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We report a case of locally advanced rectal cancer presenting with perforation that was successfully resected after preoperative chemotherapy. A 66-year-old woman visited our emergency room complaining of lower abdominal pain. Abdominal CT showed a rectal tumor with fluid collection and free air in the pelvis. The patient was diagnosed with panperitonitis secondary to cancerous perforation and underwent sigmoid colostomy. A biopsy specimen of the rectal tumor showed well-differentiated tubular adenocarcinoma and wild-type RAS. After 8 courses of mFOLFOX6 plus panitumumab, the tumor shrank remarkably, and radical surgery(low anterior resection with D3 lymph node dissection)was performed. Microscopic examination of the resected specimen showed that almost half of the tumor cells were replaced by histiocytes and necrotic tissue. Preoperative chemotherapy with panitumumab may be an effective treatment for RAS wild-type locally advanced colon cancer, even if the primary tumor develops perforation.

We report a case of nephrotic syndrome induced by ramucirumab for metastatic rectal cancer. A 48-year old woman who had received FOLFIRI plus ramucirumab for rectal cancer with liver, lung, and bone metastases presented to our hospital with edema and increased body weight. Laboratory studies showed hypoalbuminemia and severe proteinuria, and the patient was diagnosed with nephrotic syndrome. After administration of an angiotensin II receptor blocker and thiazide diuretic, her symptoms disappeared and serum albumin level normalized. To the best of our knowledge, this is the first detailed report of nephrotic syndrome related to ramucirumab. This case serves to emphasize that the possibility of nephrotic syndrome should be considered during anti-vascular endothelial growth factor therapy.

患者は82歳，女性．憩室穿孔術後の腹壁瘢痕ヘルニアに対し，Composix Kugel patchを用いた修復術施行．その2年3カ月後に発熱を伴う腹痛のため来院した．CT上腹壁に膿瘍を指摘された．本人の希望と全身状態を鑑み，保存的治療を選択した．約2カ月間保存的治療を行うも難治性であり，メッシュの摘除術を行った．術中所見ではメッシュに腸管が癒着しており，microperforationを生じたためメッシュ感染を引き起こしたものと思われた．メッシュ含め癒着した腸管も切除した．術後経過は良好で術後12日目に退院した．術後約2年経過も感染徴候及びヘルニア再発を認めていない．腹壁瘢痕ヘルニアの術後2年を経過してメッシュ感染を発症した1例を経験したので文献的考察を加え報告する．

患者75歳の男性で，左鼠径部膨隆と左鼠径部痛を主訴に当科を受診した．来院時陰嚢は人頭大に腫脹し，陰茎は埋没していた．CTでS状結腸を内容物とする左鼠径ヘルニアと診断した．用手的還納を試みるも整復できず，緊急手術を施行した．左鼠径部を切開し鼠径管を開放し，脱出するS状結腸を確認したが，鼠径法では還納が困難であり，追加した正中切開からの操作で脱出腸管を還納した．Direct Kugel Patch®(Mサイズ）を用い，ヘルニア門を修復した．術後腹腔内圧の上昇もあり，呼吸状態が悪化したため人工呼吸器管理を余儀なくされたが，術後3日目に抜管した．その後の経過は順調で，術後9日目に退院となった．現在ヘルニアの再発は認めてない．

Sleep deprivation has been shown to affect the production of steroid hormones in peripheral steroidogenic organs, but little is known about the influence of sleep disturbance on the metabolism of steroid hormones in the brain. To elucidate a possible association of the sleep-wake cycle with brain neurosteroid metabolism, the influence of short-term sleep disturbance on the expression of mRNA encoding steroid 5alpha-reductase, the enzyme converting progesterone and other steroid hormones to their neuroactive 5alpha-reduced metabolites, was investigated. Rats were first subjected to non-selective disturbance of the sleep-wake cycle, and the expression of steroid 5alpha-reductase mRNA in rat hippocampus and brainstem was determined using a semi-quantitative one-step RT-PCR technique. Non-selective disturbance of the sleep-wake cycle resulted in the elevation of 5alpha-reductase mRNA levels in the brainstem, but not in the hippocampus, and the elevated mRNA expression returned to the basal levels after a short period of the sleep recovery. Further studies showed that selective REM sleep deprivation significantly elevated 5alpha-reductase mRNA levels in both hippocampus and brainstem, thus proposing the possibility that REM sleep reduction may largely contribute to the elevation of steroid 5alpha-reductase mRNA levels observed during short-term disturbance of the sleep-wake cycle. Since the enhancement of steroid 5alpha-reductase gene expression may result in the elevation of neuroactive 5alpha-reduced steroid production in the brainstem, the findings presented here provide further evidence for suggesting that neuroactive steroids may play a physiologically important role in the neuronal network for REM sleep initiation and maintenance.

