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Background Amoebiasis caused by the protozoan species Entamoeba histolytica rarely develops into fulminant amoebic colitis (FAC), but when it does, it shows an aggressive clinical course including colonic perforation, necrotizing colitis, and high mortality. Surgical treatment for FAC patients should be carried out urgently. However, even after surgery, the mortality rate can be 40–50%. Although FAC is one of the most unfavorable surgical diseases with a poor prognosis, there are a few reports on the perioperative diagnosis and management of FAC based on autopsy findings. We herein report the surgical case of a 64-year-old man who developed multiple colon necrosis and perforation due to FAC. A detailed autopsy revealed FAC as the cause of death. Additionally, we reviewed the existing literature on FAC patients who underwent surgery and followed their perioperative diagnosis and management. Case presentation A 64-year-old man presented with anorexia, diarrhea, and altered consciousness on arrival to our hospital. Computed tomography revealed a large mass in the upper right lobe of his lung, and the patient was admitted for close investigation. Bloody diarrhea, lower abdominal pain, and hypotension were observed soon after admission. Urgent abdominal contrast-enhanced computed tomography scan revealed extensive intestinal ischemia, intestinal pneumatosis, and free intra-abdominal gas. The preoperative diagnosis was bowel necrosis and perforation with intussusception of the small intestinal tumor. Emergency subtotal colectomy and enterectomy were performed soon after the contrast-enhanced computed tomography. He was taken to an intensive care unit after surgery. However, he could not recover from sepsis and died with disseminated intravascular coagulation and multiple organ failure on the 10th-day post-surgery. A histopathological examination of the resected colon showed transmural necrosis and massive amoebae invasion. He was diagnosed with FAC. An autopsy revealed that he had developed pulmonary large cell carcinoma with small intestinal metastasis. The death was caused by intestinal ischemia, necrosis and the perforation of the residual bowel caused by amoebae invasion. Conclusions Since FAC is a lethal disease with a high mortality rate and antibiotic therapies except metronidazole are ineffective, preoperative serological testing and perioperative metronidazole therapy in FAC patients can dramatically improve their survival rates.

Background Intraductal papillary neoplasm of the bile duct (IPNB) is a subtype of biliary tumor. The 5-year survival rate of patients with IPNB who underwent curative resection is 81%. However, IPNB is known to often recur in other parts of the bile duct. Nevertheless, its mechanism remains poorly understood. Herein, we report the case of a patient with recurrent IPNB, which was considered to be attributed to intraductal dissemination in the common bile duct at 12 months after curative resection. We also made a review of the existing literature. Case presentation A 69-year-old man was referred to our hospital for the evaluation and dilation of an intrahepatic bile duct (IHBD) mass. Computed tomography (CT) findings confirmed a mass in the left hepatic duct. Left trisectionectomy, extrahepatic bile duct resection with biliary reconstruction, and regional lymph node dissection were performed. Intraoperative examination of the resection margin at the common bile duct and posterior segmental branch of the hepatic duct was negative for the presence of malignant cells. Histologically, the tumor showed intraductal papillary growth of the mucinous epithelium and was diagnosed as non-invasive IPNB. It had a papillary structure with atypical epithelial cells lined up along the neoplastic fibrovascular stalks. Immunohistochemically, this was as a gastric-type lesion. At 12 postoperative months, CT revealed a 1.5-cm mass in the lower remnant common bile duct. We performed subtotal stomach-preserving pancreaticoduodenectomy. The tumor exhibited papillary growth and was microscopically and immunohistochemically similar to the first tumor. At approximately 16 months after the patient’s second discharge, CT showed an abdominal mass at the superior mesenteric plexus, which was diagnosed as recurrent IPNB. Chemotherapy is ongoing, and the patient is still alive. In this case, as described in many previous reports, IPNB recurred below the primary lesion in the bile duct. Conclusion Based on our review of previous reports on IPNB recurrence, intraductal dissemination was considered one of the mechanisms underlying recurrence after multicentric development. Considering the high frequency and oncological conversion of recurrence in IPNB, regular follow-up examination is essential to achieve better prognosis in patients with recurrent IPNB.

