Biomedical subjects
P Fuentes
Publications and source records attributed to P Fuentes.
Bilateral bronchioloalveolar lung carcinoma: is there a place for palliative pneumonectomy?
OBJECTIVE: Bronchioloalveolar lung carcinoma (BAC) is characterized by bronchial and lymphatic dissemination explaining multifocal and bilateral spreading. Bilateral BAC is usually considered as a contraindication to surgery. Regarding poor efficacy of symptomatic and oncological treatments, we hypothesized that surgery might play a role to palliate hypoxemia associated with serious intrapulmonary shunting, as well as continuous bronchorrhea. METHODS: We retrospectively studied here four consecutive patients, who underwent palliative pneumonectomy. RESULTS: The shunt was confirmed again at the time of the surgery by a pulmonary artery occlusion demonstrating immediate improvement in arterial oxygen saturation from 89% at baseline to 98% after occlusion. Lung resections consisted of a left pneumonectomy in three cases and a right pneumonectomy in one. PaO(2) levels under 5l/min oxygen therapy improved dramatically when comparing preoperative data (mean 50.5 mmHg) to post-operative results (mean 150 mmHg). One patient died postoperatively. Three patients, who experienced an uneventful immediate post-operative course, received chemotherapy after surgery. Improvement of quality of life is testified by the absence of both symptoms and any need for oxygen therapy for few months. Disabling symptoms reappeared at 1, 8 and 10 months. Survival of these patients was 3, 12 and 18 months. CONCLUSIONS: These results support the interest of consideration of a surgical resection for highly selected patients presenting with bilateral BAC and severe intrapulmonary shunting.
[Surgery of bronchial cancer after radiochemotherapy or chemotherapy. Risks and benefits].
The purpose of this study was to evaluate the conditions and results of lung cancer surgery, following chemo and/or radiotherapy. This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (n = 25), temporary functional impairment (n = 4); doubtful resectability (n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received 2 to 4 sessions of chemotherapy (average = 2.9 +/- 0.8 sessions) and 43 +/- 8 Gy (20 to 60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 sessions). Exploratory thoracotomy was performed in 4 patients (6%). There were 33 pneumonectomies, 1 bilobectomy, 23 lobectomies and 8 lung sparing resections. The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were 4 reoperations (6%): 3 for bronchial fistula and 1 for bleeding. Thirty five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). The overall 5 years survival was 22% [19-32]. In the group of patients who had a complete resection, five-years survival for patients classified pathologically as N0 or N1 was 31% and, for those classified as N2, 8% (p = 0.19). Surgical management after induction chemo and/or radiotherapy of NSC lung cancer should be considered, in the absence of N2 disease, when a complete resection is achievable. However this surgery is associated with an increased risk.
Passive immunization with antisperm monoclonal antibody ZAP-7 increases preimplantation embryo mortality in the mouse.
OBJECTIVE: To evaluate the effect of VIC-1 and ZAP-7 antihuman sperm monoclonal antibodies on in vivo fertility in the mouse. DESIGN: A randomized blinded study using a mouse model. SETTING: University-based laboratory. ANIMALS: B6CBAF1 mice (n = 6 per experimental group). INTERVENTION(S): Antisperm antibodies were administered intravaginally to female mice before mating. Control mice received no treatment, saline, or nonspecific antibodies. Number and viability of preimplantation embryos were determined by microscopic observation. Mouse sperm, oocytes, and normal preimplantation embryos were used in indirect immunofluorescence assays with antisperm antibodies. The effect of antibody treatment on sperm motility and vitality was evaluated. MAIN OUTCOME MEASURE(S): Antigen expression, sperm motility and vitality, number and viability of embryos. RESULT(S): ZAP-7 antibody recognizes a sperm antigen expressed in zygotes and early preimplantation embryos. Passive immunization with ZAP-7 increases embryo mortality significantly (more than 40% above controls). Passive immunization with VIC-1 has no deleterious effect. CONCLUSION(S): ZAP-7 monoclonal antibody disrupts fertilization and embryogenesis in the mouse.
Anti-CD20 monoclonal antibody therapy in Epstein-Barr Virus-associated B cell lymphoma following lung transplantation.
