Are the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and the undifferentiated connective tissue disease (UCTD) related to each other? A case-control study of environmental exposures.

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is an entity that includes different autoimmune conditions observed after exposure to an adjuvant. Patients with undifferentiated connective tissue disease (UCTD) present many signs and symptoms of ASIA, alluding to the idea that an exposure to adjuvants can be a trigger also for UCTD. The aim of this case-control study was to investigate exposure to adjuvants prior to disease onset in patients affected by UCTD. Ninety-two UCTD patients and 92 age- and sex-matched controls with no malignancy, chronic infections, autoimmune disease nor family history of autoimmune diseases were investigated for exposure to adjuvants. An ad hoc-created questionnaire exploring the exposure to vaccinations, foreign materials and environmental and occupational exposures was administered to both cases and controls. Autoantibodies were also analyzed (anti-nuclear, anti-extractable nuclear antigens, anti-double-stranded DNA, anti-cardiolipin, anti-ß2 glycoprotein I). UCTD patients displayed a greater exposure to HBV (p = 0.018) and tetanus toxoid (p < 0.001) vaccinations, metal implants (p < 0.001), cigarette smoking (p = 0.006) and pollution due to metallurgic factories and foundries (p = 0.048) as compared to controls. UCTD patients exposed to major ASIA triggers (vaccinations, silicone implants) (n = 49) presented more frequently with chronic fatigue (p < 0.001), general weakness (p = 0.011), irritable bowel syndrome (p = 0.033) and a family history for autoimmunity (p = 0.018) in comparison to non-exposed UCTDs. ASIA and UCTD can be considered as related entities in the "mosaic of autoimmunity": the genetic predisposition and the environmental exposure to adjuvants elicit a common clinical phenotype characterized by signs and symptoms of systemic autoimmunity.

Subcutaneous administration of interleukin-2 and interferon-alpha 2b in advanced renal cell carcinoma: long-term results.

Clinical data have supported the combination of subcutaneous r-interleukin-2 (rIL-2) and r-interferon-alpha (rIFN-alpha) as a promising combination for advanced renal cell carcinoma (RCC), with a reduced toxicity. We evaluated the activity and safety of this outpatient immunotherapy and report on the clinical results and the long-term survival analysis. Objective responses was observed in 9 of 50 (18%) patients, 6 of whom (12%) achieved a complete response. Overall median survival is 12 months, six patients were surviving at a median follow-up of 24 months, and three (6%) are still progression-free.

Possible correlation between some biologic effects and the clinical course in patients treated with continuous infusion of interleukin-2 plus alpha-2 interferon for metastatic renal cell carcinoma.

BACKGROUND: Interleukin-2 therapy is known to cause many biologic effects, which are enhanced by the administration of interferon prior to or immediately after interleukin-2 infusion. Some of these effects could be related to the clinical response. METHODS: Sixteen patients with metastatic renal cell carcinoma were treated with continuous infusion of interleukin-2 plus alpha-2 interferon. Differential leukocyte count and lymphocyte subset evaluation were performed every 3 days during interleukin-2 treatment. At each cycle, the presence of the following antibodies was tested: antithyroid, antinuclear, antiplatelet and antierythrocyte. RESULTS: Fifteen patients were evaluable for response. No complete response was observed. Five patients obtained partial response (33%) and 3 stable disease (20%): 2 of them underwent surgical resection of metastases and obtained complete response. Some of our patients showed a significant increase in eosinophils, CD25+ lymphocytes and antithyroid antibodies. The association of these parameters, calculated with a "score" system, was also related to a better clinical response. CONCLUSIONS: Eosinophils, CD25+ lymphocytes and antithyroid antibodies could have a predictive value for the efficacy of interleukin-2 and alpha-2 interferon therapy in metastatic renal cell carcinoma.

Proliferation index as a prognostic marker in breast cancer.

