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Objective: To study how the information gained from axillary dissection in women (75 years old or more) with breast cancer influenced postoperative adjuvant treatment., Design: Retrospective review of casenotes., Setting: University departments of surgery and oncology, Sweden., Subjects: 166 women (aged 75 years or more) operated on for primary breast cancer between 1980-1989., Main Outcome Measures: Type of operation and postoperative therapy given., Results: In 138/166 (83%) women axillary dissection was done, but in only 21/59 (36%) of these patients did information gained from the procedure influence the postoperative treatment according to the treatment guidelines for breast cancer. None of the 28 patients who did not undergo axillary dissection were subjected to further operations or radiotherapy for axillary nodal recurrence after a mean follow up of 47 months., Conclusions: Axillary dissection should be reserved for local control of disease and for those patients who preoperatively agree to undergo postoperative irradiation or chemotherapy if metastases are found.

The paper presents long-term results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus surgery alone including 1,347 postmenopausal patients with histologically negative axillary nodes and a tumour diameter less than or equal to 30 mm. Data on the estrogen receptor status of the primary tumour were available in 1,136 patients (84%). At a median follow-up of 7 years (range 1.7-13.0 years) there was a significant prolongation of the recurrence-free survival among those allocated to tamoxifen (p less than 0.01), significantly fewer deaths due to breast cancer (p = 0.02) and a trend towards improved overall survival (p = 0.11). The treatment benefit was restricted to patients with ER-positive tumours. There was no significant reduction of breast cancer recurrences in the tamoxifen group among patients whose tumours were classified as ER-negative. The results support and extend previous studies in showing a long-term benefit of tamoxifen in postmenopausal breast cancer patients with node-negative, estrogen receptor positive disease.

Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

From 1976 to 1984, 427 postmenopausal women with high-risk breast cancer (pN + or pT greater than 30 mm) were randomized between postoperative radiation therapy (RT), radiation therapy plus tamoxifen (RT-TAM), adjuvant chemotherapy (CT), or chemotherapy plus tamoxifen (CT-TAM). Surgery was a modified radical mastectomy in all cases. The radiation therapy was given with high-voltage techniques and included the chest wall and regional nodes. The dose was 4600 cGy/4 1/2 weeks. Tamoxifen was given at a dose of 40 mg daily for 2 years. The adjuvant chemotherapy consisted of 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (or chlorambucil, methotrexate, and 5-fluorouracil [LMF] for patients entered before 1978). At a median follow-up time of 6 1/2 years the recurrence-free survival was significantly better for patients allocated to radiation therapy compared to chemotherapy and for patients allocated to tamoxifen compared to no adjuvant endocrine treatment (P less than 0.01). At 10 years the recurrence-free survival for patients in the RT-TAM, RT, CT-TAM, and CT groups was 63%, 57%, 47%, and 31%, respectively. A significant reduction of treatment failures with tamoxifen was only observed among patients with estrogen receptor-positive tumors. The overall survival difference in favor of patients allocated to radiation therapy or tamoxifen was not significant: the respective survival percentage at 10 years in the RT-TAM, RT, CT-TAM, and CT group was 65%, 62%, 52%, and 50%. The results indicate that postoperative radiation therapy continues to play an important role in the primary management of postmenopausal women with high-risk breast cancer and that the addition of tamoxifen may further improve the results among ER-positive patients.

The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P less than 0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P less than 0.01) and deaths by 7% (P greater than 0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.

The frequencies of splenectomy and post-splenectomy septicemia over a 10-year period in the Stockholm area were studied. The main observation was a significantly increased risk of pneumococcal septicemia in splenectomized patients, in particular HD patients. At the two clinics for infectious diseases in Stockholm, 1310 septicemia patients were treated, and among these, 14 splenectomized patients. In the total material, pneumococci were the causative agent in 4.7% but splenectomized patients had pneumococcal septicemia in 71% (10/14). In the 12 surgical clinics of Stockholm, 1148 splenectomies had been performed during the period, among these, 76 in HD patients. Pneumococcal septicemia occurred in 5 splenectomized HD patients.

