Subjective assessment and IOTA ADNEX model in evaluation of adnexal masses in patients with history of breast cancer.

OBJECTIVE: To evaluate the performance of subjective assessment and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in discriminating between benign and malignant adnexal tumors and between metastatic and primary adnexal tumors in patients with a personal history of breast cancer. METHODS: This was a retrospective single-center study including patients with a history of breast cancer who underwent surgery for an adnexal mass between 2013 and 2020. All patients had been examined with transvaginal or transrectal ultrasound using a standardized examination technique and all ultrasound reports had been stored and were retrieved for the purposes of this study. The specific diagnosis suggested by the original ultrasound examiner in the retrieved report was analyzed. For each mass, the ADNEX model risks were calculated prospectively and the highest relative risk was used to categorize each into one of five categories (benign, borderline, primary Stage I, primary Stages II-IV or metastatic ovarian cancer) for analysis of the ADNEX model in predicting the specific tumor type. The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal tumors and between primary and metastatic adnexal tumors was evaluated, using final histology as the reference standard. RESULTS: Included in the study were 202 women with a history of breast cancer who underwent surgery for an adnexal mass. At histology, 93/202 (46.0%) masses were benign, 76/202 (37.6%) were primary malignancies (four borderline and 72 invasive tumors) and 33/202 (16.3%) were metastases. The original ultrasound examiner classified correctly 79/93 (84.9%) benign adnexal masses, 72/76 (94.7%) primary adnexal malignancies and 30/33 (90.9%) metastatic tumors. Subjective ultrasound evaluation had a sensitivity of 93.6%, specificity of 84.9% and accuracy of 89.6%, while the ADNEX model had higher sensitivity (98.2%) but lower specificity (78.5%), with similar accuracy (89.1%), in discriminating between benign and malignant ovarian masses. Subjective evaluation had a sensitivity of 51.5%, specificity of 88.8% and accuracy of 82.7% in distinguishing metastatic and primary tumors (including benign, borderline and invasive tumors), and the ADNEX model had a sensitivity of 63.6%, specificity of 84.6% and similar accuracy (81.2%). CONCLUSIONS: The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal masses in this series of patients with history of breast cancer was relatively similar. Both subjective assessment and the ADNEX model demonstrated good accuracy and specificity in discriminating between metastatic and primary tumors, but the sensitivity was low. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Emerging and re-emerging infectious disease in otorhinolaryngology.

SUMMARY: Emerging and re-emerging infectious disease in otorhinolaryngology (ENT) are an area of growing epidemiological and clinical interest. The aim of this section is to comprehensively report on the epidemiology of key infectious disease in otorhinolaryngology, reporting on their burden at the national and international level, expanding of the need of promoting and implementing preventive interventions, and the rationale of applying evidence-based, effective and cost- effective diagnostic, curative and preventive approaches. In particular, we focus on i) ENT viral infections (HIV, Epstein-Barr virus, Human Papilloma virus), retrieving the available evidence on their oncogenic potential; ii) typical and atypical mycobacteria infections; iii) non-specific granulomatous lymphadenopathy; iv) emerging paediatric ENT infectious diseases and the prevention of their complications; v) the growing burden of antimicrobial resistance in ENT and the strategies for its control in different clinical settings. We conclude by outlining knowledge gaps and action needed in ENT infectious diseases research and clinical practice and we make references to economic analysis in the field of ENT infectious diseases prevention and care.

Morphological changes in rat rectus abdominis muscle induced by diabetes and pregnancy