BACKGROUND: The proliferative activity of tumors has been extensively investigated with different approaches, among which the use of the monoclonal antibody Ki-67 represents an easy and reliable means of assessing cell proliferation. In this study, the proliferative activity of 129 primary breast cancers was investigated, and the results were related to prognosis. METHODS: Tumor samples, obtained from 129 patients who underwent surgery between January 1987 and December 1988, were processed for staining by an immunohistochemical procedure (avidin-biotin complex). The median time of observation was 42 months (range, 31-55 months). Life-table analysis (Mantel-Cox) was used to assess the probability of disease-free survival (DFS) and overall survival (OS). RESULTS: Tumors with high Ki-67 proliferation indices (> 20%) were associated with a higher 4-year probability of relapse of disease (55.3% versus 79.1%; P = 0.003) and death (71% versus 95.6%; P = 0.00005) when compared with tumors with low Ki-67 values. In addition, this proliferative parameter maintained its prognostic significance when the patients were stratified according to lymph node involvement, menopausal status, and nuclear estrogen receptor content. CONCLUSIONS: Tumor proliferative activity as evaluated by the monoclonal antibody Ki-67 seems to be an effective indicator of prognosis in breast cancer for DFS and OS.

[Treatment results in pT2, NO1 breast cancer. )A retrospective analysis of 85 cases)]. / Risultati del trattamento del carcinoma mammario pT2, NO-1. (Analisi retrospettiva su 85 casi).

The authors report on 85 T2 breast carcinoma treated from March 1984 to February 1991. The median age was 55.7 years (range: 24-82). The most common type of tumor was infiltrating ductal carcinoma (88.2%). T pathological diameter was in 69 cases < or = 3 cm (81.2%). 47 patients showed pathologically positive axillary nodes (55.3%). Radical mastectomy with total axillary dissection, preferably modified by Patey or Madden (78.8%), was the treatment of choice. Only 5 patients were submitted to conservative surgery (quadrantectomy plus radiotherapy). Mean follow-up time was 42 months. For all considered patients, crude and without evident disease 3 and 5 years actuarial survival was evaluated. Distant metastases were observed in a total of 12/85 patients (14.1%), mainly in N+ with more than 3 nodes (31.5%) three times associated to loco-regional failures. Results at June 1992, as occurrence of first failure from the date of surgery are described. Different therapeutic managements are discussed. Prognosis of T2 breast carcinoma remains still poor. Limited surgery in association with radiotherapy and/or pre- and postoperative chemotherapy in N+ patients with more than 3 nodes or N- patients with high cell proliferation index, seems to be encouraging to T2 cases with a diameter less than 3 cm, when local conditions are suitable for good final aesthetic results.

[Clinical and prognostic usefulness of Ki67 determination in breast carcinoma]. / Utilità clinica e prognostica della determinazione del ki67 nel carcinoma mammario.

We studied the correlation between tumor size, nodal status, menopausal status, nuclear oestrogen receptors, disease free survival and Ki67 (proliferation rate) measured by mean of immunohistochemical analysis with monoclonal antibody. Median value was 10%. From December 1986 to October 1989 we studied 236 consecutive patients (pts). Median follow up was 34 months (range 7-51 months). Median age was 56 years (r. 26-82). We observed: 1) lower levels in smaller tumors; 2) poor correlation with nodes involvement; 3) lower levels when nuclear oestrogen receptors were positive. Preliminary data seem to suggest longer disease free survival when Ki67 is low.

Histology as a prognostic factor in early gastric cancer.

Of 431 patients with gastric cancer observed in our institution, 23 (5.3%) had early gastric cancer (EGC). Macroscopic presentation, histology, depth of invasion, and lymph node involvement were evaluated in all the cases. All patients underwent surgery and an intensive follow-up was performed. Five of the 23 patients progressed, and the risk factors were examined. Histology seemed to be the main prognostic factor in our study, since intestinal type of EGC was associated to a significantly better prognosis. Total gastrectomy is indicated in the proximal localization of EGC, and should perhaps be performed also in cases presenting undifferentiated histology.

Age as a prognostic factor in primary non Hodgkin lymphoma of the stomach.

We present 20 cases of primary non-Hodgkin lymphoma of the stomach. Histological classification, staging, age of patients and therapeutical approach were evaluated. Median overall survival was 30 months, and 5-year survival was 44%. In our small series, the age of the patients plays an important role: median overall survival is 18 months in patients greater than 60 y.o. (compared to 90 months in patients less than 60 y.o.) and 5-year survival 12.5% (compared to 62%).

Pancreatic cystadenocarcinoma and pregnancy: a case report.

We report a case of cystadenocarcinoma occurring in a pregnant woman. After child birth, a subtotal pancreatectomy was performed, without rupture of the cyst. The patient is asymptomatic, 24 months after surgery. The presentation of cystadenocarcinoma in pregnancy has been reported in another single case. The possibility of hormonal dependence is discussed.