Vascular collagens: spotlight on the role of type VIII collagen in atherogenesis.

Collagens play a central role in maintaining the integrity and stability of the undiseased as well as of the atherosclerotic vessel wall. An imbalanced metabolism may lead to uncontrolled collagen accumulation reducing vessel wall velocity, frequently resulting in arterial occlusion or thrombosis. A reduced production of collagen and its uncontrolled degradation may affect the stability of the vessel wall and especially of the atherosclerotic plaques by making them prone to rupture and aneurysm. This review presents an overview on the four groups of vascular collagens and on their role in atherogenesis. The major focus was to highlight the extraordinary role and importance of the short chain network forming type VIII collagen in the extracellular matrix of undiseased arteries and of atherosclerotic plaques. The molecular structure of type VIII collagen, its cellular origin, its implication in atherogenesis, its temporal and spatial expression patterns in human and experimental models of atherogenesis, the factors modulating its expression, and--not at least--its potential function is discussed.

Concomitant chemoradiotherapy followed by adjuvant chemotherapy in parotid gland undifferentiated carcinoma.

AIMS AND BACKGROUND: Undifferentiated carcinoma of the parotid gland is a poor-prognosis lesion. Results in unresectable lesions, treated with radiotherapy alone, are very disappointing. METHODS: Six patients with T3-4 N0-1 inoperable lesions were treated with conventional radiotherapy (64-70 Gy, 2 Gy per fraction 5 times a week) and concomitant cisplatin (100 mg/m2, days 1, 22 and 43). Four weeks after radiotherapy, adjuvant chemotherapy (cisplatin, 80 mg/m2, day 1, + VP16, 100 mg/m2, days 1, 3 and 5, q = 3 weeks, for 3 cycles) was given. RESULTS: A median dose of 66 Gy (range, 64-70 Gy) was delivered, and all patients received 3 courses of cisplatin during radiotherapy. Five of 6 patients received all three chemotherapeutic adjuvant courses. Two months after the end of treatment, 3 CR (50%), 2 PR (33%) and 1 NC (16%) was observed. Median CR and PR duration was 26+ and 10 months, respectively. Median overall survival was 18 months. No severe acute or late toxicity was observed. CONCLUSIONS: Concomitant chemoradiotherapy followed by adjuvant chemotherapy in advanced unresectable undifferentiated parotid carcinoma is feasibile and well tolerated. The high percentage of long-lasting CR is encouraging.

Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinoma.

BACKGROUND: Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive illness. Here we report long-term results of high-dose chemotherapy (HDC) as late intensification, with autologous peripheral blood stem cell (PBSC) support. METHODS: Six patients (5 men, 1 woman; median age 41years; median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone metastasis, 2) have been enrolled. All patients had been previously treated with neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a re-irradiation. Every patient received three courses of cisplatin + epirubicin and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 x 10(6)/kg (range, 4.5-18) CD34+ cells were reinfused. HDC was according ICE scheme: ifosfamide, 2.5 g/m(2)/d, + carboplatin, 300 mg/m(2)/d, + VP-16, 300 mg/m(2)/d days 1 through 4. RESULTS: After conventional chemotherapy, we had 1 CR (16%), 3 PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%),1 PR (17%), and 1 MR (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14-50), two patients are alive without disease (34%), one is alive with bone disease (16%), and three (50%) died of disease at 16, 18, and 24 months. CONCLUSIONS: HDC has an acceptable toxicity, can convert PR in CR, and seems effective, with long-lasting CRs.

Phase II randomized trial comparing vinorelbine versus vinorelbine plus cisplatin in patients with recurrent salivary gland malignancies.

