Marc Riquet

Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation.

Background and Objectives:Lymphedema complicating breast cancer treatment remains a challenging problem. The purpose of this study was to analyze the long-term results following microsurgical lymph node (LN) transplantation. Methods:Twenty-four female patients with lymphedema for more than 5 years underwent LN transplantation. They were treated by physiotherapy and resistant to it. LNs were harvested in the femoral region, transferred to the axillary region, and transplanted by microsurgical procedures. Long-term results were evaluated according to skin elasticity, decrease, or disappearance of lymphedema assessed by measurements, isotopic lymphangiography, and ability to stop physiotherapy. Results:The postoperative period was uneventful; skin infectious diseases disappeared in all patients. Upper limb perimeter returned to normal in 10 cases, decreased in 12 cases, and remained unchanged in 2 cases. Five of 16 (31%) isotopic lymphoscintigraphies demonstrated activity of the transplanted nodes. Physiotherapy was discontinued in 15 patients (62.5%). Ten patients were considered as cured, important improvement was noted in 12 patients, and only 2 patients were not improved. Conclusion:LN transplantation is a safe procedure permitting good long-term results, disappearance, or a noteworthy improvement, in postmastectomy lymphedema, especially in the early stages of the disease.

Endothelin-1 in the lungs of patients with pulmonary hypertension

BACKGROUND Pulmonary hypertension (PH) is characterized by an increase in vascular tone and an abnormal proliferation of muscle cells in the walls of pulmonary arteries. Recent studies have found high plasma endothelin-1 (ET-1) concentrations in patients with PH. This study was conducted to assess whether elevated circulating ET-1 levels in PH really reflect excessive local pulmonary production. METHODS We prospectively studied ET-1 concentration in lung specimens from 6 control subjects and 13 patients with severe PH referred for lung or heart-lung transplantation (6 patients had primary PH and 7 PH secondary to congenital heart defect). Endothelin-like immunoreactivity (ET-LI) was measured in plasma and lung tissue, using a radioimmunoassay, after ET-1 extraction. Reverse-phase high-performance liquid chromatography was also performed. RESULTS Peripheral venous plasma ET-LI concentrations in patients with PH, whatever the cause, were greater than those in controls (10.7 +/- 0.8 vs 5.3 +/- 0.7 pg/ml; P < 0.0005). Pulmonary ET-LI was significantly higher in patients with PH, irrespective of its cause, than in controls (25.2 +/- 5.1 vs 8.1 +/- 1.1 pg/mg, P < 0.03). ET-LI pulmonary concentrations were slightly higher in Eisenmenger than in primary PH, but this was not significant (27.1 +/- 8.6 vs 22.8 +/- 5.4 pg/mg). Linear regression analysis indicated a small but significant correlation between ET-LI pulmonary concentrations and pulmonary vascular resistance in the patients with PH (r = 0.38; P = 0.047). In each case, HPLC separation of ET indicated that most of the immuno-reactivity was detected in the same fraction as ET-1. CONCLUSIONS The striking increase in ET-1 pulmonary concentration provides new evidence that excessive local pulmonary ET-1 production may contribute to the vascular abnormalities of pulmonary hypertension.

Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor

BACKGROUND Visceral pleura invasion (VPI) by non-small cell lung cancer is a factor of poor prognosis. A tumor of any size that invades the visceral pleura is classified as T2. Few studies have been conducted concerning the prognostic significance of VPI relative to other staging factors. METHODS Between April 1984 and December 1996, 1,281 patients with T1 (n = 430) and T2 (n = 851) non-small cell lung cancer underwent curative surgical resection. Adjuvant radiation therapy was performed in 455 patients. There were 176 women and 1,105 men aged 30 to 86 years (mean, 60.9 years). Five hundred nineteen pneumonectomies, 742 lobectomies, and 20 segmentectomies were performed. In all patients, a complete mediastinal lymph node dissection was performed. International staging was stage IA and B (n = 697); stage II A and B (n = 247), and stage III A (n = 337). The patients were divided into two groups according to the existence of VPI (group I without, group II with). Both groups were compared with regard to the size of the tumors, histology, associated lymph node involvement, survival rates, and cause of death. Univariate and multivariate analyses were conducted. RESULTS VPI (group II) was identified in 19.1% of the resected specimens: group I, n = 1036; group II, n = 245. The VPI was present in only 10% of non-small cell lung cancer 3 cm or less in size, reaching 33% of patients with non-small cell lung cancer larger than 5 cm (p = 0.0001). Squamous non-small cell lung cancer were significantly less accompanied by VPI (13.5%) than the other histologic categories. The VPI was associated with a higher frequency of N2 involvement (group I = 24.6%, group II = 33.4%, p = 0.01) and N2 involvement was more extensive (two or more N2 involved stations: group I = 8.2%, group II = 15.6%, p = 0.003). Actuarial survival rates were 51.8% at 5 years and 33.8% at 10 years in group I (median, 66 months), and 34.6% at 5 years and 27.9% at 10 years in group II (median, 30 months) (p = 0.000002). Long-term survival rates significantly decreased for larger tumors. Even in patients with N2 stage tumors, the difference of survival curves between the two groups was statistically significant. Cancer-related deaths were more frequent in group II and were mainly caused by distant metastases. By multivariate analysis, visceral pleura invasion proved to be a significant independent factor of poor prognosis. CONCLUSIONS The VPI is a factor of poor prognosis. Its frequent association with extensive N2 involvement supports the hypothesis that exfoliated tumor cells are drained through the pleural lymphatics by the mediastinal lymphatic pathways and then into the bloodstream. The VPI is an important prognostic factor and, as such should stimulate more studies to better select the patients who could benefit from adjuvant therapy.

Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung

BACKGROUND N1 disease represents a heterogeneous group of non-small cell lung carcinoma with varying 5-year survival rates. Specific types of N1 lymph node involvement need to be further investigated and their prognostic significance clarified. METHODS From 1984 to 1993, 1,174 patients with non-small cell lung cancer had complete mediastinal lymph node dissection: N0, 50.25% (n = 590); N1, 21.8% (n = 256); and N2, 27.95% (n = 328). The N1 subgroup cases were reviewed. Four levels of N1 nodes were identified using the New Regional Lymph Node Classification for Lung Cancer Staging. Their prognostic significances were tested and 5-year survival rates were compared with those of N0 and N2 patients of the whole group. RESULTS The overall 5-year survival rate of N1 patients was 47.5%. Survival was not related to site of the primary lung cancer, pathologic T factor, histologic type, type of resection, number of N1 station involved, nor type of N1 involvement (direct extension or metastases). Five-year survival was significantly better when N1 involvement was intralobar (levels 12 and 13, n = 102), as compared with extralobar (hilar) involvement (levels 10 and 11, n = 154): 53.6% versus 38.5% (p = 0.02). Intralobar N1 5-year survival was similar to that of N0 (53.6% vs 56.5%, p = 0.01), and extralobar 5-year survival with that of N2 (38.5 vs 28.3%, p = 0.01) when N2 was present in only one station in the ipsilateral mediastinum. CONCLUSIONS N1 disease is a compound of two subgroups: one located inside the lobes is related to N0, and the other (extralobar or hilar) behaves like an early stage of N2 disease. This offers further information for clinical, therapeutic, and research purposes.

Catamenial pneumothorax: retrospective study of surgical treatment

BACKGROUND Catamenial pneumothorax is a rare entity characterized by recurrent accumulation of air in the thoracic space during menstruation. Catamenial pneumothorax is also associated with a high rate of postoperative recurrence. The aim of this study was to discuss the etiology and to determine the optimal surgical treatment of this entity. METHODS From December 1991 to September 2000, 10 patients with catamenial pneumothorax were treated at our institution. Median age at time of operation was 37 years (range, 21 to 44 years). We retrospectively evaluated the pathologic findings, the operation performed, and the results in all patients. The mean follow-up was 55.7 months. RESULTS Pleurodesis alone was performed in 5 patients and an associated diaphragmatic procedure was performed in 5 patients. In 5 patients, no diaphragmatic anomaly was discovered: 3 experienced one or more recurrences and all still suffer from chronic catamenial chest pain. Hormonal therapy temporarily improved outcome for 6 months in 2 patients. On the contrary, in 5 patients surgical pleurodesis was associated with the repair of diaphragmatic defects (simple closure or coverage by a polyglactin mesh): these patients experienced no recurrence (n = 0/5, p = 0.0016) and no subsequent catamenial chest pain. CONCLUSIONS The postoperative outcome is influenced by the diagnosis of diaphragmatic defects with or without endometriosis. Surgical treatment should be accomplished during menstruation for an optimal visualization of pleurodiaphragmatic endometriosis. Because diaphragmatic lesion is frequent and may be occult, we propose the systematic coverage of the diaphragmatic surface by a polyglactin mesh to prevent catamenial pneumothorax recurrence even when the diaphragm appears normal.

