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Clinical and morphological characteristics of colitis carcinoma and colorectal carcinoma in young people.

Two series of young patients (less than 40 years of age) with colorectal carcinoma (22 idiopathic carcinomas and 25 carcinomas complicating ulcerative proctocolitis), well matched for age and sex, were compared with regard to clinical features, tumour morphology and stage, and ultimate outcome after surgery. The cure rate in both series was low. Although a failure to diagnose colitis carcinoma accurately at an early stage might have contributed to the poor results, such a delay could hardly be responsible for the bad prognosis in patients with idiopathic carcinoma. The vast majority of the patients in both groups studied had highly malignant and/or mucoid adenocarcinoma, and surgery was palliative in about 40% of the patients in both series, owing to widespread dissemination. The general impression gained from this study of factors of histologic grade of malignancy, extent of spread, and survival rate was that colorectal carcinomas in the young, irrespective of being idiopathic or complicating ulcerative colitis, run a rapid course and have a gloomy prognosis. The outloook depends largely on the biologic characteristics of the tumours concerned. The results support previous statements that prophylactic surgery is justified in patients with long-standing ulcerative colitis with total involvement of the colon, particularly in the young. Regrettably, patients with idiopathic carcinoma will not have this chance.

Adenocarcinoma, Mucinous

Colorectal carcinoma in young black patients: a report of eight cases.

Colorectal carcinoma in the black population of South Africa is very uncommon when compared with incidence among whites. Even in whites the proportion of patients with colorectal carcinoma under 25 years of age is less than 1% (Hardin, 1972). Eight cases of colorectal carcinoma in black patients under 25 years of age are presented. None had any evidence of premalignant lesions of the colon. The prognosis of colorectal carcinoma in young adults is poor in most series and this group of patients was no exception. Reasons for this poor prognosis are mentioned. A more aggressive approach to the early detection and treatment of the lesion in young patients is essential.

Adenocarcinoma, Mucinous

Plasma carcinoembryonic antigen and erythrocyte sedimentation rate in patients with colorectal carcinoma.

Preoperative and postoperative plasma carcinoembryonic antigen (CEA) levels in patients with colorectal carcinoma have been reported to correlate with tumour mass and prognosis. The erythrocyte sedimentation rate (ESR) has previously been reported to be elevated in most patients with metastatic carcinoma. In this study of 17 patients with advanced colorectal carcinoma and of nine patients who were disease-free more than three years after resection of their tumour, the plasma CEA and ESR levels demonstrated a close correlation, both in frequency and in degree of elevation, with the disease status. Of nine patients who were disease-free more than three years after resection of their colorectal carcinoma, all except one had plasma CEA levels of less than 20 ng/ml and an ESR less than 20 mm in one hour respectively. The incidence of plasma CEA more than 20 ng/ml and ESR more than 20 mm in one hour in the locally advanced and distant metastases groups, as compared with those patients in the more than three years group, was increased at a level of statistical significance (P less than 0.05). This study showed that the ESR, an inexpensive and simple estimation, may be as effective as the estimation of plasma level of CEA in monitoring the disease status of patients with colorectal carcinoma.

Aged

Monoclonal antibodies in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma.

Hybridoma-derived monoclonal anti-melanoma antibodies and anti-colorectal carcinoma antibodies were found to mediate in vitro antibody dependent cell-mediated cytotoxicity (ADCC) reactions against melanoma and colorectal carcinoma cells, respectively. The antigen(s) detected in ADCC on melanoma cells maintained for more than one hundred passages in tissue culture were also found on two recently established melanoma cell lines. These antigens were not detected on skin fibroblasts of the same patients from whom the melanomas were obtained. The ADCC reactivities of anti-melanoma and anti-colorectal carcinoma antibodies were found to be specific for melanoma cells and colorectal carcinoma cells, respectively.

Animals

Clinicopathologic and Molecular Analysis of Colorectal Carcinomas With Spectrum of Neuroendocrine Carcinoma Components.

