Bladder cancer and squamous metaplasia in spinal cord injury patients

The influence of long-term indwelling urethral catheterization was studied by random bladder and urethral biopsies in 62 spinal cord injury patients. Six patients (10 per cent) had diffuse squamous cell bladder carcinoma, 4 of whom had no tumor visible endoscopically. Five of the patients with cancer were among 25 patients (20 per cent) managed with an indwelling urethral catheter for more than 10 years (average 21 years, range 15 to 30 years). The other cancer patient had been free of the catheter for 27 years after suprapubic cystotomy for 4 years. Gross and microscopic hematuria was associated with cancer. Squamous metaplasia of the bladder was significantly greater in patients who had been catheterized for more than 10 years (80 per cent), compared to those catheterized for less than 10 years (42 per cent) and patients without catheters (20 per cent). Urethral squamous metaplasia increased slightly in long-term catheterization patients. Urinary infection was universal and did not distinguish patients with inflammation, metaplasia or cancer. Therefore, the duration of indwelling catheterization seems to be the major factor in squamous changes in these patients.     

Inadequate documentation and resection for gastric cancer in the United States: a preliminary report

Patients entered into Southwest Oncology Group gastric adjuvant protocol INT 0016 (SWOG 9008) after a "curative" gastric resection were assessed to determine practice patterns of more than 300 surgeons nationwide who performed "curative" gastric resections for 453 gastric cancer patients. The most common gastric resection performed was distal in 256 patients, proximal in 118, and total in 79. Extragastric organs resected were omentum (285), spleen (59), pancreas (18), and bowel (17). The extent of lymphadenectomy as staged by Japanese rules was 246 (54.2%) D0 resections, 173 (38.1%) D1 resections, 28 (6.2%) D2 resections, and 7 (1.5%) D3 resections. Staging of the cancer was poorly documented, with no statement made regarding the status of the primary cancer in 6 per cent, liver in 10 per cent, lymph nodes in 17 per cent, and omentum in 17 per cent. The greater the lymph node clearance, the greater the chance of resecting to a level of negative lymphatics, given that 45 per cent of nodes were involved when 10 or less were removed, whereas only 17 per cent were positive when more than 40 were cleared. The lack of adequate clearance of lymph nodes and poor documentation of tumor stage suggests that a more regimented surgical approach to this uncommon cancer is required.     

A clinicopathologic study of thymomas: a review of 52 cases, with particular reference to results of treatment

The possible use of spleen-derived mononuclear cells (SPMC) for the intentional and economical adoptive immunotherapy of cancer patients was studied. SPMC were obtained from spleens resected surgically from patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP). When SPMC were cultured in recombinant interleukin 2 (rIL2), SPMC, in the form of interleukin-activated killer spleen cells (IL-SP) proliferated in six of eight cases. CD8+ lymphocytes were the major expanding cell population in most SPMC cultures and IL-SP showed a significant cytolytic activity against cultured tumor cells during cell proliferation. When cultured with a streptococcal preparation, OK-432, for 24 to 48 h, SPMC showed cytotoxic activity against tumor cells and were expressed as OK-432 activated killer spleen cells (OK-SP). The effects of supernatants from IL-SP and OK-SP on tumor cell growth were also examined. The supernatants from IL-SP and OK-SP significantly inhibited cell growth in 3 and 10 out of 11 cases, respectively, while those from OK-SP showed higher growth inhibitory activity than those from IL-SP. The results of this study indicate the potential of SPMC as effector cells for the adoptive immunotherapy of cancer patients.     

