Vincenzo Ambrogi

Longterm results after resection of simultaneous and sequential lung and liver metastases from colorectal carcinoma.

BACKGROUND Although simple lung or liver metastasectomy from colorectal cancer have proved effective in selected patients, the value of simultaneous biorgan metastasectomies is still debated. STUDY DESIGN Of 155 patients who underwent operation for lung or liver colorectal metastases between March 1987 and December 1998, we retrospectively reviewed 29 patients who presented simultaneous (n = 12) or sequential liver-->lung (n = 10) and lung-->liver (n = 7) metastases. All metastases were successfully resected in a total of 56 separate procedures. In 35 thoracic procedures, 45 metastases were removed by wedge resection (n = 36) or lobectomy (n = 9). In addition, 47 liver metastases were resected with wedge (n = 24), segmentectomy (n = 13), or lobectomy (n = 10). There were no perioperative deaths and the morbidity rate was low (10.7%). All patients were followed for a minimum of 3 years. Factors possibly influencing survival were evaluated by univariate and subsequently by multivariate analyses. RESULTS Median survival from the second metastasectomy was 41 months, with a 5-year survival rate of 51.3%. Risk factor distribution among the three metastastic pattern groups was insignificant. Premetastasectomy elevated levels of both CEA and CA19-9 (p = 0.0001), and mediastinal or celiac lymph node status (p = 0.03) were significantly associated with survival in the univariate analysis, although number of metastasectomies, disease-free interval, and simultaneous versus sequential diagnosis were not. In the multivariate analysis, only elevated CEA plus CA19-9 (p = 0.01) was significantly associated with survival. CONCLUSIONS We conclude that either simultaneous or sequential lung and liver metastasectomy can be successfully treated by surgery. Poor results were obtained in the presence of high levels of CEA plus CA19-9.

The impact of cardiovascular comorbidity on the outcome of surgery for stage I and II non-small-cell lung cancer

OBJECTIVE The association between lung malignancy and cardiovascular disease has been frequently reported though its therapeutic and prognostic implications not thoroughly analyzed. This study aims at assessing the possible impact of coexisting cardiovascular disease on the outcome of surgical treatment of non small cell lung cancer (NSCLC). METHODS Among 247 consecutive patients undergone surgery for stage I and II NSCLC between 1990 and 1997, 34 (13.7%) had a cardiovascular comorbidity going to be treated by surgery, namely coronary artery disease (n=14), carotid stenosis (n=21), abdominal aortic aneurysm (n=9) and lower limbs arteriopathy (n=7). Among 22 patients (64.7%) who underwent cardiac/vascular surgery first, operation was performed after a median interval of 4.5 weeks. In five of this subset lung cancer was incidentally detected. In the other patients the cardiovascular disease was diagnosed and treated after the lung cancer had been detected and operated with a median interval of 3.5 months from thoracic procedure. Surgical procedures for lung cancer were three pneumonectomies, 12 lobectomies, 19 wedge resections. Uni and multivariate analysis for risk factors was carried out. RESULTS In the group with cardiovascular comorbidity overall postoperative mortality was 9%, while morbidity rate was 58.8%, both of them primarily caused by cardiovascular disease and significantly higher for major resections. The 3- and 5-year survival rates were 54.8% and 35.5% compared to 69.2% and 56.4% among patients without cardiovascular comorbidity (P=0.01) while the timing of vascular surgery (before or after thoracic procedure) did not significantly affect survival. Multifocal vascular disease resulted the only positive factor at multivariate analysis (P=0.005, Odd Ratio=3.51, 95% Confidence Interval=1.4-8.4). CONCLUSIONS Cardiovascular disease seems to have significant impact on survival and morbidity in patients undergone surgery for lung cancer, especially in presence of multifocal vascular disease and following major resections. The timing of vascular surgery and the extension of resection should rely on the severity of vascular disease, anaesthesiologists and surgeons final evaluation.

Factors Influencing Long-Term Survival After Lung Metastasectomy

BACKGROUND Disease-free interval, histology of primary tumor, and number and size of metastases resected (at first metastasectomy) were studied after resection of pulmonary metastases. METHODS Between 1980 and 1993, 276 consecutive patients underwent lung resections for curative removal of metastatic disease. At subsequent relapse, 63 patients had a second-stage metastasectomy, 12 went on to a third phase, and 2 patients had four stages. RESULTS The primary tumor was sarcoma in 126 cases (46%), teratoma in 88 (32%), carcinoma in 53 (19%), melanoma in 5, and miscellaneous in 4. Actuarial survival was 69% at 2 years (95% confidence interval 62% to 74%), 48% at 5 years (40% to 55%), and 35% at 10 years (23% to 44%). CONCLUSIONS Survival was not related to disease-free interval. Multivariate analysis showed that nearly all predictive information can be obtained through histologic studies (p < 0.0001); inclusion of the number of metastases resected contributed to a lesser degree (p = 0.032). Short disease-free intervals, numerous lung metastases, or even deposits recurring after a first or second metastasectomy should not preclude patients from operation.

