Clinical and pathologic features of breast cancers in women treated for Hodgkin's disease: a case-control study.

The goal of this study was to assess whether there are clinical or pathologic differences between radiation-associated breast cancers developing after treatment for Hodgkin's disease and spontaneously arising breast cancers. Clinical and pathologic data were reviewed for 26 Hodgkin's disease patients who received irradiation and subsequently developed breast cancer (cases) and 26 age- and stage-matched patients with sporadic breast cancers (controls). The median age at diagnosis of Hodgkin's disease was 21 years (range 11-40 years), and the median interval between Hodgkin's disease and breast cancer diagnosis was 15 years (range 4-27 years). There were no differences between cases and controls with regard to clinical factors. Cases had a lower frequency of histologic grade III tumors (38% versus 65%, p = 0.09) and moderate to marked mononuclear inflammatory cell reaction (11% versus 35%, p = 0.03). When these covariates were combined, grade III tumors in conjunction with mononuclear inflammatory cell reaction were also seen less frequently in the case group than in the control group (11% versus 31%, p = 0.06). Seven cases developed additional cancers, but no additional cancers developed in the control group (p = 0.01). Patients who developed breast cancers after Hodgkin's disease did not differ from patients with spontaneous breast cancers, with regard to clinical factors. However, the lower frequency of high-grade tumors and moderate to marked mononuclear inflammatory cell reaction among the cases suggests that radiation-associated breast cancers may differ from spontaneously arising cancers in their pathogenesis. Cases appeared to be at increased risk of developing additional cancers, but we cannot exclude surveillance as a possible contributing factor.

Diamond-Blackfan anemia. Natural history and sequelae of treatment.

To define further the natural history of treated Diamond-Blackfan anemia (DBA), a congenital anemia characterized by a paucity of erythroid precursors, we analyzed 76 patients diagnosed or followed at Children's Hospital, Boston, between 1931 and 1992. Although DBA is generally defined as macrocytic, we found that mean corpuscular volume in infants aged <5 months rarely exceeded the normal range and is of little diagnostic value. Macrocytosis in patients aged > or = 5 months was more striking. Nine of 16 patients who never received steroids experienced remissions, sometimes after years of transfusions. Thirty-one of 56 patients receiving corticosteroids responded. Of these 31, 13 experienced remissions, 11 remained steroid dependent and 7 later required transfusions. Most nonresponders maintained transfusion dependence. Patients frequently (64%) experienced treatment-related morbidity, most commonly hemosiderosis. The relative risk of leukemia was profoundly elevated (RR, 200; 95% CI, 54.5-512.1) and hematologic parameters at long-term follow-up were often abnormal. While potential responsiveness to steroids and relative ease of red cell transfusion make DBA one of the most treatable congenital marrow failure syndromes, both disease-related and treatment-related factors contributed to a limited prognosis (median survival, 38 years). Patients should be carefully monitored longitudinally for evidence of leukemia and adverse effects of therapy, and alternative treatment strategies should be considered on an individual basis.

Pregnancy outcome in survivors of advanced Hodgkin disease.

BACKGROUND: Pregnancy outcome was reported by 139 survivors of advanced Hodgkin disease treated on nine protocols of Cancer and Leukemia Group B from 1966 to 1986. METHODS: These patients provided data on 302 singleton pregnancies of a duration of at least 20 weeks that occurred before, during, or after treatment for Hodgkin disease (252, 26, and 24 pregnancies, respectively). RESULTS: There were 4 perinatal deaths, as compared with 5.7 expected. Cancer subsequently developed in 2 offspring (expected, 1.2). However, 22 newborn infants had low a birth weight, exceeding the expected number of 13.7 (relative risk 1.6; 95% confidence interval, 1.0-2.4). The excess number of low weight births occurred primarily during the period of Hodgkin disease diagnosis and treatment but is based on small numbers. CONCLUSION: No increase in adverse outcome occurred in pregnancies that antedated the development of Hodgkin disease.

Cancer in relatives of survivors of childhood sarcoma.

Relatives of 88 long-term survivors of childhood sarcoma were examined for the familial cancer syndrome of sarcoma, breast cancer, and other neoplasms (Li-Fraumeni syndrome). Twenty-six of 402 close relatives developed cancer (expected, 23.8), including breast cancer in four mothers (expected, 3.1). Two sarcoma probands who developed second malignant tumors have multiple relatives with cancer and might have an inherited predisposition. An increased cancer risk and exceptional requirement for disease screening appear to be confined to first-degree relatives of a small fraction of children with sarcoma, notably probands with second cancers.

Hypertension in long-term survivors of childhood renal cancers.

The prevalence of hypertension was investigated in 119 adults who have survived for up to 53 years following the diagnosis of renal cancer in childhood (Wilms' tumor, 116 patients; renal carcinoma, three patients). Twenty-four (20%) have developed definite or borderline hypertension, as compared with 18.1 cases expected based on US population rates (relative risk [RR], 1.3; 95% confidence interval [CI], 0.9 to 2.0; P = .20). This nonsignificant excess is due to the heightened prevalence of definite hypertension among one subgroup of male patients. The findings are not explained by cigarette smoking, obesity, age, and stage at diagnosis of Wilms' tumor, or family history of hypertension. A case-comparison analysis within the cohort showed no consistent hypertensive effect associated with radiation therapy dose, radiotherapy concurrent with dactinomycin chemotherapy, or extent of renal surgery. Hypertension is not a common late complication of Wilms' tumor in our patients.

Improved survival in epidermoid carcinoma of the anus in association with preoperative multidisciplinary therapy.