The HER2/neu-derived peptide p654-662 is a tumor-associated antigen in human pancreatic cancer recognized by cytotoxic T lymphocytes

The protooncogene HER2/neu encodes a 185-kDa transmembrane protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as pancreatic cancer. Previously, we demonstrated that cytotoxic T lymphocytes (CTL) derived from breast, ovarian, and non-small cell lung cancer recognized a peptide derived from HER2/neu. To evaluate whether this HLA-A2-binding peptide is a tumor-associated antigen (TAA) in pancreatic cancer, the ability of HER2/neu-reactive CTL to lyse human pancreatic carcinoma cells was tested. CTL were generated from tumor-associated T lymphocytes from HLA-A2+ HER2/neu+ breast and ovarian cancer patients. All CTL recognized autologous and allogeneic HER2/ neu+ tumor cells in an HLA-A2-restricted fashion. Furthermore, all CTL recognized p654-662 (GP2) derived from HER2/neu. These CTL also recognized HER2/neu+ pancreatic cancer cells in an HLA-A2-restricted fashion. HER2/neu+ HLA-A2- pancreatic cancer were not or only poorly lysed. Repeated stimulation of HLA-A2+ PBL from pancreatic cancer patients using the HER2/neu-derived peptide resulted in specific recognition of this peptide and, more importantly, HER2/neu+ pancreatic tumors in an HLA-A2-restricted fashion. Autologous HLA-A2+ fibroblasts or HLA-A2+ malignant melanoma cells were not recognized. HLA-A2- peptide-stimulated T lymphocytes showed no significant cytotoxicity. These results demonstrate that this HER2/neu-derived peptide is a shared TAA among several adenocarcinomas including pancreatic carcinoma, suggesting a common mechanism of recognition of these human tumors by T lymphocytes. The identification of the HER2/neu-derived peptide GP2 as a TAA in pancreatic cancer provides an opportunity for the design of novel immunotherapy and vaccine strategies.     

Genetic alterations in primary and secondary hyperparathyroidism

OBJECTIVE: To evaluate treatment of patients with primary liver cancer. DESIGN: Prospective protocol including subsets of randomised studies. SETTING: University hospital, Sweden. SUBJECTS: 123 patients with primary liver cancer. INTERVENTIONS: 64 patients underwent hepatic resection, 25 were included in a trial of adjuvant chemotherapy. 24 further patients whose tumours were not resectable were included in a trial of intra-arterial infusion of doxorubicin. MAIN OUTCOME MEASURES: Survival and postoperative morbidity. RESULTS: The median survival time for patients who had had resections was 11 months (range 0-111). Twelve per cent survived more than 5 years. No prognostic factor had any significant effect on outcome. The postoperative mortality was 11% (7/64). The patients allocated to adjuvant chemotherapy survived a median of 10 months (range 1-47) and the controls 29 months (range 8-111) (p=0.04). Patients with unresectable liver cancer treated with intra-arterial doxorubicin lived no longer than untreated controls (median 8 months (range 1-56) compared with 7 months (range 1-28)). CONCLUSIONS: Treatment of patients with primary liver cancer is still an unsolved problem. Adjuvant chemotherapy with doxorubicin had no beneficial effect on survival.     

Functional results of the laparoscopic treatment of gastroesophageal reflux (followup greater than 2 years)

Adjuvant immunotherapy with interferons and/or interleukin 2 (IL-2) is widely used for advanced kidney cancer. However, the results are not satisfactory so far. The purpose of this study is to evaluate the inducible activity of lymphokine-activated killer (LAK) cells against autologous human renal cell carcinoma. The effect of interleukin 7 (IL-7) on IL-2-induced LAK activity was assessed by the autologous assay system which we have established. Peripheral blood lymphocytes from patients with renal cell carcinoma were stimulated with IL-2 and/or IL-7, and tested for antitumor activity against autologous renal cell carcinoma. In all 10 cases tested, IL-7 alone induced LAK activity. Moreover, IL-2-induced LAK activity was augmented by the concomitant addition of IL-7. Flow cytometry revealed an increase in IL-2-receptor-positive lymphocytes following incubation with IL-7. These results suggest that combination therapy using IL-2 and IL-7 may be a useful treatment for patients with advanced renal cell carcinoma.     

