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PubMed1993

The efficacy of preoperative 5-fluorouracil, high-dose leucovorin, and sequential radiation therapy for unresectable rectal cancer.

BACKGROUND: The encouraging results seen in patients who received postoperative combined modality therapy in the adjuvant setting have prompted increased interest in preoperative combined modality therapy for patients with unresectable rectal cancer. The authors report the local control and survival of a previously reported Phase I dose escalation trial of combined preoperative 5-fluorouracil (5-FU), high-dose leucovorin (LV), and sequential radiation therapy followed by postoperative LV-5 FU for the treatment of patients with unresectable rectal cancer. METHODS: Twenty patients (13, primary and 7, recurrent disease) received LV-5-FU for one cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of LV-5-FU was given concurrently with week 4 of radiation. Six patients received intraoperative brachytherapy. Postoperatively, the patients received LV-5-FU. The pathologic complete response rate was 20%, and 89% underwent a complete resection with negative margins. RESULTS: The crude local failure rate was 26%, and the 3-year actuarial local failure rate was 29% (95% confidence interval [CI], +/- 8.94%). The crude abdominal and distant failure rates were 40% and 30%, respectively. The 3-year actuarial disease-free survival was 64% (95% CI, +/- 6.75%), and the overall survival was 69% (95% CI, +/- 7.65%). CONCLUSIONS: These preliminary data revealed encouraging local control and survival rates. Preoperative combined modality therapy is an attractive approach in patients with unresectable rectal cancer.

Aged↗
PubMed1994

Primary linitis plastica carcinoma of the colon and rectum.

BACKGROUND: Linitis plastica carcinoma (LPC) usually shows a scirrhous growth pattern with a severe stromal desmoplastic reaction. Another growth pattern showing lymphangiosis carcinomatosa rather than scirrhous growth pattern, however, was noted. This study was designed to clarify the clinical and pathologic characteristics of colorectal LPC. METHODS: Linitis plastica carcinoma was reviewed clinicopathologically and classified into two types according to the histologic growth pattern: The first was a scirrhous type (nine patients) and the second, a lymphangiosis type (three patients). RESULTS: Grossly, the mucosal surface of the scirrhous type had a granular, cobblestone, gyriform-like appearance. The cancer cells were composed mainly of poorly differentiated or signet-ring cells and were accompanied by a severe stromal desmoplastic reaction; lymphatic permeation was not so marked. Most patients with this type of cancer died of peritonitis carcinomatosa. The mucosal surface of the lymphangiosis carcinomatosa had a smooth and glossy appearance. The cancer cells were composed mainly of moderately differentiated cells, frequently with a glandular formation. Stromal desmoplastic reaction was not so marked. The growth pattern was characterized by lymphangiosis carcinomatosa and marked venous invasion. All patients who had this type died of distant metastases. CONCLUSION: Perhaps with earlier diagnosis and aggressive treatment, the peritoneal dissemination of scirrhous LPC and distant metastasis of lymphangiosis LPC may be minimized.

Adenocarcinoma, Scirrhous↗
PubMed1986

Radioimmunolocalization and selection for surgery in recurrent colorectal cancer.

The value of radioimmunolocalization (RIL) of cancer depends on its performance in situations where the result determines the choice of management. A rise in serum carcinoembryonic antigen (CEA) values after apparently curative resection of colorectal cancer implies localized, resectable recurrence in some patients and widespread unresectable tumour in others. This study investigated the ability of RIL with radiolabelled antibody to CEA and a novel numerical method for analysis of results to determine the extent of disease in 31 patients with raised serum CEA but no physical signs of recurrence. Surgical exploration or conventional radiology later confirmed the presence of tumour in 94 per cent of sites which were positive by RIL. Negative RIL predicted the absence of disease in 53 per cent of patients. The investigation could discriminate between localized and disseminated disease and often performed better than conventional radiology. RIL appears useful in selection of patients for second look laparotomy.

Carcinoembryonic Antigen↗
PubMed1993

Cytogenetic analysis of 52 colorectal carcinomas--non-random aberration pattern and correlation with pathologic parameters.

Cytogenetic analysis of short-term cultures from 52 colorectal carcinomas revealed a normal karyotype in 13 and clonal chromosome aberrations in 39 tumors. In the abnormal group, 13 tumors had simple numerical changes only, whereas 26 had at least one structural rearrangement with or without concomitant numerical changes. The most common numerical abnormalities were, in order of decreasing frequency, +7, -18, -Y, +8, +13 and -14. The most common structural rearrangements affected, again in order of decreasing frequency, chromosomes 8, 1, 6, 7, 17, 3, 11, 13, 14, 16, 2 and 10. The chromosome bands most frequently involved in the structural changes were 8q10, 17p11, 11q13, 8p11, 6q21, 7p15, 7q36, 12q13, 13q10, and 16q13. The most frequent genomic imbalances brought about by the structural rearrangements were losses from chromosome arms 8p, 1p, 6q, 17p, 7p, and 16q, as well as gains of 7q, 8q, 13q, and 11q. A statistically significant (p < 0.05) correlation between the karyotypic pattern and tumor grade was found, with the poorly differentiated carcinomas generally having more massive chromosomal abnormalities.