Background Acute mediastinitis is a rare disease that rapidly progresses with a high mortality rate. Its most common cause is direct injury of the mediastinum, including iatrogenic causes such as cardiac surgery or upper endoscopy. Enzymatic mediastinitis is a rare complication of a pancreatic fistula caused by the inflammatory digestion of the parietal peritoneum spreading to the mediastinum. Here, we present two cases of enzymatic mediastinitis caused by total gastrectomy with splenectomy. One of them was successfully treated and cured after early diagnosis and transabdominal drainage. Case presentation Case 1 was that of a 60-year-old man (body mass index [BMI] 27) with a medical history of diabetes and hypertension who was diagnosed with advanced gastric cancer in the upper body of the stomach. A total gastrectomy with splenectomy was performed. The patient experienced acute respiratory failure 24 h after surgery. Pulmonary embolism was suspected, so a computed tomography (CT) scan was performed; however, no relevant causes were found. Although he was immediately intubated and treated with catecholamine, he died in the intensive care unit (ICU) 40 h after surgery. Post-mortem findings revealed retroperitonitis caused by a pancreatic fistula spreading towards the mediastinum, causing severe mediastinitis; a review of the CT scan revealed pneumomediastinum. We concluded that the cause of death was enzymatic mediastinitis due to post-gastrectomy pancreatic fistula. Case 2 involved a 61-year-old man (BMI 25) with a medical history of appendicitis who was diagnosed with advanced gastric cancer at the gastric angle between the lesser curvature and the pylorus, spreading to the upper body of the stomach. A total gastrectomy with splenectomy was also performed. The patient had a high fever 3 days after the surgery, and a CT scan revealed pneumomediastinum, indicating mediastinitis. As the inflammation was below the bronchial bifurcation, we chose a transabdominal approach for drainage. The patient was successfully treated and discharged. Conclusion Acute mediastinitis caused by gastrectomy is rare. The acknowledgment of abdominal surgery as a cause of mediastinitis is important. In treating mediastinitis caused by abdominal surgery, transabdominal drainage may be a minimally invasive yet effective method if the inflammation is mainly located below the bifurcation of the trachea.

Key Clinical Message We encountered a patient with a large retroperitoneal solitary fibrous tumor, in whom we could preserve approximately 150 cm of the ileum even after pancreaticoduodenectomy combined with resection of the superior mesenteric artery, thus preventing short bowel syndrome.

Mesenteric phlebosclerosis is a recently discovered rare ischemic colon disease. The relationship between mesenteric phlebosclerosis and the use of herbal medicine containing gardenia fruit was recently reported. Although the relationship between colon cancer and mesenteric phlebosclerosis has not been described, some cases of colorectal cancer coincident with mesenteric phlebosclerosis have been reported. We treated a 63-year-old female who was diagnosed with ascending colon cancer coincident with mesenteric phlebosclerosis. She had been taking a Chinese herb containing gardenia fruit for over 18 years. The ascending colon cancer was clinically diagnosed as T2, N0, and M0 according to Japanese classification of colorectal carcinoma and the mesenteric phlebosclerosis had spread from the cecum to the descending colon. She underwent laparoscopic subtotal colectomy with en bloc removal of the regional lymph nodes, and both the ascending colon cancer and mesenteric phlebosclerosis were completely resected. The microscopic findings show that the tumor was well-differentiated tubular adenocarcinoma invading the muscular propria with no regional lymph node metastasis, and the mesenteric phlebosclerosis lesion was characterized by marked fibrous thickening of the venous walls with calcification, marked transmural fibrosis and deposition of the collagen in the mucosa, accompanied by macrophages within the vessel walls. In literature review, 10 cases with colorectal cancer coincident with mesenteric phlebosclerosis were reported. 9 of 10 cases (90%) had cancer in the right-side colon affected by mesenteric phlebosclerosis, and 5 of 10 cases (50%) were associated with the use of a Chinese herb containing gardenia fruit. It was recently demonstrated that genipin, which is a metabolite bio-transformed from gardenia fruit, possesses carcinogenesis. We speculate that genipin may be associated with not only the development of mesenteric phlebosclerosis but also carcinogenesis in the right-side colon. In conclusion, our findings suggest that the safety of gardenia fruit should be re-evaluated, and gastroenterologists should be aware that gardenia fruit may be risk factor for not only the development of mesenteric phlebosclerosis but also carcinogenesis in the proximal colon.

