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This randomized phase II trial compared tegafur–uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer. From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/m2 oxaliplatin on days 1 and 15, 300 mg/m2/day UFT and 75 mg/day LV on days 1–28, every 35 days for five cycles) or UFT/LV. The primary study endpoint was disease-free survival. The 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P < 0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P < 0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups. TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer. UMIN ID: 000007696, date of registration: April 10, 2012

This randomized phase II trial compared tegafur-uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer.From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/mThe 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups.TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer.UMIN ID: 000007696, date of registration: April 10, 2012.

患者は79歳,女性.乗用車乗車中の交通事故にて受傷し近医に入院した.右血胸と診断され胸腔ドレーンの挿入を受け軽快したので退院した.受傷半年後の胸部単純X線検査にて右下肺野異常陰影を認め,精査するも無症状のため経過観察となっていた.受傷3年後,食後に嘔吐が出現し近医受診,胸部単純X線検査にて右横隔膜ヘルニアと診断され翌日当院入院となった.胸腹部CTにて胸腔内に腸管,肝,胆嚢の脱出を確認した.外傷性右横隔膜ヘルニアの診断にて開腹したが,回腸がヘルニア門に陥入しており他に肝内側区域,胆嚢もヘルニア門に陥入していた.横隔膜の右側に径7×5cmの裂傷を認め,結節縫合にて閉鎖した.術後経過は良好で術後第15病日に退院した.遅発性の発症で発生部位が右側横隔膜である外傷性横隔膜ヘルニアは稀であるが,若干の反省を含め文献的考察を加え報告した.

症例は55歳,女性.近医で胃潰瘍の加療中,症状が軽快しないため当科を受診.上部消化管内視鏡検査にて上十二指腸角から下行部にかけて,乳頭側3/4周を占める白苔を伴った潰瘍を認めたため入院.腹部超音波検査および造影CTでは膵鈎部に腫瘤を認め,肝外胆管および16番リンパ節の腫脹も認められた.閉塞性黄疸,肝機能異常も出現したため,膵癌あるいは十二指腸癌の可能性も考え,手術を行った.十二指腸下行部および膵頭部は一塊となっており根治切除不能と判断し,十二指腸を球部にて離断し十二指腸球部空腸吻合および胆道バイパスを行った.術後経過は良好で画像上腫瘤は縮小したが, 4カ月後黒色便および貧血が出現したため再手術を行った.十二指腸下行部を切開すると膵側に4cmの潰瘍を認め,中央には血管が露出していたため,膵頭十二指腸切除術を行った.術後経過は良好であった.

A 65-year-old woman with a gastrointestinal stromal tumor(GIST)underwent a total gastrectomy in 1999. In 2004, she was diagnosed with an intra-abdominal recurrence and was treated with 300mg/day of imatinib. Because of the side effects of imatinib, we interrupted the treatment and were forced to reduce the dose from 300mg/day to 100mg/day. However, at present, the tumor remains controlled. In conclusion, this case suggested that, even if given irregularly or at a low-dose, continuous treatment with imatinib might contribute to long-term survival in patients with GIST.

A 56-year-old man was admitted to the hospital because of abdominal distension. Dynamic CT and MRI revealed a giant tumor, a part of which was enhanced. Angiography of the inferior mesenteric artery visualized hypervascularization. Original site was obscure, but the patient was diagnosed as having an intraperitoneal malighant tumor. Laparotomy was carried out and it was found that the tumor was located in the mesosigmoid and invaded the jejunum. Tumor extripation with partial resection of the jejunum was performed. Extirpated tumor was 18×17cm in size and 2200g in weight, and there existed a cystic part due to hemorrhage and necrosis and a solid part concomitantly. It was diagnosed as mesosigmoid leiomyosarcoma histopathologically. The patient has been doing well for 8 months after the operation. Mesenteric leiomyosarcoma is a rare entity and only 52 cases have been reported in Japan. Of the 52 cases, 42 cases were capable of being reviewed, especially for prognosis. The 5-year cumulative survival rate after operation was 49.2%, which was relatively favorable for considering its freqrent recurrence.

We experienced a case of early cancer of gallbladder accompanied with adenomyomatosis, in which the histological continuity with adenomyomatosis was suspected. The patient was a 74-year-old man, complaining of epigastralgia. By endoscopic retrograde cholangiography the tumor with irregular surface was found at the fundus of gallbladder. Slow injection dynamic CT showed a tumor shadow in the continuity with the gallbladder wall at the fundus enhanced by contrast medium (iopamiron). This case was diagnosed cancer of the gallbladder accompanied with adenomiomatosis. And extended cholecystectomy with regional lymphadenectomy (R2) was done. Histopathological examination of the specimen revealed adenomyomatosis, mucinous papillary adenoma, papillary adenocarcinoma (m-RAS ss) at the fundus simultaneously, so histological continuity between adeno-myomatosis and cancer of gallbladder was suspected.