The urethral muscle of diabetic pregnant rats is affected by long-term mild diabetes and short-term severe diabetes, which plays a crucial role in the pathogenesis of pelvic floor disorders. We hypothesized that muscles outside the pelvis are subject to similar changes. The current study aimed at analyzing the effects of long-term mild and short-term severe diabetes on the structure and ultrastructure of fiber muscles and collagen in rats' rectus abdominis (RA) muscle. Therefore, the RA muscle of virgin, pregnant, long-term mild diabetic, short-term severe diabetic, long-term mild diabetic pregnant and short-term severe diabetic pregnant 3-month-old Wistar rats were collected. The structure was analyzed by picrosirius red staining, immunohistochemistry for fast and slow muscle fibers and transmission electron microscopy. We investigated two levels of STZ- induced diabetes: long-term mild diabetes (blood glucose level: 120-200 mg/dL) and short-term severe diabetes (blood glucose level >300 mg/dL). Long-term mild diabetic pregnant and short-term severe diabetic pregnant rats had decreased fast fibers and increased slow fibers, disrupted areas of sarcomere, intermyofibrillar mitochondria and myelin figures in the RA muscle. Both groups enabled us to analyze the specific influence of pregnancy, separately from diabetes. The current study demonstrated that diabetes and pregnancy induced intramuscular transformation and reorganization of RA muscle with a switch of fiber type adjusting their architecture according to intensity and duration of hyperglycemic insult within pregnancy.

Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST).

BACKGROUND: The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G). METHODS: A total of 433 stage IIIB-IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine-cisplatin (GP), gemcitabine-vinorelbine, gemcitabine-ifosfamide-cisplatin or gemcitabine-ifosfamide-vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets. RESULTS: For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3-4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3-4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3-4 nausea-vomiting was significantly increased in P-containing regimens. CONCLUSIONS: This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

A multicentre Phase II study of non-pegylated liposomal doxorubicin in combination with trastuzumab and docetaxel as first-line therapy in metastatic breast cancer.

To evaluate the cardiotoxicity, general toxicity, and activity of non-pegylated liposomal doxorubicin, in combination with docetaxel and trastuzumab, as first-line therapy in metastatic breast cancer. Thirty-one patients with metastatic human epidermal growth factor receptor 2-overexpressing breast cancer, who had not previously received chemotherapy for metastatic disease, received non-pegylated liposomal doxorubicin (50 mg/m(2)), docetaxel (75 mg/m(2)) and trastuzumab (2 mg/kg/week) for up to eight cycles, followed by trastuzumab alone for up to 52 weeks. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) to below 45%, or a decrease in LVEF of at least 20% from baseline. Mean LVEF was maintained at baseline level also in the subset of patients who had received anthracycline previously. Cardiotoxicity developed in three patients during the treatment cycles, and in two further patients after the end of the study. The most common adverse events were haematological toxicity, alopecia, asthenia and fever. The best overall response rate was 65.5%. Median time to progression was 13.0 months. The combination of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab combines acceptable cardiac and general toxicity and promising activity as first-line therapy in metastatic breast cancer.

Targeted therapy with trastuzumab in dysplasia and adenocarcinoma arising in Barrett's esophagus: a translational approach.

AIM: Human epidermal growth factor receptor (HER2) protooncogene, overexpressed/ amplified in preneoplastic lesions and in adenocarcinoma (ADC) of the esophagus, can be considered a target for treatment of esophageal dysplasia/ADC. The aim of this study was to evaluate the therapeutic role of the anti-HER2 monoclonal antibody, trastuzumab, in the management of ADC originating from HER2-positive Barrett's esophagus (BE). METHODS: Two patients with high-grade dysplasia and ADC of the esophagus after esophageal mucosectomy and no metastatic disease were studied. Patients were not eligible for radical surgery or chemo-radiotherapy because of age and comorbidities. HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. Additional immunohistochemical analyses were performed. The whole panel was analysed at baseline, after treatment and at follow-up. RESULTS: At baseline, the two patients showed HER-2 overexpression/amplification in all areas of dysplasia and ADC but not in BE. Six months after treatment no significant differences in terms of endoscopical and histological patterns of the disease were found. HER-2, EGFR, TOPOII-alpha and anti-ssDNA analysis demonstrated a down-regulation of these markers and increased apoptosis. CONCLUSION: This study demonstrates that this treatment is feasible. No clear evidence of dysplasia regression was observed. However, HER2 and TopoII-alpha downregulation and induction of apoptosis occurring 6 months after treatment encourages further investigation.

Solitary breast metastases from a renal cell carcinoma.

