... En conclusion, une tumeur kystique du pancr6as peut ~tre de nature endocrine et dans l&am... more ... En conclusion, une tumeur kystique du pancr6as peut ~tre de nature endocrine et dans l'6re de la cyto-logie en ... A. FASSINA, Cinzia GIACOMETTI, L. GIACOMELLI, Giovanna COSTANTIN Section of Pathology and Cytopathology, Department of Oncology and Surgical Sciences ...
In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alo... more In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alone are suboptimal. Many studies have been conducted in which the treatment regimen consists of surgery in combination with radiation and chemotherapy to improve local control and outcome. Neoadjuvant chemoradiotherapy is a fairly recent approach that appears to be feasible in resectable and locally advanced pancreatic cancer. In resectable tumors, chemoradiation therapy has been shown to be at least as effective in a neoadjuvant setting as in an adjuvant setting. Neoadjuvant therapy offers a few theoretical advantages: (1) beginning the multimodality treatment with chemoradiation therapy increases the chance that more patients will receive all of its components; (2) preoperative chemoradiation therapy provides an observation period to exclude from surgical resection those patients with rapidly progressive disease; and (3) in locally advanced tumors, it provides the opportunity for downstaging and infrequently allows patients to undergo resection. To evaluate the scope and applicability of neoadjuvant treatment, a number of areas need to be addressed. First, the definition of locally advanced disease needs to be more adequately standardized because the resectability definition sometimes varies among surgeons. In addition, because imaging examinations may underestimate the effectiveness of preoperative chemoradiation therapy, some researchers have tried to evaluate treatment response via a pathological examination of the tumor specimen; however, complete pathological response appears to be rare. Finally, more efficient novel neoadjuvant approaches are required to address the high metastatic potential of pancreatic cancer. These areas are discussed in depth.
Surgical resection of advanced nonmetastatic forms of cervical cancers is controversial, but impr... more Surgical resection of advanced nonmetastatic forms of cervical cancers is controversial, but improve local control. The local and regional staging assessment, comprising an examination under general anaesthesia, endocavitary ultrasonography, computed tomography (CT) and/or magnetic resonance imaging (MRI) allows staging, evaluation of the main prognostic factors and selection of the therapeutic strategy. Pelvic and lumboaortic lymph nodes can be investigated by CT, MRI or laparoscopic lymphadenectomy. Surgical resections consist of colpohysterectomy possibly combined with radical lymphadenectomy or pelvic exenteration, followed by pelvic reconstruction using various procedures: low colorectal anastomosis, continent urinary diversion, and vaginal reconstruction with pelvic filling. The mortality and morbidity of pelvic exenteration remain high. It is therefore important to prevent the most frequent complications as effectively as possible. The local control, overall survival and recu...
This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal ca... more This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy.
In patients with locally advanced cervical cancer, most of the treatment failures occur within th... more In patients with locally advanced cervical cancer, most of the treatment failures occur within the pelvis. In an attempt to improve local control, 40 patients with bulky tumors (stage IB > 5 cm, stage IIB with distal parametrial invasion, and stage III-IVA) were treated between 1988 and 1992 with concurrent chemoradiation (CCR). The whole pelvis received a midplane dose of 45 Gy over 33 days. Daily radiation dose was 1.8 Gy, with twice-daily fractionation in the last 20 patients. Chemotherapy was administered on the 1st and 21st days of radiation therapy (RT) consisting of cisplatin (60 mg/m2), followed by 5-fluorouracil (600 mg/m2/day continuous i.v. infusion) over 96 hr (and decreased to 40 and 400 mg/m2, respectively, in the last 23 patients). CCR was first followed by a single intracavitary application and then by a parametrial boost in stage IIB-III patients and in stage IVA patients with disease reaching the pelvis side wall. Then surgery (colpohysterectomy with lymphadenectomy or pelvic exenteration) was performed in 35 patients. Median follow-up time was 2.6 years (0.6-5.6 years). Acute toxicity (WHO grade 3-4 diarrhea) in 13 patients led to 6 RT interruptions and 4 incomplete RTs. One patient died of a septic episode without leukopenia after completion of CCR. Five postexenteration complications required a second surgical procedure, of which one patient died with tumor and small bowel fistula. One patient developed small bowel late complication and another patient developed urinary late complications. No postoperative or late complications were observed in patients treated with twice-daily fractionation. Pelvic control was achieved in 32 of 40 patients (81 and 74% in stage IB-IIB and stage III-IVA, respectively). Sites of failure were the pelvis (6 cases), metastases (7 cases), and both (2 cases). Two-year survival and DFS rates were 61 and 66%, respectively, in stage IB-IIB and 77 and 65% in stage III-IVA. High SCC-TA4 values significantly worsened DFS rates. In patients with stage III-IVA tumors, additional surgery could be an important component of this treatment strategy and may be compatible with CCR using twice-daily fractionation radiotherapy. However, these results must be confirmed by a large-scale prospective study.
