Search

To study the hemodynamics in the lower extremities before and after opera tions, ankle blood pressure and muscle blood flow in exercise testing were measured in 19 patients with chronic obstructive arterial disease and a chief complaint of intermittent claudication. The ankle and brachial pressures were measured before and just after exercise and the ankle pressure index (API) was obtained. The muscle blood flow was measured by 133Xe clearance method at thigh and calf. Arterial reconstruction was performed in 19 lower extremities of 17 patients and the claudication disappeared in all. The API of the revascularized lower extremities improved as much as the API of the nonclaudicatory lower extremities. The muscle blood flow during exercise of these extremities increased markedly in the calf after operation. The API and muscle blood flow in exercise testing increased in 2 lower extremities of a patient who received PGE 1 intraarter ial infusions but not significantly. However, the API and muscle blood flow did not change in 1 lower extremity after lumbar sympathectomy.

The greater omentum has specific properties to exhibit a potent protective function against infection and easily to reach the outside of the abdominal cavity with its high movability. In the treatment of postoperative infected focus in thoracic surgery, we tried omental pedicle flap method in 7 consecutive patients. Four of them had empyema with bronchopleural fistula and three had infected median sternotomy wound. Although one patient who suffered from bronchopleural fistula after right lower lobectomy died of contralateral pueumonia in spite of omental pedicle flap closure method, the remaining 6 cases obtained primary cure. We think this series demonstrates the value of omental pedicle flap method which lacks in symptoms due to defected organ and offers an excellent therapeutic effect with easy operative procedure. Further active application of this method can be expected in the management of chest problems.

We developed a new ultrasonically activated device (USAD) for endoscopic surgery. The current investigation was conducted to evaluate the security of the arteries occluded and divided by this USAD.The intraperitoneal arteries of anesthetized living pigs were individually occluded by the USAD at power levels of 70% or 100%. The burst pressures of the harvested arteries were measured in vitro. For comparison, arteries occluded by laparoscopic clips or silk ligatures were evaluated in the same manner.The pressures to burst the occluded artery ranged from 353 to 2,148 mmHg with an average of 1,204 mmHg in the USAD group at 70% power level; from 324 to 2,207 mmHg with an average of 1,193 mmHg in the USAD group at 100% power level; from 794 to 1,868 mmHg with an average of 1,421 mmHg in the clip group; and from 618 to 3,207 mmHg with an average of 1,586 mmHg in the silk ligature group.The data suggest the improbability that small- to medium-size arteries appropriately occluded and divided by the USAD can burst when exposed to intravascular pressures commonly found in living animals.

To determine a new taxane plus platinum treatment regimen for squamous cell carcinoma of the uterine cervix (CSCC), a phase I feasibility study of docetaxel (DTX) plus nedaplatin (CDGP) combination therapy was conducted.Twenty consecutive patients were enrolled into the study. The starting dose of DTX/CDGP was 60 mg/m2 / 80 mg/m2, every 4 weeks for at least three courses and the dose was escalated to 70 mg/m2 / 100 mg/m2. DTX 60 mg/m2 / CDGP 100 mg/m2 was also evaluated as an extra dose level.Dose-limiting toxicity was granulocytopenia and the maximum tolerated dose was determined as 70 mg/m2 / 100 mg/m2. All 20 patients had measurable disease and a partial response was achieved in 8 (40.0%) patients.DTX/CDGP therapy appears to be a tolerable regimen for cervical squamous cell carcinoma, even in patients previously treated by cisplatin concurrent chemoradiotherapy. The recommended doses of DTX and CDGP were determined to be 60 mg/m2 and 100 mg/m2, respectively.

Bronchoplastic procedures were used in 104 patients with various bronchial disorders. Ten had benign lesions and 94, malignant tumors. The principal operative procedures were sleeve lobectomy and sleeve pneumonectomy for bronchogenic carcinoma, but 11 limited bronchial resections were performed in patients with benign lesions, minute bronchogenic carcinomas, and low-grade malignant tumors. Of the 94 patients with malignant tumors, 79 underwent a bronchoplastic procedure without carinal resection (sleeve lobectomy in 75 and limited bronchial resection in 4), and there was one operative death (1.3%). The overall 5-year survival rate for the patients with bronchogenic carcinoma in this group was 45% and that for patients undergoing curative resection, 57% (survival of patients in stages I, II, and IIIA was 79%, 55%, and 30%, respectively). A bronchoplastic procedure with carinal resection was performed in 15 patients. Twelve in this group underwent sleeve pneumonectomy. There were two operative deaths, and 1 patient has survived for longer than 4 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and are still alive. We believe that bronchoplasty is a safe and valuable procedure and that limited bronchial resection appears to be the procedure of choice for localized bronchial lesions.

We have studied the immunological status of patients treated with streptococcal preparation OK-432. Two KE of OK-432 was injected intramuscularly once every week for more than three years unless the patients died. The natural killer (NK) activity in those patients who underwent curative surgery for lung cancer and had no sign of recurrence was significantly increased (P less than 0.01) during the OK-432 treatment. However, the NK activity in the patients who had persistent disease (non-resected cases, incompletely resected cases or recurrent cases) was not significantly increased in comparison with that before the immunotherapy. Also, in the cases with no clinical symptoms of recurrence, both the lymphoblastogenetic reactions to the mitogens and the IL-2 production were significantly enhanced (P less than 0.01) during the administration of OK-432. Reactions in the SU-PS (polysaccharide taken from the cell-wall fraction of the Streptococcus pyogenes SU strain and containing 7.2% of protein) skin-test appeared to significantly correlate with the immunological status of the patients under OK-432 therapy, but the PHA and PPD skin reactions showed no definitive enhancement. The survival rate of the patients whose SU-PS skin tests were positive during the OK-432 immunotherapy was significantly higher (P less than 0.01) than that of the patients with negative reactions.

