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Patterns of recurrence following curative resection of adenocarcinoma of the colon and rectum.

This study explores the patterns of recurrence after "curative" operation for colorectal cancer. For an 11-year period, 1960-1971, 281 evaluable patients were resected at the Peter Bent Brigham Hospital. Crude five-year survival in these patients was 49%, but only 10% of those with recurrence lived five years. A total of 69 patients relapsed during their lifetime and 34 additional patients were found to have metastases at death. The initial site of metastases were regional in 23 patients (33%) and distant in 32 (46%). Simultaneous regional and distant metastases were found in 13 (19%) for a total of 65% of patients having initial distant metastases. Approximate recurrence rates by site were: 30% for sigmoid and rectum, 20% for right colon, and 10% for transverse and left colon. Tumor size was a significant determinant of recurrence but did not select for regional or distant sites. Recurrence by Astler-Coller modification of the Dukes-Kirklin classification revealed 10% for A + B1, 33% for B2, 35% for C1, and 50% for C2. More than half of the patients with distant metastases (18/32) had solely hepatic metastases yet the total incidence of liver metastases as the initial site was only 8% of the total. In general, the site of the primary cancer was the most important determinant of the type of recurrence; the stage and site of the primary tumor were most predictive for eventual relapse.

Adenocarcinoma↗

Patterns of recurrence following curative resection alone for adenocarcinoma of the rectum and sigmoid colon.

Two-hundred-four patients with previously untreated adenocarcinoma of rectum, rectosigmoid, and sigmoid colon were retrospectively evaluated to determine patterns of recurrence following curative resection. Seventy-eight (38%) subsequently developed recurrent disease. Of these, 40% (31/78) presented with local recurrence alone, 28% (22/78) with regional recurrence, 15% (12/78) with concomitant local recurrence and distant metastasis, and 17% (13/78) with distant metastasis alone. The degree of tumor anaplasia and depth of tumor penetration into the bowel wall influenced the rate of local recurrence. Through five years local recurrence without clinical evidence of distant metastasis was the most common cause of death. Need for adjuvant radiation therapy is discussed.

Adenocarcinoma↗

Controlled trial of adjuvant chemotherapy following curative resection for gastric cancer. The Gastrointestinal Tumor Study Group.

Following curative resection for gastric adenocarcinoma, 142 patients were randomized to receive adjuvant chemotherapy of methyl-CCNU and 5-FU or to be closely followed without chemotherapy. The median patient has been followed for four years. At the present time, there have been 38 recurrences and 40 deaths among the 71 patients in the control arm and 28 recurrences with 29 deaths in the group of patients randomized to chemotherapy. Median survival for control patients is 33 months whereas it is estimated to be in excess of four years for the adjuvant therapy group. A survival advantage appears to be associated with adjuvant treatment, a test for treatment difference being significant (P less than 0.03) after adjustment for important covariates. Survival and disease-free intervals are longer in the chemotherapy arm for patients in all prospective stratification subgroups (proximal and total vs distal subtotal gastrectomy, presence or absence of lymph node metastases, invasion of adjacent organs vs confined to stomach wall and location of tumor within the stomach). A final assessment of this surgical adjuvant approach must await complete results of this trial, as well as of others currently in progress evaluating this same concept.

Adenocarcinoma↗

Carcinoma of the esophagus twelve years after curative resection for carcinoma of the esophagus.

A patient is presented who developed a second squamous cell carcinoma of the esophagus twelve years after a curative esophagogastrectomy for a similar lesion in the proximal stomach. Factors predisposing to local recurrence at an esophageal anastomosis are reviewed. The long disease-free interval in this patient, however, strongly suggests a metachronous primary tumor rather than local recurrence.

Aged↗

Palliative and curative electrocoagulation for rectal cancer. Experience and results.

The 18-year experience with electrocoagulation of rectal cancer in 51 patients is reported. The "boiling" technique used in this study is described. Electrocoagulation for palliative purpose was carried out in 18 patients. One patient is alive without evidence of disease after 4 years. The remaining 17 patients died within 2 years. Electrocoagulation for cure was performed in 33 patients. In two patients abdominoperineal resection was needed for residual tumor. All cases were strictly followed, and none of the patients died of cancer. Recurrent tumor was never seen, and the crude 5-year survival was 71%. The authors describe the criteria for selection any patient should meet in order to be eligible for electrocoagulation with curative purpose and advocate caution in making the choice between radical and local surgery.