Colorectal cancer in the young patient

Although predominantly a disease of older adults, colorectal cancer affects the younger population with an incidence of two to six per cent. It is thought to carry a less favorable prognosis in the young than in the general population. This may be due to advanced stage of the tumor at diagnosis. This study is composed of 37 patients, aged 40 and younger, treated over a 20-year period for colorectal cancer at Louisiana State University Medical Center-Shreveport and E. A. Conway Hospital. It was performed to investigate the incidence, stage at diagnosis, and prognosis of colorectal cancer in these young patients. The location of the primary tumor was fairly evenly distributed throughout the colon and rectum in this population. Pain, weight loss, rectal bleeding, and nausea and vomiting were the most common presenting symptoms. A family history of colon cancer or premalignant lesions were not risk factors in this study. Seventy per cent of all patients were treated with curative intent, and 42 per cent of these patients developed recurrent disease. The patients in this review presented with a higher incidence of advanced disease. Thirty-seven per cent of the lesions were Duke's C and 22 per cent were Duke's D, with poor 5-year survival (11% and 0%, respectively) when compared with national studies. The absolute 5-year survival for all young patients with colorectal cancer was 26 per cent (5 of 19 patients). It is important for the surgeon to be aware of the potential for colorectal cancer in young patients and to take an aggressive approach to the diagnosis and early treatment of the disease.     

Pituitary adenylate cyclase-activating polypeptide (PACAP38) modulates lymphocyte and macrophage functions: stimulation of adherence and opposite effect on mobility

The effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) in a concentration range from 10(-13) to 10(-6) M were studied, in vitro, on two functions of peritoneal rat lymphocytes and macrophages: adherence and mobility (spontaneous and chemotaxis). The results show that PACAP38 raised the adherence of the two cell types, increased the mobility of macrophages and decreased the mobility of lymphocytes. The maximal effects were observed at 10(-10) M in macrophages and at 10(-9) M in lymphocytes. Moreover, incubation with increasing concentrations of phorbol myristate acetate (PMA), a protein kinase C (PKC) activator, resulted in a progressive enhancement of adherence and chemotaxis of both macrophages and lymphocytes. In contrast, retinal, a PKC inhibitor, significantly decreased these capacities. Incubation of macrophages with both PMA and PACAP38 did not have a synergistic effect on chemotaxis and adherence whereas, with lymphocytes, adherence was increased and chemotaxis was partially decreased. On the other hand, incubation with forskolin (an enhancer of intracellular cyclic AMP [cAMP] levels) caused inhibition and stimulation of chemotaxis and adherence, respectively, in both cell types. PACAP38 prevented the inhibitory effect of forskolin on chemotaxis of macrophages but not of lymphocytes, whereas the simultaneous presence of PACAP38 and forskolin was synergistic for adherence of both peritoneal cells. In addition, PACAP38 was chemoattractant for macrophages but not for lymphocytes. Furthermore, a VIP receptor antagonist was able to partially reverse the modulatory effects of PACAP38 on lymphocytes, but not on macrophages. These data suggest that PACAP38 exerts its action through the binding to type I PACAP receptors and PKC activation in macrophages and through the elevation of intracellular cAMP levels by binding to type II PACAP receptors in lymphocytes. The present work reveals an additional link between neuropeptides and the immune system and suggests that the peptide PACAP modulates the immunological function of macrophages and lymphocytes.     

Cross-sectional epidemiological survey of rheumatoid arthritis patients seen in private practice in France. Descriptive results (1629 cases)

