New surgical technique for endoscopic management of anterior glottic web.

OBJECTIVES: In this study we report a new endoscopic technique for the management of anterior glottic web (AGW). Previously, various procedures with endoscopic or open surgical approaches have been described for the treatment of symptomatic AGW. We present an original, highly effective endoscopic technique that seems to have several advantages over traditional approaches. METHODS: We used this novel technique in a preliminary series of four patients. Using a CO2 laser, a curvilinear mucosal flap based on the web is elevated from the superior surface of one vocal chord. The web is divided, and the flap is sutured at the inferior surface of the opposite vocal chord, ensuring that no raw surfaces will be left exposed on this side of the larynx. We accurately describe the technique, displaying diagrams of the surgical steps. RESULTS: In three cases, a restoration of the laryngeal airway, with complete resolution of the AGW, was achieved. A limited residual web persisted close to the anterior commissure in the fourth patient. CONCLUSIONS: The new endoscopic technique utilized in our preliminary series of patients is a simple, repeatable, and effective surgical procedure for managing AGW.

Reduction incidence of myocardial infarction associated with a national legislative ban on smoking.

AIM: The aim of the present study was to assess change in admissions for acute myocardial infarction (AMI) in the period immediately subsequent to the coming into force of law no. 3/2003 ''Protection of the health of non-smokers''. METHODS: Four Italian regions (Piedmont, Friuli Venezia Giulia, Lazio and Campania) took part in the study. Data regarding admissions for AMI were taken from the daily discharge papers of patients aged between 40 and 64 (cod. ICD9-CM 410.), in the period 10 January-10 March 2001-2005. Repeated admissions were excluded. Admission rates standardised by age and overall total, and specifically by region, age and gender were calculated. The hypothesis of a significant reduction between 2005 and 2004 was also checked. RESULTS: The results showed a decrease in the number of cases and in the standardised rates between 2004 and 2005. The number of admissions estimated with a linear regression model for 2005 was significantly higher than that really observed (+13%). The decrease between the 2005 and 2004 rates was noteworthy for all four regions. Analysis by gender shows that the effect is observed only in male patients and in the age classes 45-49 and 50-54. CONCLUSION: This study shows that there has been an appreciable reduction in the incidence of heart attacks in the period immediately subsequent to the coming into force of the non-smoking Law in the populations surveyed, and that this reduction mainly regards men of working age. The reduction reverses a trend that has been evident for a number of years, namely that of a decidedly upward trend in the number of admissions for AMI.

Surgical management of surgery and radiation induced peristomal neck ulcerations.

UNLABELLED: PROBLEMS/OBJECTIVE: Non-healing cervical skin ulcerations with concomitant necrosis of the subcutaneous tissue and muscle is a rare but feared complication of radiotherapy that can arise in cervical regions. Constant erosion of the surrounding tissue by the expansion of the necrotic front can threaten important structures. Very few reports in the literature deal with the surgical management of these injuries. METHODOLOGY: This paper reports on two cases of non-healing, slow-growing cervical ulcerations that occurred as a result of radiotherapy and surgery. RESULTS: After unsuccessful conservative treatment, definitive surgical repair was performed to achieve reparation of the defect and protect deep structures. The onset and characteristics of the ulcerations as well as the reconstructive options are discussed. CONCLUSIONS: In the treatment of surgery and radiotherapy induced chronic cervical wounds, non surgical medical treatment should be always attempted for at least 6 months, and should always include hyperbaric oxygen therapy. If conservative methods fail, surgical repair by means of transposition of well vascularized tissue is mandatory to prevent serious complications such as major vessel rupture or fistulas.

The Italian register of cardiovascular diseases: attack rates and case fatality for cerebrovascular events.

BACKGROUND: The Italian register of cardiovascular diseases is a surveillance system of fatal and nonfatal cardiovascular events in the general population aged 35-74 years. It was launched in Italy at the end of the 1990 s with the aim of estimating periodically the occurrence and case fatality rate of coronary and cerebrovascular events in the different geographical areas of the country. This paper presents data for cerebrovascular events. METHODS: Current events were assessed through record linkage between two sources of information: death certificates and hospital discharge diagnosis records. Events were identified through the ICD codes and duration. To calculate the number of estimated events, current events were multiplied by the positive predictive value of each specific mortality or discharge code derived from the validation of a sample of suspected events. Attack rates were calculated by dividing estimated events by resident population, and case fatality rate at 28 days was determined from the ratio of estimated fatal to total events. RESULTS: Attack rates were found to be higher in men than in women: mean age-standardized attack rate was 21.9/10,000 in men and 12.5/10,000 in women; age-standardized 28-day case fatality rate was higher in women (17.1%) than in men (14.5%). Significant geographical differences were found in attack rates of both men and women. Case fatality was significantly heterogeneous in both men and women. CONCLUSIONS: Differences still exist in the geographical distribution of attack and case fatality rates of cerebrovascular events, regardless of the north-south gradient. These data show the feasibility of implementing a population-based register using a validated routine database, necessary for monitoring cardiovascular diseases.

