Long-term follow up of patients affected by pulmonary carcinoid at the Istituto Nazionale Tumori of Milan: a retrospective analysis.

Neuroendocrine tumors of the lung involve an heterogeneous group of tumors representing a wide range of histological variants, from well-differentiated typical carcinoid (TC) tumors to poorly differentiated small cell carcinomas. The epidemiology, clinical outcome, and management of these neoplasms differ significantly from other lung malignancies. The main aim of this report consists in describing the single Center experience of the Istituto Nazionale Tumori of Milan on neuroendocrine lung tumors, with an emphasis on bronchopulmonary carcinoid subtypes. From 1986 to 2009, 91 cases of carcinoid tumors were diagnosed; these were divided in two series, according to typical (66 patients) or atypical [25] histotypes. These two groups were compared in relation to various features, including pathologic classification, clinical behavior, treatment modalities and long-term survival. At the moment of diagnosis 11 patients had locally advanced/metastatic disease, while 80 patients showed non metastatic disease. The comparative analysis between typical and atypical series disclosed significant differences in terms of long-term survival; in fact, 5-year and 10-year survival rates were 98 % and 94 % for the first carcinoid series versus 76 % and 18 % for the atypical series, respectively (p<0.001). The median overall survival (OS) was 76 months (range 3-182) for atypical carcinoids and has not yet been reached for TCs patients.

Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients.

We evaluated whether the amount of circulating DNA in plasma could discriminate between lung cancer patients and healthy individuals and whether it is related to disease progression, and we analyzed the kinetics of plasma DNA in disease-free, surgically resected patients. Plasma DNA quantification and analysis of microsatellite alterations were performed in a consecutive series of 84 patients with non-small cell lung cancer, who were studied during follow-up, and 43 healthy controls. In patients, the mean values of plasma DNA concentration were higher than in controls even considering stage Ia patients. Sensitivity and specificity estimates were calculated as the area under the receiver operating characteristic curve (AUC-ROC) curve and showed a value of 0.844. Variations in DNA level and in microsatellite changes correlated with the clinical status of 38 patients monitored during follow-up. The data suggest that quantification and molecular characterization of plasma DNA in lung cancer patients are valuable noninvasive diagnostic tools for discriminating patients from unaffected individuals and for detecting early recurrence during follow-up.

Bronchoscopically-guided conformal radiation therapy for radiographically occult lung carcinoma.

Radiographically occult lung carcinoma has a very good prognosis after complete surgical resection. In medically inoperable patients three-dimensional conformal radiation therapy cannot be performed, as computed tomography scan images fail to localize the disease. Presented here is an original technique of marking radiographically occult tumors by fiberoptic bronchoscopy, applied on four patients. No short-term complications were recorded. All the patients are alive, with no evidence of disease, after a mean follow-up of 15 months.

Extrapleural pneumonectomy for sarcomas report of two cases.

AIMS AND BACKGROUND: Extrapleural pneumonectomy (EPP), which is a very uncommon surgical procedure, is electively indicated only in patients with early stages of malignant pleural mesothelioma, a rare condition. Two adults suffering from sarcomas and treated with EPP are described here. METHODS: A 29-year-old male with four left-sided lung metastases and ipsilateral pleural effusion from a chondrosarcoma of the mandibula and a 64-year old woman with a megamass in the left chest due to a local recurrence of a hemangiopericytoma underwent EPP. RESULTS: Extra-EPP-field multiorgan progression was diagnosed 14 months following surgery in the first patient who died at the 24th postoperative month but remained free of disease at the site of surgery. The second patient had a chest wall relapse at the forty-third month following EPP, which was treated by partial resection of the second and third ribs. She is alive and disease-free at the twelfth postoperative month. DISCUSSION: EPP may be considered for salvage treatment in selected patients with intrathoracic sarcomas not amenable to other effective therapies to achieve mid- to long-term disease control, even in the case of advanced spread.

Radiotherapy and concurrent continuous infusion of cisplatin with adjuvant surgery in nonresectable Stage III lung carcinoma: short- and long-term results of a Phase II study.

PURPOSE: Cisplatin-enhanced radiotherapy plus adjuvant surgery was evaluated in nonresectable non-small cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Doses of 50 Gy (administered in standard fractionation in 5 weeks) were delivered with concurrent cisplatin in continuous infusion (daily dose: 4 mg/m2), to 32 Stage IIIa and 45 Stage IIIb patients enrolled in a Phase II study. Patients without progression underwent surgery. RESULTS: Esophagitis (64%), nausea/vomiting (34%), and pulmonary toxicity (14%) were the main side effects. Grade 3 toxicity occurred in 4 instances. A clinical locoregional major response was achieved by 55 patients (there were 10 complete responses). Forty patients underwent surgery, 7 with a nonradical procedure. Seven patients died due to surgery-related complications, which were significantly impacted by right pneumonectomy (71% vs. 6% of the other procedures, p < 0.0001). Eighteen of the 40 surgical patients were assessed to be without viable tumor and 11 with microresidual carcinoma. There were 13 disease-free, 5-year survivors. CONCLUSIONS: Toxicity was low but activity high with the chemoradiotherapy. Adjuvant surgery increased the rate of complete responses, but right pneumonectomy had an unacceptable mortality. The role of surgery needs further refinement. Integration of the chemoradiotherapy schedule with cisplatin-based induction chemotherapy is advisable.