Postoperative adjuvant therapy for stage IB non-small-cell lung cancer

OBJECTIVE Although surgical resection alone is considered adequate treatment in stage IB non-small-cell lung cancer (NSCLC), long-term survival is not satisfactory and the recurrence rate is quite high. The validity of postoperative chemotherapy at stage IB in terms of disease-free and overall survival was assessed in a randomised trial. METHODS The trial was designed as a randomised, two-group study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure. Chemotherapy consisted of treatment with cisplatin (100 mg/m(2) on day 1) and etoposide (120 mg/m(2) on days 1--3) for a total of six cycles. RESULTS Between January 1988 and December 1994, 66 patients were included in the study. Thirty-three belonged to the adjuvant chemotherapy group and 33 to the control group. Groups were homogeneous for conventional risk factors. There was no clinical significant morbidity associated to chemotherapy. Patients were followed for a minimum period of 5 years. The rates of locoregional recurrence and distant metastases were 18 and 30%, respectively, in the adjuvant chemotherapy group and 24 and 43%, respectively, in the control group. The 5-year disease-free survival rates were 59% in the adjuvant group and 30% in the control group (P = 0.02). The difference in the Kaplan--Meier survival between the groups was significant as assessed using the log-rank test (P = 0.04). CONCLUSIONS Our results suggest that adjuvant chemotherapy may reduce recurrences and prolong overall survival in patients at stage IB NSCLC deemed radically operated. Despite being difficult to accept, the use of adjuvant chemotherapy might have better long-term results.

Prolonged survival after extracranial metastasectomy from synchronous resectable lung cancer

Background:Combined resection of solitary synchronous brain metastases and non–small-cell lung cancer has been shown to be successful. Thus, we proposed combining the surgery of solitary, extracranial metastases, and resectable lung cancer.Methods:Between March 1987 and December 1994, surgery was performed on nine patients with non–small-cell lung cancer with synchronous, solitary, extracranial, or distant metastasis: adrenal (n = 5), cutaneous (n = 2), axillary lymph node (n = 1) and kidney (n = 1). Criteria for operating on these patients included: primary tumor that was locally resectable in a radical manner, non–small-cell histology, no preoperative evidence of N2 disease, complete resection of histologically proven metastasis, and absence of other metastases found with computed tomography or bone scan.Results:Resection of the primary tumor and solitary metastases was achieved in all patients. Primary tumor was always resected by lobectomy. No mortality or major morbidity was reported. Five-year survival rate was 55.6%. Five patients who had adrenal (n = 3), or skin (n = 1), or axillary (n = 1) metastases, survived more than 5 years. All N2 patients (n = 2) died.Conclusions:The presence of solitary, distant metastasis should not be considered, per se, a factor for denying surgery for locally resectable, non–small-cell lung cancer. Unexpected, prolonged survival was demonstrated in our limited series.

Adjuvant pneumomediastinum in thoracoscopic thymectomy for myasthenia gravis.

To facilitate initial visualization and subsequent mobilization of the thymus, adjuvant pneumomediastinum was preoperatively induced in 4 patients who underwent video-assisted thoracoscopic thymectomy. Neither mortality nor technique-related morbidity was observed. This experience shows video-assisted thoracoscopic thymectomy to be a safe and reliable procedure. In addition, we believe that adjuvant pneumomediastinum seems to facilitate the dissection maneuvers and could shorten operative time.

Vascular endothelial growth factor (VEGF-A) plasma levels in non-small cell lung cancer: Relationship with coagulation and platelet activation markers

Platelet activation, commonly found in lung cancer patients, may cause the release of angiogenic factors, such as vascular endothelial growth factor (VEGF-A). The present study was designed to investigate whether plasma VEGF-A levels were associated to different stages of non-small cell lung cancer (NSCLC). Moreover, sP-selectin, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex (TATc) and D-dimer levels were measured to test the hypothesis of an involvement of platelet and coagulation activation in tumor angiogenesis. VEGF-A, sP-selectin, F1+2, TATc and D-dimer levels were elevated in 65 patients with NSCLC, particularly in metastatic patients. sP-selectin (p <0.003) and F1+2 (p <0.005) levels were independently associated to VEGF-A. In addition, patients with positive levels of both sP-selectin and F1+2 had the highest levels of VEGF-A. In conclusion, our findings support the hypothesis that thrombin generation might induce platelet activation and VEGF-A release in NSCLC.