Adult↗
PubMed2006

Increase in both CEA and CA19-9 in sera is an independent prognostic indicator in colorectal carcinoma.

BACKGROUND AND OBJECTIVES: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known to be the most common tumor markers of colorectal carcinomas. However, the significance of increase in these markers to predict the prognosis of the patients remains a problem for debate. METHODS: One hundred three patients with colorectal carcinoma, who had been treated by resection and reconstruction of digestive tracts were studied. Correlation of preoperative serum value of CEA and CA19-9 with clinicopathologic features including prognosis of the patients was investigated. RESULTS: Preoperative elevation of both of the two markers proved to be an independent prognostic indicator, however, an elevation of only one of the two markers did not obtain a prognostic significance. CONCLUSIONS: Combined data of preoperative increase in CEA and CA19-9 in sera can provide a powerful and useful information to predict prognosis of patients with colorectal carcinoma.

Aged↗
PubMed1985

Total pelvic exenteration for advanced carcinoma of the lower colon.

Thirteen patients with advanced carcinoma of the lower colon and no evidence of extrapelvic metastasis were submitted to total pelvic exenteration. Nine of the 13 patients had ureteral urinary diversion by the ileal segment conduit. Three had colonic conduit bladder using the terminal portion of the descending colon. One patient had bilateral uretero colonic anastomosis. The operative mortality rate was 7.7%. Determinate 5-year survival rate of 38.5% was achieved. Histological examinations of the surgical specimen revealed associated abscesses adjacent to the tumor in six cases, although the cancer extended to the bowel wall and adhered to the surrounding structures in all specimens. Total pelvic exenteration assures a better quality of life, lessening of symptoms, disease control and, in selected patients, a cure.

Adenocarcinoma↗
PubMed1993

A phase I/II study of intraoperative radiotherapy in advanced unresectable or recurrent carcinoma of the rectum: a Radiation Therapy Oncology Group (RTOG) study.

The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2-year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recurrent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow-up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress.

Actuarial Analysis↗
PubMed1989

Parameters affecting laser palliation in patients with advanced digestive cancers.

Ninety-nine nonsurgical patients (group I) with esophagogastric cancer were referred to the laser center for palliation of dysphagia, and another 142 nonsurgical patients (group II) with a rectosigmoid cancer were referred for palliation of abnormal rectal discharge (125 patients) or occlusion (17 patients). The immediate success rate was 83% in group I and 90% in group II. Patients were retreated monthly. The average duration of palliation was 4.3 months +/- 0.5 (+/- standard error) in group I and 9.3 months +/- 0.95 in group II. Complication rate was 4% in group I and 3.4% in group II. Parameters affecting results were found only in group I. Factors that could negatively affect the immediate success rate included annular size of the tumor basis more than two thirds of the circumference, tumor localization at the upper third of the esophagus, and recurrence after a nonlaser treatment. The average duration of improvement after initial success was affected only by the circumferential extension.

Aged↗
PubMed1984

Phase II trial of 4'-epi-doxorubicin in metastatic colorectal carcinoma.

Twenty-three patients with metastatic colorectal carcinoma were treated with 4'-epi-doxorubicin (Epirubicin, 4'-epi-DX) 90 mg/m2 i.v. every 4 weeks. Out of 18 patients evaluable for response, 11 were previously untreated. One complete response of 21 + months was observed in a patient with rectosigmoid carcinoma. Furthermore there was one minor response in pretreated rectosigmoid series, and 6 patients had stabilization of disease. Median survival for all patients, including early deaths, was 4 months. For patients who were not pretreated and who received at least 2 cycles of therapy, median survival was 15 months. Further studies in patients with rectosigmoid carcinoma are warranted.

Aged↗
PubMed1986

Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5'-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month.