The location, frequency, and spread of metastases to the mediastinal lymph nodes were examined in 124 patients with histologically proven N2 disease who underwent pulmonary resection and total lymph node resection. There were one-level metastases in 47 percent of cases, two-level metastases in 29 percent, three-level in 12 percent, and 12 percent had four or more levels of metastases. Nodal metastases to the lower mediastinum from upper lobe cancer were frequently observed as were metastases of lower lobe cancer to the upper mediastinum. The frequency of the latter was higher than that of the former. About one third of squamous cell carcinoma and adenocarcinoma in the right upper lobe produced nodal metastases in the lower mediastinum. In addition, there were often skip metastases to the nonregional parts of the mediastinum without regional nodal involvement in the mediastinum. From the results of the present study, it appears that extensive mediastinal dissection should be recommended in surgery for lung cancer irrespective of the location of the primary tumor.

基礎となる血液疾患を認めず, 後縦隔に腫瘤を形成した髄外造血の1例を経験した.症例は60歳の男性, 検診にて胸部異常陰影を指摘され精査の結果, 右後縦隔腫瘍と診断され手術を施行した.摘出された腫瘍は球状, 直径3cm暗赤色, 弾性硬であった.病理組織学的に髄外造血腫瘍と診断された。術後, 背景となる血液疾患の存在を疑い精査施行したが, 異常を認めなかった.

腫瘍径3cm以下の末梢肺野型肺癌手術例52例を対象としてcomputedradiographyと通常のフィルム法による胸部X線写真とを対比検討した. Plain CRでは縦隔側肺野に位置する例や辺縁が鋭利な結節影で評価が優れていた. 又エネルギーサブトラクション軟部画像をplainCRに付加する事で11例 (21%) に陰影の描出が改善された. 一方淡い濃度の浸潤影を呈する結節影でCRが劣る例がみられた.

過去11年間に経験した肺門部早期癌21例と, 準早期癌 (気管支壁外に僅かに浸潤しているもの) 8例について, 臨床的背景因子を検討した. 7例は, 肺癌集団検診での喀痰細胞診にて発見され, 他の22例は自覚症状 (血痰・喀血: 12, 咳噺: 5, 発熱: 3ほか) で受診し, いずれも気管支鏡検査にて確定診断されている. 非喫煙者が3例みられた. 胸部単純X線写真像にて異常所見を示したのは9例のみであった.

Gemcitabine has been recommended as an active agent for salvage chemotherapy in patients with recurrent epithelial ovarian cancer, but no clinical study of this agent has been conducted for Japanese women with ovarian cancer. To evaluate the efficacy and feasibility of gemcitabine for heavily pretreated Japanese patients with recurrent epithelial ovarian cancer, we conducted a single-institute phase II clinical trial.All patients had received a minimum of two previous chemotherapy regimens, In this study, gemcitabine was administered at 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle.A total of 28 patients participated in this study. Although 5 patients (17.9%) needed dose reduction to 800 mg/m(2) because of thrombocytopenia and granulocytopenia, all patients completed an average of 6.7 courses (range, 2-24 courses). The overall response rate, including five partial responses, was 17.9% (95% confidence interval [C I], 6.0-36.9). The median time to progression was 8.8 months and the median survival period was 11.2 months. Grade 3/4 hematological toxicities included leucopenia, 35.7%; granulocytopenia, 39.3%; anemia, 46.4%; and thrombocytopenia, 10.7%. However, no grade 3/4 nonhematological toxicity was observed. The mean delay in treatment was 5.0 +/- 7.7 days (range, 0-15 days) in a total of 562 cycles.Single-agent gemcitabine is an effective salvage chemotherapy regimen in heavily pretreated Japanese patients with recurrent epithelial ovarian cancer.

Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo is not well understood.hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR).No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p0.001) in partially responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p = 0.059) in tumors treated with four or more courses of Pt-chemo.A change in hMLH1 MET is a major molecular cause of acquired resistance to Pt-chemo in EOC.

5591 Background: The benefit of cytoreductive surgery for uterine carcinosarcoma (CS) is unknown. The objective of this study was to assess the impact of optimal debulking surgery on survival of ad...

Summary. We performed aorto-bifemoral bypass by mini-laparotomy for an 80-year-old patient complaining of intermittent claudication. Angiography revealed multiple stenosis of the bilateral iliac arteries. Computed tomography did not demonstrate any calcification of the lower abdominal aorta. For mini-laparotomy, a 7 cm medial skin incision and bilateral 3 cm inguinal skin incisions were made. After the retroperitoneum was incised, an aorto-bilateral femoral artery bypass route was created by blunt finger dissection. Aorto-bifemoral artery bypass grafting was easily performed in a routine fashion. The patient did not complain of severe post-operative wound pain, and could eat on the 2nd post-operative day. We recommend this method of mini-laparotomy for distal anastomosis involving the common femoral artery in the selected cases with no advanced atherosclerotic changes at the proximal anastomosis site.