Post-transplant lymphoproliferative disease is a complication of bone marrow and solid organ transplantation, mostly associated with Epstein-Barr virus infection and chronic immunosuppression. Even if spontaneous resolution after cessation of immunosuppressive therapy can be observed, the prognosis of this disorder is usually poor with a low response to specific treatment. We describe a case of B-cell lymphoma of the nasopharynx occurring 6 months after double-lung transplantation. In spite of its monoclonal nature, anti-CD 20 monoclonal antibody given in the presence of reduced immunosuppression resulted in a complete response. The patient also received "consolidation" radiation therapy to prevent the recurrence. The treatment was well tolerated with minimal side effects. The patient was asymptomatic and had a well functioning graft more than 1 year after therapy.
Early detection of airway involvement in obliterative bronchiolitis after lung transplantation. Functional and bronchoalveolar lavage cell findings.
As defined by the International Society for Heart and Lung Transplantation, the diagnosis of posttransplant obliterative bronchiolitis (OB) is based on histopathologic features and/or spirometric staging criteria, using FEV(1) to determine the extent of disease. However, this last parameter reflects an advanced bronchiolar process. The present study investigated whether physiologic parameters reflecting smaller airways dysfunction on one hand, and neutrophils in bronchoalveolar lavage fluid (BALF) on the other hand, could be useful for the earlier detection of bronchiolitis obliterans syndrome (BOS). We analyzed data obtained both from 765 pulmonary function test results and from 467 BALF specimens from 45 patients who survived at least 1 yr after surgery (n = 47, including two retransplantations). Of the transplant procedures, 22 were associated with BOS and 25 were not. The mean delay from transplantation to the diagnosis of BOS was 578 d (range: 122 to 2,619 d). The threshold values of the following parameters were studied: decline in the forced expiratory flow rate at 25% to 75% of FVC (FEF(25-75)) to </= 70% of the predicted value and of baseline values, increase in the slope of the nitrogen washout curve (DeltaN(2)) > 3%, and alveolar neutrophilia >/= 20% of the total BALF cell count. Agreement on the diagnosis of BOS (using the decline in FEV(1)) was equally good for each of the four markers (kappa coefficient > 0.65, p < 10(-)(5)). In the OB group, mean delays after the threshold was reached for each of these parameters were 110 d (p = 0.09), 173 d (p = 0.03), 150 d (p = 0.003), and 131 d (p = 0.1), respectively, before the FEV(1) criteria were fulfilled. At the chosen threshold values, the decline in FEF(25-75), increase in DeltaN(2), and development of a substantial alveolar neutrophilia all occurred significantly before a decline in FEV(1) in posttransplant OB.
[Postoperative complications after radiochemotherapy or chemotherapy for bronchial cancers].
OBJECTIVE: The purpose of this study was to evaluate the risk of lung cancer surgery, following induction chemo and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA; n = 25), temporary functional impairment (2 stages IB and 2 stages IIIA [N2]; n = 4); doubtful resectability (stage IIIB [T4]; n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received 2 to 4 cycles of chemotherapy (average = 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (20 to 60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in 4 patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were 4 reoperations (6%): 3 for bronchial fistula and 1 for bleeding. Thirty five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSION: Surgery for lung cancer after induction chemo and/or radiotherapy is associated with an increased risk. While the mortality seems "acceptable", the morbidity rate however is high.
[Role of video-thoracoscopy in the pretreatment evaluation of lung carcinoma].
INTRODUCTION: Lung cancer is the first cause of cancer mortality in male patients in France. Treatment varies depending on the histological type and the disease extent at diagnosis. CURRENT KNOWLEDGE AND KEY POINTS: Videothoracoscopic staging appears to be an accurate method to assess the stage of lung cancer to guide rational management as it allows for 1) an accurate tissue diagnosis when standard methods failed, 2) the identification of a parietal or mediastinal invasion when suspected by CT-scan findings, 3) lymph node sampling of sites that are poorly or not reachable with mediastinoscopy, 4) the diagnosis of pleural or pericardial metastases in patients with effusion or indeterminate nodules, and finally 5) the conclusive answer to the diagnostic dilemma caused by the presence of a contralateral pulmonary nodule in patients with a potentially curable tumor. FUTURE PROSPECTS AND PROJECTS: Video-assisted thoracoscopy thus appears to have a complementary role in intrathoracic lung cancer staging when conventional methods are equivocal. Its main side-advantage is the opportunity to proceed without delay to the surgical treatment, when appropriate, in the same operative settings, or to perform in the same session various procedures, i.e., talc poudrage and pericardial window, to palliate adverse symptoms occurring in some of those patients. Obviously, equally efficient and less invasive approaches should have been considered previously. To date, however, videothoracoscopic evaluation of tumor resectability is not achievable. Finally, one may suppose that positron emission tomography will probably reduce the role of those invasive surgical procedures in a near future.