Rehabilitation protocol of dysphagia after subtotal reconstructive laryngectomy.

Dysphagia is a constant complication of subtotal reconstructive laryngectomy, due to modifications in the anatomy and in sensitivity of the larynx and pharynx. The reduced sphincteric activity of the larynx can enhance aspiration with a higher risk of pneumonia. In our opinion, the presence of the tracheotomy tube in the first weeks after surgery interferes with proper mobility of the laryngo-tracheal axis during swallowing, as it anchors the trachea to the skin. We have conducted swallowing rehabilitation, without the tracheotomy tube, ready to aspirate eventual saliva or food debris dropping into the trachea. This protocol has been applied in 33 patients undergoing subtotal reconstructive laryngectomy and better patient compliance and swallowing performance were observed. The period to recover complete autonomous oral intake is less than one month and none of these patients showed signs or symptoms of aspiration pneumonia during hospitalisation or follow-up. This rehabilitation protocol is, therefore, a valid and effective alternative to other well-known procedures.

Evolution of elective neck dissection in N0 laryngeal cancer.

Management of cervical lymph node metastasis is one of the most challenging problems facing clinicians dealing with head and neck cancer. A retrospective evaluation has been made of results in N0 laryngeal cancer patients treated from 1978 to date by comparing historical data reported in related papers previously published by our institution. The medical records of 2207 consecutive patients with cN0 SCC of the larynx were used as the source of data in the present study. Together with primary treatment, 759 (34.4%) received at least unilateral elective neck dissection, while the remaining 1448 (65.6%) were admitted to a wait-and-see protocol. Overall, in the electively dissected patients (ED): 128 (16.9%) cases were submitted to classical radical neck dissection, while 403 (53.1%) cases were submitted to functional neck dissection (FND) and 228 (30.0%) cases to jugular node dissection (JND, removing Level II, III and IV). In 125 of the ED group, a neck procedure on the contralateral N0 neck was associated, of which 15 were RNDs, 35 FNDs and 75 JNDs, respectively. Based on this large series population, the change in the philosophy was evaluated concerning elective neck treatment in N0 laryngeal cancer, from RND through FND towards JND. As far as concerns the reliability as a staging procedure, no statistically significant difference was found between RND, FND and JND (p = 0.794). The 5-year neck recurrence rate, as estimated by the Kaplan Meier, method, for all ED patients, was 7.7%. No significant difference in the rate of 5-year neck recurrence was detected between RND, FND and JND groups (p = 0.178). In the survival curves, no differences, in terms of actuarial survival by Kaplan Meier analysis, were observed, in our series, as far as concerns type of elective neck dissection performed (p = 0.222). In conclusion, following a critical revision of 25 years' experience, at our Institution, in the management of cN0 necks in laryngeal cancer patients, definitive changes were observed in the surgical approach to the treatment of occult disease in cN0 cases. JND, compared to more extensive neck dissections, did not show statistically significant differences in terms of neck control (p = 0.233), in terms of impact on survival (p = 0.122) and in terms of accuracy as staging procedure (p = 0.794).

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

Randomized cooperative study of perioperative chemotherapy in breast cancer.

PURPOSE: The aim of this multicentric randomized trial was to determine whether reducing the interval between surgery and chemotherapy improves the outcome of breast cancer patients. PATIENTS AND METHODS: Between June 1985 and July 1992, 600 breast cancer patients, clinical stages T1-3A,N0-2,M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 (CMF). In addition, N+ patients received concomitant or sequential 5-year tamoxifen therapy. RESULTS: At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of borderline significance in relapse-free survival (RFS; 76% v 70%, P = .053) was evident. A significant survival advantage for the PC arm was detected only in the estrogen receptor-negative (ER-) patients (P = .003). RFS was significantly improved in N- patients, postmenopausal patients, and ER- patients. Multivariate analyses show that pathologic tumor size, nodal status, receptor status, and treatment (only in ER- patients) are significantly correlated with survival and RFS. PC toxicity did not influence wound healing. CONCLUSION: This study provides preliminary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients.

