgical stress alone. These results suggest that PSK restores the abnormality of the biological responses induced by surgical stress and corrects the reduced Th1/Th2 cytokine balance to a normal level.

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 broad-spectrum antibiotic therapy.