Intrathoracic benign metastasizing leiomyoma with extrapulmonary growth pattern. A case report.

The authors report a case of a woman in whom complete resection of an extrapulmonary differentiated leiomyomatous tumor of uterine origin was performed 39 years after hysterectomy for uterine leiomyomas.

Quality of center day care and attunement between parents and caregivers: center day care in cross-national perspective.

In a sample of 43 Dutch infants and toddlers (mean age = 1.7 years), the quality of care at day-care centers was assessed and compared with similar quality ratings in other European and North American countries. It was hypothesized that formal characteristics of care settings and caregivers as well as attunement between caregivers and parents would be associated with quality of care. Quality of center care was assessed with the Early Childhood Environment Rating Scale (T. Harms & R. M. Clifford, 1980), the Infant/Toddler Environment Rating Scale (T. Harms, D. Cryer, & R. M. Clifford, 1990), and the Caregiver Interaction Scale (J. Arnett, 1989). The children's interactions with both their mothers and their fathers at home were rated with several sensitivity scales. Caregivers and parents also completed questionnaires about childrearing attitudes and attunement. The results showed that the quality of center care in the Netherlands was rather good compared with that of other European and North American countries. Better quality of center care was associated with older caregivers who had less professional education, fewer years of experience, and who worked fewer hours per week. Communication and attunement between caregivers and parents did not appear to be important for quality of care.

Extrapericardial solitary fibrous tumour of the pericardium.

Solitary fibrous tumour (SFT) occurs most commonly in the pleura and is extremely rare in the pericardium. The authors report a case of a 60-year-old man in whom a large mediastinal mass was accidentally discovered. Computed tomography showed involvement of the left anterosuperior mediastinum with displacement of the trachea, large vessels and oesophagus; histopathological findings after complete resection of the neoplasia demonstrated an SFT of the pericardium, the first reported case with extrapericardial pattern of growth. A review of the literature on SFTs of the pericardium is provided.

Long-term infusion in cancer chemotherapy with the Groshong catheter via the inferior vena cava.

AIMS AND BACKGROUND: Vascular access through a vein draining into the superior vena cava is commonly used for long-term infusion of drugs inr cancer chemotherapy; prolonged cannulation of the inferior vena cava is generally considered as having an excessively high complication rate. METHODS: Prolonged cisplatin infusion via the inferior vena cava by means of a Groshong catheter was evaluated in 20 consecutive patients with thoracic malignancies showing evidence of superior vena cava infiltration or obstruction. RESULTS: We achieved 1,291 catheter days for our survey with a mean duration of vascular access of 64.5 days per patient and a mean duration of infusion time of 40 days. There were 2 complications, a catheter obstruction after a 7-day rest period and an ileo-femoral thrombosis 6 days after catheter placement. CONCLUSIONS: Our experience compared favourably with the results obtained by long-term central venous access via the supraumbilical route, and demonstrated the reliability and safety of this approach in cases where the superior vena cava cannulation is technically difficult or impossible.

Ambulatory low-toxicity chemotherapy in non-small-cell lung carcinoma by continuous 28-day infusion of alternating cisplatin and 5-fluorouracil.

BACKGROUND: One regimen consisting of a continuous infusion of cisplatin and fluorouracil was designed to be minimally toxic, and suitable for application with radiotherapy in non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Forty-four NSCLC patients received daily 8 mg/m2 of cisplatin on days 1-2, 8-9, 15-16, 22-23, and 300 mg/m2 of fluorouracil on days 3-7, 10-14, 17-21, 24-28 (35-day courses). RESULTS: Two patients experienced grade 3-4 toxicities. Eleven achieved objective responses. The median progression-free and observed survival was 22 and 39.5 weeks. CONCLUSIONS: The schedule management was fully ambulatory. Toxicity was negligible. The activity was moderate, but the combination with radiotherapy is advisable due to the radioenhancing properties of both of the drugs.

Surgery after radiochemotherapy for stage III lung cancer: postoperative complications and late results.

