Correlation between clinical response to interleukin 2 therapy and sustained production of tumor necrosis factor.

Twenty-five previously untreated patients with metastatic renal cell carcinoma were treated with 5-day cycles of continuous infusion of interleukin 2 (IL2) and lymphokine-activated killer cell reinfusion. Five achieved a partial response. Three patients were found to have detectable tumor necrosis factor (TNF) in serum before initiation of therapy. On the fifth day of therapy, 24 patients had circulating TNF with immunoradiometric assay whereas 13 had detectable biological activity. Two days after the end of IL2 therapy, TNF concentration (immunoradiometric assay) decreased in most cases but was still detectable in 17 patients. Thirteen patients had still circulating TNF bioactivity. Although there was no significant difference between TNF levels observed on the fifth day of therapy in the responder and nonresponder groups, 48 h after the end of IL2 infusion, both the TNF concentration and the biological activity were significantly higher in the group of responder patients. This result suggests that the clinical response to IL2 therapy in patients with metastatic renal cell carcinoma is correlated to a sustained production of TNF after the end of IL2 infusion.

Cryosurgery as a means to improve surgical treatment of patients with multiple unresectable liver metastases.

BACKGROUND: The aim of the study was to evaluate the results of cryosurgery in patients with multiple (five or more), heavily pretreated, unresectable liver metastases. MATERIALS AND METHODS: Nineteen patients with multiple unresectable liver metastases were entered into a prospective nonrandomized trial. The liver tumours were treated during surgery under ultrasound guidance. All the patients were followed-up to assess complications, treatment response and sites of recurrence. RESULTS: 140 metastases were identified in 19 patients (mean, 7; range, 5-25) and 13 patients had a synchronous liver resection. Cryosurgery was used to treat 90 metastases (mean diameter, 30 mm; range, 10-135). There were no treatment-related deaths and the overall rate of complications was 21%. During a mean follow-up of 28 months (range, 5-60), tumours recurred at the site of cryosurgery in two patients (10%), in the remaining liver in nine patients (47%) and elsewhere in five patients (26%). Three patients had no evidence of disease 48, 50 and 60 months after liver cryosurgery, respectively. CONCLUSION: Cryosurgery may be effective in the treatment of patients with multiple unresectable liver metastases and should be investigated in multimodality treatment programmes.

Assessment of tumour response to chemotherapy for metastatic colorectal cancer: accuracy of the RECIST criteria.

Evaluation of tumour size modifications in response to treatment is a critical issue in the management of advanced malignancies. In 1981, the World Health Organization (WHO) established guidelines for tumour response assessment. These WHO1981 criteria were recently simplified in a revised version, named RECIST (Response Evaluation Criteria in Solid Tumours), which uses unidimensional instead of bidimensional measurements, a reduced number of measured lesions, withdrawal of the progression criteria based on isolated increase of a single lesion, and different shrinkage threshold for definitions of tumour response and progression. In order to validate these new guidelines, we have compared results obtained with both classifications in a prospective series of 91 patients receiving chemotherapy for metastatic colorectal cancer. Data from iterative tomographic measurements were fully recorded and reviewed by an expert panel. The overall response and progression rates according to the WHO1981 criteria were 19% and 58%, respectively. Using RECIST criteria, 16 patients were reclassified in a more favourable subgroup, the overall response rate being 28% and the progression rate 45% (non-weighted kappa concordance test 0.72). When isolated increase of a single measurable lesion is not taken into account for progression with the WHO1981 criteria, only 7 patients were reclassified and the kappa test was satisfying, i.e. > or =0.75, for the whole population as well as for each of the responding and progressive subgroups. Since it provides concordant results with a simplified method, the use of RECIST criteria is recommended for evaluation of treatment efficacy in clinical trials and routine practice.

[Standards, options, and recommendations for radiotherapy of kidney cancer]. / Standards, Options et Recommandations pour la radiothérapie du cancer du rein.

CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary expert group, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the diagnosis, management and treatment of patients with renal cancer. This review is part of previously published complete guidelines and focuses on the place of radiotherapy in this disease. METHODS: The data was identified by literature search using Medline (up to June 1999) and personal reference lists. The main endpoints considered were survival, risk factors for late effects of radiotherapy, safety and quality of life. RESULTS: The key recommendations are: 1) In localised renal cancer, adjuvant radiotherapy has a limited role: it is not indicated for T1 and T2 tumours and there is no proof of a survival benefit for T3 N1-N2 tumours. Postoperative radiotherapy can be considered in young patients without risk factors for the development of post-radiotherapy complications and without loco-regional invasion (renal capsule, renal pelvis, vena cava, regional lymph nodes); 2) For metastatic tumours, the multidisciplinary team must decide whether palliative radiotherapy is appropriate after consideration of the prognostic factors. An isolated metastasis can be treated by radiosurgery and stereotaxic radiosurgery may be of benefit in the case of one or two cerebral metastasis. The optimal dose for palliative treatment is not known. Radiotherapy followed by immunotherapy can also be considered if the patient has no contraindication to such treatments.

[Cryosurgery of liver neoplasms]. / La cryochirurgie des tumeurs du foie.

Cryosurgery is the in situ destruction of tissue using subzero temperatures. Its use for the treatment of some unresectable liver tumors has been clearly established as a therapeutic option. Experimental studies have demonstrated the feasibility of freezing of large liver volumes without any major metabolic and hemorrhagic complications. Modern cryosurgery has received substantial impetus from the development of automated cryosurgical apparatuses using liquid nitrogen. Intraoperative ultrasound has enhanced the process by enabling visualization of tissue freezing and ensuring precise and optimal treatment of the tumor. Clinical reports of cryosurgery for liver primary tumors and metastases have confirmed the safety of the procedure. Major complications include myoglobinuria, coagulopathy and pleural effusions. The benefit of cryosurgery is that it broadens the number of patients that can be brought to surgery and can potentially become disease-free.

[Optical assistance in guiding punctures under x-ray computed tomographic control]. / Assistance optique de guidage des ponctions sous contrôle TDM.

The authors describe a new technic for realisation of CT-guided punctures. This original device uses a buna tourniquet placed on the table for drawing on the skin the site of puncture and a movable light-visor for guiding the needle during the puncture. The advantages of this device are: no using of disposable or sterilised material; total freedom of the hand during the puncture; to be simple and quick.

[Percutaneous vertebroplasty in the treatment of metastases. Technic and results]. / Vertébroplastie percutanée dans le traitement des métastases. Technique et résultats.

The authors studied 20 patients with vertebral metastases. They injected in these metastases orthopaedic cement by a percutaneous technique under local anesthesis. The results are good for 16 patients, nul for 2 patients and we observed 2 complications. The authors conclude that the best indication is the painy somatic lysis of a vertebra without peri-radicular tumor.

Safety of percutaneous internal jugular catheterization in cancer patients: prospective observational study.

PURPOSE: To determine predictors for failure and early complications of percutaneous internal jugular catheterization (IJC) in cancer patients. METHODS: Six hundred and thirty consecutive cancer patients who required central venous catheterization were included in a prospective observational study. The rates of failure (defined as the intervention of a second physician and/or failure at initial insertion site) and of early complications were prospectively ascertained. Logistic regression analysis estimated odds ratio (OR) and 95% confidence intervals (95% CI) for independent predictors for failure and early complications of percutaneous IJC. RESULTS: The failure rate was 6.7%, and the early complication rate was 6.7%. In multivariate analysis, left-side initial catheterization (p<0.01), prior catheterization at the same site (p=0.001) and physician inexperience (p<0.0001) were independently associated with failure. Placement requiring more than one needle pass (p<0.01 for two and p<0.0001 for three and more) and absence of fluoroscopy (p<0.0001) were independently associated with early complications. CONCLUSIONS: Percutaneous IJC is a valid option in the central venous catheterization of cancer patients due to its reliability and safety. Skilled physicians must manage difficult placements. If placement requires more than one needle pass or is made without fluoroscopy, patients must be carefully followed for potential complications.