Overall prognosis of adenocarcinomas of the gastro-esophageal junction remains poor as most patie... more Overall prognosis of adenocarcinomas of the gastro-esophageal junction remains poor as most patients present with advanced disease. To examine the effects of preoperative chemoradiotherapy in locally advanced adenocarcinomas of the gastro-esophageal junction. Forty-two consecutive patients received a course of radiotherapy (45 Gy, administred in 25 fractions) with concurrent infusion of 5-Fluorouracil and cisplatin, followed by surgery. Endoscopic ultrasonography was used to assess response to chemoradiotherapy. A transhiatal or a transthoracic approach was used for surgical resection. Tumor size, node invasion and margins of resection were analyzed. Thirty-eight patients underwent subsequent surgery and complete resection (RO) was achieved in 34. Operative mortality was 13.2% (5/38). A histological complete response was observed in 6 patients. Median survival was 23 months (range: 15-31) and median disease-free survival was 19 months (range: 15-23). At one and two years, 70.7 and 45.6% of the patients were alive, respectively. The pTNM status, node involvement and tumor size were predictors of survival. Pre-operative chemoradiotherapy is effective in patients with locally advanced carcinoma of the gastro-esophageal junction, resulting in high resection rates. However it seems to increase operative morbidity and mortality. Certain prognostic factors such as resection margins, need to be examined in further detail.
The aim of this study was to evaluate the efficacy and outcomes of treatment by endoscopic mucosa... more The aim of this study was to evaluate the efficacy and outcomes of treatment by endoscopic mucosal resection (EMR) of patients with high-grade dysplasia (HGD) or carcinoma. Between January 1995 and January 2002, 50 patients (35 men, 15 women) were treated by EMR for 52 sessile polyps. The median size of the polyps was 27.5 mm (range 10-60). The "lift and cut" EMR technique was used. If the lesion was poorly differentiated or infiltrated the muscularis mucosae to more than 1000 microm, the patient was referred for colectomy. In the other cases, follow-up was proposed. Complications occurred in 9.6 % of cases and were always treated conservatively. The rate of endoscopically complete resection was judged to be 98.1 %. Argon plasma coagulation was applied to the margins of the lesion in 21.6 % of cases. Histological examination showed 38 HGDs and 14 carcinomas. Seven patients had a lesion reaching the deep or lateral margin; four were referred for surgery; two patients for whom surgery would have been high risk were followed up, and both developed local recurrence; and one patient was followed up, without recurrence, because infiltration was less than 1000 microm. A total of 43 patients were followed up after complete excision. Two patients died during follow-up; neither death could be reliably attributed to colorectal carcinoma. Seven patients were lost during the follow-up. For 34 patients, information from a mean follow-up of 17.3 months (6 - 57) was available and recurrence was observed in five cases (15 %). EMR appears to be a safe and efficient treatment of HGD and early colorectal cancer. However, correct analysis of submucosal infiltration is essential to assess the completeness of the resection.
To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRI... more To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRINOX. Patients with histologically proven primary colorectal cancer and bidimensionally measurable liver metastasis, not fully resectable based on technical inability to achieve R(0) resection, but potentially resectable after tumor reduction, were given FOLFIRINOX: oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), bolus fluorouracil 400 mg/m(2) and fluorouracil 46-h continuous IV infusion 2,400 mg/m(2), every 2 weeks for a maximum of 12 cycles. Thirty-four patients were enrolled. Response rate before surgery was 70.6% (95%CI: 52.5-84.9). Twenty-eight patients (82.4%) underwent hepatic resection and nine achieved R(0) resection [26.5% (95% CI: 12.9-44.4%)]. The rate of clinical complete remission after surgery was 79.4%. Two-year overall survival was 83%. The most frequent grade 3 or 4 toxicities were neutropenia (64.8%), diarrhea (29.4%), fatigue (23.5%), abdominal cramps (14.7%), neuropathy and nausea (11.8% each), and AST/ALT elevation (14.7/11.8%). Only one patient experienced febrile neutropenia, four patients withdrew due to toxicity and no toxic death was observed. FOLFIRINOX, with an acceptable toxicity profile, shows a high response rate in liver metastases from colorectal cancer. The rate of hepatic resection in patients initially not resectable, is attractive and warrants further assessment of this regimen in randomized studies compared to standard regimens.