A 13-year-old girl was admitted to the hospital with a diagnosis of congenital bile duct dilatation (CBD) which was made by a nearby hospital to where she visited because of epigastralgia. After admission the patient was diagnosed as von Willebrand's disease on preoperative laboratory findings. Choledochotectomy with hepatichojejunostomy was performed without administrating heat-treated factor VIII concentrates. With repeated administration of 1-deamino-8-D-argininn-vasopressin (DDAVP) starting immediately before to after the surgery, this radical procedure was safely performed without any serious hemorrhage. It has become a serious problem that repeated infusion of factor VIII concentrates can cause factor VIII inhibitor, AIDS and hepatitis type C. This case appears to be the first report that choledochotectomy for CBD was carried out in a patient with von Willebrand's disease without using antihemophilic factor concentrate.

進行食道癌92症例の術前合併療法施行時の栄養管理について, 術前栄養状態維持と術後肺合併症発生の面からretrospectiveに検討した.高カロリー投与により術前栄養指標はほぼ正常域内の値が維持され, rapid turnover serum proteinの上昇により栄養状態の改善が示唆された.体重と血清総蛋白値の推移からは35NPkcal/kg/day以上の維持投与カロリーが望ましいと思われ, 照射により一過性に低下した免疫学的指標も術直前までに回復傾向を示した.しかし, 血清アルブミン値の推移は, 栄養管理法, 投与カロリーの多寡に関わらず低下傾向で, 70歳以上の症例では70歳未満の症例に比べて低値での推移であった.また, 術直前の血清アルブミン値が3.5g/d1未満の場合に, 70歳以上の症例では70歳未満の症例に比べて高率に術後肺合併症を起こした.このことから, 高齢者の術前栄養管理では, 適切な投与カロリーの決定などさらに綿密に検討する必要があると考えられた.

We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.

We studied the dynamic profile of respiratory and circulatory activities during sustained isocapnic hypoxia in healthy males. In response to end-tidal PO2 depression to about 55 Torr, minute ventilation first increased briskly and then depressed. Such biphasic response to hypoxia was also observed in the heart rate. A significantly positive correlation was found between the magnitudes of ventilatory and heart rate responses. No significant increases were found in arterial noradrenaline and potassium, but adrenaline significantly increased gradually with time. Furthermore, when VT and f were intentionally maintained constant so as to prevent the biphasic ventilatory change, the biphasic heart rate response previously seen in spontaneous hypoxic breathing disappeared. We suggest that the heart rate is mainly determined by the pulmonary vagal inflation reflex. Putative neurochemicals to elicit hypoxic ventilatory depression, and arterial catecholamine and potassium concentrations may not be directly related to the specific profile of the biphasic heart rate response during moderate hypoxia.

A time course of cardiovascular activity in 8 healthy males in relation to augmented ventilatory activity and humoral factors was observed during step CO2 elevation with constant hypoxia. During the first step increase, by 3 Torr in end-tidal PCO2 (PETCO2), the heart rate (HR) initially tended to decrease, then slowly increased to slightly below that of the previous eucapnic level, whereas ventilation maintained a gradual rise throughout this period. On the other hand, during second step PETCO2 elevation, by a further 3 Torr, both HR and ventilation progressively increased. The plasma catecholamine (CA) concentration was also significantly elevated during this period, suggesting a concomitant enhancement in sympathetic activity. Blood pressure (Bp) was progressively augmented throughout the entire hypoxic challenge. We conclude that 1) the characteristic profile of HR change may be explained by the observation that initial HR depression by peripheral chemoreceptor stimulation is gradually overridden by delayed hyperventilation, CA elevation, and enhanced sympathetic activity; 2) Bp augmentation may be elicited by increased CA release and sympathetic activity; and 3) plasma K+ concentration does not change so as to affect cardiovascular and respiratory activity.

It has been demonstrated that the doping level of the surface of a conjugated polymer poly(3-methylthiophene) significantly changes when the sample is stocked in air to yield erroneous data of the ionization potential measured by the photoelectron spectroscopy in air. In-situ measurement of the ionization potential using an open-type electrochemical cell has been proposed to avoid this difficulty. A preliminary experiment has been demonstrated to show that the change in the ionization potential during electrochemical doping taken in-situ was larger than that measured ex-situ, suggesting the usefulness of the proposed method.

