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D Grunenwald

Publications and source records attributed to D Grunenwald.

At least 19 recordsLinked to original sources
PubMed1999

Analysis of T-cell-receptor beta-chain-gene usage in peripheral-blood and tumor-infiltrating lymphocytes from human non-small-cell lung carcinomas.

Non-small-cell lung cancers (NSCLC) are often infiltrated by T lymphocytes. It is postulated that the presence of tumor-infiltrating lymphocytes (TIL) reflects a local host immune response against autologous tumors. To identify the nature of NSCLC TIL, we have characterized the molecular structure of the TCRbeta chain expressed by infiltrating T cells and paired PBL from 9 untreated patients (4 LLC, 3 ADC and 2 SCC). For this purpose, we have used a high-resolution PCR-based method that determines CDR3 size patterns in TCRVbeta sub-families in fresh tumors and their corresponding autologous PBL samples. Oligoclonality in T-cell populations was observed in 3 (Hor, Bla and Pub) out of 9 tumor biopsies analyzed. In contrast, the TCR repertoire of the 6 following patients as well as of all the autologous PBL was diverse, with virtually all Vbeta specificities expressed. Among the 3 tumors with dominant T-cell clonotypes, relative expansion of some T-cell sub-populations was observed. One patient (Hor) with significant TCRVbeta21 expansion in tumor compared with autologous PBL, showed over-expression of a particular TCRVbeta chain with unique Vbeta21-D-Jbeta2.7 junctional region not detected in autologous PBL. TCRVbeta21/Jbeta2.7 expansion was also observed in IL-2-stimulated TIL cell lines and was confirmed by sequencing analysis of the V-D-J junctional region. These results strengthen the view that local antigen-driven selection may occur, and support the hypothesis that anti-tumor immune response may take place in some NSCLC.

Aged↗
PubMed1998

Quantitative analysis of Th1, Th2 and TGF-beta1 cytokine expression in tumor, TIL and PBL of non-small cell lung cancer patients.

For understanding the local immune response in human non-small cell lung cancer (NSCLC), we investigated both Th1 and Th2-type as well as TGF-beta1 cytokine mRNA expression in 10 fresh tumor biopsies, the corresponding tumor and short term TIL cell lines as well as patient PBMC. A methodology based on a highly sensitive quantitative RT-PCR was used. We found that IL-6 mRNA was highly expressed in all tumor biopsy samples analyzed (4 LLC, 3 ADC and 3 SCC). IL-10 mRNA was expressed in 7 of 10 biopsies whereas IL-4 mRNA expression was moderate. Analysis of type I cytokines revealed a low expression level of IL-2 mRNA, while IFNgamma and GM-CSF expression was high in the majority of the tumor lesions studied. Quantitatively, high amounts of Th2-type cytokine mRNA were detected at the tumor site with IL-6 as the predominant lymphokine. A high mRNA expression level of the immunosuppressive cytokine TGF-beta1 was observed in all NSCLC. To identify the cell types responsible for the production of TGF-beta1, IL-6, IL-10 and GM-CSF at the tumor site, tumor and TIL cell lines were derived from the corresponding biopsies. All the 3 tumor cell lines analysed were found to express high amount of TGF-beta1 but not IL-10 mRNA, 2 expressing IL-6 and GM-CSF. Five short term TIL cell lines established in the presence of IL-2 expressed high level of IL-10, IL-4 and IFNgamma but not IL-2 mRNA. Strikingly, high expression of IL-10 mRNA was also observed in all 6 patient PBMC analyzed as compared to controls. Together, our results indicate the existence of a local and peripheral Th-2-type cytokine pattern in patients bearing NSCLC.

Aged↗
PubMed1998

Surgical treatment of hepatic and pulmonary metastases from colorectal cancers.

BACKGROUND: Selected patients with double hepatic and pulmonary metastases from colorectal cancer may benefit from operation. METHODS: From 1970 to 1995, 239 patients underwent operation for resection of pulmonary metastases from colorectal cancer at two French surgical centers. Among these patients, 43 (18%) had previously undergone complete resection of hepatic metastases and constitute the subject of this retrospective study. RESULTS: The median interval time between hepatic and pulmonary resections was 18 months. Two pneumonectomies, 5 lobectomies, 3 segmentectomies, 6 wedge resections, and 27 metastasectomies were performed. No postoperative mortality was observed. Two patients had major postoperative complications. Seven patients (16%) underwent subsequent pulmonary resection for recurrences. Twenty-one patients were still alive, 14 free of disease. The median survival from pulmonary resection was 19 months and the 5-year probability of survival was 11%. Prethoracotomy carcinoembryonic antigen blood levels and the number of pulmonary resection were found to be significant prognostic factors; the interval time between hepatic and pulmonary resection (> 36 months) was borderline significant (p = 0.06). CONCLUSIONS: Selected patients with combined hepatic and pulmonary metastases from colorectal cancer should be considered for surgical resection. Patients with normal prethoracotomy carcinoembryonic antigen levels and late metachronous pulmonary metastasis, appear to be the best surgical candidates.

