Successful treatment of persistent postoperative air leaks following the placement of an endobronchial one-way valve.

Treatment of persistent air leaks due to pulmonary resection in pathological conditions of the lung involve a very large spectrum of available methods, from chest drainage and placement of Heimlich valves to surgical repair or pleural decortication. However, in some of these patients surgery may be contraindicated. This report describes an endobronchial approach to the control of marked and prolonged air leaks in four patients using a newly designed one-way airway valve (Pulmonx Corporation; Redwood City, Ca.USA) placed into the segmental bronchus that is the source of air leakage. As the device is a one-way inspiratory airway blocker, it can be used to control persistent air leaks while maintaining the drainage of mucus. This approach potentially provides an effective nonsurgical and minimally invasive alternative addition to the armamentarium of treatments for patients who suffer with persistent post-operative air leaks where other methods have failed or in frail patients who are categorised as a high surgical risk.

Diagnostic value and learning curve of transbronchial needle aspiration in thoracic surgery.

AIM: Transbronchial needle aspiration (TBNA) is particularly indicated in diagnosing mediastinal masses or lymphoadenopathy proximal to the airways. Nowadays TBNA has not been widely accepted among pulmonologist and thoracic surgeons. Since its correct management could reduce patient morbidity we adopted this method. Here is presented an overview of our experience over a 18-months training period. METHODS: Fifty patients underwent TBNA. They presented non diagnosed paratracheal or peribronchial lymphadenopathy or masses of >1 cm. TBNA has been considered in order to spare patients the need for more invasive diagnostic procedures. TBNA has been performed with flexible bronchoscope and 19-gauge or 21-gauge needle. RESULTS: We made diagnosis of disease in 25 of 41 patients whose adequate sampling was obtained. 16 cases showed absence of disease despite criteria for adequacy have been confirmed, 9 cases presented an inadequate specimen. The overall diagnostic yield and sensitivity were 50% and 86%. The overall accuracy was 76%. Considering the last 6 months of the training period diagnostic yield increased from 18.7% to 88.2% (P<0.001),accuracy from 56.2% to 88.2% (P=0.04) and frequency of inadequacy decreased from 43.7% to 11.7% (P=0.046). CONCLUSIONS: TBNA resulted a successful diagnostic tool in selected cases as it is safe and permits to spare patients the need for more invasive procedures. These data revealed that experience is mandatory in order to achieve acceptable RESULTS: We think that an experienced operator should require a training period of approximately 50 procedures to obtain a good technique proficiency.

Effects of recombinant LH (rLH) supplementation during controlled ovarian hyperstimulation (COH) in normogonadotrophic women with an initial inadequate response to recombinant FSH (rFSH) after pituitary downregulation.

BACKGROUND: This study was aimed to evaluate the effect of different recombinant LH (rLH) doses on the ovarian outcome of normogonadotrophic women with an initial inadequate response to recombinant FSH (rFSH) after pituitary downregulation. METHODS: Only women undergoing a 'long protocol' with a GnRH-agonist followed by rFSH administration were enrolled. On the eighth day of stimulation, 46 patients with serum E2 levels < 180 pg/ml and with no follicle > 10 mm were randomized in two groups to receive a supplementation with a daily rLH dose of 75 (group A) or 150 IU (group B), respectively. Forty-six normal responders continuing their monotherapy with rFSH formed the control group (C). RESULTS: The mean number of oocytes retrieved and the percentage of mature oocytes in the group B (9.65 +/- 2.16, 79.0%) were comparable with those observed in the group C (10.65 +/- 2.8, 82.5%) and significantly higher when compared with the group A (6.39 +/- 1.53, 65.7%). The mean number of ampoules of rLH was significantly higher in the group B (14.4 +/- 2.0 vs. 9.65 +/- 1.1), whereas these patients received a significantly lower mean number of rFSH ampoules (44.6 +/- 7.4 vs. 36.1 +/- 3.8). Seven (30.4%), 9 (39.1%) and 22 (47.8%) pregnancies were achieved in the groups A, B and C, respectively. CONCLUSIONS: These results suggest that patients with initial inadequate responses to rFSH after pituitary downregulation benefit from the addition of a daily dose of 150 IU of rLH, starting from the eighth day of stimulation.

Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer.