A young man had a mild, slightly progressive pulmonary sarcoidosis. After 4 years he developed an acute disease with splenomegaly, anemia, marked elevation of ESR, hypercalcemia and mild renal insufficiency. The anemia and ESR elevation disappeared after splenectomy, whereas the hypercalcemia still needs corticosteroid treatment. Attempts to withdraw this treatment resulted in recurrence of the hypercalcemia, but no other abnormalities. In contrast to other organs examined, the sarcoid tissue in the spleen revealed necrosis formation, consistent with a recent process. A Kveim antigen preparation from the spleen was less potent than antigen from mediastinal lymph nodes. It is suggested that the acute phase of the disease involved mainly the spleen. Speculations about the possible role of infectious agent(s) are put forward.

Spontaneously DNA synthesizing blood and spleen lymphocytes in 9 patients with Hodgkin's disease have been studied by surface markers and by autoradiography after in vitro labelling with 3H-thymidine of cell specimens separated according to size. The findings have been related to functional characteristics of blood lymphocytes. The distribution of E and EAC rosetting cells in blood and spleen was similar also after separation according to cell size. The number of mainly large activated blood and spleen cells was increased in patients as compared to controls. Both E and EAC rosetting cells participated in this unexplained cell challenge.

The paper summarizes up-dated results of three randomized adjuvant trials from the Stockholm Breast Cancer Group. The objective of all studies included an evaluation of the role of megavoltage radiation in the primary management of patients with early breast cancer. The first trial was started in 1971 and included 960 pre- and postmenopausal patients with operable disease. The study compared adjuvant radiotherapy with surgery alone. All patients were treated with a modified radical mastectomy. There was a sustained improvement of the recurrence-free survival with radiotherapy (p less than 0.001). Among node positive cases radiation reduced the frequency of both loco-regional recurrence (p less than 0.001) and distant metastasis (p less than 0.01). This observation indicates that distant dissemination in subgroups of patients can originate from uncontrolled local deposits of tumor cells, for instance in the regional lymph nodes. No adverse effect from radiation on long-term survival was observed. The second study was started in 1976 and compared postmastectomy radiation with adjuvant chemotherapy in pre- and postmenopausal high-risk patients. At a mean follow-up of 6 1/2 years there was no significant difference in recurrence-free survival between the two treatments. However, postmenopausal patients fared better with radiotherapy (p less than 0.01). In this subgroup, radiation was more effective than adjuvant chemotherapy in reducing both distant metastases (p less than 0.01) and loco-regional recurrences (p less than 0.001). In the third trial--which only included postmenopausal patients--2 years of adjuvant tamoxifen was compared with no adjuvant endocrine treatment. The number of treatment failures was significantly reduced with tamoxifen (p less than 0.01) but there was no significant overall survival benefit. Subset analysis indicated that tamoxifen improved the recurrence-free survival among patients treated with adjuvant chemotherapy (p less than 0.01) but only to a level close to that achieved with radiotherapy alone. Addition of tamoxifen to radiotherapy failed to further increase the recurrence-free survival.

Immunological functions of 9 non-splenectomized and 8 splenectomized patients with Hodgkin's disease were studied before and after treatment. The two groups compared well with regard to age, clinical and immunological findings at diagnosis and observation time. When retested, all patients had enjoyed an unmaintained complete remission for 2 to 5 years following total nodal radiotherapy. After therapy, total lymphocyte and T-lymphocyte counts decreased in non-splenectomized patients but remained unchanged in splenectomized patients. The blood lymphocyte DNA synthesis after activation by concanavalin A or pokeweed mitogen persisted at the same low level after treatment. The delayed skin hypersensitivity and the lymphocyte activation by PPD antigen were restored in several patients in both groups. The IgM concentration decreased after therapy independent of splenectomy. The IgA level was low in non-splenectomized patients. Splenectomy seems to protect from the therapy-induced lymphocytopenia. No alterations of immunoglobulins and blood lymphocyte functions could be ascribed to splenectomy.