BackgroundPatients who undergo major surgery for cancer are at high risk of postoperative infecti... more BackgroundPatients who undergo major surgery for cancer are at high risk of postoperative infection. Postoperative immunosuppression may be due to dysregulation of cytokine production. The aim of this study was to investigate the association between changes in serum proinflammatory and anti-inflammatory cytokine concentrations and postoperative septic complications after major surgery.MethodsSerial blood samples were collected from 30 consecutive patients for determination of serum cytokine levels. Healthy volunteers were used as the control group.ResultsEleven patients developed no complications (group 1), 14 developed sepsis or severe sepsis (group 2), and five developed septic shock (group 3). On day 1 the patients in groups 2 and 3 had significantly higher levels of interleukin (IL) 6 than those in group 1. IL-6 levels remained high until day 5. Tumour necrosis factor (TNF), IL-1, interferon (IFN) γ and IL-12 levels were not affected by surgical trauma or by the occurrence of se...
Purpose: Ultrasound elastography is a new imaging procedure which allows the reconstruction of el... more Purpose: Ultrasound elastography is a new imaging procedure which allows the reconstruction of elasticity distribution by characterising the difference of hardness between pathological and normal tissue. Materials and Methods: The aim of our study was to apply real-time elastography during endoscopic ultrasound (EUS) examinations and to consequently characterise benign versus malignant lymph nodes. The pattern of real-time EUS elastography images was compared with the conventional EUS aspects of lymph nodes and with the final diagnosis obtained by EUS-FNA cytology analysis and/or by surgical pathology. Results: Patients diagnosed by EUS with cervical, mediastinal or abdominal lymph nodes were prospectively included, with a total number of 42 lymph nodes examined by EUS elastography. By using a qualitative pattern analysis, we were able to differentiate between benign and malignant lymph nodes with a high sensitivity, specificity and accuracy (91.7%, 94.4% and 92.86%, respectively), ...
ABSTRACT Background Protein tyrosine kinase-7 (PTK7) is a receptor tyrosine kinase (TK), with no ... more ABSTRACT Background Protein tyrosine kinase-7 (PTK7) is a receptor tyrosine kinase (TK), with no identified natural ligand and a catalytically inactive intracellular TK domain. PTK7 expression is up-regulated in many human cancers, including colorectal cancer (CRC), but little is known about its role in cancer biology. Here, we have examined PTK7 protein expression in tumor and matched normal tissues from CRC patients by immunohistochemistry (IHC) and addressed the phenotypic impact of PTK7 down-regulation in CRC cell lines. Methods A TMA containing both tumor and matched normal tissues was built from a cohort of 192 patients with CRC collected between 1990 and 1998 at the Institut Paoli-Calmettes, Marseille, France. PTK7 expression was analyzed by IHC using polyclonal goat antibody anti-CC4 (RD sex ratio = male (52%), female (48%); site = colon (90%), rectum (10%); stage = I-III (64%), IV (36%); median follow-up = 104 months. Staining intensity (0-1 = 65% of cases, 2 = 19% of cases, 3 =16% of cases, in tumor tissues versus 0-1 = 86% of cases, 2 = 11% of cases, 3= 3% of cases, in normal tissues; p = 1,91.10-8) as well as average percentage of stained cells (30% in tumor tissues versus 2% in normal tissues; p = 5.74.10-14) were higher in tumor compared to normal tissues. In stage I-III population (n = 122), 5-year MFS was lower in PTK7-positive (>10% of cells stained with intensity > 2) compared to PTK7-negative CRC (54% [95%CI: 38-75%] versus 75% [95%CI: 65-88%], p = 0.034, log-rank test). This impact was maintained in multivariate analysis and similar trends were observed in overall survival, while not reaching statistical significance. In vitro, PTK7 inhibition by shRNA significantly reduced cell migration. Conclusion PTK7 protein is overexpressed in CRC and is associated with reduced MFS, possibly due to an impact on cell migration. Disclosure All authors have declared no conflicts of interest.