OBJECTIVE: To conduct an epidemiological study of rheumatoid arthritis patients seen by office-based rheumatologists in France (first semester of 1996). METHODS: Cross-sectional study of 1629 rheumatoid arthritis patients conducted by 373 office-based rheumatologists who volunteered for the study (one visit per patient). Each rheumatologist was to complete a 200-variable questionnaire for the first four rheumatoid arthritis patients who came to their office. RESULTS: Women contributed 81% of the sample (mean age, 57 years); 19% of patients were seen in the Paris area, 20% in the North East, 20% in the North West, 22% in the South East and 19% in the South West. Twenty-nine per cent of patients had a paid job and 21.1% (all women) were homemakers. Among the patients with a paid job, 44% were on sick leave, with the reason for the sick leave being the rheumatoid arthritis in 36% of cases. Nineteen per cent of patients had stopped working permanently because of their rheumatoid arthritis, after a mean disease duration of six years. Mean disease duration in the overall sample was eight years. The diagnosis was established within six months of symptom onset in 75% of cases. A family history of rheumatoid arthritis was found in 11% of patients and a family history of other autoimmune diseases in 2%. The disease was precipitated by a stressful life event in 17% of cases. Follow-up was being provided only by the study rheumatologist in 59% of cases and also by a general practitioner in 39%. The disease was quiescent in 9% of cases, minimally active in 32%, moderately active in 46% and severely active in 13%. Eighty-four per cent of patients were on one (78%) or more (6%) second-line drugs including methotrexate (45%), an antimalarial (17%), intramuscular gold (14%), tiopronin (9%), D-penicillamine (6%) and sulfasalazine (12%). Fifty-two per cent of patients were on steroid therapy (mean dose, 7.5 +/- 5.7 mg/d). Other drugs included nonsteroidal antiinflammatory agents (61%), analgesics (61%), gastroduodenal protective agents (45%) and anxiety-relieving agents (10%). Twenty-four per cent of patients had had one or more surgical procedures (mean, 3/patient) for their joint disease. CONCLUSION: This nation-wide epidemiological survey conducted in France provides a database on the socioeconomic and demographic characteristics of rheumatoid arthritis patients followed in private practice.     

Enterocutaneous fistula in cancer patients: etiology, management, outcome, and impact on further treatment

Enterocutaneous fistulae that develop in patients with cancer represent a difficult management situation, which is often complicated by prior treatment including surgery, radiation therapy, and chemotherapy. A fistula may in turn delay potentially beneficial treatment of the underlying malignancy. To provide a better understanding of this problem, we reviewed the National Institutes of Health experience with enterocutaneous fistulae in adult patients with cancer. The medical records of patients with cancer who developed a fistula from the gastrointestinal tract during the period 1980 through 1994 were reviewed. Etiology, management, outcome, and impact on further treatment were assessed. Twenty-five patients with gastrointestinal fistulae were identified. The most common primary tumor site was the colon/rectum in males and the ovary in women. The majority of patients had metastatic disease at diagnosis and a history of prior therapy and presented with anorexia and weight loss. The fistula was usually single, most commonly developed from the jejunum/ileum (13 patients) or colon/rectum (6 patients), and occurred postoperatively after procedures on the small bowel (10 patients) or colon (8 patients). Malnutrition and sepsis developed in 60 per cent of patients. Thirty-day mortality was 16 per cent and correlated with prior radiation therapy, location and output from the fistula, and hypoalbuminemia. An enterocutaneous fistula negatively impacted on the provision of further therapy for the majority of patients (63%). Enterocutaneous fistula in the patient with cancer occurs most frequently in the setting of extensive prior therapy and is associated with prolonged morbidity. Identification of high-risk patients and early management of fistulas once they develop may prevent delays in subsequent cancer therapy and decrease morbidity.     

Use of the augmented ejection fraction to select patients with left ventricular dysfunction for coronary revascularization

Thirty-three patients with angina (31 men and 2 women, age 33 to 68 years, 52), as well as signs and symptoms of severe left ventricular dysfunction, were evaluated for coronary revascularization surgery. All had multiple vessel coronary artery disease and at least one prior myocardial infarction. Cardiac catheterization demonstrated abnormally elevated left ventricular end-diastolic pressure (LUEDP), low cardiac output, and depressed resting biplane systolic ejection fraction (SEF) ranging from 18 to 45 per cent (31 per cent). To evaluate potential myocardial function, a premature ventricular contraction was introduced during the ventriculogram and the SEF of the postextrasystolic potentiated (PESP) beat calculated and compared to a sinus beat SEF. Patients were separated into two groups based on the increase in SEF: those with greater than 0.10 augmentation (24 patients) and those with less than 0.10 augmentation (9 patients). Coronary revascularization was carried out with at least two bypass grafts in each patient. The operative mortality in those with more than 0.1 SEF augmentation was 9 per cent (2/24), late mortality rate 5 per cent (1/22), and 20/21 became Class I or II in the follow-up period of 11 to 57 months (25). Operative mortality in those with SEF augmentation of less than 0.1 3/9 33 per cent), late mortality rate 1/6, and only 1/5 achieved Class 1 status during the follow-up period of 10 to 35 months (22) postoperatively. These data suggest that significant augmentation of SEF by a premature ventricular contraction is a simple and useful indicator to aid in selection of patients with left ventricular dysfunction for coronary revascularization.     