The genetics of colorectal carcinoma (CRC) with neuroendocrine differentiation remain poorly understood; recent studies focusing on pure neuroendocrine carcinomas (NECs) demonstrated mutation profiles closely resembling colorectal adenocarcinomas (ACAs) with more frequent BRAF mutations and Rb/p16 pathway dysregulation. However, pathogenesis of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) and ACAs with minor NEC component (AMiNECs) remains controversial. We aimed to define the behavior and molecular underpinnings of these tumors in comparison with conventional ACAs. In total, 20 NECs, 10 MiNENs, and 8 AMiNECs were compared with 100 controls with ACAs. Well-differentiated neuroendocrine tumors of any grade were excluded. CRCs with NEC components presented at a slightly earlier age (mean, 59 vs 65 years; P = .24) in a similar sex distribution (male:female, 1:1.11 vs 1.04:1; P = .97). The majority of cases arose either from a precursor adenoma (42%) or in the setting of inflammatory bowel disease (18%), whereas 5 of 10 cases (50%) originating from the rectum were human papillomavirus driven. Despite similarity in tumor size and depth of invasion among all groups, CRCs with NEC components showed more frequent lymph node and distant metastases (P < .001 each), leading to more advanced disease stage (stage III/IV; P < .001) and worse 5-year survival outcomes (35.4% for NECs, 30% for MiNENs, and 41.6% for AMiNECs vs 85.1% for ACAs; P < .001), compared with ACAs. Next-generation sequencing revealed more frequent BRAF (40% vs 3%; P < .001) and BRCA1 alterations (15% vs 1%; P = .001) in NECs compared with ACAs. Genomic alterations in RB1 were exclusively found in NECs (10%) and MiNENs (20%). In conclusion, the presence of any NEC component (from AMiNEC to pure NEC) in CRC carries a dismal prognosis. Yet, these tumors are more likely to harbor potentially targetable mutations such as BRAF p.V600E and alterations in BRCA1/2, which are of therapeutic value.

Humans

Predictive value of plasma CEA in patients with colorectal carcinoma.

Two years follow-up of 46 patients with colorectal carcinoma resected "for cure" shows that of the nine patients with an elevated (less than 5 ng/ml) CEA plasma titer one to six months after surgery, only one, or 11%, had remained disease free. Of the 38 patients with normal (less than 5 ng/ml) plasma CEA, 27, or 71%, were free of disease two years after surgery. In another 85 patients presenting six months to ten years after resection "for cure" of their colorectal carcinoma, normal CEA levels were found in 73, and only five, or 6.4%, of these presented with disease progression when followed for two years; of the 12 patients that presented with CEA values less than 5 ng/ml, disease progression was evident in eight or 67%; in eight patients with CEA levels of greater than 10 ng/ml, the proportion of patients with disease progression increased to 87.5% (7/8). When a patient with a history of colorectal cancer, but seemingly free of disease, presents with levels not only repeatedly above normal (greater than 5 ng/ml) but above the levels found in some nonmalignant conditions (greater than 10 ng/ml), thorough re-examination of the patient to locate the site of possible disease progression is indicated. In 14 such patients further diagnostic methods showed local recurrences in four, metastasis limited to the liver in six, and other metastasis in four. In conclusion, in patients with colorectal carcinoma postoperative elevated CEA plasma levels are a sign of poor prognosis. Consistently elevated CEA levels (greater than 10 ng/ml) are a strong indication of disease progression.

Carcinoembryonic Antigen

Preoperative irradiation of primarily unresectable colorectal carcinoma.

A series of 44 patients with colorectal carcinomas considered unresectable on presentation received preoperative irradiation to a dose of 4500--5000 rad (175--200 rad/day). After a waiting period averaging 6.5 weeks, 38 patients underwent exploration. Complete resection was possible in 27 patients. Of these, 22 patients remained disease-free with a median follow-up of 27 months. While longer follow-up periods are needed, the results indicate that the large percentage of unresectable and therefore surgically incurable colorectal carcinomas can be made resectable by preoperative irradiation, and a significant number of these may have been cured.

Adenocarcinoma

Sequential antitumour immunoreactivity and carcinoembryonic antigen levels as a guide to prognosis in colorectal carcinoma.