3543 Background: The aim of our retrospective study was to evaluate the accuracy of endorectal ul... more 3543 Background: The aim of our retrospective study was to evaluate the accuracy of endorectal ultrasonography (ERUS) in case of neoadjuvant chemoradiation in locally advanced rectal cancer and to compare preoperative ERUS with pathologic results. METHODS Between January 2000 and January 2010, 181 patients with locally advanced rectal cancer were treated with neoadjuvant chemoradiation followed by radical proctectomy. ERUS was realized before and after chemoradiation to evaluate the response. The results of ERUS staging were compared with pathologic findings of the resected specimens. RESULTS See table. In our study, we found a difference between the ERUS T stage after neoadjuvant CRT and the ypT stage on pathologic specimen. Indeed, among the patients staged ypT0 at surgery, 45% were T0 on ERUS post treatment, 2% were T1, 25% were T2, 25% were T3, and 2% were T4. Moreover, 11 patients (25%) staged T3 at ERUS post treatment were in fact ypT0 on pathologic specimen. CONCLUSIONS Despite the fact that ERUS keep the most reliable method for determining initially T classification, these results points out the difficulty to evaluate tumor response after neoadjuvant chemoradiation. Results of ERUS should be interpreted with caution in account to precisely appreciate tumour response, and to define surgical strategy, especially when a conservative treatment is indicated. [Table: see text].
Revue d&'apos;Electroencéphalographie et de Neurophysiologie Clinique, 1987
... BB Mishra, W. Sommers, CK Koski and JI Greenstein, Acute inflammatory demyelinating polyneuro... more ... BB Mishra, W. Sommers, CK Koski and JI Greenstein, Acute inflammatory demyelinating polyneuropathy in the acquired immun deficiency syndrome ... A. Chapman, G. Parrot, J. Leibowitch and L. Montagnier, Acute neuropathy coincident with seroconversion for anti-LAV/HTLV III ...
Objectif de l'étude.-Même si après une chimioradiothérapie d'induction, le taux des résections « ... more Objectif de l'étude.-Même si après une chimioradiothérapie d'induction, le taux des résections « secondaires » des cancers du pancréas localement évolués est faible, il parut important d'analyser les dossiers des patients en situation de réponse, pouvant bénéficier d'une résection R0. Patients et méthodes.-Nous rapportons 18 résections chez 29 malades, dont 15 après chimioradiothérapie et trois sans traitement préopératoire en raison de l'absence de preuve histologique. Résultats.-Cinq patients ont souffert d'une complication postopératoire majeure (28 %) ; le taux de mortalité était de 7 % (un patient décédé dans le groupe qui a bénéficié d'une résection [5,5 %] et un dans le groupe des malades qui n'a pu en bénficier [9 %]). Le taux de résections R0 était de 50 %. La durée médiane de survie des 18 malades qui ont eu une résection n'était pas atteinte à la date de point, et la probabilité de survie actuarielle à trois ans était de 59 %. Les deux patients dont la pièce ne présentait aucun reliquat tumoral étaient en vie sans récidive à 15 et 46 mois ; la malade dont la pièce présentait un reliquat tumoral minime était en vie sans récidive à 36 mois. Un décès tardif sans récidive est survenu à trois ans après réintervention pour infarctus entéromésentérique total par sténose radique de l'artère mésentérique supérieure. La durée médiane de survie des 11 malades qui n'ont pas eu de résection était de 21 mois ; la probabilité de survie actuarielle à deux ans était nulle. Le taux de résections « secondaires », rapporté au nombre de cancers localement évolués vus et traités pendant la même période dans notre institution, n'était que de 9 %. Conclusion.-La chimioradiothérapie préopératoire permet de sélectionner les candidats à une résection secondaire et permet des résections R0. Cependant, les résultats des séries publiées restent difficiles à interpréter en raison de la variabilité des critères de résécabilité. La meilleure stratégie thérapeutique reste à définir, car les malades meurent pour la plupart de dissémination métastatique.
