Jerome J. DeCosse

The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis

Seven familial polyposis patients with desmoid tumors were treated with indomethacin, sulindac, or tamoxifen either as single agents or in combination. Serial computed tomographic (CT) scan examination was employed for objective measurement of tumor size since physical examination alone was an inaccurate means to evaluate intraabdominal and retroperitoneal desmoids. Only one patient with minimal tumor burden demonstrated a favorable response with complete resolution of an abdominal wall desmoid.

Conservative treatment of distal rectal cancer by local excision

From 1954 through 1982, 57 patients with invasive, distal rectal cancer had a full‐thickness local excision with curative intent. Prognostic criteria and need for further treatment were based on the histopathologic results of the operative specimen. The overall 5‐year survival rate was 83.4%. The rectal cancer‐specific mortality rate was 10.5%. None of the 27 patients without adverse prognostic factors died from rectal cancer, and for this group local excision alone was sufficient treatment. The only single factors associated with an adverse outcome were mucinous characteristics and full‐thickness invasion. Ulceration alone and penetration into the muscularis propria alone were not adverse factors. In the presence of multiple adverse prognostic factors, mucinous characteristics or full‐thickness penetration, local excision was inadequate treatment and an abdominal perineal resection was necessary.

Radiation damage to the small intestine

Although radiation therapy has proven effective in both cancer control and cure, grave side effects may occur. Among the most serious treatment complications encountered by a patient with malignant disease is that of radiation injury to the small intestine. Patients with gynecologic malignancies are most often found to have these problems of therapy. The etiology of radiation damage at the cellular level is mostly molecular damage resulting in lethal cellular injuries. Accompanying vascular and connective tissue may also be altered and cause later complications. Because of the complex nature of the patients malignant disease and treatment, diagnosis of radiation injury to the small bowel and other pelvic structures can be most difficult to determine. The management of acute manifestations of enteric radiation injury includes diet modification and drugs that affect intestinal motility. Long-term manifestations of enteric radiation injury present more serious difficulties. Initially, the patient must be stabilized to reverse the effects of chronic malnutrition, sepsis, and electrolyte imbalance. Immediate surgery may be necessary in patients with suspected perforation. Most patients, however, require further studies for complete assessment of clinical damage. In patients with enteric fistulas, an operation is always necessary for fistula control. Complete enteric bypass utilizing minimally affected intestine is mandatory to ensure the least morbidity and mortality. Prevention of enteric radiation injury requires efforts to minimize postoperative adhesions, avoidance of excessive therapy to segments of fixed small bowel, and dosimetry alteration when complications arise during initial therapy.RésuméBien que la radiothérapie soit efficace pour contrÔler et guérir le cancer, elle est susceptible dentrainer des effects nocifs secondaires. Parmi ces complications, il faut accorder une place particulière aux lésions intestinales. Elles sont le plus souvent le fait de lirradiation des tumeurs de lappareil génital de la femme. Au niveau de la cellule, la lésion radique est moléculaire et provoque la mort cellulaire; elle concerne également les vaisseaux et le tissu conjonctif et elle est ainsi à lorigine de complications tardives. En raison du caractère complexe du processus malin et de son traitement le diagnostic de lésion radique de lintestin grÊle ou des autres éléments pelviens est difficile. Le traitement des manifestations aiguËs des lésions radiques intestinales comportent un régime alimentaire particulier et des drogues agissant directement sur la motilité intestinale. Le traitement des lésions tardives est plus difficile. En premier lieu, le malade doit Être traité pour corriger les effets de la malnutrition chronique, de linfection et du déséquilibre électrolytique. Lintervention immédiate simpose seulement en cas de perforation intestinale. Le plus souvent des études plus poussées sont nécessaires pour déterminer avec exactitude létendue des lésions. Lorsque le malade présente une fistule intestinale, lopération est indispensable. Elle consiste à établir un court-circuit intestinal complet en utilisant lintestin le moins altéré de facon à réduire la morbidité et la mortalité. La prévention des lésions radiques de lintestin impose demployer une technique susceptible déviter les adhérences et lirradiation des segments fixes de lintestin; de réduire les doses de lirradiation dès que des troubles aigus se manifestent.ResumenAunque la terapia de radiación ha probado ser efectiva tanto en el control como en la cura del cáncer, graves efectos colaterales pueden ocurrir. Entre las complicaciones más serias de la radioterapia que un paciente con enfermedad neoplásica maligna debe enfrentar, está la lesión por irradiación del intestino delgado. Las pacientes ginecológicas son las que más frecuentemente se presentan con estos problemas. La etiología de la lesión por irradiación al nivel celular es principalmente el daño molecular que results en lesiones celulares letales. Los tejidos vasculares y conectivos vecinos tambien pueden resultar afectados y causar complicaciones ulteriores. Debido a la naturaleza compleja de la enfermedad neoplásica maligna y de su tratamiento, el diagnóstico de la lesión por irradiación del intestino delgado y de otras estructuras pélvicas puede ser extremadamente difícil de determinar. El manejo de las manifestaciones agudas de la lesión intestinal por irradiación incluye modificaciones en la dieta y el uso de drogas que afectan la motilidad intestinal. Las manifestaciones a largo plazo de la lesión entérica por irradiación presentan dificultades más serias. Inicialmente el paciente debe ser estabilizado con el fin de corregir los efectos de la malnutrición crónica, la sepsis y el desequilibrio electrolítico. La cirugía inmediata puede ser necesaria en casos de sospecha de perforación. La mayoría de los pacientes, sinembargo, requiere estudios adicionales para determinar en forma completa el grado de lesión clínica. En pacientes con fístulas entéricas la operación siempre es necesaria para lograr el control de la fístula. Una derivación (“by-pass”) entérica total, utilizando intestino mínimamente afectado, es mandatoria para asegurar la menor morbilidad y mortalidad. La prevención de la lesión entérica por irradiación exige esfuerzos para minimizar el desarrollo de adherencias postoperatorias, evitar el exceso de terapia sobre segmentos fijos de intestino, y la introducción de alteraciones en la dosimetría una vez que se presenten complicaciones en el curso inicial de la terapia.