Ovarian clear-cell carcinoma (OCC) is known to have a poor prognosis and selected genetic features of OCC remain unknown. We investigated microsatellite instability (MSI) and the expression of the DNA mismatch repair-related protein, p53.MSI was examined by polymerase chain reaction using mono-, di-, tri- and tetranucleotide repeat markers, and hMSH2, hMLH1, hMSH6, MSH3 and p53 were determined immunohistochemically in 24 cases of OCC.A total of 9 (37.5%) cases exhibited MSI. Two cases (8.3%) exhibited MSI-H in mononucleotide repeat loci with the negative expression of hMLH1, while another 7 cases (29.2%) exhibited selected trinucloetide repeat MSI (MSI-TR). Of these MSI-TR cases, 4 cases (57.1%) were determined to be negative for MSH3, while hMSH2, hMSH6, MSH3 and p53 expressions were normal.Our findings suggest that MSI-TR would be a feature indicating the microsatellite status in OCC, and that the loss of MSH3 expression may promote MSI-TR.

Objective Indications for surgical intervention for very limited small cell lung cancer have not yet been determined. The objective of this study is to determine whether resection followed by cisplatin and etoposide is feasible. Methods From September 1991 through December 1996, 62 patients with completely resected small cell lung cancer who were less than 76 years of age from 17 centers were entered in the trial. Of 62 patients, 61 were eligible, with a median follow-up of 65 months. Chemotherapy consisted of 4 cycles of cisplatin (100 mg/m 2 , day 1) and etoposide (100 mg/m 2 , days 1–3). There were 49 (80%) male patients, 44 with clinical stage I disease, 10 with stage II disease, and 6 with stage IIIa disease. Results Forty-two (69%) patients received 4 cycles of cisplatin and etoposide. No treatment-associated mortality was noted. Median survival time was not reached in patients with pathologic stage I disease, was 449 days in patients with stage II disease, and was 712 days in patients with stage IIIa disease. Three-year survival was 61% overall, 68% in patients with clinical stage I disease, 56% in patients with stage II disease, and 13% in patients with stage IIIa disease ( P = .02). Recurrence was noted in 26 (43%) patients overall. Local failure was noted in 6 (10%) patients. Locoregional recurrence tends to be found more frequently in patients with stage IIIA disease. Distant failure was found in 21 (34%) patients overall. Brain metastasis was found in 15% of the patients. Conclusion Major lung resection followed by postoperative cisplatin and etoposide is feasible, with a favorable survival profile. Because nodal metastasis appears to be a major prognostic factor, preoperative evaluation of nodal status remains a major concern.

Doxorubicin, irinotecan and etoposide are all associated with the debilitating side-effects of nausea and vomiting, thereby necessitating concomitant antiemetic therapy. However, this may increase the potential for drug-drug interactions by inhibition or induction of the cytochrome P450 enzymes. A study was undertaken to investigate the effects of the 5-HT(3) -receptor antagonist granisetron on the metabolism of doxorubicin, irinotecan and etoposide in vitro in human liver microsomal preparations.Doxorubicin, 20 microM, irinotecan, 10 microM, and etoposide, 50 microM, were incubated in the presence of granisetron, 0 nM, 20 nM, 200 nM and 2000 nM, in human liver microsomal preparations (250 microg). The levels of unchanged doxorubicin, irinotecan and etoposide in the incubation mixture were determined by high-performance liquid chromatography. Positive controls were ketoconazole, 20 microM, a potent inhibitor of CYP3A metabolism, for irinotecan and etoposide and quercitrin, 2 mM, a potent inhibitor of aldo-keto reductase, for doxorubicin.In the absence of granisetron, unchanged doxorubicin, irinotecan and etoposide levels decreased by 34.2 +/- 5.5%, 21.3 +/- 2.9% and 13.4 +/- 1.6% of control, respectively. Ketoconazole prevented the breakdown of both irinotecan and etoposide, while quercitrin inhibited the breakdown of doxorubicin. Granisetron had no effect on the rate of reduction of doxorubicin, irinotecan or etoposide.The results from this study suggest that granisetron neither inhibits nor induces the enzymes involved in the metabolism of doxorubicin, irinotecan or etoposide. Thus, granisetron can be used safely to treat nausea and vomiting induced by these agents with minimal risk of drug-drug interactions.

We studied the cytotoxic effects of various DNA replication inhibitors on MMR-deficient and -proficient colon carcinoma cell lines. DNA polymerase (pol) inhibitors including aphidicolin and gemcitabine, and hydroxyurea were more toxic (1.7 to 2.8-fold) to hMLH1-deficient HCT116 than to hMLH1-proficient HCT116+ch3. Similarly, pol inhibitors were more toxic to hMSH2-deficient LoVo than to hMSH2-proficient LoVo+ch2. In contrast, DNA topoisomerase I inhibitors, such as CPT-11, SN-38, and topotecan, were more toxic to MMR-proficient cells. Our results suggest that MMR-deficient colon carcinoma cells are hypersensitive to inhibitors of the pol reaction.