Several genes have been involved in the pathogenesis of hereditary breast/ovarian cancer (BOC), but mutations in the BRCA1 gene are by far the most recurrent. In this study, we report the identification of a founder mutation in a geographically and historically homogeneous population from Calabria, a south Italian region. A screening performed on 24 patients from unrelated families highlighted the high prevalence of a 5083del19 alteration in the BRCA1 gene, which accounts for 33% of the overall gene mutations. The same mutation was also detected in 4 patients, all of Calabrian origin, referred to us by research centres from the north of Italy. Allelotype analysis, performed on probands and unaffected family members revealed the presence a common allele, therefore suggesting a founder effect due to a common ancestor. Our findings underscore the importance of ethnic background homogeneity in patients' selection and highlight the usefulness of founder mutations as a potential tool for optimisation of preclinical diagnosis in gene carriers and therapeutic approaches in affected individuals.

Hereditary nonpolyposis coloretal cancer: identification of novel germline mutations in two kindreds not fulfulling the Amsterdam criteria. Mutations in brief no. 203. Online.

Hereditary nonpolyposis colon cancer results from heritable defects in the MLH1, MSH2, PMS1 and PMS2 genes, which encode proteins involved in the mismatch repair process. In this work we report the identification of two novel germline mutations in the MLH1 gene from two unrelated HNPCC families. The two affected families do not fulfill the Amsterdam criteria. In family 1 we found a missense S93G mutation, which lies in a MLH1 domain critical for its MMR functions. In family 2 we found a two nucleotide insertion (AG) in position 523 from the AUG which determines an early stop codon at position 606 (codon 203). In both families the mutant alleles cosegregate with the cancer phenotype.

A risk model for ovarian carcinoma patients using CA 125: time to normalization renders second-look laparotomy redundant.

BACKGROUND: We evaluated the incorporation of CA 125 normalization times into a prognostic model based on pretreatment variables in patients with ovarian carcinoma to determine if they could render second-look laparotomy (SLL) redundant. METHODS: A total of 54 consecutive patients with ovarian carcinoma who underwent SLL between 1985 and 1990 were included in this analysis. At diagnosis, all of the patients had abnormal CA-125 serum levels, which fell to within the normal range during chemotherapy. Cox's model was used to select pretreatment variables relevant for prognosis. The influence of the time to normalization of CA 125 (< or = vs. > 1 months) and the capability of SLL results to modify prognostic prediction, were also evaluated. RESULTS: The size of the residual tumor at the beginning of therapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently predictive of survival. The time to normalization of CA 125 serum levels (analyzed either as -a continuous or as a two-category variable) also had an independent prognostic role when included in the model. When we examined the inclusion of both CA 125 parameter and SLL into the model together, we found that only CA 125 continued to have an independent prognostic relevance. On the basis of the two pretreatment parameters (PS and tumor size) and of this response parameter (time to normalization of CA 125 values) we selected six subgroups of patients having different outcomes (log rank test of equality over-strata < 0.001). Patients with good prognostic pretreatment variables, and those with intermediate prognosis at the beginning of therapy who showed a quick normalization of CA 125, had an 80% 5-year survival, compared with 16% 5-year survival in the remaining patients. (P < 0.0001). CONCLUSIONS: Our data suggest that the survival of patients with advanced ovarian carcinoma could be accurately predicted by considering some pretreatment variables and time to CA 125 normalization together, without performing SLL. Our risk model, however, needs to be validated by larger prospective trials, to draw any definitive conclusions about the abandonment of surgically defined response.

Carboplatin (CBDCA)-hexamethylmelamine (HMM)-oral etoposide (VP-16) first-line treatment of ovarian cancer patients with bulky disease: a phase II study.