Twenty-five patients with colorectal carcinoma were tested for blood-lymphocyte anti-tumour cytotoxicity and carcinoembryonic antigen (CEA) levels at three-monthly intervals for eighteen months or more after resection, and examined clinically every three to six months. Twelve of the patients were followed for two years and one for four years. The six patients whose tumours recurred showed positive blood lymphocyte antitumour cytotoxicity and elevated plasma CEA levels at some time from six months after operation, usually well before the recurrence was clinically detectable.

Adenocarcinoma

Effectiveness of local radiotherapy in colorectal carcinoma.

The records of 144 patients with colorectal carcinoma treated with radiotherapy were reviewed. Ninety-two patients received treatment for palliative purposes only (bleeding, pain, mucus discharge, tenesmus, mass). Good palliation was achieved in the majority of patients with a dose on the range of 1200 to 1400 rets. Thirty-seven patients received radical doses of radiation for recurrent or inoperable cancer. Five out of 37 (14%) are alive without evidence of disease, 24 to 84 months following radiotherapy. Fifteen patients received pre- or postoperative radiotherapy as an adjuvant to surgery. Six out of the 15 (40%) are alive without evidence of disease.

Adenocarcinoma

A randomized study of two different schedules of methyl CCNU, 5-FU and vincristine for metastatic colorectal carcinoma.

Sixty-seven patients with measurable colorectal carcinoma were randomized to receive two different schedules of Methyl CCNU, 5-FU and Vincristine (MOF). The treatment schedule consisted of Methyl CCNU 150 mg/m2 po q 70 days, 5-FU 300 mg/m2 iv for 5 consecutive days q 35 days, and Vincristine 1 mg/m2 IV q 35 days. The same total dose was used in each arm; in MOF A, the Methyl CCNU was given on day 1, while in MOF B, the Methyl CCNU was divided and given over 5 consecutive days. In MOF A, there was a 10% partial response rate and a 10% minor response rate. In MOF B, the partial response rate was 12% and the minor response rate was 21%. This difference is not statistically significant, but the patients in MOF B experienced less gastrointestinal toxicity (p less than .001).

Adult

Colorectal carcinoma in adolescents implications regarding etiology.

Between October, 1974 and December, 1976, 13 adolescent patients with far-advanced, poorly differentiated colorectal carcinoma had been referred to a pediatric cancer center. All patients received chemotherapy with vincristine, methyl-CCNU and 5-fluorouracil. Five of 13 patients are living, one of whom remains disease-free after 12 months of chemotherapy. Four of the patients were from urban areas and nine from rural areas. One of four from urban areas had intimate exposure to chemicals used in the production of cotton and soy beans. Eight of nine patients from rural areas also had exposure to farm or agricultural chemicals, and three of these patients were intimately involved with the spraying operations. Suggestions regarding etiology and causative factors for the development of carcinoma of the colon in adults have previously been advanced. Results of these studies suggest that alternate etiologies must be suggested for adolescent colorectal carcinoma.

Adenocarcinoma, Mucinous

Lymphocyte blastogenic responses to allogeneic leukocytes and autochthonous tumor cells in colorectal carcinoma.

The blastogenic reactivity of peripheral blood lymphocytes (PBL) and mesenteric lymph node lymphocytes (LNL) against normal allogeneic leukocytes and autochthonous colorectal carcinoma cells is evaluated in 36 patients, and correlated with the patient's Dukes classification. Mesenteric LNL react significantly better than PBL to allogeneic leukocytes in both Dukes B and C (p less than 0.05). There are too few patients in Dukes A and D to permit statistical evaluation but the trend is the same. By contrast, LNL fail to react to autochthonous tumor cells in all classes, except in a few Dukes B patients. The proportion of PBL reactivity to autochthonous tumor cells seems to increase for Dukes C and D. It is possible that specific lymphocyte reactivity in colorectal carcinoma may be related to the antigenicity and immunogenicity of the tumor.

Antigens, Neoplasm

A trial of 5-fluorouracil and Corynebacterium parvum in advanced colorectal carcinoma.

