The value of screening and central registration of families with familial adenomatous polyposis. A study of 82 families in The Netherlands.

In 1984 a national registry of families with familial adenomatous polyposis was set up in The Netherlands to promote screening in those families. Eight-two families had been registered by the end of 1988. Analysis of the pedigrees showed that 204 family members at risk had not yet been screened. The diagnosis of familial adenomatous polyposis was histologically confirmed in 230 patients. These patients were subdivided into two groups. Group A comprised patients with familial adenomatous polyposis referred because they were symptomatic, and Group B relatives of these patients who were found by screening to have familial adenomatous polyposis. The authors compared these groups with respect to the occurrence of colorectal carcinoma. Fifty-four patients were found to have a colorectal carcinoma at the time of diagnosis of familial adenomatous polyposis, i.e., 49 of the 104 patients in Group A (47 percent) and five of the 126 patients in Group B (4 percent). The average age at diagnosis of the 104 patients in Group A was 35 years (range, 13 to 66 years) and that of the 126 patients in Group B was 24 years (range, 8 to 59 years). By the age of 40 years, 90 percent of the patients in group B had been diagnosed. Late onset of familial adenomatous polyposis was found in four families. Endoscopy and/or radiography of the upper digestive tract were (was) performed in 44 of the 230 patients. Nineteen patients (43 percent) were found to have polyps in the stomach or duodenum, or both. In our series, only one patient died from cancer of the upper digestive tract (ampullary carcinoma). These results show conclusively that screening leads to the early detection of familial adenomatous polyposis. The value of a national registry is proved by the finding of many at-risk family members who had not previously been screened. Screening should start between the ages of 10 and 12 and should continue up to the age of 50. In the rare cases of families with an apparently late onset of familial adenomatous polyposis, screening should be continued up to age 60. More studies are needed to determine the natural history of polyps in the upper digestive tract.

Screening of families predisposed to cancer development in The Netherlands.

Screening for hereditary tumours provides a basis for secondary prevention. In 1985, the Foundation for the Detection of Hereditary Tumours was established in The Netherlands to coordinate screening in families with hereditary tumours. In the initial period of four years a large number of families were collected. Registration started with families with the multiple endocrine neoplasia syndrome type 2 and familial adenomatous polyposis. Later, families with the familial dysplastic nevus syndrome, hereditary nonpolyposis colorectal cancer and the multiple endocrine neoplasia syndrome type 1 were also collected and inventoried, because expansion of the registry to include these syndromes was considered. As a general conclusion based on our studies, it may be said that screening of families with the multiple endocrine neoplasia syndrome type 2, familial adenomatous polyposis, familial dysplastic nevus syndrome, and hereditary nonpolyposis colorectal cancer leads to detection of these tumours in an earlier stage, which in turn may permit curative treatment and improvement of the prognosis and life expectancy. Screening of the MEN-1 syndrome may improve the prognosis by favouring appropriate management decisions. It is evident that a detailed family cancer history is extremely important as an indicator of a genetic basis and has implications for family screening and follow up. The doctor's task of ensuring that the necessary investigations are carried out is made easier by use of the facilities of the Foundation for the Detection of Hereditary Tumours. The registration system in particular has assured the continuation of periodic examination, because the specialist is kept informed at all times. The collection of data and the preparation of an inventory of the data of families with hereditary tumours on a national scale have contributed to both the understanding of these syndromes and the optimalization of the screening procedures. The study of hereditary tumours is important, because it can provide clues concerning carcinogenesis in general.

Peroperative diagnosis and treatment of metastases to the regional lymph nodes in papillary carcinoma of the thyroid gland.

The management of two groups of patients with papillary carcinoma of the thyroid gland (n = 165) was evaluated retrospectively. Total thyroidectomy was the standard procedure in both groups, but the peroperative diagnosis and treatment of metastases to the regional lymph nodes differed. In group 1 (n = 84), only clinically positive lymph nodes were resected, and if residual postoperative 131I uptake was found, an ablation dose of 131I was given. In group 2 (n = 81), all of the tissue in the tracheoesophageal groove was removed routinely at total thyroidectomy and frozen section was done of the lymph nodes lying along the internal jugular vein. If metastases were found, a modified radical dissection of the neck was performed on the affected side. The two patient groups were comparable with regard to risk factors--local tumor stage, age and sex. Almost twice as many patients were found to have metastases to the lymph nodes in group 2. There was no significant difference in the ten year over-all or recurrence free survival time between the two groups. In group 1, there were more recurrences on the explored side of the neck but fewer distant metastases; however, both findings were not significant. In group 2, significantly more instances of hypoparathyroidism and palsy of the accessory nerve were found (p less than 0.05). Thus, when a more extensive search was carried out, more metastases to the lymph node were discovered and treated, but this did not prevent recurrences in the neck nor did it improve survival time. This approach resulted in more postoperative morbidity. There seems to be no justification for prophylactic removal of regional lymph nodes in instances of papillary carcinoma of the thyroid gland, but modified radical neck dissection may be beneficial if clinically suspect regional lymph nodes are present in the lateral part of the neck.