Long-term prognosis following macroscopic complete response at second-look laparotomy in advanced ovarian cancer patients treated with platinum-based chemotherapy. The Gruppo Oncologico Nord Ovest.

Survival (S) and progression-free survival (PFS) were evaluated in 129 advanced ovarian cancer patients, who achieved a macroscopic complete response (112 pathological complete response and 17 microscopic disease) at second-look after platinum-based combination chemotherapy with or without doxorubicin (DX). The impact on S and PFS of age, performance status (PS), stage, histology, grade (G), residual disease after first surgery (RD), chemotherapy regimen, disease status at second-look and consolidation therapy were evaluated by univariate and multivariate analysis. In the 118 months observation period, median S and PFS were 81 and 34 months, respectively. Stage, G, RD, PS and disease status at second-look had significant impact on both S and PFS in univariate analysis, whereas consolidation therapy did not influence outcome. Cox's regression analysis showed that G, RD and PS had an independent impact on PFS. Test for interaction demonstrated no statistically significant relationship between RD, chemotherapy regimen and outcome. In conclusion, advanced ovarian cancer patients with macroscopically complete remission at second-look have a substantial risk of relapse after aggressive treatment. The risk of recurrence was estimated to be maximal in the first 3 years after restaging, and was correlated with poor PS, RD > 2 cm after first surgery and undifferentiated tumour.

The impact of received dose intensity on the outcome of advanced ovarian cancer.

It has been demonstrated that the prognosis of ovarian cancer is influenced by the dose intensity of cytotoxic treatment. The impact of received dose intensity of platinum-based combination chemotherapy on disease outcome was analysed in 226 stage III-IV ovarian cancer patients entered into two prospective randomised trials. All patients received either cisplatin or carboplatin and cyclophosphamide with or without doxorubicin for six courses after primary surgery. The impact of the received dose intensity of each drug (RDI), the average received dose intensity of the treatment regimen (ARDI) and the relative total drug dose (RTD) on progression-free survival (PFS) and survival were analysed. In the 198 patients receiving the full six courses of treatment, RDI of cisplatin or carboplatin, ARDI and RTD were > 0.76 in 74.2, 61.1 and 65.1% of cases, respectively. Although the differences were not significant, pathological complete response was more frequently observed in the group of patients with ARDI < 0.75, whereas the partial response rate was higher in the ARDI > or = 0.76 group. Median survival and PFS were 19 and 13 months; 22 and 10 months; 23 and 13 months for the groups of patients receiving chemotherapy at a ARDI of < 0.75, > or = 0.76-0.99 and > 1.00, respectively (P = not significant). It appears that modest dose modifications and brief treatment delays during first-line platinum-based chemotherapy do not affect response rate, survival and PFS in advanced ovarian cancer patients.

Locally advanced non-metastatic breast cancer: analysis of prognostic factors in 125 patients homogeneously treated with a combined modality approach.

125 stage III breast cancer patients, including 51 cases of inflammatory carcinoma, were treated with the following combined modality approach: three courses of primary 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) chemotherapy followed by locoregional treatment and subsequent adjuvant chemotherapy consisting of three courses of FAC alternating with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Clinical response to primary FAC was 65% (complete 10%). Residual tumour mass in the mastectomy specimen was > 1 and < or = 1 cm in 82 and 18% of cases, respectively. Complete pathological response following primary chemotherapy was achieved in only 3.5% of cases. After primary FAC and local treatment, 97% of patients were disease-free. Overall survival (S) and progression-free survival (PFS) at 5 years were 56 and 34%, respectively. Univariate analysis showed that age, receptor status and clinical and pathological response to primary chemotherapy did not appear to influence treatment outcome significantly, whereas stage, presence of inflammatory disease and number of involved nodes had a significant impact on both S and PFS.

Breast-cancer in the elderly - detection and treatment modalities in 341 women.