... En conclusion, une tumeur kystique du pancr6as peut ~tre de nature endocrine et dans l&am... more ... En conclusion, une tumeur kystique du pancr6as peut ~tre de nature endocrine et dans l'6re de la cyto-logie en ... A. FASSINA, Cinzia GIACOMETTI, L. GIACOMELLI, Giovanna COSTANTIN Section of Pathology and Cytopathology, Department of Oncology and Surgical Sciences ...
In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alo... more In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alone are suboptimal. Many studies have been conducted in which the treatment regimen consists of surgery in combination with radiation and chemotherapy to improve local control and outcome. Neoadjuvant chemoradiotherapy is a fairly recent approach that appears to be feasible in resectable and locally advanced pancreatic cancer. In resectable tumors, chemoradiation therapy has been shown to be at least as effective in a neoadjuvant setting as in an adjuvant setting. Neoadjuvant therapy offers a few theoretical advantages: (1) beginning the multimodality treatment with chemoradiation therapy increases the chance that more patients will receive all of its components; (2) preoperative chemoradiation therapy provides an observation period to exclude from surgical resection those patients with rapidly progressive disease; and (3) in locally advanced tumors, it provides the opportunity for downstaging and infrequently allows patients to undergo resection. To evaluate the scope and applicability of neoadjuvant treatment, a number of areas need to be addressed. First, the definition of locally advanced disease needs to be more adequately standardized because the resectability definition sometimes varies among surgeons. In addition, because imaging examinations may underestimate the effectiveness of preoperative chemoradiation therapy, some researchers have tried to evaluate treatment response via a pathological examination of the tumor specimen; however, complete pathological response appears to be rare. Finally, more efficient novel neoadjuvant approaches are required to address the high metastatic potential of pancreatic cancer. These areas are discussed in depth.
Surgical resection of advanced nonmetastatic forms of cervical cancers is controversial, but impr... more Surgical resection of advanced nonmetastatic forms of cervical cancers is controversial, but improve local control. The local and regional staging assessment, comprising an examination under general anaesthesia, endocavitary ultrasonography, computed tomography (CT) and/or magnetic resonance imaging (MRI) allows staging, evaluation of the main prognostic factors and selection of the therapeutic strategy. Pelvic and lumboaortic lymph nodes can be investigated by CT, MRI or laparoscopic lymphadenectomy. Surgical resections consist of colpohysterectomy possibly combined with radical lymphadenectomy or pelvic exenteration, followed by pelvic reconstruction using various procedures: low colorectal anastomosis, continent urinary diversion, and vaginal reconstruction with pelvic filling. The mortality and morbidity of pelvic exenteration remain high. It is therefore important to prevent the most frequent complications as effectively as possible. The local control, overall survival and recu...
This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal ca... more This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy.
In patients with locally advanced cervical cancer, most of the treatment failures occur within th... more In patients with locally advanced cervical cancer, most of the treatment failures occur within the pelvis. In an attempt to improve local control, 40 patients with bulky tumors (stage IB > 5 cm, stage IIB with distal parametrial invasion, and stage III-IVA) were treated between 1988 and 1992 with concurrent chemoradiation (CCR). The whole pelvis received a midplane dose of 45 Gy over 33 days. Daily radiation dose was 1.8 Gy, with twice-daily fractionation in the last 20 patients. Chemotherapy was administered on the 1st and 21st days of radiation therapy (RT) consisting of cisplatin (60 mg/m2), followed by 5-fluorouracil (600 mg/m2/day continuous i.v. infusion) over 96 hr (and decreased to 40 and 400 mg/m2, respectively, in the last 23 patients). CCR was first followed by a single intracavitary application and then by a parametrial boost in stage IIB-III patients and in stage IVA patients with disease reaching the pelvis side wall. Then surgery (colpohysterectomy with lymphadenectomy or pelvic exenteration) was performed in 35 patients. Median follow-up time was 2.6 years (0.6-5.6 years). Acute toxicity (WHO grade 3-4 diarrhea) in 13 patients led to 6 RT interruptions and 4 incomplete RTs. One patient died of a septic episode without leukopenia after completion of CCR. Five postexenteration complications required a second surgical procedure, of which one patient died with tumor and small bowel fistula. One patient developed small bowel late complication and another patient developed urinary late complications. No postoperative or late complications were observed in patients treated with twice-daily fractionation. Pelvic control was achieved in 32 of 40 patients (81 and 74% in stage IB-IIB and stage III-IVA, respectively). Sites of failure were the pelvis (6 cases), metastases (7 cases), and both (2 cases). Two-year survival and DFS rates were 61 and 66%, respectively, in stage IB-IIB and 77 and 65% in stage III-IVA. High SCC-TA4 values significantly worsened DFS rates. In patients with stage III-IVA tumors, additional surgery could be an important component of this treatment strategy and may be compatible with CCR using twice-daily fractionation radiotherapy. However, these results must be confirmed by a large-scale prospective study.