Objective Although paclitaxel and carboplatin therapy (TC) is an established effective standard regimen for patients with ovarian cancer, both treatment delay for hematologic toxicity and discontinuation of treatment due to neurotoxicity have occasionally been reported. To achieve therapeutic density, we evaluated the usefulness of weekly low-dose TC therapy (WTC) in patients with platinum-sensitive (median PFI was 11.4 ± 2.7 months) recurrent epithelial ovarian cancer. Methods A total of 25 patients were treated with paclitaxel at 60 mg/m 2 and carboplatin at AUC=2 using 3 weekly courses with a 1-week break schedule. Eighteen patients had assessable tumors for response, and the other seven patients were evaluated by CA-125-based response. All of the patients were assessable for toxicity. Results The overall response rate (OR) based on WHO criteria was 84.2% (95% CI; 0.65–0.98), including nine complete responses (CR); OR based on CA-125 was 85.7% (95% CI; 0.42–0.99), including 3 CR. The total response rate was 88.0% (95% C.I.; 0.68–0.97). The median progression-free survival of the patients was 13.5 months during the mean follow-up period of 21.9 ± 9.2 months. No patients had grade 1 or higher thrombocytopenia, and although 44% of the patients developed neurotoxicity, all cases remained grade 1. Treatment delay of over 7 days due to toxicity was observed in only two patients (16.0%) and in six cycles (1.3%) in a total of 451 cycles. Conclusion WTC combination, as used in this study, produced a high response rate with acceptable toxicity, and the optimal combination in a weekly regimen remains to be determined.

The international tumor-node-metastasis (TNM) staging system is the "international language" in cancer diagnosis and treatment. Six revisions of the TNM staging system for lung cancer have been repeated over the past 35 years after the beginning of UICC-TNM classification in 1968. The 1997 revision for lung cancer has undergone an extensive correction for many deficiencies of the old staging system. As a result, the new staging system appears to be a great improvement over previous editions. There are, however, still some controversies and proposals for revising, even when the new staging system is applied in daily diagnoses and treatment for lung cancer. In the present paper, these problems are presented and discussed. Main subjects for discussions are as follows: (1). Since the 2nd revision, T1 and T2 lesions were divided at the border of a 3 cm tumor size. Is 3 cm diameter an appropriate cut-off point for dividing T1 and T2 lesions? (2). Is it valid to subdivide T1 and T2 lesions into each A and B? (3). Is it appropriate to down-stage all of T3N0M0 to stage IIB, because there exists heterogeneity of T3? (4). Definitions of T4 lesion. (5). Controversies in three kinds of lymph node maps. Especially, where there is a boundary between N1 and N2 station in each map? (6) How to classify separate tumor nodules (STN) in the same lobe, and in the non-primary lobe. (7) Controversy exists concerning the validity of present stage grouping, because there are no significant difference of survivals between IB and IIA, IIA and IIB in most reports and also between T3N0M0 and T3N1M0 in some reports.

Discards of bycatch in fisheries is one of the most serious concerns in fisheries management. The types of discarded fish from Japanese fisheries can be mainly classified into four categories: 1) species with low value or no value in the market, 2) small sized species including young or juvenile, even if they have commercial values as adult, 3) species with substantially lower values in the market taken by fisheries targeting on highly valuable species such as tuna longline, and 4) species whose sales in the market are prohibited by the government and poisonous fish. Some methods to decrease the discarded fish are proposed: 1) effective utilization of bycatch species, 2) release to the sea in alive immediately after catch and 3) improvement on gears to avoid bycatch fishes. The improvement of utility value for the bycatch fish is considered to be the most effective solution on this issue. Preparing the circumstances to make the fishermen bring back the less value fishes without discards and the action to raise the value of the discard fish are most required at present.

Ischemic colitis occurs when the blood supply to descending and sigmoid colons is impaired as a result of surgery for abdominal aortic aneurysms. Selective and routine reimplantation of the inferior mesenteric artery was assessed to clarify which was more effective in preventing this complication. Fifty patients who underwent surgery for non-ruptured abdominal aortic aneurysms over a 5-year period were reviewed. Four patients who had occluded inferior mesenteric artery were excluded from comparison. In 27 patients operated in the first half of the period, stamp pressure of the inferior mesenteric artery was measured, and arterial blood flow was detected in the mesocolon with a Doppler ultrasonic flowmeter. Nine patients with impaired blood flow underwent reimplantation of the inferior mesenteric artery. The inferior mesenteric artery of all 19 patients operated in the second half was reimplanted. Operative blood loss, operation time, and postoperative course were compared in the selective and routine reimplantation gruops. There were no significant differences between the two groups in distribution by age, sex, incidence of previous laparotomy, or preservation of both internal iliac arteries. Operative blood loss and operation time did not increase significantly after routine reimplantation of the inferior mesenteric artery was begun. Ischemic colitis was not observed in either group. Comparison of the postoperative course in the two groups showed no significant difference in the time required to resume oral feeding or in the number of days from operation to discharge. Further studies are recommended, comparing selective and routine reimplantation of the inferior mesenteric artery.