Distant lymph node metastases in esophageal cancer: impact of endoscopic ultrasound-guided biopsy.
BACKGROUND AND STUDY AIMS: The aim of this retrospective study was to evaluate the impact of endoscopic ultrasound (EUS)-guided biopsy in patients with esophageal carcinoma where distant lymph nodes which were possibly metastatic were visualized using EUS. PATIENTS AND METHODS: Out of 198 patients (150 men, mean age 66 years) examined over a 4-year period by EUS for local staging of esophageal cancer (121 squamous cell carcinomas and 77 adenocarcinomas), there was EUS visualization of distant lymph nodes in 40 (20%). EUS-guided biopsy was carried out in the latter patients, of cervical nodes with mediastinal tumors (n = 19), of celiac nodes with cervical tumors (n = 2) or superior mediastinal tumors (n = 9), and upper mediastinal lymph nodes in the case of distal adenocarcinomas (n = 10). RESULTS: On EUS-guided biopsy, results were positive in 31 patients, eight were correctly negative (as confirmed by surgery), and in one patient there was a technical failure, with positive findings on subsequent surgery. The sensitivity and specificity of the diagnosis of malignant lymph nodes were therefore 97% and 100% respectively. The positive results of EUS-guided biopsy modified the tumor staging in 31 of these cases (77.5%), proving distant lymph node metastasis which is classified as stage M1. With regard to actual clinical management, surgery was withheld from 24 patients (60% of 40 cases) who were then treated with concomitant radiotherapy and chemotherapy. CONCLUSION: EUS-guided biopsy of distant lymph nodes was indicated in 20% of patients with esophageal cancers, and the biopsy results led to upgrading of the tumor stage in about 80% of cases and influenced the treatment decision in about 60%.
Pulmonary arteriovenous malformations: lung transplantation as a therapeutic option.
Multiple pulmonary arteriovenous malformations (PAVM) constitute an uncommon cause of respiratory disability. They may lead to severe hypoxaemia via right-to-left shunts and are sources of substantial mortality and morbidity. Conservative surgical resection has been proposed as the treatment of choice. More recently, percutaneous balloon or coil embolization of the feeding vessels offered an efficacious and safe alternative therapy for patients whose fistulas are too numerous to excise. This study reports an unusual case of respiratory disability in a patient with multiple and microscopic pulmonary arteriovenous malformations who failed to respond to embolotherapy and who received a double lung transplantation with good initial outcome.
[Video-surgery of pulmonary cancer].
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Operative risk and prognostic factors of typical bronchial carcinoid tumors.
BACKGROUND: This study estimated operative risk and examined factors determining long-term survival after resection of typical carcinoid tumors. METHODS: From 1976 to 1996, 139 consecutive patients (66 male and 73 female patients with a mean age of 47 +/- 15 years) underwent thoracotomy for typical carcinoid tumor. The tumors were centrally located in 102 patients (73.4%). RESULTS: Radical resection was performed in 106 patients (7 pneumonectomies, 13 bilobectomies, and 86 lobectomies) and conservative resection in 33 (3 segmentectomies, 3 wedge resections, 20 sleeve lobectomies, and 7 sleeve bronchectomies). There were no postoperative deaths. Complications occurred in 19 patients (13.7%). The morbidity rate was not increased after bronchoplastic procedures (chi 2 = 0.033, not significant). Staging was pT1 in 107 patients (77.0%) and pT2 in 32 (23.0%); 13 patients (9.4%) had nodal metastases. Seventeen patients have died (12.2%), during follow-up, but only three deaths were related to the disease. The overall survival rate at 5, 10, and 15 years was estimated to be 92.4%, 88.3%, and 76.4%, respectively; estimated disease-free survival was 100% at 5 years and 91.4% at 10 and 15 years. Estimated survival of patients with lymph node metastasis was 100% at 5, 10, and 15 years. Univariate analysis failed to demonstrate any prognostic significance for sex, tumor size (T1 versus T2), tumor location (central versus peripheral), and type of resection. CONCLUSIONS: These data confirm an excellent prognosis after complete resection of typical carcinoid tumors, including those with lymph node metastases. Parenchyma-saving resections should be preferred.