Adult↗

Carcinoembryonic antigen levels in peritoneal washings can predict peritoneal recurrence after curative resection of gastric cancer.

Carcinoembryonic antigen (CEA) levels were determined in the peritoneal washings from 120 patients with gastric cancer and 9 patients with benign diseases. Elevated values (greater than 100 ng/g of protein) were observed in 20 of 25 patients with gastric cancer with visible dissemination and 16 of 25 patients with serosal invasion but no dissemination. The same elevation was found in only 9 of 70 patients with no serosal invasion and none of the patients with benign disease. The 2-year survival rates after curative operation for the patients with and without elevation of CEA levels were 21% (19 patients) and 100% (66 patients), respectively (P less than 0.001). A negative correlation was found between CEA levels and survival times after noncurative operation. These results indicate that the CEA level in peritoneal washings could be a sensitive detector of invisible peritoneal dissemination and a new predictor for the postoperative prognosis of gastric cancer.

Carcinoembryonic Antigen↗

Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma.

METHODS: Eighty-three patients with hepatocellular carcinoma (HCC) were treated with curative surgical resection during the past 8 years. RESULTS: No operative deaths occurred. The cumulative recurrence rates after resection at the ends of years 1, 2, and 3 were 37.0%, 57.1%, and 71.6%, respectively. After adjusting the imbalance in clinical factors among patients by using a Cox proportional-hazards model, it was shown that multiplicity, histologic classification, and absence of antibody to hepatitis C virus were associated significantly with recurrence after resection. The size of the tumor did not affect the incidence of recurrence. Thirty-eight of 41 patients with intrahepatic tumor recurrence had undergone at least one of the following three therapies against HCC: surgical reresection, percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TAE). The most significant factor affecting the survival time of patients with tumor recurrence was the total number of tumor nodules at the time of recurrence. Although surgery and PEI were thought to be more effective treatments than TAE in prolonging life, multivariate analysis showed that they were not significant factors of survival time because choices in the method of treatment were correlated closely with the number of cancer nodules. A 65.3% 5-year survival rate from the time of first surgery was accomplished through vigorous therapy when tumors recurred. CONCLUSION: In conclusion, despite the high recurrence rate after resection of HCC, the use of multiple therapies can achieve increased survival rates.

Adult↗

Epidermoid carcinoma of the anal canal. Results of curative-intent radiation therapy in a series of 270 patients.

BACKGROUND: Epidermoid carcinoma of the anal canal is an uncommon disease, and most institutions have only a small series of patients. The current study of a large series of patients treated with radiation therapy in a single institution evaluates the outcome, prognostic factors, and the late complications for these patients. METHODS: From 1972 to 1991, 270 patients with anal canal epidermoid carcinoma without evident distant metastasis were irradiated with curative intent in the Radiotherapy Department of Tenon Hospital. The sex ratio was 1 man/5.7 women, with a mean age of 67.5 years. The histology included 59.6% well-differentiated epidermoid carcinoma, 32.2% moderately or poorly differentiated epidermoid carcinoma, and 8.2% cloacogenic. The T-classification was: T1: 8.5%; T2: 51.1%; T3: 30.4%; T4: 10%. Abnormal inguinal lymph nodes were present in 12.5% of the patients. Patients were irradiated by external beam. They received a first course of photon irradiation consisting of (mostly 18 mV or 25 mVl; some Co60 or 6 mV) 40-45 Gy (box technique) in the pelvis for 4-5 weeks. After a rest of 4-6 weeks, a second course of 15-20 gy in 2 weeks was given through a perineal field by an electron beam of suitable energy. When rectal involvement was important, a four-field, small box technique was used. Fourteen patients were given a booster irradiation of 30 Gy by interstitial brachytherapy (Iridium 192 sources), and four patients were treated with interstitial brachytherapy alone, to a mean dose of 62.5 Gy. RESULTS: At 5 and 10 years, determinate survival rates were: T1: 86% and 86%; T2: 86.2% and 82.5%; T3: 60.1% and 56.8%; T4: 45% and 45%, respectively. The overall local control rate was 80%. The overall anal conservation rate was 67%. In 154 patients (57%), the anus had maintained its normal function. At 5 and 10 years, determinate survival was 76% and 73.7%, respectively, for N0 and 53.5 and 53.5% for clinically involved inguinal lymph nodes. According to the log-rank test, survival comparisons between T2 and T3 classifications and of tumor sizes less than or equal to 4 cm in length and greater than or equal to 5 cm in length were significant (P = 0.0001 and P < 0.0001, respectively). The presence of clinical abnormal inguinal lymph nodes had a significant negative influence on survival rates (P = 0.047). Multivariate analysis indicated that T-classification and tumor size in centimeters were the only predictive variables. Nonpredictive variables included nodal status, histology, age, total dose, overall treatment time, and irradiation technique. The grade 3 complication rate requiring surgical treatment was 27/270 (10%), considering all patients (27/190 represents a 14% rate for patients who had local tumor control after radiation therapy alone without secondary salvage amputation). There was no significant relationship between complication rate and the aforementioned variables. Because of the homogeneity of the irradiation doses, no significant relationship was found between dose, local control rate, or complication rate. CONCLUSIONS: After radiation therapy, recognizing the distinction between tumor sizes of less than or equal to 4 cm in length and more than 4 cm in length (which is not considered in TNM Classification criteria [International Union Against Cancer, 1987]) could help to improve treatment strategies. For tumors more than 4 cm in length and/or with clinically involved lymph nodes, the treatment should be more extensive with combined chemotherapy and radiation therapy, but the increased local control with the addition of cytotoxic chemotherapy to irradiation has not been proven.