A case of solitary and metachronous breast metastases from a renal cell carcinoma is described nine years after surgery. The review of the literature proves that the breast is an unusual site for metastatic disease.

Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer.

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (+/- SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% +/- 3% and 86% +/- 4%, respectively. For the matched comparison group survival was 85% +/- 3% at 5 years and 74% +/- 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P =.04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.

Effects of bilateral microinjections of ibotenic acid in the thalamic reticular nucleus on delta oscillations and sleep in freely-moving rats.

The thalamic reticular nucleus (NRT) consists of a large pool of GABAergic neurons located on each side on the anterior, lateral, and ventral surfaces of the dorsal thalamus. The NRT is divided up into sectors. The aim of this study was to investigate the effects of bilateral lesions of the NRT on sleep and sleep oscillations. Only the results concerning delta oscillations will be reported here. As a first step we produced stereotaxically placed electrolytic lesions. The rats presented continuous circling behavior with electroencephalographic (EEG) theta and delta activity and subsequent sudden death. To avoid disruption of the bundles of fibers that pass through the NRT to and from the cerebral cortex, we used the excitotoxic ibotenic acid. Given its high toxicity, we concentrated on the rostral pole of the NRT, which is believed to have powerful effects on the synchronization of oscillatory activity during sleep. Immediately after surgery, the rats fell into a deep sleep during which there was an increase in EEG slow-wave activity and no spindles. On postoperative day 2, corresponding to the destruction period, the sleep/wake cycle partially recovered, but NREM sleep was quantitatively diminished and showed abnormalities (increased latency to sleep onset, sleep fragmentation, gradual elimination of the delta rhythm). It is concluded that the rostral pole of the NRT contributes to normal and pathological EEG synchronization and the organization of sleep in rats.

Intraoperative and percutaneous radiofrequency thermal ablation in the treatment of hepatocellular carcinoma.

AIMS AND BACKGROUND: The aim of the study was to evaluate feasibility, survival rate, complications and length of hospital stay in 47 patients with hepatocellular carcinoma (HCC) treated by radiofrequency thermal ablation (RFTA). Though the treatment of choice for HCC is surgical resection, the strong association of this disease with cirrhosis often rules out this procedure. Many investigations have been conducted in order to identify alternative therapies. Preliminary studies of radiofrequency thermal ablation have shown that the technique is effective and safe, achieving a predictable area of tumor tissue coagulative necrosis and sparing the surrounding cirrhotic parenchyma, without any significant side effects. In addition, this technique, which can be performed percutaneously, allows very short hospital stays. PATIENTS AND METHODS: We report the results of a series of 47 cirrhotic patients with 52 HCC nodules (mean diameter 2.9 cm, range 1-6 cm) treated in our Institute between May 1997 and June 1999 by RFTA using an expandable needle with four hooks at its tip. All patients had hepatic cirrhosis (32 Child A, 13 Child B and two Child C). We treated patients with both unifocal (35 patients) and multifocal HCC (12 patients); 33 patients underwent percutaneous RFTA (54 passes), while in 14 cases RFTA was performed during laparotomy (22 passes). RESULTS: The mean number of passes to achieve complete necrosis was 1.43 in 28 patients with unifocal HCC treated by percutaneous RFTA, 1.7 in 7 patients with unifocal HCC treated by intraoperative RFTA, 2.8 in 5 patients with multifocal HCC treated by percutaneous RFTA and 1.43 in 7 patients with multifocal HCC treated by intraoperative RFTA. No deaths related to the procedure or major complications occurred. Post-treatment dynamic CT was performed in all patients. All patients but one were followed-up for a mean period of 11.8 months (1-25 months). Six patients died during the follow-up (three Child A, two Child B and one Child C. The actuarial survival, computed by the Kaplan-Meier method, was 83% at 24 months. The mean hospital stay was 3.4 days in patients treated by percutaneous RFTA and 11.2 days in those treated by intraoperative RFTA. CONCLUSIONS: In our opinion RFTA is an effective, safe technique capable of achieving good results in the conservative therapy of small HCC. We believe that curative ablation is possible for HCC nodules measuring up to 3 cm in diameter. Further studies of longer duration are necessary.