Toluene, a commonly used industrial solvent, is known to be toxic to both neuronal and glial cells, and has been shown to increase the immunoreactivity of glial fibrillary acidic protein (GFAP) in the brain. However, the mechanism of toluene-induced GFAP expression is poorly understood. Recently, GFAP mRNA expression in cultured astrocytes has been shown to be modulated by various steroid hormones, such as progesterone, testosterone, and their 5 alpha-reduced metabolites. Therefore, it seems possible that steroid hormones may play a potential role in the enhancement of GFAP expression observed following toluene exposure. To address this possibility, the effect of toluene inhalation on the expression of mRNAs encoding GFAP and steroidogenic enzymes in rat brain was examined. Toluene exposure increased GFAP protein contents without any significant alteration in GFAP mRNA levels in the hippocampus. In contrast, the elevation of both GFAP protein contents and its mRNA levels was observed in the cerebellum following toluene exposure. Further studies indicated that toluene exposure increased steroid 5 alpha-reductase (5 alpha-R) mRNA levels prior to the elevation of GFAP mRNA in the cerebellum, whereas neither 5 alpha-R nor GFAP mRNA levels in the hippocampus were significantly affected by toluene exposure. These results suggest that toluene inhalation may enhance GFAP gene expression in the rat cerebellum, and propose the possibility that the elevation of 5 alpha-R expression, and hence 5 alpha-reduced metabolites of steroid hormones, is presumably related to toluene-induced GFAP mRNA expression.

A 5 3-year-old woman was admitted to our hospital because of vomiting. CT scan and gastroduodenoscopy showed severe stenosis of the duodenal 3rd portion. There was no evidence of malignancy. We diagnosed a stricture due to a duodenal ulcer and laparotomy was performed. By means of biopsy of No.14d lymph node in the operation, adenocarcinoma of the duodenum was pointed out and we performed a pancreatoduodenectomy. Although adjuvant chemotherapy with S-1/paclitaxel (S-1 80 mg/body, po, day 1-14 and paclitaxel 120 mg/body iv day 1, 8)was administered after operation, the patient's serum CEA was elevated and metastic lymph nodes around the supra mesenteric artery were pointed out. The patient was started on combined chemotherapy with S-1/CPT-11(S-1 80 mg/body, po, day 1-14 and CPT-11 120 mg/body iv day 1), serum CEA levels returned to normal range, and marked reduction of lymph node size was observed on CT. The patient is still alive and free of disease three years after the operation. S-1/CPT-11 could therefore be a treatment option for patients with duodenal carcinoma.

A 73-year-old man was referred to our hospital with sigmoid colon cancer in July 2009. CT and MRI showed synchronous multiple liver metastasis. After a sigmoid colon resection in August, he received convergent chemotherapy in combination with 5-fluorouracil(5-FU)/Leucovorin(LV)(RPMI regimen)and bevacizumab for liver metastasis. After two courses without any major adverse effects, liver metastasis remarkably reduced on CT and MRI examination. We thus performed a liver resection, and pathological examination revealed a complete response in liver. Combination chemotherapy of 5-FU/LV and bevacizumab can be expected to provide safe and effective treatment for liver metastasis of colon cancer.

A 62-year-old man had undergone anterior resection of rectum for rectosigmoid colon cancer with liver metastases. Postoperatively, the FOLOFOX6 regimen was performed in three courses. Metastatic liver tumors showed progressive disease(PD) on CT scan. The treatment was then changed to the FOLFIRI regimen for three courses. Metastatic liver tumors showed a partial response(PR)on CT scan. After six courses of the FOLFIRI regimen, the patient was given seven courses of the FOLFIRI +BV regimen. Hepatic resection of S2, S3, S4 and S6 segment was performed. The histological effect of chemotherapy was complete response(CR).

Selective REM sleep deprivation was carried out under the conditions designed to minimize the adverse influence of environmental conditions and restricted movement, and the influence of REM sleep deprivation on adrenocortical steroid metabolism was investigated by measuring the steady-state levels of mRNAs encoding steroid metabolism-related genes, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme cytochrome P450 (P450scc) and steroid 5alpha-reductase (5alpha-R), in rat adrenal glands. Selective REM sleep deprivation caused a significant decrease in StAR mRNA and an increase in 5alpha-R mRNA levels without any notable change in P450scc mRNA levels in the adrenal gland. In contrast, non-selective sleep disturbance, resulting in the partial reductions of non-REM and REM sleep, tended to increase both StAR and P450scc mRNA levels without any statistical significance. These results indicate that REM sleep deprivation by itself may affect the expression of steroid metabolism-related genes in the adrenal gland, suggesting a possible relation between REM sleep and adrenocortical steroid metabolism.

Environmental influence on brain function, particularly spatial learning and memory, has been extensively investigated, but little is known about the influence of environmental conditions on the functions of peripheral organs. In the present study, the effects of different housing conditions on the steady-state levels of mRNAs encoding cholesterol side-chain cleavage enzyme (cytochrome P450scc) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands was examined to investigate the environmental influence on both adrenocortical and adrenomedullary functions. Behavioral changes of the animals housed in different conditions were first examined to assess the relevance of environmental manipulation used. In consistent with previous findings, housing of the animals in enriched conditions resulted in the significant reduction of spontaneous motor activity (locomotor activity and rearing) in comparison with housing in isolated conditions, thus indicating the relevance of housing conditions used in this work for investigating the environmental influence on adrenal function. Then, the effects of these housing conditions on P450scc and PNMT mRNA levels in adrenal glands were examined using semi-quantitative RT-PCR method. In comparison with the isolated group, the enriched group showed significantly higher levels of P450scc mRNA. In contrast, PNMT mRNA levels in the enriched group were significantly lower than those in the isolated group. These results propose the possibility that the environmental conditions may cause differential alterations in adrenocortical and adrenomedullary functions, although their possible association with behavioral changes still remains to be elucidated.