Spontaneous and mitogen induced blood lymphocyte DNA synthesis was studied in relation to weight and tumor involvement of the spleen in 33 untreated patients with Hodgkin's Disease. Splenic tumor involvement was found in 14 patients. In this group there was a strong inverse correlation between spleen weight and lymphocyte DNA synthesis induced by PWM, ConA and PPD. In patients with uninvolved spleens the spontaneous blood lymphocyte DNA synthesis increased with spleen weight. No correlation with the mitogen response was observed in this group.

Thirty patients with splenic injury have been treated at Danderyd Hospital 1969-1984. All the 18 patients with splenic trauma treated until 1978 underwent splenectomy. Of the 12 patients with verified splenic injury after 1979 only six were splenectomized, two underwent laparotomy without splenectomy and four were treated nonoperatively. Thus, in half of the patients where a spleen preserving treatment was tried the spleen could be saved. A retrospective study of the previous 18 patients indicates that about the same proportion of spleen saving treatment would have been possible.

Lymphocyte counts and functional competence of lymphocytes from arterial and venous splenic blood were studied in six patients with Hodgkin's disease subjected to splenectomy. One patient was untreated, four were tested after mantle field treatment and a sixth patient had a splenic relapse after total nodal radiotherapy. The percentage of E binding cells in splenic venous blood was lower than that of arterial blood though no significant differences were found in total lymphocyte or E binding cell counts. The spontaneous lymphocyte DNA synthesis was lower in venous than in arterial splenic lymphocytes in all patients. Pokeweed mitogen (PWM)-induced DNA synthesis was much lower in lymphocytes from splenic venous blood than in those from arterial blood in two patients and marginally decreased in another two. The pattern of concanavalin A response was similar to that of PWM. The elimination of lymphocytes over the spleen could not be related to the presence of lymphocytotoxic serum factors or to splenic weight or histologically verified tumour involvement. The results support the notion that some facets of the blood lymphocyte abnormalities in Hodgkin's disease may be explained by removal of functionally active lymphocyte subpopulations in the spleen. It is also concluded that spontaneously activated lymphoid cells are detained in the spleen.

The IgG and IgA antibody subclass responses to pneumococcal polysaccharide antigens type 6A and 19F were studied after immunization with a 14-valent vaccine (Pneumovax, MSD), in 53 splenectomized patients (11 Hodgkin's disease, 13 nonHodgkin's lymphoma (NHL), 9 immune haemolytic anaemia or idiopathic thrombocytopenia purpura and 20 posttraumatic splenectomized patients) and 18 non-splenectomized controls. The antibodies were mainly restricted to the IgG2 and IgA2 subclasses. NHL patients had lower pre-vaccination values to the studied antigens and lower antibody response to vaccination than the other patient groups in which the antibody responses did not differ from those of controls. 1 vaccinated NHL patient experienced two episodes of pneumococcal septicaemia, both occurring after chemotherapy which abolished the previously normal IgG2 antibody levels to the pneumococcal antigens. It is concluded that the antibody response to 6A and 19F antigens after pneumococcal vaccination is not reduced in splenectomized patients but is impaired in immunodeficiency states associated with B-cell lymphoma and treatment with cytostatic drugs.

In a retrospective study of 39 splenectomies, patients with increased blood cell breakdown (13 cases of idiopathic thrombocytopenic purpura (ITP), 5 cases of hereditary spherocytosis, 2 of Felty's syndrome and 2 of autoimmune hemolytic anemia) were compared with those patients also presenting decreased blood cell production [14 cases of myelofibrosis (MF) with splenomegaly and 3 cases of advanced chronic myelogeneous leukemia (CML)]. Platelet regeneration post-operatively was significantly (p less than 0.01) more rapid in the ITP than in the MF group. Only 1/22 patients in the ITP group had major post-operative complications as compared to 10/17 in the MF group. None of the patients in the ITP group died within 25 days of operation as compared to 5/17 in the MF group. Only 3/22 patients in the ITP group lost more than 800 ml of blood during the operation as compared to 8/17 with MF. No statistically significant higher blood loss was found in patients with less than 30 x 10(9) platelets/l preoperatively, compared to those with higher platelet counts. However, correlation between the splenic weights and amount of blood loss was statistically significant (p less than 0.01). Thus, splenectomy seems much better tolerated in patients with ITP, even if platelets are low, than in patients with myelofibrosis.