Quality-of-life management of patients with colorectal cancer

We have reviewed management of the patient with colorectal cancer both after primary treatment and in the palliative setting. Although we have addressed quantitative measures of quality of life as applied to patients with colorectal cancer, the limitations of combining disparate variables that encompass morbidity, an idealized lifestyle, and personal variation in interpretation of that lifestyle into a single number or point on a graph are self-evident. The caring family physician has a better intuitive integration of patient complexity than does the outcomes analyst. When the apparently cured patient returns to the family physician after initial operative treatment, recovery is just beginning. We have addressed the morbidity of surgery, the role of adjuvant treatments, the short-term and long-term effects of adjuvant treatments on quality of life, and the management of these effects. Restoration of quality of life extends beyond cure or survival and embraces repair of the patients confidence and psychosocial well-being. The patient with persistent or recurrent colorectal cancer merits the entire range of medical skills of the family physician. Not all patient findings arise from cancer; other treatable medical and surgical diseases occur. If findings are from recurrent colorectal cancer, the patient may still be curable by treatment or may enjoy prolonged quality of life with or without anticancer treatment. Do not rush to judgment about remaining life span. Although pain control is the benchmark of palliative care, psychological elements that affect severity of pain and the invariably associated depression of the patient require the emotional support and compassion of the family physician.

Colonic mucosal pH in humans

Mucosal pH was measured at specific anatomic segments within the colon using a flexible pH probe in patients prepared for colonoscopy. The data revealed similar pH measurements along the length of the colon, irrespective of the presence or absence of colorectal neoplasia. Patients exhibited a relatively acidic right colon; a more alkaline transverse, left, and sigmoid colon; and a relatively acidic rectum. There were no apparent genderor age-related effects on colonic mucosal pH.