Adenocarcinoma↗
PubMed1998

[Place of surgery in a multidisciplinary approach to stage III non-small-cell cancers].

Results of isolated surgical resection for stage III lung cancer are not satisfactory, since overall 5-year survival rates rarely exceed 15%. Deaths during follow-up are mainly due to metastatic progression. The multimodality approach adds chemotherapy to surgery, with the intent to improve the control of micrometastatic disease which potentially exists at the time of diagnosis. Preoperative or neoadjuvant chemotherapy is currently under evaluation. Phase 2 trials demonstrate a treatment-related mortality of 5%: complete response and partial response are rated 5-10% and 50% respectively. About 85% of patients are operated upon within an average of 3 months after onset of treatment. Exploratory thoracotomy without resection is performed in 15% of cases; a complete resection may be performed in 75% of cases. Overall post-operative mortality is close to 5%, but considerably higher rates of 10-17.5% have been reported following pneumonectomy. Median survival after treatment may reach 20 months. Indicators of improved survival are response to induction therapy and complete resection. However, ther is no objective evidence that induction therapy improves survival after resection. Interpretation of phase 2 trials is obscured by methodologic drawbacks such as heterogenous patient samples or inaccurate staging. The spare phase 3 trials suffer from identical drawbacks, and further from too short sample sizes. Mediastinoscopy prior to induction therapy is mandatory to confirm N2 or N3 disease, because radiologic staging is not reliable. Pathologic and therefore accurate staging is achieved when surgical resection is the initial step of treatment. Previous work has concluded that post-operative or adjuvant chemotherapy does not improve survival; however, these trials did not use optimal drug regimens, and compliance to treatment was not satisfactory. In fine, the 2 major objectives of surgery in the multimodality setting are to secure local control of the disease, and to confirm stage III disease owing to pathologic stating.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Transmanubrial osteomuscular sparing approach for apical chest tumors.

The transclavicular approach improved the treatment of apical chest tumors. However, removing the internal half of the clavicle and sectioning its muscular insertions led to serious postoperative alterations. We propose a transmanubrial approach, through a manubrial L-shaped transection and first costal cartilage resection, which allows retraction of an osteomuscular flap including but sparing the clavicle and all its muscular insertions. The elevation of the osteomuscular flap affords excellent access to the subclavicular region with safe control and resection of neurovascular outlet structures during the resection of apical chest tumors. Shoulder articulations and stability of the scapular girdle are respected, thus avoiding functional and cosmetic consequences of clavicle resection.

Humans↗
PubMed1997

Prevention of air leaks after pulmonary wedge resection.

Prolonged air leak after a lung volume reduction operation for pulmonary emphysema is a major cause of morbidity and prolonged hospital stay. Staple line reinforcement is recognized as an effective adjunctive technique for decreasing the occurrence of air leaks after pulmonary wedge resection. Numerous materials have been used for staple-line reinforcement. We use expanded polytetrafluoroethylene sleeves that fit over the arms of surgical staplers to facilitate staple-line reinforcement in both thoracoscopic and open lung volume reduction procedures. The expanded polytetrafluoroethylene sleeves do not require rinsing or special handling; they are easy to use and effective in preventing air leaks. We had no prolonged air leaks or infections in any of the cases in which we used the sleeves.

Humans↗
PubMed1997

Should the number of pulmonary metastases influence the surgical decision?