In this study we tested the hypothesis that the stimulatory hypercapnic ventilatory response (HCVR) would be less in quadriplegic patients. Apart from the sheer exclusion of a substantial part of the effector of the respiratory control system due to paralysis of the respiratory muscles of the chest and abdominal wall, two lines of evidence suggest such a possibility. First, these muscles contain a rich network of mechanoreceptors, muscle spindles, and tendon organs, which are classified as proprioceptors. There is evidence showing that afferent information from these proprioceptors exerts, via ascending spinal pathways, a reflex effect on the central control of respiration, modulating the descending drive to phrenic and intercostal spinal motoneurons (Shannon, 1986). Second, chemoreceptor afferents might have a facilitatory effect on the descending drive to respiratory muscle neurons independent of the proprioceptive influences. Recent studies have shown that hypercapnia increases both internal intercostal (Fregosi and Bartlett, 1989) and abdominal expiratory (Ledlie et al.,1983) nerve activities in the absence of proprioceptive feedback from the body wall.

It is often seen that the breath is held during strenous exercise such as 100m or 200m dash. The characteristic features in this maneuver are that exercise intensity is very vigorous and duration is very short. To our knowledge, no detailed observation has been conducted on the cardiopulmonary responses during this particular physical performance.

Static isometric exercise leads to a rapid heart rate acceleration and pulmonary hyperventilation (Miyamoto et al., 1987). The heart rate acceleration is known as a muscle-heart reflex, originates in muscle receptors affected by noxious chemical and mechanical stimulation, and is mediated by group III and IV afferents (Gelsema et al., 1983). The mechanism of the hyperpnea is uncertain, as is also the role of chemical drive in both cardiac and respiratory events of static exercise.

Nine normal male subjects were studied at three levels of exercise (0, 40, and 80 W). Single vital capacity breath test was applied at rest and during exercise (phases 2 and 3). Minimum minute ventilation found within 4 breaths following the test was compared to the control value. Significant depression in minute ventilation was invariably observed. The minute ventilation was depressed more and more with increasing intensity of exercise. A significant difference was found between exercise and rest. However, the relative contribution of chemoreceptor activity remained the same 10-20% at all exercise levels. The magnitude of ventilatory depression (delta V resp) in phase 2 was larger than that in phase 3, when work rate increased to 80 W, both relative and absolute. A significant part of the exercise hyperpnea is due to peripheral chemoreceptor activity. The peripheral chemoreceptor activity is greater in phase 2 than in phase 3 at work rates of light to moderate intensity.

種々の安定同位元素により, 消化器外科患者の全身蛋白代謝, 脂肪消化吸収能, 肝細胞内の個々の機能を測定した. 全身蛋白代謝は加齢とともに低下した. 肝硬変患老では蛋白合成速度が著明に低下している症例が認められ, また蛋白合成速度とICG15分値・プロトロンビン時間とには有意の相関が認められた. 膵頭十二指腸切除術後の脂肪消化吸収能は著明に低下していた. 肝硬変患者の肝ミトコンドリア, ureacycle, ミクロゾームの各機能を測定した結果, 肝ミトコンドリア機能の障害は比較的軽度であり, 肝ミクロゾーム機能が強く障害されていた.

The cardiovascular responses to breath-holding (BH) during short-lasting supramaximal exercise (415 W) on a cycle ergometer were investigated in 15 healthy male subjects. The arterial oxygen saturation, heart rate (HR), endtidal PO2 and PCO2 were continuously monitored. Firstly, 15 subjects performed exercise during BH, preceded by air breathing (air-BH test), and secondly, exercise without BH. Then 9 of the subjects performed the same procedure as in the air-BH test, except that all subjects breathed 100% O2 for 1 min before apnoea (O2-BH test). In 2 of these subjects, the systemic arterial blood pressure was continuously measured via a catheter in the radial artery and plasma catecholamine concentration [CA] was also measured both during the air-BH and the O2-BH tests. In the later period of the air-BH test, the high HR level became progressively depressed. This response, however, was absent in the O2-BH test. There was a late increase in the arterial blood pressure in both tests, and both tests produced hypercapnia. Only the air-BH test resulted in hypoxia, substantial hypertension and HR-depression. The increase in plasma CA was similar in both tests. The marked HR-depression demonstrated here is ascribed mainly to activation of the peripheral arterial chemoreceptors by asphyxia, and partially to baroreceptor activity due to elevated blood pressure.

We studied the steady state responses of heart rate (HR) to carbon dioxide inhalation under hyperoxic, euoxic, and hypoxic conditions in 9 healthy men. With increasing end-tidal PCO2, HR generally increased slightly. On the other hand, distinct increment in VE in response to step increase in end-tidal PCO2 was observed in all three different conditions. Significant positive correlation between hypercapnic VE and HR responsiveness was found in both hyperoxic and hypoxic conditions, whereas no such tendency was seen in euoxic condition. We suggest that the effect of CO2 inhalation on HR is mainly determined by the pulmonary inflation reflex in hyperoxia, the pulmonary inflation reflex plus peripheral chemoreceptor activity in euoxia, and the additional sympathetic and humoral factors in hypoxia, respectively.