Elderly cancer patients are generally excluded from entry to clinical trials;and often managed inadequately or based on individual experience. We have retrospectively determined tumor detection modality, diagnostic and staging work-up, delay in referral and therapeutic approaches in 341 women with breast cancer aged over 70 years. Fifty-eight per cent of patients were in the 70-75 group of age. Our data suggest that tumor is detected during medical visit or hospitalization for reasons other than breast cancer in 63.1% elderly women with 74.1% of tumors diagnosed on stage I+II disease; the interval between patient's awareness of a breast nodule and first diagnostic and/or therapeutic intervention was less than 3 months in 51.4% and between 3 and 6 months in 20.7% of patients. Most of our patients received adequate treatment although in 18.6%, 26.8% and 18.2% of stage Il, III and IV respectively systemic treatment was not administered after surgery. A large proportion (22.3%) of patients received Halsted mastectomy and only 11.1% conservative surgery. We suggest breast examination should be encouraged, screening program should be extended after the age of 70 years and systemic treatment should be evaluated in elderly patients.

Comparative efficacy and safety of roxithromycin and clarithromycin in upper respiratory tract infections.

Roxithromycin 300 mg once daily was compared with clarithromycin 250 mg b.i.d. in an open randomized trial in 200 patients with upper respiratory tract infection: sinusitis, pharyngotonsillitis, and otitis media. Average treatment duration was 9 days. Roxithromycin was more effective (p less than 0.01) particularly in otitis media and pharyngotonsillitis, and better tolerated (only 4% side effects, p less than 0.05).

The incidence of narcotic-induced emesis.

Epidemiologic studies of the incidence of emesis induced by narcotic analgesics are lacking. The histories of 260 cancer patients receiving oral narcotic analgesics prescribed at the Pain Clinic of our Institute from December 1988 to December 1989 were reviewed. Of the 260 patients, 120 were women, median age 61 (range 30-90) yr and 140 were men, median age 62 (range 30-82) yr. Nausea and vomiting associated with assumption of the various narcotics were buprenorphine 8.3% and 22.7%, morphine 18.3% and 28%, codeine 16.2% and 29.7%, and oxycodone 10% and 40%, respectively. Since the use of narcotic analgesics can effectively relieve pain and improve quality of life in cancer patients, it is important to be aware of the incidence of narcotic-induced emesis in order to use appropriate prophylactic antiemetic therapy.

Metastatic breast cancer patients failing first-line, anthracycline-containing chemotherapy: is further therapy of benefit?

During the last 50 years median survival for metastatic breast cancer has not varied and remains 2-3.5 years. To assess the clinical benefit of salvage systemic therapy a retrospective analysis of metastatic breast cancer patients all homogeneously treated with a commonly used first-line anthacycline-containing cytotoxic regimen (FEC) was undertaken. The 140 patients in this report were among 375 entered in two consecutive multicenter randomized trials carried out from Dec. 1983 to Jan. 1990. All patients died during follow-up. Median number of salvage therapies was 3 (range 1-7). Response rate (CR and PR) was 41% with FEC and 7%, 3%, 15%, 0%, 14%, 0%, 0% in patients receiving salvage treatment line 1 to 7, respectively. Time to treatment failure (TTF) was 7.5 months for FEC and 3.5, 2.5, 2.1, 1.6, 2.1, 1.1, 1.6 months at first to seventh salvage treatment, respectively. Only a very small fraction of patients receiving first-line FEC respond to subsequent palliative treatment. The advantages of salvage therapy are unclear and must be weighed against the inconvenience, cost and morbidity of treatment. After first salvage therapy, patients should be considered for randomized trials comparing systemic antineoplastic therapy with best palliative care. Endpoints of all future clinical trials in metastatic breast cancer should include measurement of quality of life and accurate, sequential measurement of symptom control.

Vinorelbine as palliative therapy in advanced breast cancer.

Thirty advanced breast cancer patients received Vinorelbine (VNB) according to two different schedules: a weekly i.v. bolus of 30 mg/m (14 patients) or a continuous infusion (CI) schedule comprising 8 mg i.v. bolus on day 1 followed by 8 mg/m2/die CI day 1 to 4, q 21 days (16 patients). 36% of patients had received at least two prior chemotherapy regimens for advanced disease and 57% had been treated with anthracycline-based palliative therapy. The overall response rate (CR + PR) was 33% (soft tissue 57%, bone 17%, viscera 29%). The main toxicities were neutropenia and abdominal pain. Vinorelbine is effective in pretreated advanced breast cancer patients.

Oral ondansetron (GR38032F) for the control of acute and delayed cyclophosphamide-induced emesis.