This study has confirmed that patients who have advanced colorectal carcinoma have impaired responsiveness to delayed-hypersensitivity skin testing, and also have elevated levels of serum IgM. Serial observations of delayed-hypersensitivity skin tests, total lymphocyte counts, T-lymphocyte counts, B-lymphocyte counts, and serum immunoglobulin levels failed to reveal any consistent pattern of responses in patients treated with either chemotherapy alone or chemoimmunotherapy. In 33 patients chosen at random to receive either 5-FU alone or 5-FU in combination with intramuscularly administered C. parvum, there was no evidence of objective response or influence on survival. Intramuscularly administered C. parvum, in the dose and schedule used, produced no evident immunologic or therapeutic effect.

Antibodies, Bacterial

Colorectal carcinoma in Hong Kong.

The clinical and pathological features of colorectal carcinoma occurring in 470 Chinese patients in Hong Kong are reported. There was a preponderance of advanced stages of the disease in spite of the presence of a large number of well-differentiated lesions. Polyposis coli was the predisposing cause in 1% of our patients, and none of them had ulcerative colitis. The clinical features of our patients on presentation were generally similar to those exhibited by Caucasians. An abdominal mass was palpable in about half of patients with colonic lesions, and virtually all rectal cancers could be felt by rectal examination. Almost a quarter of our patients presented with complications. In 2% of our patients the initial diagnosis was acute appendictis. A high resection rate was achieved, but many radical resections turned out to be only palliative. Our operative mortality was 8.3%, although for social reasons, the "in-hospital" mortality was 19.2%. The corrected five-year survival rate was 42.7% when curative resection was attempted.

Adolescent

Colorectal carcinoma antigens detected by hybridoma antibodies.

Hybridoma cells which secrete colorectal carcinoma-specific antibodies have been produced and used to study the antigenic structure of these tumor cells. Nineteen antibodies have been studied in detail, and 15 of these are colorectal carcinoma specific. Only two antibodies reactive with carcinoembryonic antigen (CEA) have been discovered and five other antibodies that react with distinct epitopes on the cell surface have been defined. Several antigens with distinct molecular characteristics have been shown to exist by use of hybridoma antibodies. Six hybridoma antibodies have been shown to mediate antibody-dependent cell-mediated cytotoxicity (ADCC).

Animals

Immunoreactivity by intrinsic lymphoid cells in colorectal carcinoma.

Mononuclear leucocytes were separated by Hypaque--Ficoll from 60 unselected primary colorectal carcinomas, and then fractionated by rosetting with sheep erythrocytes, either alone (E) or coated with antibody and complement (EAC). The E-rosetting cells, putative T lymphocytes, were cytotoxic in vitro to autologous tumour cells in 18 of the 60 cases, whilst the EAC-rosetting cells were unreactive. This intrinsic T-lymphocyte anti-tumour immunoreactivity was significantly associated with the presence of "cuffs" of small dark lymphocytes at the mesocolic or pararectal edge of the primary tumours, but there was no correlation with antitumour cytotoxic lymphocytes in the patient's blood at the time of operation.

Adenocarcinoma

CEA monitoring of palliative treatment for colorectal carcinoma.

Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable.

Adult

Colorectal carcinoma: a prospect clinicopathological study.

The clinical and pathological findings in 200 consecutive cases of colorectal carcinoma treated by surgical resection have been recorded and subjected to computer analysis. This is the initial report from a long-term prospective survey of this disease. The two most frequent presenting symptoms were altered bowel habit (51.5%) and bleeding (49.5%). Symptoms due to anaemia occurred in 16% of cases and acute obstruction in 13.5% of cases. The value of the various investigations in establishing the diagnosis is discusses. At the time of resection the disease had already reached an advanced stage in a majority of the patients. In 26% of cases it was known that complete resection of tumour tissue had not been achieved. A direct relationship between stage of spread and histological grade of malignancy was noted. The incidence of advanced stage, high histological grade and mucinous tumours was greatest in the right side of the colon. A study of early carcinomas has confirmed that many have arisen from benign epithelial neoplastic polyps. The significance of these observations is discussed.

Adenocarcinoma, Mucinous