Overall prognosis of adenocarcinomas of the gastro-esophageal junction remains poor as most patie... more Overall prognosis of adenocarcinomas of the gastro-esophageal junction remains poor as most patients present with advanced disease. To examine the effects of preoperative chemoradiotherapy in locally advanced adenocarcinomas of the gastro-esophageal junction. Forty-two consecutive patients received a course of radiotherapy (45 Gy, administred in 25 fractions) with concurrent infusion of 5-Fluorouracil and cisplatin, followed by surgery. Endoscopic ultrasonography was used to assess response to chemoradiotherapy. A transhiatal or a transthoracic approach was used for surgical resection. Tumor size, node invasion and margins of resection were analyzed. Thirty-eight patients underwent subsequent surgery and complete resection (RO) was achieved in 34. Operative mortality was 13.2% (5/38). A histological complete response was observed in 6 patients. Median survival was 23 months (range: 15-31) and median disease-free survival was 19 months (range: 15-23). At one and two years, 70.7 and 45.6% of the patients were alive, respectively. The pTNM status, node involvement and tumor size were predictors of survival. Pre-operative chemoradiotherapy is effective in patients with locally advanced carcinoma of the gastro-esophageal junction, resulting in high resection rates. However it seems to increase operative morbidity and mortality. Certain prognostic factors such as resection margins, need to be examined in further detail.
The aim of this study was to evaluate the efficacy and outcomes of treatment by endoscopic mucosa... more The aim of this study was to evaluate the efficacy and outcomes of treatment by endoscopic mucosal resection (EMR) of patients with high-grade dysplasia (HGD) or carcinoma. Between January 1995 and January 2002, 50 patients (35 men, 15 women) were treated by EMR for 52 sessile polyps. The median size of the polyps was 27.5 mm (range 10-60). The "lift and cut" EMR technique was used. If the lesion was poorly differentiated or infiltrated the muscularis mucosae to more than 1000 microm, the patient was referred for colectomy. In the other cases, follow-up was proposed. Complications occurred in 9.6 % of cases and were always treated conservatively. The rate of endoscopically complete resection was judged to be 98.1 %. Argon plasma coagulation was applied to the margins of the lesion in 21.6 % of cases. Histological examination showed 38 HGDs and 14 carcinomas. Seven patients had a lesion reaching the deep or lateral margin; four were referred for surgery; two patients for whom surgery would have been high risk were followed up, and both developed local recurrence; and one patient was followed up, without recurrence, because infiltration was less than 1000 microm. A total of 43 patients were followed up after complete excision. Two patients died during follow-up; neither death could be reliably attributed to colorectal carcinoma. Seven patients were lost during the follow-up. For 34 patients, information from a mean follow-up of 17.3 months (6 - 57) was available and recurrence was observed in five cases (15 %). EMR appears to be a safe and efficient treatment of HGD and early colorectal cancer. However, correct analysis of submucosal infiltration is essential to assess the completeness of the resection.
To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRI... more To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRINOX. Patients with histologically proven primary colorectal cancer and bidimensionally measurable liver metastasis, not fully resectable based on technical inability to achieve R(0) resection, but potentially resectable after tumor reduction, were given FOLFIRINOX: oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), bolus fluorouracil 400 mg/m(2) and fluorouracil 46-h continuous IV infusion 2,400 mg/m(2), every 2 weeks for a maximum of 12 cycles. Thirty-four patients were enrolled. Response rate before surgery was 70.6% (95%CI: 52.5-84.9). Twenty-eight patients (82.4%) underwent hepatic resection and nine achieved R(0) resection [26.5% (95% CI: 12.9-44.4%)]. The rate of clinical complete remission after surgery was 79.4%. Two-year overall survival was 83%. The most frequent grade 3 or 4 toxicities were neutropenia (64.8%), diarrhea (29.4%), fatigue (23.5%), abdominal cramps (14.7%), neuropathy and nausea (11.8% each), and AST/ALT elevation (14.7/11.8%). Only one patient experienced febrile neutropenia, four patients withdrew due to toxicity and no toxic death was observed. FOLFIRINOX, with an acceptable toxicity profile, shows a high response rate in liver metastases from colorectal cancer. The rate of hepatic resection in patients initially not resectable, is attractive and warrants further assessment of this regimen in randomized studies compared to standard regimens.