Methadone dose and retention during treatment of heroin addicts with Axis I psychiatric comorbidity.

We studied 90 opioid-dependent subjects, 38 with one or more additional Axis I diagnosis and 52 with no psychiatric comorbidity. There were significant differences between these two groups regarding the methadone dose required for clinical stabilization, but not in the rate of retention in treatment. Dual Diagnosis patients, those with psychiatric comorbidity, required an average stabilization dose of 154 +/- 84 of methadone compared to 99 +/- 49 mg/day for patients whose only Axis I diagnosis was Opioid Dependence. In the 990-day period considered there were no differences between the two groups of patients in terms of retention in treatment.

Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group.

PURPOSE: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40). CONCLUSION: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.

Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.

BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.

Factors affecting baseline quality of life in two international adjuvant breast cancer trials. International Breast Cancer Study Group (IBCSG).

Quality of life (QL) is used to assess treatments in clinical trials but may be influenced by other factors. We analysed the impact of biomedical, sociodemographic and cultural factors on baseline QL indicators in two International Breast Cancer Study Group trials. Patients with stage II breast cancer were randomized within 6 weeks of primary surgery to various adjuvant treatments. They were asked to assess five indicators of QL at baseline. QL forms were available for 1231 (83%) of the 1475 premenopausal and 989 (82%) of the 1212 post-menopausal patients, who were from nine countries and spoke seven languages. Culture (defined as language/country groups) had a statistically significant impact on baseline QL measures. Premenopausal patients with poor prognostic factors showed a tendency to report worse QL, with oestrogen receptor status as an independent predictor for mood (P = 0.0005). Older post-menopausal patients reported better emotional wellbeing (P = 0.002), mood (P = 0.002), and less effort to cope (P = 0.0009) compared with younger post-menopausal patients. Co-morbidity, type of surgery, treatment assignment and sociodemographic factors showed a statistically significant impact in post-menopausal patients only. Cultural and biomedical factors influenced baseline QL and should be considered when evaluating the impact of treatment on QL in international breast cancer clinical trials.

Postmastectomy radiotherapy and concomitant adjuvant chemotherapy versus adjuvant chemotherapy alone in premenopausal breast cancer patients with positive axillary nodes.

AIMS: To evaluate the efficacy of postmastectomy radiotherapy (RT) combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone as regards overall survival (OS), overall disease-free survival (ODFS), local disease-free survival (LDFS) and distant disease-free survival (DDFS). METHODS: We reviewed retrospectively two non-randomized groups of premenopausal high-risk breast cancer patients treated from 1985 to 1990 in the following Institutions: Department of Radiation Oncology of Brescia University, "Istituto del Radio O. Alberti" (IRA), and Department of Oncology of Brescia Hospital "Beretta Foundation" (BF). A total of 163 patients was found to satisfy the criteria of the current analysis: 81 patients received adjuvant chemotherapy alone [6 cycles CMF(1-8)] at BF and 82 patients received postoperative radiotherapy and chemotherapy [8 cycles CMF(1-21)] at IRA. A modified CMF schedule was chosen at IRA to avoid the feared increase in toxicity due to the association with RT. Primary surgical treatment was modified radical mastectomy with axillary node dissection in both cases. RESULTS: A statistically significant improvement in OS was found in systemic adjuvant therapy patients compared to those also given RT (77.6% vs 59%; P = 0.0025). No statistically significant improvement in ODFS was found in the CMF(1-8) arm compared to the RT and CMF(1-21) stm: 51.6% vs 43.6%; P = 0.46. A statistically significant improvement in LDFS at 5 years was found in irradiated patients (89.3% vs 76.2%; P <0.05). The DDFS was also improved, although without evidence of statistical significance, in the CMF(1-8) group: at 5 years 65% vs 44% (P = 0.059). CONCLUSIONS: The study confirmed that RT reduces the risk of local recurrence but without a statistically significant reduction in mortality. The lack of a survival benefit may somehow reflect the dose reduction in CMF(1-21). The evidence that CMF(1-8) offers undoubtable advantages over the CMF(1-21) regimen in OS and, perhaps, in distant control suggests that the dose intensity of CMF in this setting may also be important. In fact, although many CMF(1-8) patients received a dose intensity lower than 100%, 95% of them received a dose intensity higher than the maximum one of the CMF(1-21) patients. Although our results should be interpreted with caution, they seem to provide further rationale for testing the association of postoperative radiotherapy and the CMF(1-8) regimen in stage II breast cancer with positive nodes and treated with demolitive surgery, as already done in the conservative management of breast cancer, also in view of the new support therapies now available (i.e. hematologic growth factors).