Background Hepatoid carcinoma (HC) is an extra-hepatic neoplasm that shares the morphological and immunohistochemical features of hepatocellular carcinoma. Pancreatic HC exists as either pure or combined type. Pure pancreatic HC is extremely rare, with only a few cases reported in the literature to date. Because of the rarity of pure pancreatic HC, its clinical features including incidence, behavior, and prognosis remain unclear. We herein report the case of a 56-year-old man who developed pure pancreatic HC treated with surgical resection. We also include a review of the existing literature. Case presentation A 56-year-old male patient was admitted to our hospital after a pancreatic cyst was identified by abdominal ultrasonography on a comprehensive medical examination. Endoscopic ultrasound revealed a cystic mass measuring 13 mm in size in the pancreatic head and a low-density mass measuring 16 mm in size in the pancreatic tail, which was partially enhanced on contrast-enhanced ultrasound. Contrast-enhanced computed tomography (CT) revealed a branch duct type intraductal papillary mucinous neoplasm in the pancreatic head and an early enhanced nodule measuring approximately 10 mm in size in the pancreatic tail. Endoscopic ultrasound-guided fine-needle aspiration of the hypervascular tumor was performed. The hypervascular tumor was suspected to be a solid pseudopapillary neoplasm. Laparoscopic spleen-preserving distal pancreatectomy was performed. Histology was identical to hepatocellular carcinoma of the liver. Immunohistochemically, the tumor cells were positive for hepatocyte paraffin 1, and a canalicular pattern was confirmed on the polyclonal carcinoembryonic antigen staining. The patient was diagnosed with a moderately differentiated pancreatic HC. The patient was followed up without adjuvant chemotherapy, and there was no evidence of recurrence at 6 months post-operatively. Conclusions We present a case of moderately differentiated pure pancreatic HC. For the accurate preoperative diagnosis of pure pancreatic HC, biopsy is preferred to cytology or preoperative imaging studies such as CT. The prognosis of pure pancreatic HC depends on its differentiation.

Background We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease. Methods Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings. Results Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P < 0.01). Two types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08-3.54 and odds ratio 2.85, 95% confidence interval 1.12-7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P < 0.01). One serious urological complication (intraperitoneal rupture of the bladder) occurred among women who underwent pelvic radiotherapy (0.6% vs. 0%). Conclusions Surgeons should be aware that eGFR is reduced after platinum-based chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up.

Background Neuroendocrine carcinoma (NEC) of the esophagus is a rare and highly aggressive disease but the biological features are poorly understood. The objective of this study was to analyze the clinicopathological and immunohistochemical features of NEC of the esophagus. Methods Fourteen patients diagnosed with NEC of the esophagus from 1998 to 2013 were included in this study. Clinicopathologic features, therapeutic outcomes and immunohistochemical results were analyzed. Results Eleven out of 14 cases showed protruding or localized type with or without ulceration. Only three patients were negative for both lymph node and organ metastasis and seven cases were positive for metastases to distant organs and/or distant lymph nodes. Of the six patients with limited disease (LD), three patients were treated by surgery. Three patients with LD and seven patients with extensive disease (ED) were initially treated with chemotherapy, except for one who underwent concurrent chemo-radiotherapy due to passage disturbance. The median survival of patients with LD was 8.5 months, whereas that of patients with LD was 17 months. Among the 14 cases, 12 cases (83.3%), 13 cases (91.7%) and 12 cases (83.3%) showed positive immunostaining for choromogranin A, synaptophysin and CD56, respectively. Nine of 14 cases (64.2%) presented positive staining for c-kit and most (8/9, 88%) simultaneously showed p53 protein abnormality. Two cases were negative for c-kit and p53, and positive for CK20. Conclusion Consistent with previous reports, the prognosis of NEC of esophagus is dismal. From the results of immunohistochemical study, NEC of esophagus might be divided into two categories due to the staining positivity of c-kit and p53. This study provides new insight into the biology of NEC of the esophagus.

Background Clostridium difficile (CD)‐associated colitis (CDAC) is endemic and a common nosocomial enteric disease encountered by surgeons in modern hospitals due to prophylactic or therapeutic antibiotic therapies. Currently, the incidence of fulminant CDAC, which readily causes septic shock followed by multiple organ dysfunction syndromes, is increasing. Fulminant CDAC requires surgeons to perform a prompt surgery, such as subtotal colectomy, to remove the septic source. It is known that fulminant CDAC is caused by the shift from an inflammatory response at a local mucosal level to a general systemic inflammatory reaction in which CD toxin-induced mediators’ cascades disseminate. Recently, it has been proven that polymyxin B hemoperfusion (PMX-HP) improves septic shock and recombinant human thrombomodulin (rhTM) controls disseminated intravascular coagulation (DIC). In addition, clinically and basically, it has been shown that these treatments can control serous chemical mediators. Therefore, it is considered that these treatments are promising ones for patients with fulminant CDAC. In the current report, we present that these treatments without surgery contributed to the improvement of sepsis due to fulminant CDAC. Case presentation We encountered a case who developed fulminant CDAC with septic shock and DIC after laparoscopic gastrectomy for gastric cancer. At admission to the intensive care unit, his APACHE II score was 22, which indicated an estimated risk of hospital death of 42.4 %. Our therapies were not the subtotal colectomy to remove septic sources but the combination treatments with both PMX-HP and rhTM. These combination therapies resulted in excellent outcomes, namely the dramatic improvement of septic shock and DIC and the patient’s survival. We speculate that these combination therapies completely inhibit the CD toxin-induced mediators’ cascades and correspond to the removal of septic sources. Conclusions We recommend both PMX-HP and rhTM for patients who develop fulminant CDAC with septic shock and DIC to increase the survival benefit and replace the need for surgical treatment.