[Cryosurgery with transpleurodiaphragmatic approach in the treatment of non-resectable and recurrent hepatic metastasis from the colorectum]. / La criochirurgia con accesso transpleurodiaframmatico nel trattamento delle metastasi epatiche colorettali non resecabili e recidive.

Cryotherapy allows the destruction of unresectable liver malignancies. The abdominal approach is uneasy for recurrent colorectal metastases located in the upper part of the liver and close to the inferior vena cava, the hepatic veins and the diaphragm. A transpleurodiaphragmatic access was employed. From 1999 to 2003, ten patients with recurrent colorectal liver metastases underwent transdiaphragmatic cryotherapy via a right thoracotomy. Median diameter was 30 mm. One to 4 cryoprobes were used, depending on the size and location of the metastasis. There were no operative deaths, and only 3 patients developed minor complications. Computerized tomography examination of the liver performed one week, three months after cryotherapy, assessed treatment completeness in all patients. At 14 months, 9 patients were alive and 6 were disease-free. Two patients had liver recurrences outside the cryolesion. A transthoracic access may represent the safest and easiest surgical approach for liver tumor cryoablation in selected patients with non resectable recurrent metastases of the upper liver.

Multimodality treatment of patients with liver metastases from germ cell tumors: the role of surgery.

BACKGROUND: The presence of liver metastases represents an independent poor risk prognostic factor for survival in patients with germ cell tumors. METHODS: The clinical files of 37 patients who had undergone liver resection for the treatment of disseminated germ cell tumors were reviewed to define the indications for resection of residual liver metastases after chemotherapy in patients with germ cell tumors. The histologic patterns of primary tumor and residual disease were compared. The prognostic factors for survival were studied by univariate analysis. RESULTS: All but 2 of 37 patients underwent complete resection. One patient died of postoperative complications. Thirteen complications occurred in 10 patients. Twelve patients had active residual tumor, 7 patients had mature teratoma, and 18 patients had only necrosis on histologic examination. Twenty-three of 37 patients (62%) were alive with no evidence of disease after a median follow-up of 66 months (range, 31-134 months). Three prognostic factors were found to be significant in the univariate analysis for unfavorable outcome: the presence of pure embryonal carcinoma in the primary tumor, liver metastases measuring > 30 mm in greatest dimension at the time of surgery, and the presence of viable, active residual disease. CONCLUSIONS: Because it is impossible to determine the histologic pattern of residual liver masses after chemotherapy with current imaging tools and percutaneous biopsy, patient selection for liver surgery may be undertaken according to the size of residual liver masses. Patients with masses that measure < or = 10 mm in greatest dimension should be considered for close follow-up, because they have a high probability of necrosis and are at low risk for malignant disease. Male patients with masses that measure > or = 30 mm in greatest dimension represent a high-risk group of patients who are not likely to benefit from liver surgery. Only male patients with masses that measure 10-29 mm in greatest dimension and all female patients with masses that measure > 10 mm in greatest dimension should be considered for liver resection.

Salvage liver surgery of a chemorefractory ovarian choriocarcinoma.

A 41-year-old woman with pure ovarian choriocarcinoma and widespread liver metastases became refractory to standard cisplatin-based chemotherapy regimens. As metastatic disease was limited to the liver and operable, the patient underwent complete resection of three liver metastases. The serum human chorionic gonadotrophin level promptly returned to normal values. Pathologic studies demonstrated the presence of active residual disease composed of typical syncytiotrophoblastic and cytotrophoblastic cells and large mononucleated intermediate cells. The patient remained disease-free for more than 5 years after treatment. It is concluded that liver salvage surgery may cure patients with chemorefractory ovarian choriocarcinoma with metastases to the liver.

[Mesenchymal solid hamartoma of the liver]. / Hamartome mésenchymateux du foie de forme solide pure.

The authors describe a mesenchymal hamartoma of the liver without cyst. The diagnosis was radiologically approached by US, CT and US guided cytological puncture. They discuss the radiological aspects of mesenchymal hamartomas of the liver.