Serous, mucinous, endometrioid, and clear cell adenocarcinomas arise from reproductive organs of mullerian origin. Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of endometrioid adenocarcinomas of the endometrium and ovary, the role of PTEN alteration in endometrioid adenocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma, and in particular to examine the potential role of PTEN mutation in endometrioid-type cancer of the cervix, we analyzed 32 cervical adeno- or adenosquamous carcinomas (8 endometrioid adenocarcinomas, 14 mucinous adenocarcinomas and 10 adenosquamous carcinomas) for PTEN mutations and HPV infections. PTEN mutation was detected in 2 of 8 (25.0%) endometrioid cases, 2 of 14 (14.3%) mucinous cases, and none of 10 (0%) adenosquamous cases. HPV DNA was detected in 11 out of 18 (61.1%) PTEN wild-type adenocarcinomas and 8 out of 10 (80.0%) adenosquamous carcinomas. Among 11 HPV-negative adenocarcinomas, 40.0% (2/5) endometrioid cases and 33.3% (2/6) mucinous cases were shown to be PTEN mutated, while no cases (0/21) were PTEN-mutant in the remainder (i.e. adenosquamous carcinomas and HPV-positive adenocarcinomas). The current observations suggest that PTEN mutation is frequently detected in HPV-negative adenocarcinomas of the cervix and the most prevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endometrial and ovarian carcinomas.

Background Bestatin is a potent aminopeptidase inhibitor that has immunostimulant and antitumor activity. We conducted a prospective randomized, double-blind, placebo-controlled trial to determine whether postoperative adjuvant treatment with bestatin could prolong the survival of patients with completely resected stage I squamous-cell lung carcinoma. Methods Patients with confirmed, resected stage I squamous-cell lung carcinoma were randomly assigned to receive either bestatin (30 mg) or placebo daily by mouth for 2 years. We assessed whether bestatin treatment was associated with overall survival and 5-year cancer-free survival and assessed its safety. All statistical tests were two-sided. Results From July 8, 1992, through March 30, 1995, 402 patients were entered in the study, 202 in the bestatin group and 198 in the placebo group. The median follow-up for surviving patients was 76 months (range = 58-92 months). The 5-year overall survival was 81% in the bestatin group and 74% in the placebo group for a difference of 7% (95% confidence interval [CI] = -1.4% to 15.0%). The 5-year cancer-free survival was 71% in the bestatin group and 62% in the placebo group for a difference of 9% (95% CI = -0.7% to 17.8%). Overall survival (P =.033, log-rank test) and cancer-free survival (P =.017, log-rank test) were statistically significantly different by Kaplan-Meier analysis. Few adverse events were observed in either group. Conclusions Survival was statistically significantly better for patients with completely resected stage I squamous-cell lung carcinoma who were treated with bestatin as a postoperative adjuvant therapy than for those who received a placebo. This result requires confirmation in other phase III trials.

PURPOSE Paclitaxel and docetaxel are effective anticancer agents; however, these agents can be associated with the debilitating side effects of nausea and vomiting, thereby necessitatingthe administration of concomitant antiemetic agents. This increases the potential fordrug-drug interactionsthrough inhibition or induction of the cytochrome P450 (CYP) enzymes. The 5-HT3-receptor antagonists are currently regarded as the antiemetic 'gold standard' and this study was undertaken to investigate the effects of granisetron on the metabolism of paclitaxel and docetaxel in human liver microsomal preparations in vitro. METHODS Paclitaxel, 5 nM, and docetaxel, 1.25 nM, were incubated in the presence of granisetron, 0, 10, 100, and 1000 pM, in human liver microsomal preparations (500 microg). The levels of unchanged paclitaxel and docetaxel in the incubation mixture were determined by high-performance liquid chromatography. Ketoconazole, 10 nM, a potent inhibitor of CYP3A metabolism, served as a positive control. RESULTS In the absence of granisetron, unchanged paclitaxel and docetaxel levels measured were 27.2 +/- 2.8% and 44.3 +/- 4.0% of control, respectively. Ketoconazole prevented the breakdown of both paclitaxel and docetaxel, to the degree that no unchanged paclitaxel or docetaxel was detected in the incubation mixture. Granisetron had no effect on the rate of reduction of either paclitaxel or docetaxel; unchanged paclitaxel and docetaxel decreased to 25.0 +/- 1.5%, 26.4 +/- 1.0%, and 27.6 +/- 6.4%, and 44.2 +/- 1.5%, 41.2 +/- 4.1%, and 43.1 +/- 0.5%, respectively. DISCUSSION The results from this study suggest that granisetron neither inhibits nor induces the enzymes involved in the metabolism of paclitaxel or docetaxel. Thus, granisetron can be used safely as a supportive care agent to treat paclitaxel or docetaxel chemotherapy-induced nausea and vomiting with minimal risk of drug-drug interactions.

Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC.A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen.Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism.

We report 2 patients with Herlyn-Werner-Wunderlich syndrome, 1 with advanced endometrioid adenocarcinoma of the semiobstructed side of the uterine cervix and 1 with primary clear cell carcinoma of the obstructed side of the upper vagina.

We report a patient with coronary artery steal after gastroepiploic artery grafting to the right coronary artery. The coronary artery steal syndrome involves reversed flow in the gastroepiploic artery, which siphons blood from the heart and results in myocardial ischemia.