We report an unusual case of gastric carcinosarcoma with rhabdomyosarcomatous and neudoendocrinal differentiation in a 71-year-old Japanese female. Gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation is a rare tumor. The tumor developed in the body of the stomach and was exophytic in appearance. By histochemical analysis, the tumor was shown a part of positive for desmin and myoglobin and a part of positive for synaphtophysin and vimentin. We conclude that, though rare, gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation thus is reviewed in the English literatures.

Purpose: Since a patient's obesity can affect the mortality and morbidity of the surgery, less drastic surgeries may have a major benefit for obese individuals. This study evaluated the feasibility of performing a totally laparoscopic distal gastrectomy, with intracorporeal anas- tomosis, in obese patients suffering from gastric cancer. Materials and Methods: This was a retrospective analysis of the 138 patients, who underwent a totally laparoscopic distal gastrectomy from April 2005 to March 2009, at the National Kyushu Cancer Center. The body mass index of 20 patients was ≥25, and in 118 pa- tients, it was

This paper documents the first case of gastric cancer associated with Recklinghausen's disease, which was successfully treated by a totally laparoscopic operation. A 67-year-old woman with Recklinghausen's disease was referred to this department to undergo surgical treatment for early gastric cancer. The physical examination showed multiple cutaneous neurofibromas throughout the body surface, which made an upper abdominal incision impossible. Laparoscopic surgery requiring only small incisions was well indicated, and a totally laparoscopic distal gastrectomy with lymph node dissection was performed. Billroth I reconstruction was done intra-abdominally using a delta-shaped anastomosis. The patient followed a satisfactory postoperative course with no complications. Since the totally laparoscopic gastrectomy has many advantages over open surgery, it should therefore be preferentially used as a less invasive treatment in the field of gastric cancer.

症例は72歳，男性．検診で胸部異常陰影を指摘され近医を受診，肺小細胞癌の診断にて治療目的に当センター紹介となった．PETにて左肺門部から縦隔リンパ節の他に，虫垂部にもFDGの高集積を認めた．腹部CTにて虫垂は壁肥厚を認め，その先端は嚢胞状に拡張しており，内腔の閉塞が疑われた．肺小細胞癌虫垂転移，原発性虫垂癌を鑑別診断として，穿孔の危険性を考慮し化学療法に先行して腹腔鏡下虫垂切除術を施行した．術後病理検査にて肺小細胞癌虫垂転移と診断された．術後経過は良好に経過し，現在化学療法継続中である．肺小細胞癌虫垂転移は稀だが，本症例では術前に診断し無症状のうちに切除することが可能であったので文献的考察を加え報告する．

目的:大腸癌に対する腹腔鏡補助下リンパ節郭清の安全性・根治性に関し，利点・欠点をもたらす因子を明瞭にすることを目的とした．方法:広島県内26施設の外科医に，大腸癌リンパ節郭清において開腹手術に対する腹腔鏡補助下手術の利点・欠点をアンケート調査した．手術経験総数に応じて経験豊富な施設，中等度の施設，寡少な施設に分類し，分析した．結果:経験豊富な施設，中等度の施設，寡少な施設は，それぞれ8，7，11施設認めた．この手術の利点は，経験数の多寡に係わらず，拡大視および開腹では得られない視野であった．その欠点は，経験豊富でない施設で見られ，術者の技術不足，助手の視野展開の悪さ，およびスコーピストの技術不足により良視野が獲得されないというものであった．結論:腹腔鏡補助下での大腸癌リンパ節郭清の安全性・根治性の獲得には，術者・助手・スコーピストの協調作業による良視野確保が重要であり，手術チームで解決すべき問題である．

胃癌に対する腹腔鏡下手術は有望な低侵襲手術として増加の一途をたどっているが，腹腔鏡下リンパ節郭清は，経験が少ない施設においては安全性・根治性に問題がある可能性がある．この解決には腹腔鏡下手術の利点・欠点を明確にすることが重要である．腹腔鏡下手術を施行している施設を対象とし，腹腔鏡下リンパ節郭清の利点・欠点をアンケート調査した．返答のあった28施設のうち20施設で腹腔鏡下胃悪性腫瘍手術が施行されていた．この手術経験総数が豊富な施設と少ない施設は，それぞれ10施設ずつ認めた．経験数の多寡に関わらず，鏡視下の利点は拡大視および開腹では得られない視野であった．経験の少ない施設では，術者の技術不足，助手の視野展開の悪さ，スコーピストの技術不足によって良好な視野が得られず，視野範囲制限が出現するという欠点が認められた．この欠点克服には，個人の技術向上以上にチームとしての技術向上が重要であると考えられる．