BACKGROUND: Some previous studies have shown that vinorelbine (VNB) is active in recurrent salivary gland tumors. METHODS: Between April 1993 and April 1997, 36 patients in a Phase II randomized trial received either cisplatin, 80 mg/m(2), on Day 1 plus VNB, 25 mg/m(2), on Days 1 and 8 (every 3 weeks) (for a minimum of 3 cycles (Arm A [16 patients]), or VNB, 30 mg/m(2)/week, (for a minimum of 9 wks) (Arm B [20 patients]). There were 23 males and 13 females with a median age of 59 years (range, 20-74 years) and a median Eastern Cooperative Oncology Group performance status of 1 (range, 0-2). Four patients had been treated with prior surgery (S) or radiotherapy (RT), 27 patients had been treated with S plus RT, and 5 patients had been treated with S plus RT plus mitoxantrone. Eighteen patients had major salivary gland tumors, and 18 patients had minor salivary gland tumors; 9 patients had adenocarcinoma, 22 patients had adenoid cystic carcinoma, 1 patient had a malignant mixed carcinoma, 3 patients had undifferentiated carcinoma, and 1 patient had a mucoepidermoid carcinoma. The site of recurrence was local in 16 patients, local plus metastatic in 5 patients, and metastatic only in 15 patients. These characteristics were well balanced between the 2 arms. RESULTS: In Arms A and B a complete response (CR) was noted in 3 patients (19%) and no patients, respectively; a partial response (PR) was noted in 4 patients (25%) and 4 patients (20%), respectively; no change was noted in 6 patients (37.5%) and 9 patients (45%), respectively; and progressive disease was noted in 3 patients (19%) and 7 patients (35%), respectively. The median duration of the CR was 15+ months (range, 6-27+ months) and for PR the median duration was 7.5 months (range, 3-11+ months) and 6 months (range, 3-9 months) in Arms A and B, respectively. Number of patients surviving > 12 months was 6 versus 1 in Arms A and B, respectively (P < 0.05). Grade 2-3 nausea and emesis was statistically higher (P < 0.001) in Arm A; there was no significant difference with regard to other side-effects between the two treatment arms. CONCLUSIONS: VNB is a drug with moderate activity in salivary gland malignancies. The combination of cisplatin plus VNB was found to be more active than VNB alone, with a good number of CRs and long-term survivors reported in the current study.

Combined chemo-radiotherapy for stage IV undifferentiated nasopharyngeal carcinoma.

Undifferentiated nasopharyngeal carcinoma is a chemosensitive lesion, but its role in the management of local advanced disease is under investigation. Twenty-seven untreated stage IV undifferentiated nasopharyngeal carcinoma patients were treated with radiotherapy (median dose, 66.6 Gy, 1.8 Gy/day) and concomitant cisplatin (100 mg/m2 days 1, 22 and 43). After 4 weeks, patients received, every 4 weeks, 3 cycles with cisplatin (80 mg/m2 day 1) + 5-fluorouracil (1,000 mg/m2/day continuous infusion for 96 h). After radiotherapy, we observed 74% complete responses and 26% partial responses; after adjuvant chemotherapy 96% had a complete and 4% a partial response. After a median follow-up of 36 months, 81% of the patients were alive (70% with no evidence of disease). Four-year overall and disease-free survival was 70% and 60%, respectively. Concomitant chemotherapy plus radiotherapy was well tolerated, whereas adjuvant chemotherapy was more toxic. Long-term results were significantly better than those observed with radiotherapy alone.

Radiation therapy and chemotherapy in the conservative treatment of carcinoma of the anal canal: survival and late morbidity in a series of 25 patients.

Combined radiation therapy and chemotherapy have been reported to produce a high incidence of complete regression of epithelial cancer of the anal canal. Our group has treated 25 patients since June 1986. Treatment included chemotherapy (first period: Mitomycin C + 5-Fluorouracil; second period: Carboplatin + 5-Fluorouracil) and simultaneous whole-pelvis irradiation (50.40 Gy). Our results confirm that radiochemotherapy can achieve good local control: all patients were in complete clinical remission three months after the completion of combined therapy. Seven, patients developed recurrences; the actuarial survival rate was 78.5% and the disease free survival rate 67%. Acute toxicity was tolerable, but a relatively high number of patients exhibited chronic treatment-related symptoms. In order to reduce late side effects, other studies are necessary to explore if, in patients with small tumors, less extensive locoregional treatment can be effective without reducing the survival rate.

[The results of sandwich adjuvant radiotherapy in 2nd- and 3rd-stage rectal adenocarcinoma. The authors' personal experience]. / Risultati della radioterapia adiuvante a "sandwich" nell'adenocarcinoma del retto negli stadi II e III. Esperienza personale.