OBJECTIVE: To assess, using a large homogeneous retrospective series, the prognostic value of the number of resected pulmonary metastases, and thus, to determine to what extent the number of resectable metastases should influence the surgical decision. METHODS: The survival analysis of all patients operated on for pulmonary metastases at a single center, the comparisons of 2 'histologic' groups (sarcoma and carcinoma) and, within each histologic group, of three subgroups with different numbers of resected metastases (1, 2-4, and > or = 5) were performed. The log-rank test was used to compare survival curves. RESULTS: Among 575 adult patients operated on with curative intent before December 1991, the first operation allowed the complete resection of a known number of histologically proven viable pulmonary metastases in 230 and 151 patients with metastases from carcinoma and sarcoma, respectively. The 5- and 10-year probabilities of survival (Kaplan-Meier) were 37 and 23%, respectively in carcinoma patients, and 31 and 28%, respectively in sarcoma patients (log-rank test: ns). Only the difference between patients with 1 versus 2-4 metastases from carcinoma proved statistically significant (P = 0.02), with 5-year survival estimates of 41 and 25%, respectively. Beside survival, the only significant difference between the subgroups of patients with different numbers of resected metastases was the mean interval between the diagnosis of pulmonary metastases and the resection of pulmonary metastases, which was significantly longer in patients with several metastases in both histologic groups. CONCLUSIONS: In patients with resectable pulmonary metastases from sarcoma or carcinoma, the number of metastases should have little influence on the surgical decision, except for delaying this decision in patients with several metastases until a significant interval, with or without treatment, has shown that metastatic disease remains resectable and confined to the lungs.

Adult↗
PubMed1997

Completion pneumonectomy for lung metastases: is it justified?

OBJECTIVE: To evaluate the postoperative outcome and long-term results of patients who underwent iterative and extended pulmonary resection leading to completion pneumonectomy for pulmonary metastases. METHODS: From January 1985 to December 1995, 12 patients (mean age 45 years) underwent completion pneumonectomy for pulmonary metastases. These patients represent 1.5% of all pulmonary metastases operated on. There were 5 sarcoma and 7 carcinoma patients. Before completion pneumonectomy, 8 patients had only one pulmonary resection (wedge resection, 2; segmentectomy, 2; lobectomy, 4), 3 patients had two operations and finally, 1 patient had multiple bilateral wedge resections and 1 lobectomy. The median interval time between the last pulmonary resection and completion pneumonectomy was 13.5 months (range 1-24 months). RESULTS: There were 10 left and two right completion pneumonectomies. Three patients had an extended resection (1 carina; 1 chest wall; 1 pleuropneumonectomy). Intrapericardial dissection was used in 3 patients. Two patients died within 30 days of the operation: 1 died of postoperative complications (8.3%) whereas the other died of rapidly evolving metastatic disease. The remaining 10 patients had an uneventful postoperative course. Only 1 patient is still alive and free of disease 69 months after completion pneumonectomy. One patient is alive with disease, another was lost to follow-up; 9 patients died of metastatic disease. The median survival time after completion pneumonectomy was 6 months (range 0-69 months). The estimated 5-year probability of survival was 10% (95% CI: 2-40%). CONCLUSIONS: Indications for both iterative and extended pulmonary resection for PM may be discussed only in highly young selected patients; the extremely poor outcome of our subgroup of patients should lead to even more restrictive indications of CP for pulmonary metastatic disease.

Adult↗
PubMed1997

Completion right lower lobectomy for recurrence after left pneumonectomy for metastases.

Resection of pulmonary recurrences on the residual lung after pneumonectomy for metastases is exceptional. A 37-year-old woman was submitted to left extended pleuro-pneumonectomy after left leg amputation for fibrosarcoma. At 43 months later, a wedge resection on the right lower lobe was performed followed 32 months later by a further wedge resection in the same lobe. A completion right lower lobectomy for a new recurrence was performed 17 months after the last pulmonary resection. The patient did not develop postoperative complications. She is still alive and free of disease 10 years and 9 months after pneumonectomy and 36 months after completion lobectomy on the residual lung. In highly selected patients, aggressive surgery for metastases on the residual lung can be successfully performed and it can improve survival.

Adult↗
PubMed1997

[Optimization of combined radiotherapy and chemotherapy in treatment of non-small cell lung carcinoma].