BackgroundPatients who undergo major surgery for cancer are at high risk of postoperative infecti... more BackgroundPatients who undergo major surgery for cancer are at high risk of postoperative infection. Postoperative immunosuppression may be due to dysregulation of cytokine production. The aim of this study was to investigate the association between changes in serum proinflammatory and anti-inflammatory cytokine concentrations and postoperative septic complications after major surgery.MethodsSerial blood samples were collected from 30 consecutive patients for determination of serum cytokine levels. Healthy volunteers were used as the control group.ResultsEleven patients developed no complications (group 1), 14 developed sepsis or severe sepsis (group 2), and five developed septic shock (group 3). On day 1 the patients in groups 2 and 3 had significantly higher levels of interleukin (IL) 6 than those in group 1. IL-6 levels remained high until day 5. Tumour necrosis factor (TNF), IL-1, interferon (IFN) γ and IL-12 levels were not affected by surgical trauma or by the occurrence of se...
Purpose: Ultrasound elastography is a new imaging procedure which allows the reconstruction of el... more Purpose: Ultrasound elastography is a new imaging procedure which allows the reconstruction of elasticity distribution by characterising the difference of hardness between pathological and normal tissue. Materials and Methods: The aim of our study was to apply real-time elastography during endoscopic ultrasound (EUS) examinations and to consequently characterise benign versus malignant lymph nodes. The pattern of real-time EUS elastography images was compared with the conventional EUS aspects of lymph nodes and with the final diagnosis obtained by EUS-FNA cytology analysis and/or by surgical pathology. Results: Patients diagnosed by EUS with cervical, mediastinal or abdominal lymph nodes were prospectively included, with a total number of 42 lymph nodes examined by EUS elastography. By using a qualitative pattern analysis, we were able to differentiate between benign and malignant lymph nodes with a high sensitivity, specificity and accuracy (91.7%, 94.4% and 92.86%, respectively), ...
ABSTRACT Background Protein tyrosine kinase-7 (PTK7) is a receptor tyrosine kinase (TK), with no ... more ABSTRACT Background Protein tyrosine kinase-7 (PTK7) is a receptor tyrosine kinase (TK), with no identified natural ligand and a catalytically inactive intracellular TK domain. PTK7 expression is up-regulated in many human cancers, including colorectal cancer (CRC), but little is known about its role in cancer biology. Here, we have examined PTK7 protein expression in tumor and matched normal tissues from CRC patients by immunohistochemistry (IHC) and addressed the phenotypic impact of PTK7 down-regulation in CRC cell lines. Methods A TMA containing both tumor and matched normal tissues was built from a cohort of 192 patients with CRC collected between 1990 and 1998 at the Institut Paoli-Calmettes, Marseille, France. PTK7 expression was analyzed by IHC using polyclonal goat antibody anti-CC4 (RD sex ratio = male (52%), female (48%); site = colon (90%), rectum (10%); stage = I-III (64%), IV (36%); median follow-up = 104 months. Staining intensity (0-1 = 65% of cases, 2 = 19% of cases, 3 =16% of cases, in tumor tissues versus 0-1 = 86% of cases, 2 = 11% of cases, 3= 3% of cases, in normal tissues; p = 1,91.10-8) as well as average percentage of stained cells (30% in tumor tissues versus 2% in normal tissues; p = 5.74.10-14) were higher in tumor compared to normal tissues. In stage I-III population (n = 122), 5-year MFS was lower in PTK7-positive (>10% of cells stained with intensity > 2) compared to PTK7-negative CRC (54% [95%CI: 38-75%] versus 75% [95%CI: 65-88%], p = 0.034, log-rank test). This impact was maintained in multivariate analysis and similar trends were observed in overall survival, while not reaching statistical significance. In vitro, PTK7 inhibition by shRNA significantly reduced cell migration. Conclusion PTK7 protein is overexpressed in CRC and is associated with reduced MFS, possibly due to an impact on cell migration. Disclosure All authors have declared no conflicts of interest.
