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David Malka

Publications and source records attributed to David Malka.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of two kinds of intraperitoneal chemotherapy following complete cytoreductive surgery of colorectal peritoneal carcinomatosis.

BACKGROUND: Recently, the combination of complete cytoreductive surgery followed immediately by intraperitoneal chemotherapy achieved cure in some patients suffering from peritoneal carcinomatosis (PC). It is now well established that the prognostic impact of the completeness of cytoreduction is high. However, two different modes of intraperitoneal chemotherapy are proposed: early postoperative intraperitoneal chemotherapy (EPIC), which lasts for 5 days and is normothermic, and peroperative intraperitoneal chemohyperthermia (IPCH). To date, the results of these procedures have never been compared. AIM OF THE STUDY: To compare the complications and therapeutic results of EPIC and IPCH after complete cytoreductive surgery of colorectal PC. MATERIALS AND METHODS: Twenty-three consecutive patients with colorectal PC were selected based on the completeness of cytoreductive surgery and sufficient follow-up. They received IPCH with oxaliplatin (460 mg/m(2)) in 2 l/m(2) of dextrose, for 30 min at an intraperitoneal temperature of 43 degrees C, using the coliseum technique. We retrospectively carefully selected another 23 patients, for comparison purposes, suffering from the same disease, with characteristics as similar as possible, but treated earlier with EPIC (mitomycin C 10 mg/m(2) at day 0 and 5-FU 650 mg/m(2) from days 1 to 4), in 1 l/m(2) of ringer lactate. Data concerning these two groups were verified prospectively, but this study was a comparative historical analysis. RESULTS: The two groups were statistically comparable, except for the duration of surgery which was 68 min longer for the IPCH group. Mortality and morbidity were not significantly different, even if two deaths occurred in the EPIC group, and none in the IPCH group. However, the rate of digestive fistulas was higher (P = 0.02) in the EPIC group (26%) than in the IPCH group (0%). Overall survival (OS) was higher in the IPCH group, (54% at 5 years vs. 28% for EPIC), but not significantly (P = 0.22). Peritoneal carcinomatosis recurred much (P = 0.03) more frequently in the EPIC group (57%) than in the IPCH-group (26%). CONCLUSION: This study provides strong arguments indicating that IPCH with oxaliplatin is better tolerated than EPIC with mitomycin C and 5-FU, and is twice as efficient in curing residual peritoneal carcinomatosis measuring less than 1 mm.

Adult↗
PubMed2006

Thyroid metastases from colorectal cancer: the Institut Gustave Roussy experience.

The prevalence of thyroid metastases in colorectal cancer (CRC) patients is unknown. We retrieved the records of all patients with CRC and pathologically proved thyroid metastasis for the period 1993-2004. Among 5,862 consecutive patients with CRC, 6 (0.1%) were diagnosed with thyroid metastases, a median of 61 months after the diagnosis of primary tumour, and a median of 19 months after the last surgical resection or radiofrequency ablation of other metastases (which were present in all cases). Signs and symptoms, when present (n=3), consisted of cervical pain, cervical adenopathy, goitre, dysphagia, and/or dysphonia. In other cases, the diagnosis was made by positron emission tomography scanning. Thyroidectomy was performed in the 5 patients with isolated thyroid metastases, with cervical lymph node dissection being required in all cases. The only patient treated conservatively because of concomitant liver and lung metastases developed life-threatening dyspnoea, which required emergent tracheal stenting. Median overall survival was 77 months, 58 months, and 12 months after the diagnosis of primary CRC, initial metastases, and thyroid metastasis, respectively. It is concluded that thyroid metastases are rare and occur late in the course of CRC. Thyroidectomy (with cervical lymph node dissection) may result in prevention or improvement of life-threatening symptoms and prolonged survival.

Biopsy, Needle↗
PubMed2006

Irinotecan as first-line chemotherapy in patients with advanced hepatocellular carcinoma: a multicenter phase II study with dose adjustment according to baseline serum bilirubin level.