Transxiphoid video-assisted pulmonary metastasectomy: Relevance of helical computed tomography occult lesions

BACKGROUND The new transxiphoid video-assisted approach allows manual palpation of both lungs, thus permitting better evaluation of helical computed tomography (CT) in detection of pulmonary metastases. METHODS From December 1995 to May 1999, 22 patients underwent a transxiphoid video-assisted pulmonary metastasectomy. Manual palpation of both lungs was possible in 18 patients, whereas only 13 had radiologic evidence of unilateral disease. Primaries were colon-rectum (n = 8), kidney (n = 3), uterus (n = 2), larynx (n = 2), limb osteosarcoma (n = 2), and one each of breast, skin melanoma, prostate, fibrosarcoma, and ovary. RESULTS No perioperative death occurred. Fifty-eight lesions, 49 metastatic, were resected, whereas only 46 had been predicted by helical CT scan. Twelve occult lesions were discovered, eight of which were malignant. Overall sensitivity for proved metastases was 83.7% (41 of 49) and 75.8% (22 of 29) for those less than or equal to 5 mm. Mean follow-up was 15.27 months. Only 2 patients had pulmonary relapse at 6 and 12 months. CONCLUSIONS Despite helical CT, occult metastases may still be identified in almost one-third of the patients. The transxiphoid approach allows routine bilateral palpation and safe resection, and overcomes this critical limitation of video-assisted metastasectomy.

Impact of Awake Videothoracoscopic Surgery on Postoperative Lymphocyte Responses

BACKGROUND Surgical stress and general anesthesia can have detrimental effects on postoperative immune function. We sought to comparatively evaluate postoperative lymphocytes response in patients undergoing video-assisted thoracoscopic surgery (VATS) under thoracic epidural or general anesthesia. METHODS Between October 2008 and June 2009, 50 patients with nonmalignant pulmonary conditions were randomized to undergo VATS through either sole epidural anesthesia and spontaneous ventilation (awake group, n = 25) or general anesthesia with one-lung ventilation (control group, n = 25). In both groups, assessment of total lymphocytes count and changes in proportion of lymphocyte subsets including CD19+, CD3+, CD4+, CD8+, CD4+:CD8+ ratio, and CD16+CD56+ (natural-killer cell) were evaluated by two-way analysis of variance test for repeated measures at baseline and postoperative days 1, 2, and 3. The Mann-Whitney test was performed at each time point only for significant parameters at between-group analysis of variance. RESULTS Comparisons of baseline data showed relatively homogeneous groups. Between-group analysis of variance was significant for proportion of natural-killer cells (p = 0.01). In particular, the control group disclosed a significantly lower median proportion of natural-killer cells as compared with the awake group on postoperative day 1 (5% interquartile range [IQR]: 3% to 8%] vs 12% [IQR: 8% to 14%], p = 0.003) and 2 (7% [IQR: 4% to 10%] vs 11% [IQR: 8% to 21%], p = 0.02). Total lymphocyte count was significantly decreased in the control group only (p < 0.00001). No difference was found between groups in the remaining lymphocyte subsets. CONCLUSIONS In this randomized study, awake VATS resulted in a lesser impact on postoperative lymphocyte responses than procedures performed under general anesthesia, as shown by the significant difference in postoperative proportion of natural-killer cells.

Bilateral Thoracoscopic T2 to T3 Sympathectomy Versus Botulinum Injection in Palmar Hyperhidrosis

BACKGROUND Bilateral T2 to T3 thoracoscopic sympathectomy and injection of botulinum toxin-A are presently the most effective modalities in the treatment of primary palmar hyperhidrosis. In this study we evaluated comparative merits of the two therapies. METHODS Patients suffering primary palmar hyperhidrosis were treated by either bilateral T2 to T3 thoracoscopic sympathectomy (n = 68) or by injection of botulinum toxin-A (n = 86). The groups were homogeneous for relevant demographic, physiologic, and clinical data. Quantification of sweat production was performed by Minors iodine starch and glove tests. Subjective changes were assessed by quality of life questionnaires (Hyperhidrosis, Dermatology Life Quality Index, Short Form-36, Nottinghams Health Profile) and patients satisfaction self-assessment. A cost comparison between groups was also carried out. RESULTS No operative mortality or major morbidity was recorded in either group. Minors test showed a more significant reduction in the surgical group: +94% versus +63% at 6 months and +94% versus +30% at 12 months. Compensatory sweating was significantly greater and long-lasting in the surgical group. All subjective tests improved rapidly and significantly in both groups. After 6 months, results mildly worsened in the surgical group and more significantly in the botulinum group. Patients satisfaction was initially greater in the botulinum group (p = 0.03), but after 6 months it significantly reversed (p = 0.04). Surgical treatment cost approximately as much as four botulinum treatments. CONCLUSIONS Thoracoscopic sympathectomy is superior to botulinum toxin-A injection. The greater initial costs and discomfort are offset by a greater reduction in compensatory sweating.