Hexamethylmelamine (HMM) and oral etoposide (VP-16) have shown to be active against platinum-resistant epithelial ovarian cancer. On this basis a three-drug regimen including carboplatin (CBDCA) plus HMM and oral VP-16 was tested in previously untreated ovarian cancer patients with tumor size > 2 cm. Since October 1991, 29 chemotherapy-naive ovarian cancer patients with tumor larger than 2 cm (20 stage III and 9 stage IV) have been treated for a total of 153 courses. CBDCA was administered i.v. on Day 1. The dose was individualized using the Calvert formula (the target dose was AUC = 5). VP-16 was administered orally at the dose of 50 mg/m2 Days 1-14, HMM at the dose of 150 mg/m2 po Days 14-28. Therapy was repeated every 28 days for a total of 6 courses. In order to avoid severe leukopenia and delays in the treatment administration, G-CSF 5 micrograms/kg/day sc Days 8-14 (or until postnadir recovery of neutrophil count > 10,000/mm3) and Days 22-28 was administered. All patients were evaluable for toxicity. No treatment-related deaths occurred. Myelotoxicity was the main side effect. It was grade 3-4 in a total of 13/29(45%) patients. One patient discontinued treatment after the first course due to HMM-related gastrointestinal toxicity. The actual delivered dose intensity was 89% of the planned dose. At the time of this analysis (April 1994) 26 patients are evaluable for response. Fifteen patients achieved a clinical complete remission and 9 a partial response for a 92% overall response rate. Fourteen patients accepted second-look laparotomy. We observed 11 pathological complete regressions (42%; 95% CI, 21-63). At a median follow-up of 16 months 3 deaths have occurred. Only 2 patients with NED at second-look laparotomy have relapsed. We stopped the accrual since the 95% confidence interval of the pCR-rate observed exceeded 20%. This new first-line regimen seems to be highly effective in patients with poor-prognosis advanced ovarian cancer, although the data are not yet sufficiently mature for a final analysis of time to progression and overall survival.

Computerized tomography of the abdomen and pelvis with peritoneal administration of soluble contrast (IPC-CT) in detection of residual disease for patients with ovarian cancer.

Forty-five ovarian cancer patients were submitted to abdominopelvic computed tomography after intraperitoneal administration of soluble contrast in large fluid volumes (3 liters of normal saline) (IPC-CT), for a total of 66 exams. In all cases standard abdominopelvic CT scanning had previously missed the presence of disease. Peritoneal access was achieved by a temporary Teflon catheter inserted blindly. No major complications related to peritoneal access or fluid administration occurred. Laparotomy was performed in all cases to evaluate accuracy of this new diagnostic procedure. Overall, 32/66 exams showed no abnormal findings. In 9/32 cases persistence of disease was demonstrated by laparotomy. The remaining 34 exams were suggestive of persistence of tumor. In 19 cases CT scan showed nodular images or peritoneal thickness. Persistence of disease was confirmed by laparotomy in all instances. In 15 cases only an abnormal diffusion of soluble contrast into peritoneum (suprahepatic, anterior, or parietocolic region) was demonstrated. In 11/15 persistence of tumor was found at laparotomy. To summarize, IPC-CT revealed persistence of tumor in 30/39 cases (77% sensitivity). Positive results were predictive of persistence of disease in 30/34 cases (88% specificity). This new procedure was able to detect persistence of disease in most of our patients showing negative standard CT (30/39 vs 0/39; P < 10E-8) and its diagnostic accuracy was even better than standard CT+serum tumor markers (30/39 vs 16/39; P < 0.001). In conclusion, IPC-CT could be very effective in monitoring response to treatment and could markedly reduce the number of ovarian cancer patients requiring second-look laparotomy.

Carboplatin and alpha-2b interferon intraperitoneal combination as first-line treatment of minimal residual ovarian cancer. A pilot study.

21 untreated ovarian cancer patients with stage III and minimal tumour size, were given weekly intraperitoneal (i.p.) carboplatin (150 mg/m2) and alpha-2b interferon (IFN) (30 million U/m2) for a total of 12 courses, from June 1989 to February 1993. To date, a total of 248 courses have been administered. Toxicity was seldom severe, although fever (179 courses), fatigue (141 courses) and other IFN-related side-effects were very frequent. No patient refused to continue treatment, but in 5 patients IFN dose had to be reduced, and in 1 it was discontinued. The IFN mean delivered dose intensity was 19.8 million U/m2 week. Grade 3-4 myelotoxicity occurred in 7 patients (39 courses), but no deaths related to treatment occurred. The actual mean dose intensity of carboplatin was 121.5 mg/m2 week. To date, 20 patients have completed treatment and are evaluable for response. Of 11 patients with tumour size < or = 5 mm, 10 (91%) achieved a pathological complete response (pCR) as did 4/9 (44%) of those with tumour > 5 mm at entry, for a 70% (95% confidence interval 50-90) overall pCR rate. At a median follow-up of 21 months (range 4-46), only one death occurred. The probability of being alive at almost 4 years was 91% in the entire group (100% in those with tumour size less than 5 mm). Only 1 of 14 patients who achieved a pCR relapsed. This i.p. combination seems a feasible approach to previously untreated ovarian cancer patients with minimal tumour burden. IFN dosage should be reduced to improve tolerance. In view of the very high pCR rate achieved in the group of patients with smaller tumours, a randomised trial is warranted to compare this approach to standard treatment in these patients.