Eighteen patients with advanced solid cancer were treated with daily 5'-dFUrd infusions given over 1 h on days 1-5 of a 4-week cycle. Nine patients received 3 g/m2 5'-dFUrd daily and another nine patients 5 g/m2. One patient on 5 g/m2 5'-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1-2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m2 5'-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m2 group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5'-dFUrd and its metabolites 5-FU and 5'-dFUH2 have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5'-dFUrd at the end of the infusion approximated 500 mumol/l and 1000 mumol/l for the 3 g/m2 and 5 g/m2 group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5'-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2-3 compared with the direct injection of 5-FU. Monthly infusion of 5'-dFUrd 5 mg/m2 per day on days 1-5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5'-dFUrd 3 g/m2 per day on days 1-5 were well tolerated.

Adenocarcinoma↗
PubMed1975

[The evaluation of the cyclophosphamide sensitivity of human tumours by determining the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumor cells in vitro in presence of 4-hydroxycyclophosphamide (author's transl)].

A new in vitro assay for screening the sensitivity of human tumour cells against Cyclophosphamide has been developed. While biologically activated Cyclophosphamide was unsuitable because of unpurities in the material, synthetic 4-Hydroxycyclophosphamide was shown to inhibit the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumour cells in vitro. 29 tumours including 14 mammarial carcinomas, 8 ovarial carcinomas and 7 other malignant tumours were tested. While 12 tumours showed a significant and 5 only a slight inhibition of the 3H-uridine incorporation in vitro. 12 tumours showed no effect. Histologically none-differentiated tumours were more sensitive against 4-Hydroxycyclophosphamide as compared with the more differentiated ones. First observations point to 4-Hydroperoxycyclophosphamide instead of 4-Hydroxycyclophosphamide as a more suitable form of activated Cyclophosphamid for the in vitro assay of Cyclophosphamide sensitiveness because of the higher stability and better availability of this compound.

Antineoplastic Agents↗
PubMed1993

Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: report of a case.

A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46-47 degrees C perfusate containing 40 micrograms/ml of mitomycin C (MMC) and 200 micrograms/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m2 and 21 mg/m2 of MMC, and ten doses of 710 mg/m2 of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m2 of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery.

Adenocarcinoma↗
PubMed1991

A new detachable snare for hemostasis in the removal of large polyps or other elevated lesions.

In cooperation with Olympus Optical Co. (Tokyo, Japan) the author developed a detachable snare that enables the endoscopic ligation of the base of an elevated lesion. This apparatus surrounds the base of a large polyp or other elevated lesions with a specially manufactured loop, which is then tightened. This detachable snare enables the removal of large polyps and other elevated lesions without bleeding. The loop is made of nylon because the removal of an elevated lesion required high-frequency current. At Sakura National Hospital between May 1989 and October 1990, the detachable snare was used in 11 patients, including 4 with elevated gastric lesions, 2 with elevated duodenal lesions, and 5 with elevated colonic lesions. All of these elevated lesions were pedunculated or semi-pedunculated and measured greater than or equal to 20 mm in maximal diameter. In all cases, the lesions were removed effectively, resulting in a temporary, residual shallow ulcer.

Adult↗
PubMed1980

Adjuvant chemotherapy of human colorectal adenocarcinoma after growth on mice with congenital thymic dysplasia ("nude"). 2. Tumor remission following treatment with 5-FU and VCR of xenotransplanted primary human colorectal adenocarcinomas.

The poor 5-year survival rate of patients with malignant colorectal tumors calls for clarification of the question as to whether it is advisable to carry out postoperative adjuvant chemotherapy. In the present study a simple "in vivo" test is described with which the sensitivity of individual human adenocarcinomas of the colon, primary xenotransplanted onto syngeneic "nude"-mice suffering from congenital thymic dysplasia, to cytostatic therapy with 5-FU and VCR could be determined. Five of six primary xenotransplanted tumors showed a significant reduction in size following combined therapy with these drugs in doses comparable to those administered clinically, whereas one of the transplanted tumors remained unresponsive to therapy. On the basis of these results it is absolutely necessary that a comparison be carried out between the rate of tumor remission in groups of patients and animals undergoing the same chemotherapy.

Adenocarcinoma↗
PubMed1994

[Rectal endosonography in differential diagnosis of surgical diseases of the pelvis].

Rectal endosonography was performed in 35 patients in whom a pathologic process in the pelvis was suspected. Pathologic findings were shown in various cases: abscess, tumours, ascites. It was shown that rectal endosonography can provide information that is not revealed by such established examinations as abdominal sonography and computed tomography. We recommend that the indications for transrectal endosonography can be extended beyond the established use in rectal tumours and diseases of the pelvic floor. Further systematic examinations are required.

Abscess↗
PubMed1989

Laser palliation for rectosigmoid cancers.

Lasers are now used in the rectum an colon for treatment of vascular telangiectasia [1], and benign and malignant sessile tumours [2,3]. This paper will describe the results of a 7 years experience with treatment of sessile rectosigmoid cancers.

Adult↗