Follow-up after treatment of primary breast cancer.

This study evaluates the usefulness of routine follow-up of breast cancer patients. In all, 416 patients who were treated with curative intent for breast cancer were followed according to a fixed follow-up schedule for a minimum of 2.5 years and a maximum of 13.5 years (mean about 5 years). During the 4533 routine out-patient visits, 4116 chest radiographs, 3889 pelvic radiographs and about 17,000 laboratory tests were carried out routinely. In the follow-up period, 148 patients were found to have distant recurrence of whom 34 (23 per cent) had asymptomatic metastases and 114 symptomatic metastases. Of the 8005 routinely performed radiographs, 24 (0.3 per cent) revealed asymptomatic metastases, and the 17,000 laboratory tests led to the discovery of six asymptomatic bone and four asymptomatic liver recurrences. Screening for metastases did not result in a reduction of the lead time to the diagnosis of asymptomatic metastases; the disease-free interval was equal in both symptomatic and asymptomatic patients. Of the 46 locoregional recurrences 42 were found by physical examination during a routine follow-up visit and 37 had not been noticed by the patient. Seventeen second primary breast cancers were diagnosed, six of which were in stage I (less than 2 cm). Mammography was not a part of the routine follow-up scheme. It is concluded that routine follow-up of breast cancer patients by history and physical examination is sufficient to detect local recurrence and a second primary tumour as well as giving the opportunity to track signs and symptoms of distant recurrence at an early stage. Performing annual or biannual mammography is advisable, but the use of other costly routine investigations in the follow-up is not justifiable, as no therapeutic advantages can be expected.

The familial dysplastic nevus syndrome. Natural history and the impact of screening on prognosis. A study of nine families in the Netherlands.

Since 1982, nine families with the dysplastic nevus syndrome have been identified in the Leiden area (The Netherlands). A total of 50 primary melanomas were diagnosed in 38 persons. Nineteen of these melanomas had been diagnosed before the start of the screening programme (category I), 11 were detected at the initial examination of the families (category II), and 20 were found during the course of follow-up (category III). To assess the effect of screening, we compared these categories with respect to the developmental stage of the melanomas. One of the 19 melanomas in category I, two of the 11 in category II and seven of the 20 in category III were melanoma in situ. The average thickness of the invasive melanomas in categories I, II and III was 1.75, 0.80 and 0.54 mm respectively. Sixteen of the 19 melanomas in category I (84%) were Clark III or IV, whereas 15 of the 20 melanomas in category III (75%) were Clark I or II. From these findings it may be concluded that screening can lead to the detection of melanomas at an earlier stage, which in turn can permit curative treatment and improvement of both prognosis and life expectancy. The need for supervision based on central registration of affected families to guarantee the continuity of screening is discussed.

The Akiyama procedure in the surgical management of oesophageal cardiacarcinoma.

Currently subtotal oesophagogastrectomy with reconstruction of the digestive tract by use of a gastric tube appears to be the treatment of choice in patients with a carcinoma of the thoracic oesophagus and gastroesophageal junction. The results of 96 patients with a clinically operable oesophageal-cardiacarcinoma operated upon between 1977 and 1983 are reviewed. Resection intended for cure could be performed in 57 patients (59.4%). Twenty-five patients underwent a 'standard' Ivor Lewis procedure with an intrathoracic anastomosis, whereas in twenty-one patients the Akiyama technique with a retrosternal gastric tube and cervical oesphagogastrostomy was accomplished. There was a great shift in stage-grouping from cTNM to pTNM. The major causes of mortality after oesophageal resection were respiratory and cardiac insufficiency (87% respectively 40% of the deaths) and sepsis from a mediastinitis caused by an intrathoracic anastomotic leak (20%). The postoperative mortality rate was similar in both procedures and amounted to 22.8%, but has decreased to 5% during the period 1983 to 1986. The 5-year survival rate for patients undergoing resections intended for cure was 20% as calculated by the actuarial method. There was no significant difference in long-term survival rates between the two resection groups. The late functional results were better in the cases with the Akiyama method, particularly where gastroesophageal reflux is concerned (P less than 0.05).