Bronchogenic cancer in the pediatric age group is extremely rare and less than 100 cases have been reported in the world literature. We report a 13-year-old girl with simultaneous occurrence of lung adenocarcinoma and osteosarcoma. The patient was admitted with lower leg pain, and an abnormal shadow in the right fibula was noted on X-ray examination. Further examination of the fibular lesion including tumor biopsy revealed an osteosarcoma. Following completion of the first course of preoperative chemotherapy, multiple lung shadows were found on chest X-ray films. After five courses of preoperative chemotherapy, however, all lung shadows except one in the right lower lobe disappeared. The fibular tumor was then resected. Postoperatively, an additional six courses of chemotherapy was given. However, the lung shadow in the right lower lobe was still present. Exploratory thoracotomy was performed. Pathologically, the lung tumor measured 0.8 cm in diameter with an ill-defined border, and histological examination revealed a well differentiated papillary adenocarcinoma. To our knowledge, only a few cases of pediatric lung cancers have been reported to be associated with congenital cystic malformation of the lung. However, this combination of pediatric lung adenocarcinoma and osteosarcoma has not been previously reported.

We investigated the role of hemoglobin level in chemoradiation therapy for patients with advanced cervical cancer by reviewing the literature for current therapeutic information. We found that anemia during chemoradiation therapy is an important physiological factor in determining the long-term prognosis of patients with advanced cervical cancer.

Roentgenographically occult lung cancers (ROLCs) are rare but are usually curable if they are properly diagnosed and treated. Between 1977 and 2000, we treated 51 patients with early hilar lung cancer (as defined by the Japan Lung Cancer Society) of ROLC form. If the occurrence of cancer is confined to segmental bronchi, we preserve the lung tissue as far as possible by using a sleeve segmentectomy. Eight of the 51 patients underwent sleeve segmentectomy. All 8 of these patients were men who were heavy smokers and had a mean age of 64.9 years (range, 59-74 years). The cancerous locations were R-B6 in 4 patients, L-B(1+2+3) in 2 patients, L-B(4+5) in 1 patient, and L-B6 in 1 patient. Two patients had double cancers (synchronous in one case and metachronous in the other). All 8 of the patients had squamous cell carcinoma, 3 of whose lesions were carcinoma in situ. The segments resected were R-S(6) in 3 patients, L-S(1+2+3) in 2 patients, L-S(4+5) in 1 patient, L-S(6) in 1 patient, and R-S6 combined with the middle lobe in 1 patient. There were no cases of morbidity or mortality. However, 1 patient who had undergone a left lower lobectomy for synchronous advanced squamous cell carcinoma 4 months before R-S(6) sleeve segmentectomy for contralateral early hilar lung cancer died of recurrence in the mediastinal lymph nodes 63 months after the first operation. Two patients died of other causes: one of pneumonia 61 months after L-S(4+5) sleeve segmentectomy and the other of myelopathy 36 months after L-S(1+2+3) sleeve segmentectomy. The remaining 5 patients are alive and well 178, 121, 109, 94, and 14 months after surgery. Sleeve segmentectomy is a curative operation for early stage squamous cell carcinoma of the segmental bronchus that preserves pulmonary function and should be used to treat patients carefully selected for the correct indications.

BACKGROUND: Primary vaginal clear cell carcinoma occurs in young women exposed to diethylstilbestrol (DES) in utero. Primary vaginal clear cell carcinoma not associated with DES is very rare. We report the clinicopathologic and cytopathologic features of a patient with advanced, sporadic primary vaginal clear cell carcinoma with metastases to liver, lung and paraaortic lymph nodes. CASE: A postmenopausal, 63-year-old woman presented to our department with genital bleeding. A hemorrhagic tumor found in the vagina was diagnosed as a clear cell carcinoma by cytopathologic examination of the tumor smear and by histopathologic examination of a biopsy specimen. A chest radiograph revealed multiple lung metastases, and metastases to the liver and paraaortic lymph nodes were noted on computed tomography and magnetic resonance imaging. The tumor was diagnosed as primary clear cell carcinoma of the vagina, stage IV b (FIGO) based on a normal cytopathologic examination of the cervix, endometrium and ascites; normal appearance of the uterus, ovaries and kidneys on magnetic resonance imaging; and absence of detectable tumor in the urinary tract. The patient died of respiratory failure 31 days after hospitalization. The tumor demonstrated over-expression of p53 protein and did not show microsatellite instability. CONCLUSION: This patient was the second reported Japanese woman with advanced primary vaginal clear cell carcinoma not associated with DES.

Remodeled great saphenous vein grafts were used to reconstruct both jugular and portal veins. The great saphenous vein was split longitudinally and sutured side-to-side to construct a vessel twice the diameter and one half the length of the original vessel. This graft was used with good results for reconstruction of the jugular veins in a patient after a bilateral neck dissection for tongue cancer and for a portal vein in a patient after resection for cancer in the head of the pancreas.

Composite reconstruction of the esophagus using both the mobilized stomach and free jejunal graft is described. Tension at the anastomotic site can be minimized with interposition of a jejunal autograft between the pharyngeal stump and the mobilized stomach, even when the mobilized stomach is not long enough. Furthermore, problems derived from differing calibers of the pharyngeal stump and the mobilized stomach can be resolved by creating an end-to-side pharyngojejunal anastomosis. Our method is proposed as one procedure for reconstruction of the esophagus when the pull-up organ is too short. © 1993 Wiley-Liss, Inc.