Study of serum big-insulin-like growth factor (IGF)-II and IGF binding proteins in two patients with extrapancreatic tumor hypoglycemia, using a combination of Western blotting methods.
Extrapancreatic tumor hypoglycemia (EPTH) is associated with increased amounts of high-molecular-weight precursor forms of insulin-like growth factor (IGF)-II ('big-IGF-II') that have a primary role in the pathophysiology of hypoglycemia. In the present study, using Western ligand and immunoblotting methods, we investigated IGF-binding proteins (IGFBPs), IGFBP-3 proteolysis and big-IGF-II in pre- and postoperative serum from two patients with EPTH due to benign pleural fibroma. In the preoperative serum, IGFBP-3 was reduced and IGFBP-2 was increased compared with that from an age-matched healthy control. IGFBP-3 proteolysis was dramatically reduced in one patient, whereas no major alteration was observed in the other (9% and 120% of control serum, respectively). IGFBPs progressively returned to a subnormal pattern in postoperative serum, whereas IGFBP- 3 proteolysis remained greater than in preoperative serum in both patients at days 14 and 90 after surgery. High-molecular-weight forms of IGF-II predominate in EPTH serum (65% and 57% of total IGF-II immunoreactivity in patients 1 and 2, respectively, compared with 2 5% in control serum). Two forms, of molecular mass 10 and 12 kDa ('standard big-IGF-II') were present in both EPTH and control sera, whereas two additional forms, of molecular mass 15 and 18 kDa ('big big-IGF-II') were observed in EPTH sera only. Big big-IGF-II represented 72% and 55% of total high-molecular-weight forms of IGF-II in the two EPTH sera, respectively. All big forms of IGF-II disappeared from the serum as early as 6 h after surgery. This study shows that combination of simple Western blotting methods, available routinely in most laboratories, should prove useful in providing reliable physiopathological information in EPTH.
[Ecoendoscopy in the assessment of esophageal neoplasms].
OBJECTIVE: To asses the diagnostic accuracy of endoscopic ultrasonography (EUS) for the local and regional staging of esophageal cancer, and its possible alteration resulting from the performance of preoperative chemoradiation. METHODS: Prospective study of 85 consecutive patients with esophageal cancer evaluated by EUS and operated between January 1992 and December 1995. 28 of these patients had received previous induction therapy. In all cases, EUS examination was performed by the same physician not informed about the results of previous morphological explorations. Histopathological analysis of all specimens was performed by the same pathologist, not informed about the results of the EUS. Data were collected by another independent observer. RESULTS: EUS examination resulted in incomplete staging in 8 patients (9.5%) with severe stenosis precluding endoscope passage. The accuracy, specificity and sensibility of EUS in detecting the depth of esophageal involvement (T0-2 vs T3-4) were 82.3%, 78% and 86% respectively, and 72%, 70% and 73% respectively for the lymph node metastasis. The overall accuracy of EUS in identifying the preoperative stage was 67% with a clear-cut alteration when patients had received induction therapy (61% vs 72%). On the other hand, 7(64%) of the 11 patients thought to have a complete response at endosonography had no residual tumor. CONCLUSION: EUS provides precise information for the preoperative identification of locally advanced esophageal tumor, even after induction therapy. The latter alters the diagnostic accuracy of EUS, although complete responders could be identified in two-thirds os cases.
[Neoadjuvant therapy in advanced carcinoma of the esophagus: prognostic value of the histopathological response].