From January, 1985, to June, 1993, 125 patients with stages B2-C adenocarcinomas of the rectum were submitted to pre- and postoperative irradiation according to Thomas Jefferson University protocol guidelines. Five hundred cGy were administered as a single preoperative dose 24 hours before surgery using parallel opposed (AP-PA) treatment fields including the whole pelvis. Pathologic samples were classified following the Astler-Coller staging criteria. Forty-seven patients had no postoperative treatment because their disease stage was A, B1 or D, 11 for refused consent and 9 postoperative complications preventing any further therapy. Seventy-eight patients concluded the treatment schedule and are assessable for response. Radiotherapy total dose consisted of 4400-5000 cGy administered over 5-6 weeks: the patients were treated with megavoltage photons (15-MeV photons) and one dose fraction of 2 Gy was delivered daily, 5 days a week, with the "box" or the "three-field" technique. Median follow-up time was 50.2 months from the beginning of treatment for all the patients in our series (range: 18-120 months). Radiation therapy was well tolerated: 5 patients had severe diarrhea and 2 had small bowel obstruction which required surgery. Local recurrences were observed in 13 of 78 patients (16.7%). Overall actuarial survival at 5 years was 66.8%. Our results confirm the efficacy of this treatment, which is in agreement with international literature data. However, no difference was seen relative to the results obtained with postoperative irradiation alone. We conclude that sandwich radiotherapy can be an effective tool for the local control of rectal adenocarcinoma, with acceptable morbidity, even though it fails to prevent metastases.

[RAdio-chemo-surgical combined treatment of non-small cell lung carcinoma N2]. / Trattamento integrato radio-chemio-chirurgico nel carcinoma polmonare non a piccole cellule N2.

As yet, no optimal treatment for stage-IIIA non-small-cell lung cancer (NSCLC) has been established. Particularly, in the patients with stage-IIIA N2 disease, surgical resection for cure is limited to few selected patients. Of late, a number of studies have suggested that such treatment modalities as chemotherapy, radiotherapy and surgery might be combined to improve treatment efficacy. Based on these conclusions, a cooperative study for N2 NSCLC patients was performed. Treatment included continuous CDDP infusion (6 mg/m2/day) and concomitant irradiation. Fifteen patients were examined. After neoadjuvant treatment, 4 patients were found to have unresectable lesions for local disease progression or metastasis. Eleven patients underwent complete resection (73% resectability). Follow-up ranged 6 to 32 months: 6 patients are now free from relapse (respectively at 31, 28, 23, 14, 12 and 3 months) and 1 is alive with adrenal gland metastasis. Overall and disease-free survival rates are 40.6% and 31.5%, respectively. Our preliminary results indicated that this protocol is well tolerated. Resectability was good and tumor sterilization rate was satisfying (complete T and N sterilization in 6 cases, sterilization of either T or N in 3 cases). The patients with non-adenocarcinoma histology exhibited better local control and prognosis than those with histologic diagnosis of adenocarcinoma.

[The use of cisplatin as radiosensitizing agent in advanced tumors of the head and neck. Randomized study]. / Utilizzazione del cisplatino come radiosensibilizzante nei tumori avanzati della regione testa-collo. Studio randomizzato.

This study was aimed at assessing whether c-DDP administration immediately before radiotherapy could increase frequency and duration of objective responses, as well as survival, in patients affected with locally advanced stages of squamous carcinomas of the head and neck. All patients had already undergone two induction cycles according to the CABO schedule. Ninety-six of 108 treated patients could be evaluated. Treatment schedule consisted in: 1) randomized distribution of patients into two groups before induction chemotherapy; 2) two cycles of induction chemotherapy according to the CABO schedule in all patients; 3) radiation therapy: the patients in group A were given 5 mg/mq of i.v. cisplatin, 30-60 minutes before each session. The results from the two groups were compared and no significant differences were observed regarding objective response (82.5% in group A vs. 86% in group B), response duration and overall survival rates. Even though toxicity was higher in the patients in group A, therapeutic protocol never needed be modified.

[Treatment of N2-3 pulmonary carcinoma. Preoperative radio-chemotherapy]. / Trattamento del carcinoma polmonare N2-3. Radio-chemioterapia preoperatoria.