術前multi-detector computed tomography (MDCT) のみにて胆嚢十二指腸瘻および胆石イレウスが診断しえた1例を経験した. 症例は86歳, 女性, 認知症を合併. 右下腹痛を主訴として当科受診. 受診時MDCTにて25mm径の胆嚢結石を認めたが, 主訴の原因となる病変は指摘できなかった. 入院後, 症状は軽快していたが4日目に再度臍部痛および嘔吐が出現した. 緊急MDCTを施行したところ, 胆嚢十二指腸瘻および小腸へ落下した胆嚢結石がイレウスを引き起こしている像が得られた. 超高齢で認知症を合併していたためイレウス解除術のみ施行した. MDCTを用いた“胆石イレウス+内胆汁瘻”の診断は, 低侵襲で, 簡単・迅速に施行でき, 胆石イレウスのような急性腹症例を全身状態が良好なうちに一期的根治術 (イレウス解除術+胆嚢摘出術+瘻孔閉鎖術) に導ける可能性があると思われる.

症例は58歳の女性, 2005年9月, 胃癌の診断にて胃全摘術およびD2郭清を施行した. 進行度はpT3, pN2, sH0, sP0, pCY0, cM0; fStage IIIBであり, 総合的根治度Bが得られた. 組織型は非充実型低分化腺癌 (por2) であった. 2005年11月より術後補助化学療法としてTS-1100mg/dayを開始した. この治療開始3日目に, 患者は咽頭違和感を自覚した. 患者の口腔内を観察し, 左口蓋扁桃が30mm径に腫大しているのを確認した. 生検にてgroup V (por2) の診断を得, 原発巣の組織型と類似していることより胃癌の左口蓋扁桃転移と診断した. この時点で, CT にて全身検索を施行したが, 他臓器に転移・再発を示唆する所見は認めなかった. TS-1投与開始14日目に完全奏効 (以下, CR) の腫瘍縮小効果が得られ, 2006年6月まで総合効果CRが維持された. 胃癌の口蓋扁桃転移は, 極めて予後が悪く, 患者のquality of life (以下, QOL) 低下が著しい, と報告されている. TS-1投与による胃癌口蓋扁桃転移巣の縮小効果が, 患者に予後の改善および良好なQOLをもたらすことが期待される.

Therapeutic strategies for positive peritoneal lavage cytology [CY(+)] findings have not yet been established. The aim of the present study was to compare the effects of neoadjuvant systemic chemotherapy and surgery followed by S-1 adjuvant chemotherapy for treating gastric carcinoma in patients with CY(+) status without peritoneal metastasis.Twenty-three patients with CY(+) status without peritoneal metastasis who underwent curative surgery for gastric carcinoma between October 1999 and December 2014 were included in the study. Ten patients received neoadjuvant systemic chemotherapy followed by surgery, whereas 13 patients underwent surgery, in nine cases followed by S-1 adjuvant chemotherapy.The 5-year survival in both groups was 15%, and no significant difference was observed. However, the prognosis for patients with CY(-) status after neoadjuvant systemic chemotherapy was significantly better than that of patients who were still CY(+) after neoadjuvant systemic chemotherapy (p0.01). Among all patients, the prognosis of those with less than clinical N2 disease was significantly better than that of patients with clinical N3 (p0.01). In multivariate analysis, clinical lymph node metastasis was the only independent prognostic factor for CY(+) patients without peritoneal metastasis (p0.05).The prognosis of gastric carcinoma with CY(+) without peritoneal metastasis is still stage IV disease and is dependent on the degree of clinical lymph node metastasis, in spite of therapeutic treatment.

症例は27歳の男性で, 突然の吐血でショック状態となり搬送された. 初診時Hgb3.8g/dlと高度の貧血を認めた. 腹部CTでは膵頭部に約5cmの嚢胞性病変を認め, また膵体部から尾部にかけ石灰化が存在し, 慢性膵炎の像であった. 入院中突然の下血を認め, 緊急上部消化管内視鏡検査を施行した. 十二指腸下行脚は壁外性の圧排を受け, その中心部は壊死に陥り, 同部位より持続性の出血を認めた. 出血のコントロールは困難であり, 緊急で開腹手術を施行した. 術中所見では膵頭部に嚢胞性腫瘤を認め, 周囲は浮腫状であった. 膵仮性嚢胞の十二指腸穿破による出血と診断し, 膵頭十二指腸切除術を施行した. 病理組織学的検査では膵仮性嚢胞であり主膵管との交通も認めた. 術後経過は良好で, 第18病日に退院した. 膵仮性嚢胞の消化管への穿破はまれであり, 特に十二指腸への穿破の報告は少ないが, 嚢胞が原因となる出血により急激な経過をたどることもあり, 注意が必要と思われた.