The purpose of this study was to determine the prognostic value of the histopathological response to preoperative radio-chemotherapy in patients with locally advanced oesophageal cancer. Among the 57 patients included in this open prospective study, the disease-free cervical of 48 patients who underwent an oesophagectomy was correlated with the histopathological finding. The 5-years probability of disease-free cervical was 22.1%. Cervical of the patients whose tumor had been downstaged to no residual carcinoma or superficial oesophageal carcinoma was significantly shorter than that of patients with superficial oesophageal carcinoma at presentation treated during the same period (35% vs 57%). Univariate analysis could identify 4 prognostic variables after induction therapy: adenocarcinoma, macroscopic, residual tumor, invaded oesophageal stump, and lymph node involvement. After multivariate analysis according to the Cox model, the remaining independent predictors of recurrence were: adenocarcinoma, invaded oesophageal stump, and lymph node involvement.
Colon interposition for esophageal replacement: current indications and long-term function.
BACKGROUND: In contrast to the use of the stomach as an esophageal substitute, the use of the colon is becoming uncommon. METHODS: From 1985 to 1995, 60 patients underwent colon interposition for esophageal cancer (n = 37), benign stricture (n = 13), iatrogenic fistula (n = 5), achalasia (n = 3), or necrosis of a previous substitute (n = 2). A long isoperistaltic conduit based on the left colonic artery could be used in 52 patients (86.7%). The surgical route used was through the esophageal bed in 38 patients (63.3%), under the sternum in 21 patients, and under the skin in 1 patient. RESULTS: Colon interposition represented 18.5% of all operations performed for esophageal substitution during the study period. The choice of the colon resulted from an inadequate stomach in 33 cases (55%). The operative mortality rate was 8.3%. Seven patients (13.5%) required dilation of the esophagocolonic anastomosis. At last follow-up, 34 patients (65.4%) had no difficulty eating. Multivariate analysis identified the conduit position in the posterior mediastinum as the sole independent predictor of a good functional result (p = 0.002). CONCLUSIONS: Colon interposition for esophageal substitution, usually performed when the stomach is not available, provides satisfactory function when placed in the esophageal bed.
Improved absorption and bioavailability of cyclosporine A from a microemulsion formulation in lung transplant recipients affected with cystic fibrosis.
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Endoscopic ultrasonography for assessment of the response to combined radiation therapy and chemotherapy in patients with esophageal cancer.
BACKGROUND AND STUDY AIMS: Measuring the response of esophageal cancer to combined chemotherapy and radiotherapy is difficult. Initial results using ultrasonography have been contradictory. The purpose of this study was to correlate the endoscopic ultrasonography (EUS) findings after preoperative chemoradiotherapy with the histology of the resected specimens, and to assess the accuracy of EUS in predicting the response to treatment. PATIENTS AND METHODS: From October 1991 to February 1995, 32 patients with esophageal cancer staged as T3 or T4 on EUS were treated by chemoradiotherapy, followed by surgical resection. There were 28 men and four women, with a mean age of 54 years (range 38-70 years). In 25 cases, the diagnosis was squamous-cell carcinoma, and in seven cases it was adenocarcinoma. EUS was carried out using a curved-array ultrasonic transducer (Pentax FG-32 UA). After two courses of chemoradiotherapy, the wall involvement was classified using the following modified post-chemoradiotherapy classification: T0, complete restitution of wall layers; Tw, echo-poor nodules located in the submucosa or muscularis propria, but with wall layers discernible; T2, echo-poor wall thickening without distinguishable layers, but not infiltrating beyond the fifth hyperechoic layer; T3, thickened hypoechoic or heterogeneous wall, no distinguishable layers, infiltrating beyond the fifth hyperechoic layer; T4: a hypoechoic or heterogeneous mass in contact with a mediastinal structure. RESULTS: Using this post-chemoradiotherapy classification, the sensitivity, specificity, and accuracy of EUS in detecting residual tumor (T0 + Tw versus T2, T3, and T4) were 91.3%, 77.7%, and 77.7%, respectively. The accuracy of EUS, endoscopic, and CT criteria in assessing the parietal response was 81.2%, 56.2%, and 59.3%, respectively. CONCLUSION: Complete restoration of the esophageal wall (T0) and Tw stage corresponded to disease-free histology in 78% of cases, and corresponded in all cases either to disease-free esophageal wall or to microscopic tumor residues in the mucosa. No conclusions could be drawn in the other categories (T2-T4), but residual tumor was detected in 87% of cases.