Early gastric cancer and Helicobacter pylori: 34 years of experience at Charity Hospital in New Orleans

Good survival rates have been reported for resected early gastric adenocarcinoma (EGC) in patients found via screening procedures. However, the prevalence of Helicobacter pylori in EGC in unscreened populations is unclear. The major purpose of this investigation was to analyze the clinical experience and incidence of H. pylori in unscreened patients presenting with EGC at Charity Hospital over a 34-year period. From 1963 through 1997, the tumor registry at Charity Hospital compiled data on 2497 patients evaluated for gastric carcinoma. Of these patients, 26 (1%) had lesions that were confined to the mucosa or submucosa, i.e., T1N0M0 (American Joint Commission on Cancer classification). Pathology specimens and medical records were retrieved for confirmation of diagnosis and retrospective analysis for H. pylori. H. pylori was analyzed by Steiner staining and immunohistochemistry using a polyclonal antibody. EGC was detected in 12 men and 14 women with a mean age of 62 years. Upper gastrointestinal X-ray studies were performed on 19 of the 26 patients and failed to conclusively demonstrate a lesion in any case. Endoscopy was performed on 22 patients, and preoperative biopsies were positive in 95 per cent of these. Operative procedures included 2 local excisions and 22 subtotal and 2 total gastrectomies. No extended nodal dissections were performed. Microscopic evaluation revealed lesions limited to the mucosa in 63 per cent of cases and involving the submucosa in 37 per cent of the cases. Of the 14 patients evaluable of H. pylori, 79 per cent were positive for the bacterium. The status of 2 patients is unknown, and only 1 patient died of the original gastric cancer, for a disease-free survival of 96 per cent. The 5-year and 10-year overall survival rates were calculated to be 50 per cent and 21 per cent, respectively, when all causes of death were taken into consideration. Median follow-up of the survivors was 64 months. Resection of early gastric carcinoma in unscreened patients without extended lymphadenectomy yielded excellent results. H. pylori was present in 79 per cent of cases. These data suggest an association between H. pylori and EGC. Whether H. pylori infection is an etiologic factor in gastric cancer remains an area of active research.     

Low prevalence of human papillomavirus in a geographic region with a high incidence of head and neck cancer

BACKGROUND: The main purpose of this study was to determine the prevalence of human papillomavirus (HPV) infection in patients with head and neck carcinomas from Brazil. MATERIALS AND METHODS: Forty-five patients with head and neck squamous cell carcinoma were included in the study, from 1995 to 1996. Forty-two were male and 3 female, with age ranging from 32 to 82 years (median 61). Five patients (11%) did not have previous history of use of tobacco and 38 (90.5%) were heavy smokers. Tumor sites were pyriform sinus, 10; tongue, 11 (oral, 6; base, 5); larynx, 7; floor of mouth, 3; tonsil, 6; retromolar area, 3; inferior gingiva 2; buccal mucosa, 2; and maxillary sinus in 1 patient. Twenty-five were stage IV, 17 stage III, and 3 stage II. RESULTS: The presence of HPV DNA was detected in 5 of 45 patients (11%), all of them with HPV 16. Two patients had HPV DNA in normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa, and 2 patients were positive for HPV DNA in tumor tissue. Four patients were male and 1 was female; 2 patients were nonsmokers. Three patients had tonsil carcinoma, 1 patient had a tongue carcinoma, and 1 patient had a pyriform sinus cancer. CONCLUSIONS: The role of chemical carcinogens seems to be more important in the genesis of head and neck cancer than is HPV infection. The presence of HPV DNA in 5 of 45 patients stimulates further investigation to determine the role of HPV as a risk factor for head and neck carcinoma.     