Intraperitoneal (ip) cisplatin-mitoxantrone-interferon-alpha 2b in ovarian cancer patients with minimal residual disease.

Forty-one ovarian cancer patients with less than 2 cm residual disease after systemic cisplatin-based chemotherapy received 4 courses of an ip regimen including cisplatin (75 mg/m2), mitoxantrone (20 mg/m2), and interferon-alpha 2b (30 mil IU/m2). The most important side effects were abdominal pain and fatigue. Overall 15/41 patients (37%) required narcotic analgesia for severe abdominal pain. In 1 case laparotomy was necessary due to bowel obstruction. Grade 3-4 myelotoxicity was observed in 18/41 patients (28 courses). No treatment-related death occurred. Pathological complete response (pCR) was achieved in 23/37 (62%) evaluable patients. Four-year disease-free survival was 50%, and no relapse occurred after 32 months. The estimated 4-year progression-free survival (PFS) and overall survival were 35 and 60%, respectively. Patients who achieved pCR showed significantly better survival than the others (P < 0.000). At multivariate Cox's analysis pCR achievement was the most important predictor of PFS (P < 0.005) and survival (P < 0.02). Age (< or = 60 vs > 60) and CA-125 serum levels at entry (normal vs increased) also showed independent predictive value. On the basis of multivariate analysis results we created a risk model for survival and PFS based on age and CA-125 at entry. We identified three subgroups of patients with significantly different outcomes. With this new ip combination long-term disease-free survival is achieved in a significant part of ovarian cancer patients with small tumor burden. A longer follow-up is needed to see whether it can cure some of these patients, and further comparisons with other ip or systemic regimens are needed to draw definitive conclusions about its role in these patients.

[Endometrial carcinoma with simultaneous endometrioid carcinoma of the ovary. Report of two clinical cases]. / Carcinoma dell'endometrio e simultaneo carcinoma endometrioide dell'ovaio. Presentazione di due casi clinici.

The paper reports two cases of simultaneous endometrial carcinoma and endometrioid carcinoma of the ovary. The clinical and pathological characteristics are examined. Both patients underwent radical surgery with an intraoperative examination for metastatic involvement of the lumbo-aortic, iliac and infundibulo-ovarian lymphonodes. Surgery was followed by antiblastic (cisplatin, adriamycin, cyclophosphamide), hormonal (progestogens) and immuno-modulating (thymostimulin treatment). The two patients (respectively approximately 10 and 7 years after the operation) both enjoy good health.

[Carcinoma of the vulva. Report of a case originating from Bartholin's gland]. / Carcinoma della vulva. Considerazioni su di un caso a partenza dalla ghiandola del Bartholin.

A case of vulvar carcinoma arising from Bartholin's gland is described. At admission the patient showed a large suppurated swelling of the left labium maior. The neoformation reached the groin of the same side. Malignant cells were detected in biopsy specimens of both the vulvar swelling and the lymphonodes. The histological test showed a vulvar carcinoma arising from Bartholin's gland. The vulvar swelling and the ulcerated lesion were removed and the patient was treated with radiotherapy, chemotherapy (bleomicina) and immunomodulant therapy (Timostimoline). Pulmonary methastases were detected eighteen months after the operation and the patient died two years later.

[Ascites and carcinoma of the endometrium]. / Ascite e carcinoma dell'endometrio.

The authors exopound three cases of women affected by endometrial carcinoma in which the ascithis has represented the first clinic manifestation in absence of metrorrhage (first two cases); in the third case, instead, the ascithis has appeared four years after the surgical operation of total laparohysterectomy with bilateral annexiectomy and telecobaltotherapy. The association of the malign ascithis with endometrial adenocarcinoma is of rare observation. The Authors think very likely that the intraperitoneal semination in the cases they examined, is due to the infiltration of the myometry, of the regional and iuxtaregional lymphonoids with formation of ascithis.

Bilateral Brenner tumor.

A case of bilateral ovarian Brenner Tumor of above average size with smooth surface, is reported. The Authors describe symptomatology and diagnostics, considering the uncertainty and rarity that still surround this neoplasia.

Our experience in the treatment of vulvar sclerous lichen.

The Authors refer to two cases of sclerous lichen treated with medical therapy (Vit. E, topic betametasone and lavage with K-permanganato). They conclude that when there is no association with other dystrophies of the vulva defined precancerous, the medical therapy is the only one that supplies satisfactory results.