This study assessed the clinical activity and safety of irinotecan (CPT-11) in patients with advanced hepatocellular carcinoma (HCC) using dose adjustment according to baseline serum bilirubin level. Patients with advanced HCC received CPT-11 at a dose of 350 mg/m(2) when total bilirubin level was 1.5 times upper limit of normal (ULN) (group A), or 200 mg/m(2) when total bilirubin level was between 1.51 and 3 ULN (group B). No objective response, one minor response and 12 disease stabilizations were observed in the 29 patients (group A, 23; group B, 6) enrolled. Median time to progression and overall survival were 3.1 months (95% confidence interval [CI]: 2.0-4.0) and 7.4 months (95% CI: 3.9-12.0), respectively. Grade 3-4 adverse events (mostly neutropenia [47%], anaemia [24%], and diarrhoea [17%]) were more frequent in group A (74%) than in group B (33%) (P = 0.086). This study found favourable toxicity profile using dosage adjustment to the baseline total bilirubin level in patients with bilirubin level comprised between 1.51 and 3 ULN. However, the antitumour activity of single agent CPT-11 was not significant in advanced HCC.

Adolescent↗
PubMed2006

Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: prospective evaluation.

PURPOSE: To prospectively evaluate the local efficacy of radiofrequency (RF) ablation of lung neoplasms, with a minimum follow-up period of 1 year. MATERIALS AND METHODS: Sixty patients (34 men and 26 women; age range, 27-81 years; mean age, 66 years) with 100 lung tumors gave written informed consent to be enrolled in a prospective study that was approved by the local ethics committee. There were five or fewer tumors per patient, each with a diameter of less than 40 mm (mean +/- standard deviation, 17 mm +/- 10). RF ablation was performed in tumors by using computed tomographic (CT) guidance. Follow-up CT studies were obtained within 48 hours after treatment and at 2, 4, 6, 9, and 12 months thereafter to evaluate treatment outcome and complications. Lung spirometry measurements were obtained before and 4 weeks after RF ablation. RESULTS: Ninety-seven of 100 targeted tumors were treated and required 163 RF ablations (1.68 per tumor), each lasting 14 minutes +/- 8, delivered during 74 procedures. The 18-month estimated rate of incomplete local treatment at CT was 7% (95% confidence interval: 3%, 14%) per tumor and 12% (95% confidence interval: 5%, 23%) per patient. An ablation area at least four times larger than the initial tumor was predictive of complete ablation treatment (P = .02). There was a trend toward better efficacy for tumors smaller than 2 cm in diameter (P = .066). Overall survival and lung disease-free survival at 18 months were 71% and 34%, respectively. The main adverse event was a pneumothorax, which occurred in 54% of procedures, but a chest tube was required in only 9% of the procedures. No modification of respiratory function was found when spirometry measurements obtained before and within 2 months after RF ablation were compared (P = .51). CONCLUSION: RF ablation has a high local efficacy and is well tolerated.

Adult↗
PubMed2005

Combination chemotherapy in advanced small bowel adenocarcinoma.

OBJECTIVE: To assess the efficacy of 5-fluorouracil (5-FU) and either platinum compounds or irinotecan in patients with advanced small bowel adenocarcinoma (SBA), for whom data on the efficacy of chemotherapy are scarce. METHODS: We reviewed data on all patients with advanced SBA who received chemotherapy over a 9-year period at our institution. RESULTS: Twenty patients with advanced SBA received a median of 6 cycles (range 2-15) of chemotherapy with 5-FU and either cisplatin (n=15), carboplatin (n=2), or oxaliplatin (n=3). The overall response rate was 21%, and median progression-free and overall survival 8 and 14 months, respectively. Toxicity was moderate. Second-line chemotherapy with 5-FU and irinotecan resulted in disease stabilization in 4 (50%) of 8 patients (median progression-free survival: 5 months), and in a biological complete response in another patient with non-measurable peritoneal carcinomatosis, allowing surgical cytoreduction surgery and hyperthermic intraperitoneal chemotherapy. No tumor response or disease stabilization was seen among the patients who received protracted venous infusion of 5-FU (n=4) or infusional 5-FU and cisplatin (n=1) as second-line chemotherapy. CONCLUSION: Chemotherapy with 5-FU and platinum compounds seems effective and well-tolerated in patients with advanced SBA. 5-FU-irinotecan combination chemotherapy deserves further investigation in the first-line setting.

Adenocarcinoma↗
PubMed2005

Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect.