The possible use of percutaneous low output microwave tissue coagulation therapy (PLMCT) using ultra-sonography under local anesthesia for small solitary liver cancer was studied.The subjects were 19 patients having primary or metastatic liver cancer with solitary liver tumor less than 4 cm in diameter. Consisting of 5 primary, 7 reccurent hepatocellular carcinoma and 7 metastatic liver cancers. PLMCT was performed continuously 3 times at the output of 30 watts for 30 seconds at a time. Tumors less than 3 cm in diameter were completely coagulated by irradiation from 2 to 6 times judged by enhanced CT.No tumor recurrence was recognized in the coagulation area. Thus, the results suggest that PLMCT is a useful therapy for small solitary liver cancer especially, recurrence of hepatocellular carcinoma as a minimal invasive surgery.

The purpose of percutaneous transhepatic low output microwave tissue coagulation therapy (PLMCT) is to locally treat using ultra-sonography under local anesthesia for small liver cancer. Usefulness of PLMCT has been described. This paper introduces special techniques which are useful to make the best use of PLMCT for liver cancer. Precautions necessary in procedure for PLMCT are as follows : 1) First of all, 16G needle aspiration biopsy of the liver tumor must be percutaneously performed under ultrasonographic guidance, and then 18G needle electrode is inserted into the 16G needle as a introducer. When this procedure is carried out, the needle electrode must not be pushed over the end of the introducer, for 18G needle electrode is weak. 2) While coagulating the tumor, the introducer had better be spun. 3) If the needle electrode is hot, cold alcohol had better be sprinkled on the needle electrode. We conclude that PLMCT is less invasive practical procedure for small liver cancer as a local control.

The possible use of percutaneous transhepatic microwave tissue coagulation therapy (PMCT) using ultrasonography under local anesthesia for small solitary hepatocellular carcinoma was studied.The subjects were 7 patients having primary or reccurent hepatocellular carcinoma with solitary liver tumor less than 3 cm in size, consisting of 4 primary and 3 reccurent hepatocellular carcinoma, PMCT was performed continuously 3 times at the out put of 30 watts for 30 seconds at time. Tumor was completely coagulated by irradiation from 2 to 6 times judged by enhanced CT.No reccurence of tumor was recognized in the coagulation area. Thus, the results suggest that PMCT is a useful therapy for small hepatocellular carcinoma as a local control.

胃癌症例165例について術中腹腔内洗浄細胞診の意義を検討した.腹腔洗浄細胞診陽性例 [以後cy (+)] は165例中41例に認め, 細胞診の陽性率は24.8%であった.切除例141例中, P0症例をP (-), P1～P3症例をP (+) とすると, 50%生存期間はP (+) cy (+) 例5.5か月, P (+) cy (-) 例22.0か月, P (-) cy (+) 例11.9か月, P (-) cy (-) 25.5か月であった.非切除例24例では3.7か月であった.P (-) cy (+) 例の3年生存率は9.1%で, 他の群との間で生存率に有意差を認めた (p

Seventy-eight patients who were operated on for colorectal cancer from November 1994 to December 1995 were divided into two groups with random sampling; 33 patients were orally administered antibiotics (kanamycin+clindamycin) for chemical cleaning (Chemical Cleaning Group) and 45 patients were not administered antibiotics (No Chemical Cleaning Group) preoperatively. The frequency of leakage and wound infection were compared between the Chemical Cleaning Group and No Chemical Cleaning Group. There was no significant difference in the frequency of leakage and wound infection between two groups. Furthermore, these patients were divided into another two groups by the presence of stenosis (more than one third of the intestinal lumen was stenosed) based on barium enema study, and a similar study was conducted in the stenotic and non-stenotic groups. Entirly no significant difference in the frequency of leakage and wound infection was noted in non-stenotic cases (x2=0.000, p=1.000). It was thought that non-stenotic cases demanded no chemical cleaning. But, there was a tendency in stenotic cases that the leakage and wound infection were found more frequently in the No Chemical Cleaning Group than in the Chemical Cleaning Group. More studies in stenotic cases are needed. This study suggested that the chemical cleaning would not be necessary for patients with colorectal cancer who had no stenosis.