Epidermal Growth Factor Receptor Mutation in Lung Cancer are Linked to Bronchioloalveolar Differentiation

In lung cancer, an association was made between drastic clinical response to epidermal growth factor receptor (EGFR) inhibitors and the presence of somatic mutations within the tyrosine kinase domain of the EGFR. In some cases, patients with partial response or disease stabilization do not always have EGFR-mutated tumors. To go further in the characterization of the EGF pathway, we screened EGFR, ERBB2, ERBB3, KRAS, BRAF, and PIK3CA for mutations in 2 groups of White patients with nonsmall cell lung cancer (45 cancers from women and 46 cancers from men). Associations between TP53 mutations, clinicopathologic parameters, and EGF pathway molecular alterations were analyzed. All mutations were exclusive and essentially found in EGFR and KRAS. We demonstrated that EGFR mutations were linked to female sex, absence of smoking, late age at diagnosis, and adenocarcinoma (ADC) with bronchioloalveolar (BAC) features. Moreover, in invasive ADC with BAC component, microdissection assays showed that mutations were retrieved in both tumor subtypes suggesting that EGFR mutations appear early in lung carcinogenesis. On the contrary, KRAS mutations correlated with smoking, younger age at diagnosis, and ADC subtype regardless of BAC differentiation. These results suggest the existence of distinct carcinogenesis pathways both leading to disruption of EGF regulation and targeted either by tobacco carcinogens or by unidentified toxic. The identification of BAC features in ADC helps clustering patients that are more likely to fit the EGFR-mutated group.

Microlymphatic surgery for the treatment of iatrogenic lymphedema.

Lymphedema is a chronic and progressive condition that occurs after cancer treatment. Autologous lymph node transplant, or microsurgical vascularized lymph node transfer (ALNT), is a surgical treatment option that brings vascularized vascular endothelial growth factor-C-producing tissue into the operated field to promote lymphangiogenesis and bridge the distal obstructed lymphatic system with the proximal lymphatic system. Operative techniques for upper- and lower-extremity ALNT are described with 3 donor lymph node flaps (inguinal, thoracic, cervical). Surgical technique is described for the combination of ALNT with abdominal flaps and nonabdominal flaps. Imaging showing restoration of lymphatic drainage after ALNT is shown.

Management of superior sulcus tumors: experience with 139 cases treated by surgical resection.

BACKGROUND The management of non-small cell carcinomas of the lung involving the superior sulcus remains controversial. The goal of this retrospective study was to evaluate the role of surgery, radiotherapy, and chemotherapy for the treatment of superior sulcus tumors, to define the best surgical approach for radical resection, and to identify factors influencing long-term survival. METHODS Between 1983 and 1999, 139 patients underwent surgical resection of superior sulcus tumors in seven thoracic surgery centers. According to the classification of the American Joint Committee, 51.1% of cancers were stage IIB, 13.7% stage IIIA, 32.4% stage IIIB, and 2.9% stage IV. RESULTS The resections were performed with 74.1% using the posterior approach and 25.9% using an anterior approach. A lobectomy was accomplished in 69.8% of the cases and a wedge resection in 22.3%. Resection of a segment of vertebrae or subclavian artery was performed, respectively, in 19.4% and 18% of the cases. Resection was complete in 81.3% of cancers. The overall 5-year survival rate was 35%. Preoperative radiotherapy improved 5-year survival for stages IIB-IIIA. Surgical approach, postoperative radiotherapy, or chemotherapy did not change survival. CONCLUSIONS The optimal treatment for superior sulcus tumors is complete surgical resection. The surgical approach (anterior/posterior) did not influence the 5-year survival rate. Preoperative radiotherapy should be recommended to improve outcome of patients with a superior sulcus tumor.