Adult↗

Impact of age and sex on survival after curative resection for carcinoma of the esophagus.

BACKGROUND: The impact of age and sex-related changes in the endogenous hormonal milieu on survival after curative resection for esophageal epithelial cancer is explored. Adami et al. have suggested that the event of puberty has a favorable impact on survival after treatment of epithelial cancers. METHODS: The database consisted of 469 patients with esophageal cancer treated surgically with an intent to cure (without any gross residual disease at the end of the primary treatment) at Tata Memorial Hospital between 1980 and 1989. RESULTS: Life-stable analysis revealed a significantly better 5-year survival for women younger than 49 years (35%, CI 24-48) compared with men of the same age (16%, CI 8-27) (P < 0.008). There was no difference in survival between men (17%, CI 12-23) and women (26%, CI 16-37) older than 49 years (P = 0.08). A Cox proportional hazard model showed sex to be the second most significant determinant of survival (P = 0.002) after lymph node metastasis (P < 0.0001). CONCLUSION: The finding that the survival benefit is confined to women younger than 49 years is consistent with the hypothesis that the endocrine milieu in premenopausal women may prevent the establishment of micrometastases and thus improve the prognosis for esophageal epithelial cancer.

Adult↗

The identification of patients at high risk following curative resection for colorectal carcinoma.

Thirty-five consecutive patients undergoing apparently curative resection for colorectal carcinoma were staged by conventional methods (Dukes', degree of tumor differentiation and pre- and postoperative CEA). In addition, the presence or absence of occult hepatic metastases at the time of surgery was determined by sequential CT scanning. Thirteen patients died within 30 months of surgery. Conventional prognostic indices failed to define clearly those patients who died. In contrast, the presence or absence of occult hepatic metastases at the time of surgery clearly defined two groups of patients. Only 9 per cent of patients who possessed occult hepatic metastases survived 30 months compared with 88 per cent of patients in whom these metastases were not detected. The clinical implications of these results are discussed.

Carcinoembryonic Antigen↗

Local recurrence following 'curative' surgery for large bowel cancer: I. The overall picture.

The Large Bowel Cancer Project is a collaborative prospective study of 4228 patients with a histologically proven adenocarcinoma, of whom 2336 (55 per cent) survived a 'curative' resection. Follow-up information is available on 2220 patients (95 per cent). Subsequently, 309 (14 per cent) have developed a local recurrence confirmed by: biopsy (127; 41 per cent), clinical examination (77; 25 per cent), X-ray (15; 5 per cent), a raised CEA (2; 1 per cent), or some other method - e.g. CT scan or a confident unbiopsied laparotomy finding (88; 29 per cent). Statistically significant factors (chi2 test, P less than 0.05) associated with local recurrence are: Dukes' classification: A 4 per cent; B 13 per cent; C 18 per cent Tumour differentiation: Well 11 per cent; Moderate 14 per cent; Poor 21 per cent Obstruction: Absent 13 per cent; Present 21 per cent Perforation: Absent 13 per cent; Present 28 per cent Tumour mobility: Freely mobile 11 per cent; Others 21 per cent Operation performed (rectal and rectosigmoid tumours): Abdomino-perineal 12 per cent; Anterior resection 18 per cent; Surgeon (Consultant only): Range less than 5 per cent to greater than 20 per cent. Stratification of the above variables altered only the statistical significance pertaining to tumour differentiation (P less than 0.1, d.f. = 2). In particular, the differences between Consultant surgeons remained.

