Kazuyo Naito

Bestatin administration and the change in cellular immunity

The change in cellular immunity by Bestatin (ubenimex) treatment--30 mg/day orally--was investigated in 23 gastrointestinal cancer patients for: 1), functional T cell subsets; 2), IL-2 receptor; 3), PHA-induced blastogenesis; and 4), PPD skin reaction. The absolute number of helper T cells (Th) and cytotoxic T cells (Tc) increased in 74 and 79% of cases, respectively, compared with pretreatment values. On the other hand, the absolute number of suppressor T cells (Ts) decreased in 79% of cases. IL-2 receptor increased in 56% of patients, PHA blastogenesis increased in 67% of patients and PPD skin reaction was elevated in 75% of cases comparing to pretreatment values. These results suggest that Bestatin could increase cellular immunity in cancer patients.

Double cancer of the cystic duct and gallbladder associated with low junction of the cystic duct

We report a case of double cancer of the cystic duct and gallbladder associated with low junction of the cystic duct. A 73-year-old woman was admitted to the hospital complaining of upper abdominal pain. Endoscopic retrograde cholangiography showed a stenotic lesion in the lower common bile duct and no visualization of the cystic duct or gallbladder. Enhanced computed tomography revealed a heterogeneously enhanced tumorous lesion around the lower bile duct in the pancreatic head. A diagnosis of cancer arising from the cystic duct that entered the lower part of the common hepatic duct was made by intraductal ultrasonography, which showed an intraluminal protruding lesion in the cystic duct. Isolated gallbladder cancer was also diagnosed, by abdominal computed tomography. She underwent pancreaticoduodenectomy with dissection of regional lymph nodes. Histological examination revealed moderately differentiated adenocarcinoma of the cystic duct and well-differentiated adenocarcinoma of the gallbladder. Double cancer of the cystic duct and gallbladder is extremely rare, and this case also suggests a relationship between a low junction of the cystic duct and neoplasm in the biliary tract.

Active Specific Chemoimmunotherapy of Lymph‐node Metastasis from a Poorly Immunogenic Murine Fibrosarcoma

The fibrosarcoma MCA‐SP, which was recently induced with methylcholanthrene (MCA) in C3H/ HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA‐SPN1, which bears a tumor‐specific transplantation antigen (TSTA) cross‐reactive with the parental line MCA‐SP, was selected because of its proclivity for axillary lymph‐node metastases. Although these lymph‐node metastases were resistant to sinecomitant (post‐excisional) immunity, they were susceptible to combined active and passive specific Chemoimmunotherapy, using tumor‐specific, 1‐butanol‐extracted, preparative isoelectric focusing‐purified, TSTA (1 fig weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re‐stimulated in vitro with extracted TSTA and interleukin‐2. This triple regimen both reduced the incidence of spontaneous lymph‐node metastases, and prolonged the survival of tumor‐bearing, as well as tumor‐resected hosts. The results from local adoptive transfer assay using T‐lymphocyte snbpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2+ cytotoxic T‐lymphocytes (CTL) mediated in vivo tumor‐neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA‐SP tumor and its lymph‐node metastases.

A Case of Neuroendocrine Cell Carcinoma with Sigmoidovesical Fistula.

Colonic neuroendocrine cell carcinoma (NEC), which is a rare subtype of colon epithelial neoplasm, has been reported to show extremely aggressive characteristics with a 1-year survival rate of 20%. We report herein a resected case of NEC that manifested bacterial sepsis due to sigmoidovesical fistula. Staged surgery consisted of resecting the sigmoid colon and part of the bladder four weeks after construction of an ileostomy to alleviate septic shock. The resected specimen was histologically diagnosed as NEC invading the wall of the urinary bladder with metastasis to the regional lymph nodes. The patient underwent four cycles of FOLFOX after surgery for additional treatment of residual metastatic lymph nodes around the abdominal aorta diagnosed preoperatively. Although the patient showed stable disease measured by computed tomography scan for the first three months after surgery, he rejected additional chemotherapy thereafter, and died ten months after the initial admission due to progression of residual tumor in the urinary bladder as well as the lymph nodes. This is the first case report describing colonic NEC manifesting perforation into the urinary bladder. Although the optimal chemotherapeutic regimen for colonic NEC has not yet been established, FOLFOX may be one of the choices.