Cold abscess of the chest wall: a surgical entity?

BACKGROUND Cold abscesses of the chest wall are rare tuberculous locations. Because of the resurgence of tuberculosis, this diagnosis must be considered more frequently. METHODS During a 15-year period (1980 to 1995), 18 patients with one or more cold abscesses of the chest wall were managed in our department. Epidemiologic characteristics, indications, methods and results of operation, and pathogenesis of the abscesses were considered in this retrospective study. RESULTS Most of the patients were immigrant men. A previous history of tuberculosis was noted in 15 cases (83%). Six patients had concomitant active pulmonary tuberculosis. There was mostly a solitary lesion in the chest wall, the most frequent location being the rib shaft (60%). Before operation the diagnosis was confirmed only in 4 patients (by needle aspiration of the abscess) and presumed in 4 others: an antituberculous chemotherapy was therefore given preoperatively to 8 patients. One patient did not undergo operation after a favorable response to medical treatment. In the other patients, an operation was indicated because of lack of response in 5 patients and the absence of diagnosis in 12 patients. Adequate debridement and a postoperative antituberculous regimen were performed with recurrence prevention in mind. A follow-up was obtained in 11 of the 17 patients undergoing operation. The only patient who required a second operation because of a recurrence at the same location had refused the antituberculous therapy after the first surgical procedure. Locations of the abscesses, computed tomographic scan results, and histologic examinations are in favor of a lymph-borne dissemination of tubercle bacilli. CONCLUSIONS Because fine-needle aspiration remains an inaccurate diagnostic tool and antituberculous medical treatment is not always efficient, chest wall tuberculous cold abscesses remain in most cases a surgical entity.

Thoracic duct tributaries from intrathoracic organs

BACKGROUND The thoracic duct (TD) is the main collecting vessel of the lymphatic system. Little is known about the intrathoracic tributaries of the TD, which are named intercostal, mediastinal, and bronchomediastinal trunks. The purpose of the study was to identify the lymphatic tributaries from intrathoracic organs to the thoracic duct. METHODS The study was performed on 530 adult cadavers. The lymphatics of different organs were catheterized and injected with a dye: lungs (n = 360), heart (n = 90), esophagus (n = 50), and diaphragm (n = 30). The lymphatic tributaries draining the lymph from these organs to the thoracic duct were dissected along their course to the thoracic duct and classified. RESULTS The TD tributaries were observed in 147 cases: right lung (n = 46), left lung (n = 69), heart (n = 8), esophagus (n = 13), and diaphragm (n = 11). Connections with the TD were observed at its origin (n = 13), within the mediastinum (n = 87), and at the level of the TD arch (n = 47). Tributaries from the lung issued from lower paratracheal nodes 4 R (n = 14) and 4 L (n = 31), subaortic 5 (n = 4), subcarinal 7 (n = 18), pulmonary ligament 9 (n = 7), upper tracheal 2 L (n = 28), paraortic 6 (n = 11), and celiac nodes (n = 2). Tributaries from the heart connected with the TD in the mediastinum in 1 case (4 L) and with the TD arch in 7 cases. Tributaries from the esophagus connected with the thoracic duct within the mediastinum in 13 cases; anodal routes were frequent (n = 5). The TD tributaries from the diaphragm were observed in 11 cases, always connecting with the TD at its origin. CONCLUSIONS Injection of intrathoracic organs permits visualization of TD tributaries. These tributaries appear located at unchanging levels. Lymph of intrathoracic organs may thus drain into the general circulation through the TD. The tributaries may represent a potential route for tumor cells dissemination. When incompetent, due to valve insufficiency, they permit chylous lymph to backflow into the intrathoracic lymph nodes. Injury at this level may lead to intrathoracic chylous effusions.