Paclitaxel, ifosfamide, and carboplatin for the treatment of stages IIIB and IV non-small cell lung cancer: preliminary results.

We have treated 26 consecutive chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer with an innovative regimen based on a 1-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 125 to 250 mg/m2, ifosfamide 3 g/m2 (with mesna), and carboplatin dosed to an area under the concentration-time curve of 5, every 21 days for a total of six cycles in responding or stabilized patients. Among 22 fully evaluable patients, 14 (64%) achieved a partial remission, six had disease stabilization, and two had disease progression. Hematologic toxicity was remarkably mild; only one patient had grade 3 neutropenia (on day 21). Arthralgias/myalgias (grade 3 in nine patients, grade 4 in one patient) and neurologic toxicity (a cumulative sensory neuropathy of grade 3 or 4 in five patients) were the most common side effects and seem to be dose related. To date, few patients are fully evaluable and survival data are clearly immature. Nevertheless, this regimen seems highly active and quite well tolerated, and deserves further evaluation.

High-dose chemotherapy with autologous stem cell transplantation is feasible and safe in a regional hospital. A 6-year experience in southern Switzerland.

High-dose therapy with bone marrow (BM) or blood stem cell (BSC) support is a high-technology technique usually administered in specialized tertiary centers. The use of BSC has made this technique simpler and accessible also to smaller hospitals. We retrospectively analyzed the data of patients with lymphoma, leukemia and other tumors who received high-dose therapy and BM or BSC transplantation in our district hospital, looking at the type of procedure performed, complications, use of growth factors, and progression-free and overall survival. A total of 40 patients were transplanted over 6 years. No procedure-related deaths and no permanent organ toxicities were seen. The use of BSC brought about a great reduction in the duration of hospital stay, septic complications and transfusion of blood components. For patients with lymphoma (n = 20) the probabilities of progression-free survival and of overall survival at 2 years are 48% (95% C.I. 28-68%) and 68% (95% C.I. 46-84%), respectively. Based on these data, we believe that ABMT and BSC transplantation are feasible and safe in a peripheral hospital when the appropriate human and technical conditions are present. Treatment outcome is then comparable to that of specialized centers.

Cisplatin, etoposide and bleomycin infusion (PEBi regimen) in good-risk patients with germ cell tumors.

Patients with good-risk germ cell tumors have an approximately 85-95% chance of cure with standard chemotherapy. However, acute and late toxicity may be severe and negatively influence the quality of life. In an attempt to reduce toxicity, we evaluated a new schedule including bleomycin administered-as a continuous infusion in patients with low and intermediate volume metastatic disease. Patients were treated as follows: cisplatin, 100 mg/m(2) day 4; etoposide, 100 mg/m(2) days 1 through 5; bleomycin, 15 unit bolus on day 1 followed by 30 mg as a continuous infusion for 72 h, with cycles repeated every 21 days. Between 1992 and 1996, 25 patients entered the study and were assessable for response and side effects. Major patient characteristics were: performance status ECOG 0-1; minimal disease, 13 patients, intermediate disease, 12; median age, 33 years (range 15-50). Twenty-one of 25 patients (84%) achieved a complete remission, 2 patients achieved a partial remission, and 2 patients did not respond to the regimen. At a median follow-up of 24 months, 24/25 patients were alive, 23 were without evidence of disease, and I had persistent disease. Grade III/IV side effects included leuko/neutropenia (8 patients), anemia (3 patients), and nausea/vomiting (3 patients). No drug-related deaths were observed, and no evidence of pulmonary toxicity was registered. In conclusion, the PEBi regimen is an effective and well-tolerated regimen in patients with good-risk germ cell tumors and may be considered as a front-line chemotherapy.