The efficacy of the serotonin antagonist ondansetron (GR38032F, Glaxo) was evaluated in the prevention of nausea and vomiting induced by combinations containing cyclophosphamide (CTX) greater than or equal to 600 mg/m2 IV day. At their first treatment course, 55 patients (10 males, 45 females) median age 55 years (range 31-76) were given ondansetron 8 mg orally tds for a minimum of 3 to a maximum of 5 days. 54 patients were evaluable. Complete and major control of acute (day 1) emesis was observed in 94.5% of patients and acute nausea was graded as absent or mild in 83.3% of cases. Complete and major control of emesis improved on subsequent study days from 96.1% on study day 2 to 100% on study day 5. Side effects were mild. Ondansetron is a safe and effective antiemetic drug.

Serial determination of platinum, protein content and free sulfhydryl levels in plasma of patients treated with cisplatin or carboplatin.

We report here the results of serial determinations of free-sulfhydryl, protein content and platinum levels in plasma of cancer patients following either cisplatin (cis-DDP, 3 patients, 60 mg/m2) or carboplatin (JM-8, 3 patients, 300 mg/m2) i.v. administration. After treatment with cis-DDP, significant platinum binding to plasma components with MW greater than 25 kD was observed; the ratio free-sulfhydryls/protein content decreased during the first two hours, returning to normal values at 24 hours after injection. In contrast, no evidence of platinum binding to plasma components with MW greater than 25 kD was noted after JM-8 i.v. administration, and the ratio free sulfhydryls/protein content did not change significantly after treatment. In vitro experiments show that at a molar ratio cis-DDP:JM-8 1:10, the two compounds bind to low MW thiols with the same kinetics. These data seems to suggest different interactions at the plasma level of these drugs, which may be correlated with their different toxicity.

Mitoxantrone in elderly women with advanced breast cancer: a phase II study.

Comorbidity has important implications in older breast cancer patients. Whether elderly patients are more likely to have a decreased tolerance to antineoplastic agents is still a question of debate. Chemotherapy-naive women with metastatic or locally advanced breast cancer aged > or = 68 years entered a phase II trial of Mitoxantrone given day 1 q 21 days. The dose of the drug was dependent on performance status (PS) and number of "minor" comorbid conditions: patients with ECOG PS = 2 and/or > or = 2 comorbid conditions received 10 mg/m2 and those with PS < 2 and < 2 comorbid conditions received 14 mg/m2. Twenty-seven patients, median age 77 years (range 68-86), received a median number of 5 courses (range 1-9). All 27 patients were evaluable for toxicity and 23 cases (patients receiving at least 3 courses) were evaluable for response. Partial response was observed in 6/23 cases (26%) and median duration of response was 6 months (range 3-9). Median overall survival was 8 months (range 2-34). Among cases receiving 10 mg/m2, 4 PR, 4 SD and 2 P were observed and in cases treated with 14 mg/m2, 2 PR, 5 SD and 6 P occurred. Treatment was well tolerated and no grade 4 toxicity was encountered. Mitoxantrone is an effective and well-tolerated regimen in elderly breast cancer patients presenting with comorbid conditions.

Prevention of delayed emesis with metoclopramide and dexamethasone in patients receiving moderately emetogenic cytotoxic treatment.

Forty-three untreated cancer patients receiving moderately emetogenic polychemotherapy entered a phase II trial in order to evaluate the effectiveness of the combination of metoclopramide (40 mg every 6 hrs) and dexamethasone (8 mg every 12 hrs) in the prevention of delayed emesis (days 2-3). For the control of acute emesis all patients received on day 1 ondansetron 8 mg for 3 times. Results of antiemetic treatment were as follows: complete/major protection from acute emesis (day 1) was observed in 72%/88% of patients. Worst day analysis of delayed emesis (days 2 and 3) showed that complete/major protection was obtained in 93%/95% of cases, respectively. Delayed nausea was not as well controlled: complete/major protection was observed in 44%/79% of patients. Extrapyramidal reactions occurred in 3 patients and moderate epigastric pain was reported by 3 patients. Since control of acute emesis could be one of the most important factors influencing delayed emesis, the absence of acute symptoms in 72% of our patients may be partially responsible for the excellent control of delayed emesis. The combination of metoclopramide and dexamethasone is a feasible and effective treatment for delayed emesis in outpatients receiving moderately emetogenic chemotherapy.