Abnormal DNA ploidy and proliferative patterns in superficial colonic epithelium adjacent to colorectal cancer

Superficial colonic cells were taken from normal‐appearing mucosa at 2, 5, and 10 cm proximal and distal to colorectal cancer margins in 37 patients. The DNA ploidy and proliferative pattern of each sample were determined using flow cytometry. In 11 patients, histology of mucosal sections from the same sites also was analyzed. We found a higher frequency of aneuploidy than previously reported in mucosa up to 10 cm from a colorectal cancer; 62% (23/37) of the primary cancers were aneuploid, and of these, 48% (11/23) were associated with adjacent aneuploid mucosa. The mucosa adjacent to the 14 diploid cancers had only diploid characteristics. The proliferative activity (as reflected by synthetic (S) phase fraction) of aneuploid cancers (21.1 ± 2.0% SEM) and aneuploid mucosa as far as 10 cm away (21.2 ± 2.1% SEM) was higher than in normal controls (10.2 ± 0.7% SEM) (P < 0.0005). Parallel cytology excluded shed cancer cells as an explanation for these findings. Histology showed diffuse, generally mild and reactive, mucosal abnormalities in eight of 11 patients. Ploidy did not correlate with histologic abnormalities. The findings of aneuploidy and high S‐phase fraction in uninvolved superficial mucosa provide evidence for a field defect in mucosa adjacent to colorectal cancer and support the concept that the large bowel mucosa behaves as a unit in carcinogenesis.

Early cancer detection colorectal cancer

Persons with symptoms or signs suggestive of colorectal cancer require complete exam of the large bowel either by sigmoidoscopy, preferably flexible, with barium enema, or by total colonoscopy. A test for fecal occult blood (FOBT) is not necessary here. In asymptomatic persons at average risk for colorectal cancer, the following screening recommendations are made: from age 40, annual digital rectal exam and FOBT; and, from age 50, sigmoidoscopy, preferably flexible, every 3 to 5 years after two negative annual exams. If there is a family history of colorectal cancer in one or more first‐degree relatives, annual digital rectal exam and FOBT should begin at age 40, with either barium enema and sigmoidoscopy or total colonoscopy every 3 to 5 years. Persons with a history of chronic ulcerative colitis, polyposis syndromes, or prior colorectal adenomas or cancer merit special attention.

Ploidy in invasive colorectal cancer. Implications for metastatic disease

A retrospective study was performed to determine the ploidy of superficial (above muscularis propria) and deep (below muscularis propria) biopsy specimens from the primary colorectal cancer of 88 patients with Dukes Stage C2 and D colorectal tumors. The ploidy of lymph node and liver metastases was compared with that of the superficial and deep specimen from the corresponding primary tumor. Among the tumors studied, 78% exhibited nondiploid stemlines. In 19% of the tumors, the ploidy of the superficial biopsy differed from that of the deep biopsy. Among these discordant tumors, all of the deep biopsy specimens corresponded in ploidy to the liver metastases, whereas most of the superficial specimens were similar in ploidy to the lymph node metastases. Our observations suggest that measurement of a single site may not be sufficient to detect nondiploid stemlines within a tumor. They also suggest that measurement of deeper parts of invasive tumors may be more reflective of the phenotype of distant metastases than measurement of superficial specimens.

Subject-reported compliance in a chemoprevention trial for familial adenomatous polyposis.

A high level of compliance with an assigned treatment regimen is fundamental to accurate assessment of treatment effectiveness in any clinical trial. If compliance is poor, an effective treatment may be confounded by inadequate delivery of the regimen. Although much research has focused on broad aspects of compliance dealing with clinical therapeutic situations, there was a need for further research dealing specifically with adherence issues in a long-term chemoprevention trial since subject motivation in the latter is likely to differ from that of the former. Examining subject-reported compliance over the first 2-year treatment periods of a long-term chemoprevention trial for familial adenomatous polyposis, it was found that (1) compliance decreased over time, (2) fiber compliance was lower than vitamin compliance, and (3) four explanatory variables which may be amenable to individualized study-team interventions emerged as useful prognosticators of fiber compliance.

Colonoscopic diagnosis of grumbling appendicitis

2A timely diagnosis is often clouded by atypical presentation leading to other diagnoses, particularly Crohn’s disease or, in women, gynaecological disease. Patients with chronic appendicitis should be distinguished from the 6·5–10% of patients who have a short history of episodic acute abdominal pain, a pattern termed recurrent appendicitis. 1,3 We describe two patients in whom colonoscopy illuminated a long history of appendicitis and could have led to an earlier diagnosis. We also found one case report where colonoscopy was useful in the diagnosis of acute appendicitis. 4