BACKGROUND: The presence of extrahepatic disease (EHD) is considered a contraindication to hepatectomy in patients with colorectal liver metastases. After resection, the prognosis is based more on the total number of resected metastases (located inside and outside the liver) than on the site of these metastases (only inside the liver or not). METHODS: A total of 308 patients with colorectal cancer underwent hepatectomy, and 84 (27%) also underwent resection of miscellaneous EHD. The study was a prospective data registration and retrospective analysis. When considering the total number of resected metastases, each liver metastasis and each EHD location was counted as one lesion. Univariate and multivariate analyses were performed. RESULTS: The median follow-up was 99 months. The overall 5-year survival rate was 32%. In the multivariate analysis, the total number of metastases (inside or outside the liver) had a greater prognostic value than the criterion "presence or absence of EHD." Considering the total number of resected metastases (whatever their site), 5-year survival rates were 38% (SD: 4%) in the group with one to three metastases, 29% (SD: 5%) in patients with four to six metastases, and 18% (SD: 5%) in patients with more than six metastases (P = .002). A very simple prognostic score based on sex and the total number of metastases is proposed. CONCLUSIONS: EHD, when resectable, is no longer a contraindication to hepatectomy. More importantly, the total number of the metastases, whatever their location, has a stronger prognostic effect than the site of these metastases.

Adolescent↗
PubMed2005

Inguinal canal as an anatomic sanctuary site of relapse in peritoneal carcinomatosis previously treated with intraperitoneal chemotherapy.

Early postoperative intraperitoneal chemotherapy (EPIC) and intraoperative peritoneal hypertermic chemotherapy (IPHC) are used in addition with cytoreductive surgery to treat with curative intent peritoneal carcinomatosis arising from colorectal adenocarcinomas. Three patients with such a disease were treated with perioperative intraperitoneal chemotherapy in addition to cytoreductive surgery and presented isolated local recurrence located in the inguinal canal (round ligament in two and spermatic cord in one). All these patients were treated by local surgical excision. No patient showed evidence of intra-abdominal recurrence at the last follow-up, but one developed pulmonary metastasis. When communicating with the peritoneal cavity, the inguinal canal may act as a sanctuary site for peritoneal carcinomatosis, since it is not totally soaked by the intraperitoneal chemotherapy solution. A local recurrence is thus possible. New clinical presentations such as this one have first to be described in order to improve patient follow-up.

Adenocarcinoma, Mucinous↗
PubMed2005

Impact of the extent and duration of cytoreductive surgery on postoperative hematological toxicity after intraperitoneal chemohyperthermia for peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis (PC) is a major disease, currently treated using complete cytoreductive surgery and intraperitoneal chemohyperthermia (IPCH). Morbidity is a significant limitation of this procedure, usually related to the extent of surgery, and hematological toxicity, which is considered as dependent upon the chemotherapy dosage alone. The aim of our study was to investigate whether surgery alone had an impact on the hematological toxicity associated with the standardized drug protocol that we routinely prescribed. METHODS: Data were prospectively recorded from 83 consecutive patients who underwent complete cytoreductive surgery followed by IPCH with intraperitoneal oxaliplatin (360 mg/m(2)) and irinotecan (360 mg/m(2)), in 2 L/m(2) of dextrose over 30 min at 42-45 degrees C, using the Coliseum technique. Sixty minutes prior to IPCH, patients also received an intravenous perfusion of leucovorin (20 mg/m(2)) and 5-fluorouravyl (400 mg/m(2)). The doses and volume of IPCH were determined on the basis of the body surface area, so that all patients received the same concentration of drugs. Severe aplasia were defined as a leucocyte count of <500/ml, platelets <50,000/ml, and reticulocytes <6.5 g Hb/L. RESULTS: Postoperatively, severe aplasia was seen in 40 of the 83 patients (48%). There was no difference in the characteristics of patients with and without aplasia, other than the extent of surgery. The incidence of severe aplasia was only related to the duration of surgery (537 min in the aplastic group versus 444 min in the non aplastic group) (P = 0.002), and to the extent of the peritoneal disease (peritoneal index of 19.5 in the aplastic group, vs. 15.3 in the nonaplastic group) (P = 0.02). CONCLUSION: We report for the first time that the duration of surgery may increase the incidence of hematological toxicity following intraperitoneal chemotherapy. We also hypothesized that intra- and postoperative transient biochemical disorders, such as hypoalbuminemia, hemodilution, liver, and renal insufficiency and stress can be involved in this process. These hypotheses may allow improved postoperative care.

Adult↗
PubMed2005

Hepatectomy plus intraoperative radiofrequency ablation and chemotherapy to treat technically unresectable multiple colorectal liver metastases.