[Contribution of imaging in the diagnosis and follow-up of brain tumors]. / Apport de l'imagerie dans le diagnostic et le suivi des tumeurs encéphaliques.

With the use of modern radiological imaging (US, CT-scan, MRI), the most important informations to recognize a tumor remain the morphological features (localization, size, extension, number of lesions...). The precision of these informations is constantly improved (use of contrast medium, various slices angulations...) and in this field, MRI is the most precise examination. Moreover, these less aggressive investigations allow a repeated and more efficient therapeutic follow-up. In contrast with initial expectations, these radiological investigations do not always allow a formal histological characterization of the different tumor types of the central nervous system, even if some intratumoral components are recognized (fat, calcifications, liquids...).

Hepatic cryosurgery precision: evaluation of ultrasonography, thermometry, and impedancemetry in a pig model.

One of the main problems of the use of liver cryosurgery is to be sure that a defined hepatic volume has been completely destroyed. We undertook an experimental pig study to determine histopathological evolution of cryolesions, to evaluate the value of intraoperative sonography, thermometry, and impedancemetry to monitor necrosis and to evaluate clinical and biological repercussions of hepatic cryosurgery. Forty-eight cryolesions were obtained by freezing each liver lobe of 12 experimental pigs during a 5-min contact with a flat cryoprobe cooled with liquid nitrogen. Cryolesions and the surrounding liver were monitored during cryosurgery by six thermocouple electrodes, five impedance electrodes, and intraoperative sonography. Animals were sacrificed immediately, 6 hr and between day 1 and day 32 after the procedure. Cryolesions were excised, and a full size pathological study was carried out. No morbidity or mortality was observed. At the end of the freezing time, cryolesions were hemispheric in shape, and their radius measured by sonography was 17.7 +/- 1.2 mm (mean +/- SD). Microscopic study showed sequential tissue alterations with edema, ischemic necrosis, tissue slough, and granulation. Cryolesions were sharply delineated from the normal liver tissue. The radius of necrosis at days 2 and 3 was 17 +/- 0.3 mm (mean +/- SD). It showed good correlation with the cryolesion size measured by intraoperative sonography. The temperature threshold to obtain complete normal liver necrosis was -15 degrees C. We found impedancemetry too difficult to use and not precise enough to monitor cryonecrosis. We conclude that intraoperative sonography and thermometry are useful means to monitor the extent of cryonecrosis during liver cryosurgery.

Patients with metastatic renal carcinoma candidate for immunotherapy with cytokines. Analysis of a single institution study on 181 patients.

This study was performed with the aim of discovering the characteristics and survival of patients with metastatic renal carcinoma who undergo immunotherapy with an Interleukin 2 based regimen. One hundred and eighty-one patients with metastatic renal carcinoma were referred to our institute from October 1987 until August 1991; 129 were treated with Interleukin 2 with or without Interferon alpha in three successive protocols. Fifty-two patients were not treated with immunotherapy due to the exclusion criteria of the protocols. Sixty-four patients with the same disease who had been referred to our institute before the initiation of this programme (1982, 1987) were also analysed as a control group. The main characteristics of the three different cohorts of patients were analysed and compared with univariate statistical tests; the median survival of the patients was calculated and compared. The referral rate increased from 13 a year to 45 a year while the IL2 trials were being conducted. Patients treated with cytokines have a median survival of 18 months after occurrence of metastases, compared to 6 and 8 months, respectively, in excluded patients and the control group. This parameter is of 15 months when the 181 patients, treated with cytokines or not, are considered. The survival of treated vs excluded patients is significantly different (P < 10(-6); so is the survival of the 181 patients recently included when compared to the historical group (P:10(-5). When the 181 recent patients are compared to the historical control group, a number of differences appear in their characteristics, which prevent us from drawing any conclusion about the role of immunotherapy in the improvement of survival observed. This study clearly evidences the selection of the patients receiving immunotherapy and the modification in referrals of a disease induced by a new available therapy. This emphasises the need for prospective studies in this setting.