From 1972 to 1983, we treated 78 patients who had primary epidermoid carcinoma of the anus. Forty-four of these patients were treated by protocol, while 34 patients were not treated according to protocol. Protocol consisted of fluorouracil (750 mg/m for 5 days) and mitomycin (10 to 15 mg/m on day 1), followed sequentially by 3000 rad (30 Gy) over three weeks, followed by surgery. There were 20 local excisions and 29 abdominoperineal resections in the protocol group, and 11 local excisions and 14 abdominoperineal resections in the nonprotocol group. In the protocol group, 26 patients (59%) had no residual cancer in their operative specimens, while only ten (29.9%) of the nonprotocol patients had no remaining cancer. Four (11.7%) of the 34 nonprotocol patients had pathologically positive inguinal nodes, compared with only three (4.5%) of 44 protocol patients. Thirty-four (77%) of 44 protocol patients remained free of disease, while ten patients experienced local or pelvic recurrence. In contrast, only 17 (50%) of 34 patients in the nonprotocol group remained free of disease. Of 17 recurrences, five were at distant sites. The status at this writing of all patients in the protocol group was 32 (75%), with no evidence of disease, four alive with disease, and eight dead of or with disease. Of the untreated patients, only 11 (32%) remained without evidence of disease, two were alive with disease, and 19 were dead of or with disease. Smaller carcinoma size (less than 5 cm, 27 of 32 had no evidence of disease), younger age, female gender, and deep infiltration also predicted a statistically significant survival advantage after protocol treatment. Controlled, prospective, multi-institutional trials should stratify for these factors when comparing new treatment modalities.

En bloc pelvic lymphadenectomy and sphincter preservation in the surgical management of rectal cancer.

From 1968-1976, 412 patients were operated on for rectal cancers. One hundred fifty-six underwent abdominoperineal resection (APR) and 256 underwent low anterior resection (LAR). One hundred ninety-two underwent en bloc pelvic lymphadenectomy in conjunction with their resection, while 220 patients underwent more conservative or conventional resection. Thirty-day hospital mortality was 1.7%. The cancer-related 5-year survival was 58.8% for all patients. The proportion of patients surviving 5 years after LAR (62.8%) was significantly better than those surviving after APR (52.4%), p = 0.008. Statistically significantly superior survival was observed after extended dissection when compared to conventional resections in Dukes' A, B, and C patients as a whole (63.8 and 54.3%) and in Dukes' C patients in particular. Superiority of en bloc pelvic lymphadenectomy versus conventional resection was observed in all cases of Dukes' Stage C, Astler-Coller Stage C1, Level II (adjacent) lymph nodes, and Level I (proximal) lymph nodes and was most effective in combination with sphincter-preserving operations. Patient groups were compared for bias and/or case selection, using both contingency tables and Cox-based multiple covariant linear regression analysis, and none was found. In the face of current adjuvant therapy, which is of questionable benefit and which carries its own treatment morbidity, en bloc pelvic lymphadenectomy is advocated as an adjunct to the curative operations for rectal cancer. To improve the overall benefit, patients can be selected for pelvic lymphadenectomy as an adjuvant to resection when preoperative examination suggests that the rectal cancer penetrates the bowel wall. Accurate preoperative staging may help to define a more restricted group of patients warranting (pelvic lymphadenectomy) (PLND). A control randomized trial of the effectiveness of PLND is appropriate to further test its value.

Flow cytometry of colorectal carcinoma with three-year follow-up.

Flow cytometry DNA measurements were carried out on colorectal carcinomas from a series of 33 patients who have since been followed for three to four years. The tumors could be subclassified by this technique into 15 that had near-diploid DNA and 18 that were aneuploid. Prior reports had suggested that the near-diploid tumors carry a better prognosis than aneuploid tumors, but in this study the distribution by Dukes' stage and survival were the same in both groups.

Peranal coloanal anastomosis following low anterior resection for rectal carcinoma.

Since 1978, 41 patients (12 percent of all restorative operations) have undergone peranal coloanal reconstruction following anterior resection (LAR) for cancers of the midrectum. Twenty-seven patients (66 percent) were men and 14 patients (34 percent) were women (mean, 58.8 years). The mean distance of the primary tumor from the anal verge was 6.7 cm and 50 percent of the primary tumors were considered highly mobile. In 29 patients, a hand-sewn anastomosis was performed between the colon and the dentate line. In the 12 most recent patients, the anastomosis was performed using a circular stapling instrument. A diverting colostomy should be employed in all cases and is closed approximately three months later. There has been no operative mortality. Morbidity included anastomotic separation (two patients), minor anastomotic defects (three patients), pelvic sepsis (two patients), and bacteremia of unknown origin (two patients). Where fecal diversion was employed, there were no instances of anastomotic leak. Two patients with hemorrhage were returned to the operating room. Thirty-seven of the 41 patients underwent curative resections. Thirty-three percent of the patients had Dukes' C lesions. With a median follow-up of 31 months for the curative resections, 73 percent remain free of disease. Sixty-four percent of evaluable patients have either excellent or good anorectal function nine to 12 months after colostomy closure. Of 26 operations performed by one surgeon, 22 patients (85 percent) are currently evaluable. Nineteen (86 percent) of the 22 have normal or near-normal bowel function. Four guidelines for performing a functionally successful operation are presented. Coloanal reconstruction following LAR, were pull-through operations were previously required, is an excellent sphincter-preserving operation. The functional results one year after the operation are gratifying, with the majority of patients leading an active life with normal bowel function.