To clarify the clinical significance of definitive chemoradiotherapy (CRT) and CRT followed by esophagectomy for cT4 esophageal cancer.The treatment results for cT4 esophageal cancer were examined in 81 patients who received definitive CRT [radiation 50-70 Gy, cisplatin and 5-fluorouracil; group I] and 19 patients who underwent esophagectomy after preoperative CRT [40Gy, Group II].Among the 81 patients in group I, toxicities (grade 3 or 4) were observed in 32 patients, while partial response and complete response were recognized in 8 and 47 patients, respectively. Of the 19 group II patients, an R0 resection was performed in 16 patients, and the mortality rate was 5%. The 5-year survival rates were 19% and 42% in groups I and II, respectively.Long-term survival can be expected after multimodal therapy, even for patients with cT4 esophageal cancer. Esophagectomy is therefore a valid treatment option when down-staging can be achieved.

The safety and efficacy of docetaxel plus S-1 combination chemotherapy as a first-line treatment in patients with advanced or recurrent gastric cancer was verified retrospectively.Eighteen patients with advanced or recurrent gastric cancer were enrolled. The regimen used was intravenous docetaxel, 40 mg/m(2), on day 1 and oral S-1, 80 mg/m(2)/day, on days 1-14 every three weeks.In total 101 cycles were administered. One and 11 patients achieved complete and partial responses, while six and zero patients showed stable and progressive disease, respectively. The median time to progression (TTP) and median overall survival were 7.0 and 14.3 months, respectively. Neutropenia was the most common grade 3/4 hematological toxicity. Nausea and stomatitis were the most common grade 3 nonhematological toxicities. No treatment-related death was observed.Docetaxel plus S-1 combination is an active and tolerable regimen as a first-line treatment in patients with advanced or recurrent gastric cancer.

Anti-tumor effector cells were generated by stimulating peripheral blood lymphocytes with cultured dendritic cells (DCs) and mRNA extracted from the gastric cancer cell line MKN45 or ascites tumor cells of gastric cancer patients. DCs were generated from an adherent fraction of peripheral blood mononuclear cells (PBMCs) in the presence of GM-CSF and IL-4. mRNA was extracted from tumor cells and subjected to T7-amplification. The DCs were electroporated (150 V/150 microF) with amplified mRNA and used after maturation with TNF-alpha to stimulate PBMCs to generate tumor RNA-introduced DC-activated killer (TRiDAK) cells. It was found that tumor RNA could efficiently be introduced into cultured DCs by electroporation (55% efficiency, 78% viability), and tumor RNA-introduced DCs could reproducibly stimulate lymphocytes to be tumor-reactive TRiDAK cells. The TRiDAK cells expressed an IFN-gamma response specific for tumor cells, but not for normal cells. Mock DCs or normal cell RNA-introduced DCs did not induce any killer cells. RNA-specific recognition of the effector cells generated was demonstrated using an amplified EGFP-mRNA system. The tumor killing activity of TRiDAK cells was inhibited not only with the anti-HLA class I antibody but also with the anti-HLA class II antibody as well as the anti-TCR antibody. TRiDAK cells reactive with autologous tumor cells could be generated in a CEA-positive gastric cancer patient with malignant ascites, in whom effector cell generation using DCs and CEA peptides had failed. These results suggest that TRiDAK cell generation is safe, feasible, and active in gastric cancer patients with malignant ascites, and is superior to other effector cell generation systems using DCs and epitope peptides. The adoptive immunotherapy of cancer using TRiDAK cells may be warranted in a clinical setting. This is the first study investigating anti-tumor effector cell generation using cultured DCs and tumor mRNA from gastric cancer cells.