Prognosis of patients after open mitral commissurotomy. Actuarial analysis of late results in 100 patients

The continuing controversy between proponents of open and closed commissurotomy might be clarified by analysis of late follow-up with modern actuarial techniques that provide a true perspective of patient risk. We have used open mitral commissurotomy exclusively for 15 years in 100 patients. There was one operative death from pancreatitis and one late death from cancer; the actuarially projected survival rate (+/- the standard error) at 10 years is 97 per cent (+/- 2). Thirteen patients had preoperative emboli, 6 of whom were in sinus rhythm and 7 in atrial fibrillation. Two patients had postoperative emboli, both in sinus rhythm. The actuarial chance of remaining free of embolism at 10 years is 97 per cent (+/- 2). Sixteen patients required reoperation on the mitral valve for functional deterioration. The remaining survivors were in Class I or II when last seen. The actuarial chance of not requiring a reoperation after 5 years is 91 per cent (+/- 4) and at 10 years, 38 per cent(+/- 16). Results in different centers are difficult to compare for many reasons, but imprecise statistical methods further obscure such comparisons. The use of actuarial techniques may help to define the role of open mitral commissurotomy.     

Lung cancer--management and outcome in Glasgow, 1991-92

Current practice and outcome for patients with lung cancer were determined by retrospective case note review of a random sample of all lung cancer cases registered for a calendar year and augmented by review of all surgical and radical radiotherapy cases. A total of 262 patients - 231 patients less than 75 years of age and 31 patients more than 75 years of age - represented 83% of the random sample. Eighty-three per cent of patients were seen within 2 weeks of referral. One-third reported symptoms occurring for less than 1 month and one-third had experienced symptoms for more than 3 months. The median time interval from first hospital contact until the making of a management decision was 18 days. The median interval from first contact to surgery was 63 days, and to starting radical radiotherapy 70 days. Histological confirmation was obtained in 69% of patients. Ten per cent of all lung cancer patients were calculated to have received chemotherapy. Five per cent of the whole cohort had definitive surgery and 64% of these were judged to be free of the disease at 3 years. Overall survival was 9% at 3 years, with no differences relating to cell type or area of residence. Many areas of good practice have been identified, but the lack of tumour staging or performance status data, the low proportion receiving chemotherapy or definitive surgery and the poor outcome after radical radiotherapy indicate the need for prospective audit and feedback of results. The long time interval from management decision to surgery and radiotherapy suggests organizational issues which need attention.     

Childhood sarcoidosis (author's transl)

Between 1972--1974 26 children (15 boys and 11 girls) aged 11--14, with sarcoidosis were observed in county Szabolcs-Szatmár, Hungary. The number of cases varied between 1--6 per year, so the incidence of sarcoidosis is about 2--11/100000 for the age group 10--14 years of this county. Sarcoidosis was detected because of complaints in 4 cases, and by mass radiographic surveys in 22 cases. In each of the patients the thoracic form of sarcoidosis was in the foreground (in 6 cases mild bilateral hilar adenopathy, in 2 cases only unilateral hilar adenopathy, in 18 cases typical BHL-syndrome sometimes with "tumorous" adenopathy and in 7 cases out of the 18, hilar adenopathy and mottling in the lungs). The laboratory data were an unsatisfactory basis for the diagnosis. The tuberculin test was negative in 65 per cent. There was no proof for infection with atypical mycobacteria by intradermal tests. The most important basis of diagnosis was the biopsy (mediastinoscopy), especially in cases of simultaneous infection with tuberculosis. Prednisone treatment was carried out in the first place in cases of adenopathy and mottling, and in the cases of elevated serum calcium. Prednisone resistance was observed in two cases; in one of the patients it was secondary since it manifested itself only at the relapse of the BHL-syndrome; in the other patient the drug resistance was primary.     