A retrospective study of male breast cancer in Holland.

A retrospective study has been undertaken of 104 men with breast cancer, all of them having a follow-up period of at least 5 years. In 78 cases a histological diagnosis was obtained. The preferred treatment for operable cases was radical mastectomy, in which 60 per cent positive axillary nodes were found. Five-year survival is 54 per cent and the disease-free interval is 42 per cent. Local recurrence occurred in 26 per cent and 16 per cent had developed distant metastases. The overall results are similar to those in the literature with the exception of those for stage III who did better in this series. The generally held beliefs that Klinefelter's syndrome is the strongest predisposing factor to developing male breast cancer and that gynaecomastia is not a premalignant condition are supported by this study. Comparison of results from this series, with those of women of the same age having breast cancer leads to the conclusion that the prognosis in male breast cancer is no worse than for women with comparable disease.

Early-stage rectal cancer: electrofulguration in comparison to abdominoperineal extirpation or low-anterior resection.

For some small rectal cancers electrofulguration can be an attractive alternative to more extensive surgical procedures. This report is a review of 49 patients who, after careful selection, were considered ideal candidates for curative fulguration in the period 1959-1982. All had rectal adenocarcinomas and were clinically staged as Dukes' A tumors. To put the results of this analysis into perspective, they are compared to the results of those patients (34) who also had early clinical stage rectal adenocarcinomas, but for a variety of reasons underwent abdominoperineal excisions (APE, 11 patients) or low-anterior resections (LAR, 23 patients) instead of fulguration. Postoperative complications after fulguration were minimal, there were no postoperative deaths, and all patients retained anal continence. After APE or LAR there were two postoperative deaths (one myocardial infarction, one ruptured iliac aneurysm); postoperative morbidity was greater. All LAR-treated patients remained continent. Of the patients at risk 55% remained disease-free after fulguration, while 77% remained disease-free after APE or LAR (P = 0.023). This is due to a higher percentage of loco-regional recurrences occurring after fulguration than after APE or LAR (31% vs 9%, respectively, P = 0.021). The percentage of patients with distant metastases in both groups are similar. It seems that electrofulguration of rectal cancers, even in strictly selected patients in a specialized institution, can lead to an unacceptably high percentage of patients with loco-regional recurrences. Nearly all local failures occurred in patients with tumors that measured more than 3 cm in diameter and/or occupied more than one-third of the rectal circumference. Salvage operations for loco-regional failure were performed in 13 patients, 5 of whom are alive with no evidence of disease. Since there seems to be a direct relation between tumor size and the chance of loco-regional recurrence and since salvage operations for local failure are not uniformly successful, electrofulguration for cure must be reserved for the very rare patient with a very small early-stage rectal cancer.

Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions.

The optimal single dosage of melphalan in isolation perfusion of the limbs for malignant melanoma was assessed. For this purpose a method to determine the volume of the isolated region in the individual patient and a grading system for the reaction of the normal tissues were introduced. A strictly standardized pharmacosurgical routine was developed that permitted an analysis of the correlation between dosage and the grade of toxic reaction in 90 perfusions. The optimal dosage of a cytostatic drug was considered to be the highest amount tolerated at an acceptable risk. Melphalan at 10 mg/l perfused tissue was determined as the likely optimum. This dose provoked remarkably little variation in toxicity, all reactions falling within a safe range. No exception to the applicability of this dosage was encountered.

Prognostic factors of neck node metastasis.

A retrospective clinico-pathological study has been carried out in a series of 405 patients with squamous cell carcinoma of the head and neck who underwent a total of 484 radical neck dissections. The recurrence rate in the neck in 327 patients who had histological positive nodes was 21.1%. Recurrence in the neck after a standard radical neck dissection almost invariably proved fatal. A statistical analysis has been carried out to evaluate the clinical and pathological factors which are of importance in regards to recurrence in the neck. Histological factors such as extra-nodal spread and the number of histological positive nodes have been shown to be of much more prognostic importance than clinical parameters. When corrections are made for interdependencies between variables, histological extra-nodal spread proved to be the most important single prognostic factor (P less than 10(-7)).