Fifty-seven stage III lung cancer patients underwent radiochemotherapy and subsequent surgery. Forty radical (R-), six non-radical, and eleven exploratory operations were performed. Pneumonia (five cases), pulmonary insufficiency (one case), bronchial fistula (one case) were the major non-fatal complications. Four deaths due to adult respiratory distress syndrome (ARDS) or pulmonary embolism occurred. Sixty percent of the 10 patients who had no viable tumor at operation survived 3 years, as well as 41% of those who achieved a complete remission by resection and 11% of those with residual disease (R+) after operation. However, the 1- and 2-year survival rates were similar. The main pattern of failure in R- and R+ patients was extra- and intra-RT-field progression, respectively. A slightly higher rate of postoperative complications, with respect to current practice, was observed. However, data lead to argument on the improvement of locoregional control and long-term survival following radical surgery.

Safety of absorbable suture for sternal closure after pulmonary or mediastinal resection.

The reliability of polyglyconate monofilament (Maxon) suture for sternal closure was tested on 216 consecutive sternotomies, performed on 208 patients in our department from January 1986 to December 1990. The reason of sternotomy was primary lung cancer in 34 cases (16%), lung metastases in 127 (59%), and disorders of the thymus in 55 (25%). Mean age was 38 years (range 3 to 78 years); multiple lung resections were performed in 102 patients (average 7 lesions, range 2 to 30); maximum extent of the operation was pneumonectomy in 2 cases, lobectomy in 53, segmentectomy in 27, and wedge resection in 74. Prior chemotherapy had been administered in 75 cases (35%). A second sternotomy was performed in 8 cases. No cases of sternal dehiscence, sternal infection, or empyema were observed, after a median follow-up of 27 months. Overall perioperative mortality was 0.9% (2/216). Our series demonstrates the safety of polyglyconate monofilament (Maxon) suture for sternal closure. Absorbable sutures appear to be a safe alternative to steel wire closure in patients undergoing extended pulmonary or mediastinal resection.

Non-resectable Stage IIIa-b lung carcinoma: a phase II study on continuous infusion of cisplatin and concurrent radiotherapy (plus adjuvant surgery).

Thirty-eight patients with non-resectable non-small-cell Stage IIIa-b lung cancer were treated in a Phase II study with radiotherapy (50 Gy in a 25-fraction split-course) plus con-current continuous infusion of cisplatin given at a daily dose of 6 mg/m2, with the aim of investigating its radiopotentiation properties. Treatments were given on an outpatient basis by means of a central venous catheter and a portable pump. Adjuvant surgery was undertaken when feasible. Toxicity was mild to moderate. The probability of a partial or complete locoregional response at 4 weeks after treatment completion was 83% (confidence limits at 95%: 13). Eighteen patients were resected. Overall 1-, 2- and 3-year progression-free survival probabilities were 42, 24 and 21%. These figures were 63, 37 and 24% in observed survival curves. Patients with squamous-cell tumors had observed survival rates of 82, 50 and 28% at 1, 2 and 3 years, compared to 42, 19 and 19% in patients with non-squamous histology. The high response and survival rates obtained at a low price according to toxicity require further investigation.

Primary childhood osteosarcoma: the role of salvage surgery.

The overall results of salvage surgery for lung metastases were evaluated on 174 consecutive patients with primary osteosarcoma below the age of 20, resected in Milan between 1970 and 1988. Seventy-two children treated in the years 1970-1981 were compared with 102 children treated in the years 1982-1988. In the latter period, adjuvant chemotherapy was replaced by neo-adjuvant programs and salvage surgery was applied systematically to all patients with resectable lung metastases through median sternotomy. During the last period, the overall 5 year survival improved significantly from 35% to 58% (P less than 0.001), while the disease free survival rose from 38% to 45% (median 15 vs. 33 months, P = 0.3). The proportion of patients with completely resected lung metastases rose from 17% (7/42) to 55% (27/49), without operative mortality, and the overall survival from detection of lung metastases (including unresected cases) improved from 0 to 28% at 5 years (P less than 0.001). The survival benefit was observed only in the group of children with resected metastases. These data indicate that systematic bilateral pulmonary resection, combined with neoadjuvant chemotherapy, has contributed to improve the final cure rate of childhood osteosarcoma.

The contribution of salvage surgery to the management of childhood osteosarcoma.