Objective: We retrospectively reviewed nodal status of the patients with peripheral small-sized lung cancer grouped by cell type and tumor size to evaluate the necessity of systematic nodal dissection in this group of patients. Methods: From 1973 to 1998, 1713 patients underwent pulmonary resection for primary lung cancer in Kanazawa University. Among them, 225 patients (13.1%) with peripheral smallsized (2 cm or less) lung cancer underwent lobectomy and systematic nodal dissection were retrospectively reviewed. The maximum diameter of the tumor was measured on formalin-fixed surgical specimens. Results: The histological types were adenocarcinoma in 170 (75.6%), squamous cell carcinoma in 20 (8.9%), small cell carcinoma in 19 (8.4%) and others in 16 (7.1%). Among 170 adenocarcinoma patients, 38 (22.4%) showed hilar or mediastinal lymph node metastases. No mediastinal lymph node metastasis was encountered in all squamous cell carcinoma (n ¼ 20), adenocarcinoma # 1c m ( n ¼ 16), small cell carcinoma # 1c m ( n ¼ 4), and adenocarcinoma of Noguchi’s classification type A or B (n ¼ 24). Conclusions: Mediastinal nodal dissection would be unnecessary in the patients with peripheral small-sized lung cancer fulfilling these criteria: (1) squamous cell carcinoma # 2 cm; (2) adenocarcinoma # 1 cm; (3) localized bronchioloalveolar carcinoma # 2 cm without foci of active fibroblastic proliferation in histology (Noguchi’s classification type A or B adenocarcinoma); (4) small cell carcinoma # 1 cm. Candidates fulfilling above criteria were 28.4% (64/225) of small-sized lung cancer and 10.9% of stage IA patients. The establishment of a universally accepted therapeutic strategy for small-sized lung cancer is indispensable in the clinical spread of various sort of limited resections. q 2001 Elsevier Science B.V. All rights reserved.

Background: The number of N2 stations (single vs multiple N2 stations) is an important prognostic factor in patients with completely resected stage IIIA-N2 non–small cell lung cancer. However, the significance of both the N2 station(s) actually involved and the primary tumor location remains unclear. Methods: The database was built with the use of a questionnaire survey on the survival of patients with pathologic stage IIIA-N2 non–small cell lung cancer completely resected between January 1992 and December 1993. The survey was performed by the Japan Clinical Oncology Group as of July 1999. The data include information on the survival and N2 stations of 402 patients. Results: A frequently metastasized single N2 station was the lower pretracheal station in primary tumors in the right upper lobe, the subaortic station in the left upper lobe, and the subcarinal station in the right middle or lower lobe and the left lower lobe. In multiple N2 stations, the frequency of metastasis of the N2 station observed in a single N2 station was as high as 72% to 89%, and one or two other frequently metastasized stations were added to each group. Regarding the survival of patients with a primary tumor in each lobe except for the left lower lobe, a single N2 station resulted in a significantly better survival than did multiple N2 stations. Furthermore, the overall survivals classified according to each primary site showed a significant difference among the four primary sites ( P =.04). Conclusions: The primary tumors in each lobe showed a prevalence of N2 station(s). The number of N2 stations is a good prognosticator except in patients with a primary tumor in the left lower lobe. In addition, the site of a primary tumor itself is also considered to influence the survival of the patients.

Background: the group of completely resected stage IIIA-N2 non-small cell lung cancer patients (NSCLC) is considered to be heterogenous in various aspects including survival and the recurrent pattern. In the present study, we attempted to clarify the factors which separate these patients into high and low risk groups based on the survival and local recurrence. Methods: a questionnaire survey on the survival and local recurrence of non-small cell lung cancer patients with pathological stage IIIA-N2 disease who underwent a complete resection from January 1992 to December 1993 was performed by the Japan Clinical Oncology Group as of July 1999. The information on the survival of 406 patients and that of local recurrence in 332 of them was available. Results: the 5-year survival of the 406 patients was 31.0%. In a univariate analysis, the age, clinical and pathological T status, number of N2 stations, pathological N1 disease, operative modality and postoperative radiotherapy were all found to be important prognostic factors. Clinical N2 disease marginally influenced the survival (P=0.07). In a multivariate analysis of these variables including clinical N2 disease, the survival was significantly worse in the case of multiple N2 stations (hazard ratio=1.741), the presence of pathological N1 disease (1.403), pathological T2 or 3 disease (1.399) and an age older than 65 (1.327). The rate of freedom from any local recurrence at the bronchial stump, or in the hilar, mediastinal or supraclavicular lymph nodes at 5 years was 64%. In a univariate analysis of the freedom from local recurrence, the clinical N status, pathological T status, pathological N1 disease and number of N2 stations were all found to be important prognostic factors. A multivariate analysis revealed the freedom from local recurrence to be adversely influenced by multiple N2 stations (hazard ratio=2.05), and the presence of either clinical N1 or 2 (1.733) disease. The 5-year survival and the rate of freedom from local recurrence at 5 years were 43 and 75% in patients with a single N2 station and 17 and 48% in those with multiple N2 stations, respectively. Conclusions: the number of N2 stations (single vs. multiple N2 stations) was found to be a useful prognostic factor, which can separate completely resected stage IIIA-N2 patients into high and low risk groups regarding both the overall survival and local recurrence.

We report herein the cases of two patients who underwent complete resection of a superior sulcus tumor (SST) plus adjuvant brachytherapy, with the area to be irradiated determined by a computer program system designed to minimize unnecessary irradiation to the normal components and to optimize the effect on the targeted area. Although the efficacy of brachytherapy on the inhibition of local relapse needs to be observed over a long period, the selective and alternative use of delivering adjuvant brachytherapy by this method appears to enhance the quality of life of patients with a SST.