BACKGROUND: Results and indications of intra-operative radiofrequency (RF) ablation of liver metastases (LM) are not well defined in the literature. AIM: To appreciate the survival rate of patients with strictly unresectable LM (defined on technical but not oncological criteria) when undergoing liver resection plus RF, along with optimal systemic chemotherapy. PATIENTS AND METHODS: Sixty three patients with technically unresectable LM (either >5, or bilateral with no sparing of at least one sector of the liver, or with tumor proximity to central major vascular structures) were treated. Extrahepatic metastases were also resected in 27% of patients. All patients received perioperative chemotherapy. The median follow-up was 27.6 months (range: 15-74). RESULTS: There was no postoperative mortality and the morbidity rate was 27%. The 2-year overall survival rate of the 63 patients was 67% with a median survival of 36 months. The local recurrence rates were similar for the three types of local treatments: 7.1% for the 154 RF ablations, 7.2% for the 55 wedge resections, and 9% for the 44 segmental anatomic resections (P = 0.216). Hepatic recurrences occurred in 71% of patients. CONCLUSION: The combination of anatomic segmental and wedge resections, RF ablation, and optimal chemotherapy in patients with technically unresectable LM results in a median survival of 36 months.

Adult↗
PubMed2005

Ex vivo sentinel lymph node study for rectal adenocarcinoma: preliminary study.

Intraoperative sentinel lymph node (SLN) detection has been reported for colon cancer, but no study has focused on rectal cancer. Only an ex vivo technique can be performed easily in this location. We evaluated SLN detection using blue dye injection in patients with rectal adenocarcinoma. This prospective study included 31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After proctectomy the surgical specimen was examined in the operating room. Submucosal peritumoral injections were done. One to three SLNs were retrieved. The SLNs were sectioned at three levels and examined histologically and then, if negative by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7 abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses, and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7-38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs was 2 (0-3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was used on multisection levels, thus changing the stage to pN1. Each time the only positive lymph node was the SLN. IHC evaluation did not change the result, as only isolated tumor cells were discovered in one case. Only four of seven N+ patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo detection of SLNs is possible for rectal cancer and is a simple technique. Classic analysis using H&E remains the gold standard. However, SLNs detection can change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3 N+.

Adenocarcinoma↗
PubMed2005

Surgical treatment of peritoneal carcinomatosis from well-differentiated digestive endocrine carcinomas.

BACKGROUND: The presence of peritoneal carcinomatosis (PC) in association with endocrine carcinomas (EC) is generally considered to have no impact on life expectancy, contrary to liver metastases. This study was aimed at assessing the actual prognostic impact of PC and to evaluate a new treatment with respect to survival times. PATIENTS AND METHODS: Among 111 patients undergoing surgery for progressive, well-differentiated EC, 37 (33%) presented a histologically proven PC, with synchronous liver metastases in 36 of them. The origin was ileal or appendiceal (carcinoid tumors) in at least 81% of cases. The patients were divided into 2 groups. Patients in group 1 (n = 20) could not undergo complete resection of PC, while those in group 2 (n = 17) underwent complete cytoreductive surgery, followed by immediate intraperitoneal chemotherapy. Partial hepatectomy was performed in 65% of patients in group 2. The median follow-up was 6.9 years. RESULTS: There was no postoperative mortality, and the morbidity rate was 47%. In group 1, 15 of the 20 patients died (5-year survival rate, 40.9%). Deaths were caused either by liver failure (60% of patients) or bowel obstruction from PC (40%). In group 2, six of the 17 patients died (5-year survival rate, 66.2%; P = .007). These patients died of liver failure (n = 4, 23.5%), bowel obstruction (n = 1, 5.8%), and cerebral hemorrhage (n = 1, 5.8%). CONCLUSIONS: PC associated with EC is not a rare event; it is mainly caused by carcinoid tumors and is always associated with liver metastases. When present, PC is the direct cause of death in 40% of patients if no specific treatment is undertaken. Treatment of PC with maximal cytoreductive surgery and immediate intraperitoneal chemotherapy appears promising, even though it can only be considered as palliative.

Adult↗
PubMed2005

Cutaneous side-effects of kinase inhibitors and blocking antibodies.

Although kinase inhibitors raise hope for people with cancer, patients and their clinicians are commonly confronted with the cutaneous side-effects that are associated with the use of these drugs. This review is the result of collaborations between dermatologists, medical oncologists, and pathologists, and discusses the cutaneous side-effects seen after treatment with the inhibitors of epidermal-growth-factor receptor (EGFR), imatinib, sorafenib, and sunitinib. Some of the side-effects caused by these agents are very distressing, partly because they are chronic owing to the long duration of treatment. Therefore, patients need early and appropriate dermatological management. Moreover, several studies have reported a link between the antitumour efficacy of EGFR inhibitors and cutaneous side-effects. Elucidation of this connection could lead to the identification of crucial predictive factors for tumour response.

Antibodies, Blocking↗