Colorectal cancer in patients under forty: presentation and outcome

Colorectal cancer is the third most frequent malignancy in adults of both sexes in this country, with 90 per cent of patients diagnosed after age 50 years. This disease is unusual in patients under 40 years of age, and controversy persists as to prognosis in this subset of patients. Patients diagnosed with invasive adenocarcinoma of the colon and rectum from 1985 to 1997 were identified. They were then grouped according to age (< 40 or > or = 40). Charts were reviewed with respect to patient epidemiologic characteristics, clinical presentation, tumor staging, and survival. Twelve women and 24 men less than 40 years of age (median, 31 years/range, 13-39 years) were diagnosed with colorectal adenocarcinomas. This represented 8.6 per cent of the total patients diagnosed with colorectal cancers during this time. Thirty-five (97%) had symptoms (pain, blood per rectum, weight loss, or alteration in bowel habits) before diagnosis, and 23 (64%) had multiple symptoms. Younger patients had more poorly differentiated tumors (28%) and more mucinous adenocarcinomas (26%) than the older group. Younger patients were more likely to present with stage III or IV disease (78%) as well. Despite these findings, the median survival for younger patients was no different than the older patients when compared by stage. Colorectal cancer in young adults is rare, but should be considered in the differential diagnosis for all patients with gastrointestinal symptomatology. The presentation of these patients is not unlike that of older patients. Those patients with early-stage disease should be treated aggressively, as long-term survival may be anticipated, whereas the outcome for those with metastatic disease is poor.     

Thyroid malignant neoplasms. Therapeutic results in 305 patients

Between 1960 and 1972, 305 patients with malignomas of the thyroid gland were surgically treated, irradiated (megavoltage therapy and/or iodine-131), and treated with thyroid hormone according to principles formerly stated. Differentiated adenocarcinomas (34.4% of all the patients) were observed more frequently in women and younger patients, whereas dedifferentiated carcinomas (33.8%) are found relatively more often in men and in an advanced age. Only in 12% of the cases the tumor was discovered in an early stage; thus, an early diagnosis is much too rare so far. In almost two thirds of the patients a spread of metastases occurred. Of these, 11% grew manifest later than five years following the therapy. Distant metastases from differentiated adenocarcinomas accumulated I-131 in sixty per cent, those from undifferentiated carcinomas still in twenty per cent. Treatment results are influenced decisively by histology, tumor spread, age and sex, women less than forty years old with differentiated adenocarcinomas and a circumscribed extension of the tumor having the best prognosis. More prognostic importance is due to the extension of the primary tumor than to the presence of metastases to regionary lymph nodes. Patients with metastases accumulating I-131 have a better chance of survival than those whose metastases do not accumulate. By means of standardized therapeutic rules, utilizing modern therapeutic techniques and based on interdepartmental cooperation, it was possible to improve the results partly by the two- or threefold as compared to a previously treated group of patients.     

Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene

To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 +/- 14.6 years, mean +/- SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine = 48.1 micrograms/24 hours). Thyroid tumors were follicular or Hürthle cell adenomas (no. = 3), follicular carcinomas (FC, no. = 4), papillary carcinomas (PC, no. = 2) and anaplastic carcinomas (no. = 2). Eleven patients (age 47.1 +/- 15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine = 95.2 micrograms/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76 +/- 0.33 vs 1.80 +/- 1.22 mU/l, p = 0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no. = 6), Hürthle cell carcinoma (no. = 1), FC (no. = 2), PC (no. = 2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70-80% of the tumor cells) than in the other two cancers (1+; < 5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.     

Immunological responsiveness and adjunct immunotherapy in lung cancer

Immunocompetency was assessed before and after the operation in 40 patients with lung cancer by skin reaction against tuberculin (PPD) and dinitrochlorobenzene (DNCB), lymphocyte response to PHA, proportion of T-cells, macrophage migration inhibition test (MIT) and the presence of blocking factor. MIT was positive in 27 per cent and blocking factor was positive in 42 per cent. Immune response paralleled the clinical stage of the lesion. In curative resection cases, the immune response rose postoperatively, but declined in non-resectable or recurrent cases. The influence of postoperative radiation therapy, cancer chemotherapy and host mediated agents on the patients was observed. The feasibility of adjuvant specific immunotherapy is discussed.