Adenocarcinoma↗

Local recurrence following 'curative' surgery for large bowel cancer: II. The rectum and rectosigmoid.

1988 patients with an adenocarcinoma of the rectum (1292; 65 per cent) or rectosigmoid (696; 35 per cent) have been studied. A resection (1700 patients) or polypectomy (124 patients) was performed in 1824 (92 per cent) and, of the former, 1376 patients either underwent abdominoperineal (AP) excision of the rectum (788 patients) or an anterior resection (598 patients). The in-hospital mortality was 63 patients (8 per cent) for AP and 44 (7 per cent) for anterior resection, and a curative resection had been performed in 504 (71 per cent) of those undergoing an AP, and 393 (71 per cent) of those undergoing an anterior resection. Follow-up information is available for 478 patients (95 per cent) who underwent an AP and 370 (94 per cent) who underwent an anterior resection. More patients have developed a local recurrence after an anterior resection (67; 18 per cent) than after AP (57; 12 per cent) (Logrank chi2 = 6.6, d.f. = 1, P less than 0.02) (stratified for sex and Dukes' stage). This difference is not accounted for by a lesser margin of distal clearance after an anterior resection; firstly because the margin of clearance was not different in those who did and those who did not develop a local recurrence (AP: whole group = 4.4 cm, local recurrence = 4.5 cm; anterior resection: whole group = 3.0 cm, local recurrence = 3.1 cm) and secondly because for each centimetre of distal clearance there was a consistently greater probability of recurrence for anterior resection (Logrank chi2 = 9.1, d.f. = 1, P less than 0.01) (stratified for sex, Dukes' stage and distal clearance margin).

Adenocarcinoma↗

Adjuvant treatments following curative resection for gastric cancer. The Italian Gastrointestinal Tumor Study Group.

The results of a prospective randomized trial of adjuvant treatment after curative resection for gastric cancer are reported. The study consisted of three arms: (1) surgery only; (2) chemotherapy (5-fluorouracil (FU) and 1-(2-chloroethyl)-3-(4-methylcyclohexil)-1-nitrosourea (Me-CCNU] after surgery; (3) chemo-immunotherapy (FU, Me-CCNU and levamisole) after surgery. Between March 1977 and June 1981, 235 patients were included in the study by 18 co-operating institutions. Thirteen per cent of patients in arm 2 and thirteen per cent in arm 3 suffered major toxicity, necessitating interruption of treatment. Two of these patients died of marrow aplasia. Statistical analysis of survival showed that prognosis was influenced by the well-known prognostic variables, invasion of the wall, nodal status and site of tumour. The different treatments in the three arms, however, did not show any impact on prognosis, even when adjustments were made for the most relevant prognostic variables. Given the lack of effect on survival and the presence of clinically important toxicity, FU and Me-CCNU +/- levamisole cannot be recommended as adjuvant therapy for resected gastric cancer.

Adult↗

Norwegian multicentre study of survival and prognostic factors in patients undergoing curative resection for gastric carcinoma. The Norwegian Stomach Cancer Trial.

The influence of clinical and tumour-related variables on long-term survival in patients with gastric carcinoma was studied in a national prospective multicentre study. A total of 532 patients underwent curative surgery with a 5-year survival rate of 40 per cent. In a Cox multivariate analysis, age, stage of disease and macroscopic appearance of tumour were the only factors that independently affected survival. The estimated probability of survival to 5 years for a 50-year-old patient with a flattened tumour type and stage I disease was 71 per cent, but 50 per cent for an 80-year-old with the same tumour type and stage. For stage II disease the rates were 56 and 32 per cent, for stage III 39 and 13 per cent and for stage IV 19 and 3 per cent, respectively. A 70-year-old patient with stage II linitis plastica tumour type had an estimated probability of 5-year survival of 20 per cent. Stage of disease was the single most important factor in determining survival. Laurén histopathological type and location of tumour, Karnofsky performance index, weight loss and type of resection had no significant effect on long-term survival.