Characterization of a cytogenetic 17q11.2 deletion in an NF1 patient with a contiguous gene syndrome.

We report on a rare patient screened as a putative carrier of a contiguous gene syndrome on the basis of a complex phenotype characterized by sporadic neurofibromatosis type 1 (NF1), dysmorphism, mental retardation and severe skeletal anomalies. A cytogenetically visible 17q11.2 deletion was detected in the patient's karyotype by high-resolution banding and confirmed by fluorescence in situ hybridization with yeast artificial chromosomes targeting the NF1 region. Analysis of the segregation from parents to proband of 13 polymorphic DNA markers, either contiguous or contained within the NF1 gene, showed that the patient is hemizygous at sites within the NF1 gene-the AAAT-Alu repeat in the 5' region of intron 27b, the CA/GT microsatellite in the 3' region of intron 27b, and the CA/GT microsatellite in intron 38- and at the extragenic D17S798 locus, distal to the 3' end of NF1. The patient may be an important resource in the identification of genes downstream of NF1 that may contribute to some of his extra-NF1 clinical signs.

Low-dose continuous intravenous infusion of 5-fluorouracil for metastatic breast cancer.

BACKGROUND: Third-line chemotherapies for advanced breast cancer are difficult to tailor to the individual patient because of reduced tolerance and significant toxicity. Treatment with a continuous intravenous infusion of low-dose 5-fluorouracil (FU-LDCI) is generally well tolerated and thus, a reasonable option for heavily pretreated patients. PATIENTS AND METHODS: From 1989 to 1995, 106 consecutive patients with advanced breast cancer were treated with FU-LDCI. 5-Fluorouracil was given at an initial daily dose of 250 mg/m2 administered continuously with the aid of an elastomer, non-electronic pump through a permanent central venous line for 21 days followed by a 7-day rest. The median age was 56 years (range, 30-82), the median ECOG Performance Status was 1 (range 0-4) and the median number of metastatic sites was 2 (range 1-4). Sixty-one percent of the patients had previously received more than 2 chemotherapy regimens which in 81% included adriamycin, and in 90% 5-fluorouracil. RESULTS: Eighty patients were evaluable for objective response: 17 of them had partial responses (21%, 95% CI: 14%-31%) and 23 stable disease (29%, 95% CI: 20%-40%). One-hundred five patients were evaluable for subjective response, with 46 reporting improvement (44%, 95% CI: 35%-54%). Previous treatments with either 5-fluorouracil or adriamycin did not predict response to FU-LDCI. Median time to progression for patients with a partial response or stable disease was 259 days (range 82-737). The overall survival for the populations as a whole was 274 days (range 13-2264), and the median dose received was 1904 mg/week (range 753-4329). The main toxic effects were grades I and II mucositis, and nausea and vomiting (observed in 31% and 28%, respectively). Grade III toxicities were uncommon: mucositis in 3%, nausea and vomiting in 3%, anemia, thrombocytopenia and hepatitis in 2%, and skin toxicity (hand-foot syndrome) in 1%. Catheter-related thrombosis was observed in 2% of the patients, and there were no pump failures. A questionnaire concerning the impact of the treatment upon quality of life was completed by all of the 13 patients who were alive at the time of evaluation of the results, and all of them rated FU-LDCI as easy to tolerate. The monthly cost of FU-LDCI (US$1,051.00 in Switzerland) was lower than the cost of weekly low-dose adriamycin (US$1,483.00 in Switzerland), a treatment which is often used as a palliative regimen in similar circumstances. CONCLUSION: FU-LDCI is a useful, cost-effective third-line treatment for patients with metastatic breast cancer who need palliation with cytotoxic drugs.