Intestinal Protrusion by Parastomal Abdominal Rupture as a Late Complication Following Colostomy-A Case Report

人工肛門造設術後の後期合併症としては, 狭窄, 傍ストーマヘルニア, 腸脱出 (人工肛門からの翻転脱出) などがある. 今回, 傍ストーマの腹壁破裂により小腸脱出を認めた極めてまれな合併症を経験した. 症例は86歳の男性で, 1997年8月にイレウスに至ったS状結腸癌に対して緊急にてハルトマン手術を施行されていた. 再発や合併症なく外来通院中の2002年12月, 腹痛を主訴に本院救急受診した, 左側腹部のストーマに接した腹壁が破裂し小腸脱出および絞扼状態となっており, 緊急手術にて絞扼小腸切除および人工肛門再造設術を施行した. ストーマ近傍の創感染を合併したが, 保存的に軽快した. 今回のような傍ストーマの腹壁破裂により小腸脱出を認めた後期合併症は, 本邦での報告例がなく, また致命的になりうる合併症であるといえる.

A CASE OF INTUSSUSCEPTION CAUSED BY DIVERTICULUM WITH A BLEEDING POLYP

患者は36歳,男性.ヘマトクリット値が24.2%で強度の貧血のため平成13年10月24日下血を主訴に来院緊急入院した.緊急内視鏡検査,出血シンチ, Meckel憩室シンチ, CT,血管造影,小腸透視のいずれでも確定診断には至らなかった.そのため12月5日診断的開腹術を施行した.術中所見では回腸末端部より100cm口側部に存在したMeckel憩室が内翻し腸重積(小腸-小腸-小腸)を呈していた.憩室を切除し,内部を検索すると憩室より発生したと考えられるポリープを認めた.病理検査は炎症性ポリープであった.以上憩室内ポリープによる腸重積症という稀な1例を経験したので若干の文献的考察とともに報告する.

Clinicopathological Studies of Central Type of Cholangiocarcinoma Compared with Hilar Bile Duct Cancer.

胆管細胞癌中枢型肝切除例10例と肝門部胆管癌肝切除例13例を比較検討した.腫瘍の肉眼型は, 胆管細胞癌10例中9例では肝内に明らかな腫瘤を形成し周囲の肝実質に浸潤性に発育していたのに対し, 肝門部胆管癌では腫瘤形成よりも胆管壁に沿う浸潤が主体であった.腫瘍の体積は, 胆管細胞癌では肝門部胆管癌に比較して有意に大きかった.胆管細胞癌では, 肝門部胆管癌に比較して大血管浸潤のほかに肝胆道の周囲臓器への浸潤を高率に認めた.胆管細胞癌でも12, 13, 8番へのリンパ節転移, ly, v, pn (+) を肝門部胆管癌と同じく高率に認めた.ew (+) は両者とも80%以上の高率であり, 主にly, v, pnの存在によった.hw (+) は肝門部胆管癌で有意に高率であった.肝門部胆管癌の5年生存率は62.5%と良好であったが, 胆管細胞癌では3年生存率17.9%と不良であった.両者は同一の規約で検討されるべき多くの類似点を有しているが, 進展様式, 予後などに違いが認められた.

Therapeutic Efficacy of a Tumor-Infiltrating Lymphocyte Clone in Combination with Soluble Tumor-Specific Transplantation Antigen and Cyclophosphamide

Tumor-specific cytotoxic Tlymphocyte (CTL) clones were selected for therapeutic use from bulk cultures (BC) of tumor-infiltrating lymphocytes (TILs) derived from the methylcholanthrene(MCA)-induced fibrosarcoma in C3H/He mice. The adoptive transfer of a tumor-specific TIL clone named CTL-8 (lxlO7 cells, intravenously on days 7 and 14) was combined in an immunotherapy model in which hosts bearing 4-day established MCA-F tumors were treated with weekly subcutaneous injections of isoelectrophoretically purified 1-butanol-extracted tumor-specific transplantation antigen (TSTA, lμg) and intraperitoneal injections of low-dose cyclophosphamide (CY, 20mg/kg, days 4 and 11). This regimen (TSTA/CY+CTL-8) inhibited outgrowth of tumors more significantly than TSTA/CY treatment and greatly prolonged host survival. The effectors of TSTA/CY+CTL-8 bore Lyt2+ as well as L3T4+ in spleens of tumor bearing hosts, although the TSTA/CY regimen induced activated L3T4+ cells alone.

Influence of pre-operative irradiation and surgical interviention for immunity of esophageal cancer patients. A study of lymphocytes and T cell subsets.

食道癌に対する術前照射が宿主の免疫能, とくに外科手術後の免疫能に与える影響を解析し, 術前照射を併用する場合の問題点を明らかにした. 1期的に切除しえた食道癌15例を対象とし, 照射前後, 手術前後にin vitroで細胞性免疫能の検査を行った. 術前照射群は, 照射によって総リンパ球数は1,000/mm3以下となり, この低下は手術後30日を経過しても改善されなかった. T cellサブセットでは, OKT4の低下が著明で, この低下はhelper T cellに起因しており, 手術後30日を経過しても改善されておらず, 手術単独群と比べて有意に低下していた (p<0. 001).宿主免疫能の立場からは, 食道癌に対する術前照射はマイナスの因子と考えられた.