PURPOSE: To report the results of CEBI 140 and 142 trials. These trials were aimed at improving the local control in stage III non-small cell carcinoma with concomitant chemotherapy and radiotherapy in the CEBI 140 trial, and with concomitant chemotherapy and radiotherapy followed by local excision in the CEBI 142 trial. MATERIAL AND METHODS: Thirty-four patients presenting with stage III non-small cell lung carcinoma were included into the CEBI 140 trial from December 1989 to December 1992. Patients were treated with a combination of daily cisplatin (6 mg/m2 per day, 144 mg/m2 in total), vindesine once a week (2.5 mg/m2, 15 mg/m2 in total) and bifractionated radiotherapy (60 Gy/48 fractions/6 weeks) followed by two cycles of cisplatin 120 mg/m2 (at d18 and d45 after completion of radiochemotherapy) and three cycles of vindesine (6 mg/m2 at d24, d31, and d38 after completion of radiochemotherapy). Twenty-eight patients presenting with stage IIIB non-small cell carcinoma-were included into the CEBI 142 trial since January 1993. Patients received a combination of cisplatin (100 mg/m2 at d1 and d24, 200 mg/m2 in total), vinblastine (4 mg/m2 at d1 and d24, 8 mg/m2 in total), 5-fluorouracil in continuous infusion (1,000 mg/m2 from d1 to d3, and from d24 to 26, 6,000 mg/m2 in total) and bifractionated radiotherapy (two series of 21 Gy/14 fractions/9 days, 11 days apart) followed by a new evaluation and surgical excision. RESULTS: In the CEBI 140 trial, all patients received a complete course of radiotherapy, but the dose of cisplatin was decreased in 27% of the cases, and the dose of vindesine in 88%. There were two toxicity-related deaths. Three months after completion of the protocol, there were 50% of complete responders. The overall survival rates at 1, 2 and 3 years were 53, 33, and 11%, respectively, and disease-free survival rates 21 11, and 11%, respectively. In the CEBI 142 trial the immediate tolerance was good. Twenty-one patients (75%) underwent surgical resection. Four tumors could not be resected. Resection was histologically incomplete in one case, and complete in the 16 remaining cases. With a median follow-up of 14 months, ten patients were alive and disease-free. CONCLUSION: Preliminary results of the CEBI 142 trial are encouraging. More patients and longer follow-up are needed for definitive conclusion. It would be of interest to implement a randomized trial comparing the CEBI 142 scheme and classical radiation therapy.

Adult↗
PubMed1997

Lung resection for recurrence after pneumonectomy for metastases.

Resection of pulmonary recurrences after pneumonectomy for metastases is exceptional. Nevertheless in carefully selected patients surgery on the residual lung might be successfully performed. From January 1987 to February 1996, 5 patients underwent metastasectomy on single lung after pneumonectomy performed for the same metastatic disease. There were 3 male and 2 female with a mean age of 38 years at the time of surgery on single lung. All patients had a FEV1 > 40%. One patient (n degree 1) had 2 consecutive operations (wedge resections) on the right lower lobe followed 17 months later by right inferior lobectomy for metastases of soft tissue sarcoma. Three patients had only an operation on the residual lung (patient n degree 2 had 2 wedge resections for carcinoma; patient n degree 3 had 7 wedge resections for carcinoma; patient n degree 4 had 6 wedge resections for osteogenic sarcoma). The last patient (n degree 5) had 2 wedge resections on the right upper lobe and a large wedge resection on the right lower lobe for metastases of malignant corticosurrenaloma using a cardiopulmonary femoro-femoral by-pass without cardiac arrest. She postoperatively developed a right lower lobe venous infarction treated subsequently with a completion right lower lobectomy. She died in the postoperative course from cardiorespiratory insufficiency. The other patients had an uneventful postoperative course. Two patients (n degree 2 and n degree 4) died of their disease 14 and 12 months respectively after the surgery on the residual lung; by contrast 2 patients (40%) (n degree 1 and n degree 3) are still alive without recurrences 36 and 27 months after the last resection. In selected patients aggressive surgery for metastases on the residual lung can be successfully performed but the benefits in terms of long-term disease-free survival remain to be determined.

Adult↗
PubMed1997

[New therapeutic strategies and current research in inoperable locally advanced non small-cell lung cancers (stage IIIB)].

Treatment of patients with inoperable locally advanced non small-cell lung cancer (NSCLC) remains disappointing with less of 5% of patients alive at 5 years. Both initial local control and circumvention of concomitant undetectable metastatic chemoresistant cells are the critical targets for the oncologists in charge of this disease. Results of a recent meta-analysis including 22 randomized studies comparing standard treatment (i.e. radiotherapy) to sequential chemoradiotherapy have undoubtabely well defined the role of cisplatine-containing chemotherapy in stage IIIB NSCLC, even if the 5 year survival benefit remains modest. However, high complete response rates and prolonged overall survival were observed with combinations of new promising chemotherapy regimens and new fractionated radiation schedules in several phase II studies. These results have to be corroborated by prospective randomized trials. Integration of more aggressive and more toxic strategies such as radical surgery in these initial inoperable locally advanced NSCLC are evaluating. Around these conventional therapies, the stage IIIB NSCLC represent a favoured target to elaborate innovative therapeutic approaches based on emergence of biotherapies as recombinant cytokines, antitumoral vaccine and gene therapy programs. The contribution of these new therapeutic options opens new directions in the therapeutic strategy and leads to hope a new promising era in the management and outcome of patients with these tumors.

Antineoplastic Combined Chemotherapy Protocols↗