3543 Background: The aim of our retrospective study was to evaluate the accuracy of endorectal ul... more 3543 Background: The aim of our retrospective study was to evaluate the accuracy of endorectal ultrasonography (ERUS) in case of neoadjuvant chemoradiation in locally advanced rectal cancer and to compare preoperative ERUS with pathologic results. METHODS Between January 2000 and January 2010, 181 patients with locally advanced rectal cancer were treated with neoadjuvant chemoradiation followed by radical proctectomy. ERUS was realized before and after chemoradiation to evaluate the response. The results of ERUS staging were compared with pathologic findings of the resected specimens. RESULTS See table. In our study, we found a difference between the ERUS T stage after neoadjuvant CRT and the ypT stage on pathologic specimen. Indeed, among the patients staged ypT0 at surgery, 45% were T0 on ERUS post treatment, 2% were T1, 25% were T2, 25% were T3, and 2% were T4. Moreover, 11 patients (25%) staged T3 at ERUS post treatment were in fact ypT0 on pathologic specimen. CONCLUSIONS Despite the fact that ERUS keep the most reliable method for determining initially T classification, these results points out the difficulty to evaluate tumor response after neoadjuvant chemoradiation. Results of ERUS should be interpreted with caution in account to precisely appreciate tumour response, and to define surgical strategy, especially when a conservative treatment is indicated. [Table: see text].
Revue d&'apos;Electroencéphalographie et de Neurophysiologie Clinique, 1987
... BB Mishra, W. Sommers, CK Koski and JI Greenstein, Acute inflammatory demyelinating polyneuro... more ... BB Mishra, W. Sommers, CK Koski and JI Greenstein, Acute inflammatory demyelinating polyneuropathy in the acquired immun deficiency syndrome ... A. Chapman, G. Parrot, J. Leibowitch and L. Montagnier, Acute neuropathy coincident with seroconversion for anti-LAV/HTLV III ...
Objectif de l'étude.-Même si après une chimioradiothérapie d'induction, le taux des résections « ... more Objectif de l'étude.-Même si après une chimioradiothérapie d'induction, le taux des résections « secondaires » des cancers du pancréas localement évolués est faible, il parut important d'analyser les dossiers des patients en situation de réponse, pouvant bénéficier d'une résection R0. Patients et méthodes.-Nous rapportons 18 résections chez 29 malades, dont 15 après chimioradiothérapie et trois sans traitement préopératoire en raison de l'absence de preuve histologique. Résultats.-Cinq patients ont souffert d'une complication postopératoire majeure (28 %) ; le taux de mortalité était de 7 % (un patient décédé dans le groupe qui a bénéficié d'une résection [5,5 %] et un dans le groupe des malades qui n'a pu en bénficier [9 %]). Le taux de résections R0 était de 50 %. La durée médiane de survie des 18 malades qui ont eu une résection n'était pas atteinte à la date de point, et la probabilité de survie actuarielle à trois ans était de 59 %. Les deux patients dont la pièce ne présentait aucun reliquat tumoral étaient en vie sans récidive à 15 et 46 mois ; la malade dont la pièce présentait un reliquat tumoral minime était en vie sans récidive à 36 mois. Un décès tardif sans récidive est survenu à trois ans après réintervention pour infarctus entéromésentérique total par sténose radique de l'artère mésentérique supérieure. La durée médiane de survie des 11 malades qui n'ont pas eu de résection était de 21 mois ; la probabilité de survie actuarielle à deux ans était nulle. Le taux de résections « secondaires », rapporté au nombre de cancers localement évolués vus et traités pendant la même période dans notre institution, n'était que de 9 %. Conclusion.-La chimioradiothérapie préopératoire permet de sélectionner les candidats à une résection secondaire et permet des résections R0. Cependant, les résultats des séries publiées restent difficiles à interpréter en raison de la variabilité des critères de résécabilité. La meilleure stratégie thérapeutique reste à définir, car les malades meurent pour la plupart de dissémination métastatique.
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