A whole blood assay using antigenic peptide was established to predict host cytotoxic T lymphocyte (CTL) precursor status. Blood samples from HLA-A24 donors and colorectal cancer patients were directly diluted with RPMI-1640 medium to a 20% blood concentration, then distributed to tubes and a peptide of an HLA-A24-restricted CEA peptide panel (20 microM) was added to the tubes. Incubation was performed for 4-5 days and supernatants were subjected to ELISA specific for IFN-gamma protein. It was observed that certain CEA peptides could stimulate the diluted blood samples to produce IFN-gamma. Only the peripheral blood mononuclear cells (PBMCs) that were purified from the IFN-gamma-positive samples of the whole blood assay showed positive spots, detected with IFN-gamma ELISPOT assay, and could proliferate with the stimulation of immobilized anti-CD3 antibody plus interleukin-2 (CD3/IL-2 system). The proliferating PBMCs expressed cytotoxic activity against HLA-A24+ CEA-expressing tumor cells and the TISI target cells pulsed with the CEA peptide that had been used to stimulate the PBMCs to produce IFN-gamma, but they did not kill the target cells pulsed with peptides that had failed to stimulate IFN-gamma production, nor did they kill the target cells alone. Theses findings suggest that the IFN-gamma production of the blood samples detected by the whole blood assay identifies the peptide that can induce the CEA antigen-specific CTL response. Detection of IFN-gamma gene expression using real-time-PCR analysis could identify the peptide within 6 hours, which is earlier than the protein analysis by ELISA. The whole blood assay using the CEA peptide panel for healthy donors and colorectal cancer patients revealed that IFN-gamma-inducible peptides were different among the individual samples tested, indicating that the CEA peptides that should be used for generating CTLs are different in individual patients. The whole blood assay using a CEA antigen peptide panel is simple and beneficial for identifying candidate peptides. The host-oriented peptide evaluation (HOPE) approach may provide hope for the augmentation of clinical efficacies for peptide-based cancer immunotherapy.

In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied. A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine of 11 (82%) patients treated with OK-432 alone and in all five patients treated with OK-432 plus IL-2. Flow cytometric analysis revealed that OK-432 plus IL-2 locally induced acute inflammation-like responses, including serial cellular infiltrations of granulocyte migration within a matter of hours, and activation of macrophages and T lymphocyte involvement within the following days, and that a predominant expansion of CD3+CD4+ lymphocytes (CD: cluster of differentiation) was induced by in vitro stimulation with IL-2 of locoregional cells after the OK-432 administration (OK/IL-2AK cells). The OK/IL-2AK cells produced tumour necrosis factor-alpha and interferon-gamma, but these cells did not produce IL-4 and IL-6. The OK/IL-2AK cells expressed potent killing activity against autologous tumour cells. This activity was abrogated by treatment of the lymphocytes with anti-CD3, -CD4, -TCRalphabeta antibody, and by the treatment of target cells with anti-human leukocyte antigen (HLA)-DR antibody. The OK/IL-2AK cells expressed Fas-L gene, and flow cytometric analysis demonstrated HLA-DR expression in approximately 75% of CEA+ or cytokeratin+ effusion cells. TCRVbeta gene analysis of the OK/IL-2AK cells showed an oligoclonal usage of TCRbeta20, which was also involved in the cytotoxic mechanism of the OK/IL-2AK cells. Single-strand conformational polymorphism analysis demonstrated the clonotypes for the TCRVbeta20 gene, and the CDR3s of the gene were sequenced. The clonotypic PCR using the TCRVbeta20-CDR3 sequences could detect the CDR3-identical TCRs in effusion lymphocytes from the other patients. Taken together, it is suggested that locoregional administration of OK-432 plus IL-2 is highly effective for the management of malignant effusion from colorectal cancer. OK-432 plus IL-2 induces autologous tumour-reactive CD4+ Th1 killer lymphocytes, which recognise tumour antigen(s) presented with HLA class II molecules on effusion tumour cells by means of preferential usage of TCRVbeta20. The clonotypic PCR using the TCRVbeta20-CDR3 sequences may be informative for treating malignant effusion from colorectal cancer using OK-432 plus IL-2.

We studied the thymidine kinase (TK) gene and the interleukin (IL)-2 gene co-transduction into tumor cells for a possible strategy of cancer gene therapy. A murine ovarian cancer cell line, OVHM, was retrovirally transduced with the TK (OVHM/TK) or the IL-2 gene (OVHM/IL-2). The TK or IL-2 expression was permanent in OVHM/TK or OVHM/IL-2. OVHM/TK cells were susceptible to gancyclovir (GCV) in vitro, and their intraperitoneal growth was completely regulated with GCV administration. The bystander effect was not observed in vitro and in vivo in this model, and only the marginal emergence of immune involvement was observed in the OVHM/TK-cured mice with GCV. OVHM/IL-2 cells produced IL-2 biologically active to be immunogenic, but still tumorigenic to kill the mice when inoculated intraperitoneally. Then, OVHM/TK cells were co-transduced with the IL-2 gene to establish OVHM/TK/IL-2 cells. OVHM/TK/IL-2 cells were also susceptible to GCV and transiently produced active IL-2. A significant resistance against the challenge of parental tumor cells was observed in the mice that were inoculated with OVHM/TK/IL-2 cells and cured with GCV administration. It is suggested that tumor cells transduced with both TK and IL-2 genes could be regressed with GCV administration with subsequent generation of immune activation in the host. Since the bystander effect may not always be a common phenomenon in gene therapy using the TK gene, this type of combination may be advantageous in the clinical application of gene therapy for human cancers.