Between January 1970 and December 1988, 174 consecutive patients under the age of 20 years with curatively resected primary osteosarcoma were treated at our institute; 72 in the years of 1970 to 1981 and 102 in the years 1982 to 1988. In the latter period, adjuvant chemotherapy was replaced by neoadjuvant programs, and new criteria were adopted for the management of lung metastases, consisting in early bilateral surgical staging and lung resection through median sternotomy for all patients with purely intrathoracic relapse. Follow-up was updated in December 1989. During the last period, the overall 5-year survival improved significantly from 35% to 58% (P less than .001). The disease-free survival rose from 38% to 45% at 5 years, with median values of 15 months versus 33 months, while the frequency of isolated lung metastases dropped from 58% to the actuarial 48%. The proportion of patients who underwent complete resections of their pulmonary metastases rose from 17% (seven of 42) to 55% (27 of 49), without operative mortality. Due to such a high proportion of patients eligible for salvage surgery, the overall survival from detection of lung metastases improved from 0% to 28% at 5 years (P less than .001). Contralateral occult metastases were resected in three of 15 subjects with monolateral clinical lesions, and five patients underwent subsequent lung resections. These data indicate that systematic bilateral pulmonary resection plays an important role in improving the final cure rate of childhood osteosarcoma, beyond the benefit resulting from neoadjuvant chemotherapy.

Limited resection for Stage I lung cancer.

We have reviewed our experience of limited resections for Stage I lung cancer for the years 1971-88. Sixty-one cases of sublobar resection (wedge or segmental) were compared with 411 lobar resections (lobectomies or bilobectomies), performed over the same period. Operative mortality was 0% in the limited resection group and 3% (12/411) in the control group. Cancer recurrence was detected respectively in 36% and 38% of patients, and actuarial survival at 5 years was 55% versus 49% overall. Sublobar resection had a slightly better outcome than lobar resection in pathological T1 (5-year survival of 73% vs 55%) but a worse outcome in pT2 (35% vs 46%); however, none of the differences was statistically significant. In 28 patients with pre-existing cardiac or pulmonary co-morbidity, limited resection yielded the same 5-year survival as lobectomy (53% vs 51%) with no peri-operative deaths (0 vs 5%). Although derived from a retrospective analysis, these data offer a further confirmation that limited resection combined with adequate nodal staging is a reliable and effective technique for early stage lung cancer management.

Prolonged venous infusion of cisplatin and concurrent radiation therapy for lung carcinoma. A feasibility study.

Fifty patients with non resectable and/or inoperable bronchogenic carcinoma were entered into a feasibility study of cisplatin (CDDP) given in continuous infusion with concurrent radiation therapy. The radiation therapy regimen consisted of 2 Gy given 5 days a week in the first 3 and last 2 weeks of a 7-week split course (50 Gy of total dose). The CDDP (daily dose of 4 to 6 mg/m2) was administered to cover the days of radiation treatment by means of a central venous catheter and a portable pump. Less than 1% of predicted duration of infusion was lost due to complications related to venous access and pump. Toxicity was moderate. The overall probability of a locoregional major response (complete + partial) within 1 month after treatment completion was 86%. Twenty-three patients underwent resection. The 1-year actuarial probability of survival was 64%. The high response and survival rates warrant further studies on concurrent CDDP continuous infusion and radiation therapy in inoperable lung carcinoma.

Results of salvage surgery for metastatic sarcomas.

Between January 1970 and December 1988, 105 consecutive patients underwent complete resection for lung metastases from sarcoma, 33 of them in the years from 1970 to 1983 and 72 between 1984 and 1988. In the latter period, new criteria consisting of early bilateral surgical staging and lung resection through median sternotomy were adopted for the management of lung metastases, in all patients with purely intrathoracic relapse. There was no operative mortality, follow-up was updated in August 1989, and actuarial survivals were calculated by the logrank method at 36 months from the time of first lung resection. During the second period, the overall actuarial survival at three years improved significantly (24% vs. 50%, P less than 0.02), notwithstanding the higher incidence of patients with unfavourable prognostic factors. The three-year survival was also significantly better in the subset of patients with a disease-free interval less than or equal to 12 mos. and/or multiple pathological lesions (9% vs. 45%, P less than 0.05). Contralateral occult metastases were resected in 10 of 29 subjects who underwent sternotomy for monolateral clinical lesions. Of 26 patients with further intrapulmonary recurrence, 16 (62%) were amenable to re-operation and eventual surgical rescue. These data suggest that median sternotomy and early management of occult contralateral disease may contribute to an improvement in the long-term survival of patients with metastatic sarcomas. On the other hand, it is possible that the effectiveness of salvage surgery is related to the higher activity and wider application of adjuvant and salvage chemotherapy.

[Esophagogastric anastomosis at the inferior cricoid margin]. / Esofagogastroanastomosi meccanica al margine cricoideo inferiore.

In esophageal resections, esophagogastric anastomosis can be performed either at cervical or intrathoracic level. A recent paper showed a greater incidence of postoperative leakages in cervical vs. intrathoracic anastomosis (26% vs. 4%). In the present paper we describe 55 cases of esophagectomy with a modified technique of cervical stapled anastomosis, where the incidence of fistula was 5%.