Because it was still uncertain whether a stimulation of beta1-adrenoceptors accelerated alveolar fluid clearance in hyperoxic lung injury, the effect of denopamine, a selective beta1-adrenergic agonist, on alveolar fluid clearance was determined in rats exposed to 93% oxygen for 48 and 56 h. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue labeled albumin instilled into the alveolar spaces over 1 h at 37 degrees C in isolated rat lungs. The principle results were as follows: 1) Although lung water volume increased in rats exposed to hyperoxia for 48 and 56 h, basal alveolar fluid clearance did not change for up to 56 h; 2) Denopamine increased alveolar fluid clearance in rats exposed to hyperoxia as well as in rats without exposure to hyperoxia; 3) Denopamine primarily increased amiloride-insensitive alveolar fluid clearance in rats exposed to hyperoxia; 4) The potency of denopmaine was similar to that of terbutaline, a selective beta2-adrenergic agonist. In summary, denopamine is a potent stimulator of alveolar fluid clearance in rats exposed to hyperoxia.

Expression of autocrine motility factor receptor (AMFR) associates with increased cell migration and poor survival in certain types of human cancers. We assessed the possible correlation between AMFR, clinicopathologic features, and survival in stage I non-small cell lung cancer (NSCLC).AMFR expression was analyzed immunohistochemically, using a monoclonal antibody (3F3A) in tumor specimens from 97 patients with curative resection. Vascular endothelial growth factor (VEGF) expression was also examined after accounting for AMFR expression.Out of 97 tumors, 38 (39.2%) were positively stained with AMFR. The AMFR expression was significantly associated with histologic type of tumor, mainly in adenocarcinoma. Overall survival of patients with AMFR-positive tumors was significantly worse than that of AMFR-negative tumors (p = 0.0050). The AMFR expression appears to be associated with VEGF expression. Patients who were AMFR positive and had high VEGF expression had a worse prognosis compared with the AMFR-negative and low VEGF-expression group (p0.0001). Multivariate analysis revealed an independent prognostic impact of AMFR on survival (p = 0.0039).These results indicate that evaluation of AMFR expression may provide useful guidance in follow-up of patients with NSCLC.

The current status of the surgical treatment of patients with pleural diffuse mesothelioma in Japan was surveyed from the results of a questionnaire sent to members of The Japanese Association for Chest Surgery. Physicians at 57 institutions returned the questionnaire, and a total of 189 surgical cases of diffuse mesothelioma between 1987 and 1996 were analyzed. The age of the patients ranged between 18 and 80 years. They consisted of 154 males and 33 females (the gender of two patients was not indicated). By histological type, 104 cases had the epithelial type, 29 cases had the sarcomatous type, and 46 cases had the mixed type of diffuse mesothelioma (the histology of 10 patients was not indicated). As to the type of surgery, pleuropneumonectomy was performed in 116 cases (61%), and limited resection [including decortication (5 cases) and tumorectomy (68 cases)] was performed in 73 cases (39%). The goal of pleuropneumonectomy is radical resection of the tumor, which often requires combined resection of adjacent structures. The tumor was completely removed macroscopically in 84 (72%) of the 116 cases who underwent pleuropneumonectomy; however, among those with an epithelial-type tumor that was completely removed by pleuropneumonectomy, the tumor recurred postoperatively in 43% of these patients. Perioperative adjuvant therapy was performed in 83 of the 116 patients who underwent pleuropneumonectomy. The 2-year and 5-year survival rates of those who had undergone pleuropneumonectomy were 29.7 and 9.1%, respectively, and the perioperative mortality rate of this procedure was 6%. Limited resection, on the other hand, did not involve radical resection of the tumor. The 2-year and 5-year survival rates of the patients who had undergone limited resection were 26.1 and 9.5%, respectively, and the perioperative mortality rate was 6%. The survival rates and perioperative mortality rate of the patients who had undergone pleuropneumonectomy or limited resection did not significantly differ. The prognostic factors for survival included gender (P=0.0019) and adjuvant therapy (P=0.0034) by Cox's Regression Analysis. The goals of surgical treatment of pleural diffuse mesothelioma are relief of symptoms and prolongation of survival time. Selecting the appropriate surgical procedure and more effective adjuvant therapy for each particular case is necessary under a new, accurate staging system for diffuse mesothelioma.

Objectives to examine the role of plasminogen activators (PAs) and matrix metalloproteinases (MMPs) in the healing of prosthetic grafts. Methods thirty explanted grafts (16 Dacron and 14 PTFE) were studied immunohistochemically using antibodies to PAs, MMPs, and their inhibitors. The percentages of immunostain-positive multinucleated giant cells (MGC) were related to duration of implantation (early vs late), type of lesion (stenosis vs false aneurysm), graft material (Dacron vs PTFE), and graft status (occluded vs patent). Results all specimens were positive for PAs and MMPs. There were no significant differences in the percentages of MGCs positive for PAs, MMPs, or tissue inhibitor type 2 of MMP (TIMP-2) between the groups. The percentage of TIMP-1 in the aneurysm group (mean, 26%) was significantly lower than that of the stenosis group (mean, 46%) ( p Conclusion after the implantation of a vascular prosthesis, PAs and MMPs are expressed in cell migration, proliferation and matrix construction. Under-expression of TIMP-1 may be related to the formation of an anastomotic aneurysm.