Age Factors↗

Colonoscopic surveillance after curative resection for colorectal cancer.

Colonoscopic surveillance after resection for colorectal cancer has been advocated to improve detection of anastomotic recurrence, and of synchronous and metachronous tumours. The benefit provided by colonoscopy remains unproven, and the best timing of examination is unclear. To determine the value of colonoscopy after curative resection for large bowel cancer, the efficacy of an endoscopic surveillance programme in the early detection of intraluminal bowel recurrence in a series of patients admitted with colorectal cancer was examined. Between April 1983 and December 1988, 132 patients underwent colonoscopy. Eight (6.1 per cent) were found to have intraluminal recurrence without evidence of extraluminal spread. Six of these recurrences were at the site of anastomosis and two represented metachronous tumour development. All of these patients were symptomatic at the time of diagnosis. In 15 patients (11.4 per cent), adenomatous polyps were discovered during the initial endoscopic examination. These results indicate that colonoscopic surveillance will rarely allow early detection of asymptomatic intraluminal bowel recurrence, but is valuable in the detection of synchronous lesions. Frequent surveillance is not justified in the early postoperative years and colonoscopy should probably be confined to a single procedure to exclude synchronous lesions.

Adenomatous Polyps↗

Local recurrence of rectal adenocarcinoma after 'curative' surgery with and without preoperative radiotherapy.

The natural history of locally recurrent rectal cancer was analysed to assess whether preoperative irradiation altered the clinical course of the disease. In a randomized controlled trial of 849 patients, the value of preoperative radiotherapy in those with operable rectal adenocarcinoma was examined. After a minimum follow-up of 4 years, 156 patients who developed local recurrence were studied retrospectively. There were no differences concerning symptoms and the site of local recurrence between irradiated and non-irradiated patients. Curative treatment was rarely possible and median survival was only about 1 year, irrespective of adjuvant treatment. Local recurrence was the only manifestation of disease in 30-50 per cent of patients. An earlier and more aggressive surgical approach might improve survival.

Adenocarcinoma↗

Long-term outcome following curative surgery for malignant large bowel obstruction.

This study determined whether the long-term outcome of patients with obstructing colorectal cancer could be related to conventional pathological prognostic variables or to other clinical, operative or histological features. Ninety-eight patients with bowel obstruction who had undergone potentially curative surgery and survived the postoperative period were studied. Features related to poor long-term outcome after a median follow-up of 5 years included bowel perforation at initial operation (P = 0.007), advanced tumour stage (P < 0.001), poor tumour differentiation (P = 0.02), mucin production by tumour (P = 0.004) and the presence of vascular (P = 0.08) and neural (P = 0.004) invasion. Outcome was not significantly related to the seniority of the operating surgeon (P = 0.52), even when this was adjusted for potentially confounding variables (adjusted hazard rate ratio for trainee surgeons 1.4 (95 per cent confidence interval 0.9-2.4), P = 0.16). Conventional prognostic features may help to identify the majority of patients with obstructed colorectal cancer at high risk of tumour recurrence and death.

Adult↗

Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma.

Adjuvant oral chemotherapy was studied in 67 patients with stage II hepatocellular carcinoma who underwent curative resection between May 1988 and December 1990. Patients were stratified into two groups according to preoperative liver dysfunction: 55 had stage I disease (mild dysfunction) and 12 had stage II (moderate dysfunction). A randomized controlled study of postoperative oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) was conducted in each group. From October 1994 HCFU administration was suspended because of side-effects in nine patients with stage I liver dysfunction and in three with stage II dysfunction who had received the drug for more than 4 weeks. Cumulative survival and recurrence-free survival rates of patients with stage I disease in the treatment group were higher (P = 0.08 and P = 0.04 respectively) than those in the control group. However, in patients with stage II disease no significant difference was observed (P = 0.77 and P = 1.0 respectively). This study suggests that the potential benefits of HCFU on tumour recurrence should be weighed against the risk of adverse reactions in patients with mild liver dysfunction.

Antineoplastic Agents↗