Preoperative integrated neo-adjuvant radio-chemotherapy was performed in 8 patients suffering from NSCLC bronchial carcinoma at stages IIIA-IIIB (N3 mediastinal). After treatment, 7 patients underwent apparently radical pulmonary exeresis, whereas the patient with adenocarcinoma (T2 N2 M0) was not operated due to the recurrence of disease following supraclavicular lymph node metastasis. Preoperative radio-chemotherapy allows the sub-staging of the disease and the insertion of these patients into the operating programme.

[The use of electrons in oncologic radiotherapy: our experience]. / L'uso degli elettroni nella radioterapia oncologica: nostra esperienza.

The authors describe the interaction of electrons with tissues, the characteristics of depth isodose curves with sharp dose fall-off. These characteristics reduce the utilization of electron therapy only for tumors situated some 5 cm depth below the skin surface and with regular surface. The authors report their experience from 1978 in the treatment of vulvar carcinoma, chest-wall recurrences from breast carcinoma, and cutaneous lymphomas. All these neoplastic diseases were treated with electron beam of adequate energy. Initially betatron was used, successively a linear accelerator (Siemens) about for two years. Results obtained in the treatment of vulvar carcinoma are reported. Two and five years disease free survival rates was respectively 33% and 19% (it is remarked the importance of prophylactic treatment on inguinal lymphnodes). Local control observed in 44 patients with cutaneous lymphomas was 85% until three years; a greater number of recurrences was observed in centrocytic-centroblastic lymphomas. Moreover, local control of breast recurrences was 65% with 5 years survival rate of 22% (34% in patients with only one skin recurrence). Only 22% of the further local failures appear within the treatment field while 78% appear out of field.

[Preoperative endocavitary curietherapy of stage Ib-IIa-IIb cervical carcinoma. Personal observations]. / Curieterapia endocavitaria pre-operatoria nel carcinoma della cervice uterina agli stadi Ib-IIa-IIb. Osservazioni personali.

From 1980 through 1984, 41 patients with squamous cell cervix carcinoma and 1 with adenosquamous carcinoma were treated with preoperative irradiation. Clinical stages were Ib in 6 patients, IIa in 24, and IIb in 12. At surgery, lymph node metastases were found in 5 cases, and residual tumors in 8. The latter risk patients were given further external radiotherapy after surgery. Overall three-year survival rates for FIGO stage Ib was 100%; 91.6% for stage IIa, and 83% for stage IIb (minimum follow-up: 3 years). Two patients died from locoregional recurrence of the disease 12-24 months after the treatment, and 2 from distant metastases; 5 patients have showed signs of local improvement. Our results seem to point to pelvic lymph node involvement as the major prognostic factor: in fact, 40% only of the patients with involved lymph nodes is alive. Actuarial survival rates show 90.4% of patients to be alive at 5 years. Tolerance to the combined use radiotherapy and surgery was fair: no severe side-effects were observed. Even though our results are encouraging, a randomized study is still recommended to verify the actual value of this treatment versus combined surgery and radiotherapy or radiotherapy alone.

[Quadrantectomy and adjuvant radiotherapy in carcinoma of the breast. Initial results of our cases]. / Quadrantectomia e radioterapia adiuvante nel carcinoma della mammella. Primi risultati della nostra casistica.

The conservative treatment of early breast cancer always requires irradiation of residual mammary tissue. The preliminary results obtained in 45 early breast cancer patients, who received quadrantectomy plus axillary dissection, followed by radiation of residual breast are reported. Radiation was performed by the two opposed field technique. In some cases the residual breast tissue was compressed using a special accessory provided with the Theratron 780. In addition to the tumor dose of 50 GY, 10 GY boots was added to the surgical scar using 7 MeV electrons. The 6 patients with positive axillary nodes received 6 courses of adjuvant chemotherapy (CMF) after radiotherapy. All patients are currently alive and free of disease. The 64% (29 patients) were followed up for at least 5 years, and 36% (16 patients) for at least 3 years. Only 2 cases of local recurrence were encountered (4.4%). The esthetic result was satisfactory in all cases. No side effects due to treatment were noted.