PULMONARY NODULES IN PATIENTS WITH A HISTORY OF RADICAL NEPHRECTOMY FOR RENAL CELL CARCINOMA

Background:
Nine patients with a history of radical nephrectomy for renal cell carcinoma underwent surgical removal of newly detected pulmonary nodules at the Hiroshima University Hospital. Six patients had metastatic lung tumors two patients had bronchogenic primary carcinomas and one had a granulomatous infection.
Methods:
To determine if any characteristics can distinguish a new primary carcinoma from metastatic renal cell carcinoma, we reviewed the nine patients described above. The patients with pulmonary metastases and those with new primary lung cancers did not differ in age, sex, history of smoking, clinical stage and pathological findings of the renal primary site, on the location and size of the pulmonary nodules.
Results:
Only the interval between the nephrectomy and the appearance of the new pulmonary lesion may be a predictive factor. This interval was 48 and 51 months for the patients with new primary lung cancers but varied from 0 to 39 months for the patients with metastatic renal cell carcinoma. A solitary nodule had an equal chance of being metastatic or primary. Conclusions: These results indicate that a solitary nodule that is detected at a longer inferval after radical nephrectomy may be a new primary lung cancer. Once new pulmonary nodules are identified in a patient with a history of radical nephrectomy for renal cell carcinoma, surgical excision is required for a final diagnosis before initiating therapy for metastases.     

LAPAROSCOPIC NEPHRECTOMY FOR INFLAMMATORY RENAL CONDITIONS

PURPOSE: Inflammatory and infectious renal conditions may result in severe perirenal fibrosis, making the laparoscopic approach challenging. The theoretical advantages of laparoscopy for managing inflammatory and infectious renal conditions have been questioned. We identified whether laparoscopy for inflammatory renal conditions is associated with higher morbidity than for other benign renal conditions. Furthermore, several technical modifications are discussed that may help to improve the outcome. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent laparoscopic nephrectomy for inflammatory and infectious renal conditions between 1998 and 2000. The transperitoneal approach was used and specimens were removed after morcellation. Operative data were compared with those from a similar group of patients who underwent laparoscopic nephrectomy for other benign conditions. RESULTS: Laparoscopic nephrectomy done for inflammatory or infectious conditions in 12 cases and for other benign conditions in 9 matched cases was completed successfully in 10 (83%) and 9 (100%), respectively. In the inflammatory and benign groups mean blood loss plus or minus standard deviation was 155 +/- 163 and 59 +/- 23 ml. (p = 0.099), mean operative time was 284 +/- 126 and 226 +/- 62 minutes (p = 0.225), and mean postoperative hospital stay was 4.1 +/- 2 and 3 +/- 1 days (p = 0.157), respectively. CONCLUSIONS: Laparoscopic nephrectomy can be performed safely in most cases of inflammatory renal conditions. Although they were not statistically significant, a higher conversion rate and longer operative time should be expected. Early conversion may be required due to failure to progress. Similar advantages were observed in patients with inflammatory and other benign renal conditions via the laparoscopic approach.     

ADRENAL SPARING SURGERY DURING RADICAL NEPHRECTOMY IN PATIENTS WITH RENAL CELL CANCER: A NEW ALGORITHM

PURPOSE: Ipsilateral adrenalectomy is usually performed during radical nephrectomy because of renal cell cancer. Because renal tumors are detected more often in the earlier stages due to widespread use of ultrasound and computerized tomography, we define a subset of patients who would be eligible for adrenal sparing surgery. In a retrospective analysis we evaluated whether parameters obtained preoperatively are able to predict adrenal metastasis. MATERIALS AND METHODS: A total of 866 consecutive patients who underwent nephrectomy and ipsilateral adrenalectomy from 1983 to 1999 were evaluated. Preoperative parameters, including tumor size, location, clinical stage, number of tumors, and patient age and sex, were retrospectively compared with the histological results. Univariate and multivariate analyses were performed. RESULTS: A total of 27 (3.1%) adrenal metastases were noted in the 866 patients, and 63% were on the left side and 37% on the right side. Mean tumor size was 10 cm. with versus 6 cm. without adrenal involvement. Of the 27 patients 21 had multiple metastases at diagnosis and only 6 (0.7% of all 866) presented with solitary ipsilateral adrenal metastasis. Univariate and multivariate analyses revealed tumor size and M stage as best preoperative predictors of adrenal involvement. CONCLUSIONS: Adrenal sparing surgery is possible, and we suggest a new algorithm. If maximum tumor size measured by computerized tomography is less than 8 cm. and staging examination does not show organ or lymph node metastases, adrenalectomy is not necessary because of oncological reasons. This algorithm has to be validated by a prospective analysis.     

ROBOT ASSISTED LAPAROSCOPIC NEPHRECTOMY

PURPOSE: The feasibility and safety of remote laparoscopic surgery using a surgical telemanipulator have been demonstrated in laboratory experience and recently in clinical practice. To our knowledge we report the first robot assisted, laparoscopic nephrectomy in a human. MATERIALS AND METHODS: A 77-year-old woman was diagnosed with a nonfunctioning hydronephrotic right kidney due to ureteropelvic junction obstruction. Robot assisted, transperitoneal right laparoscopic nephrectomy was performed. RESULTS: Complete dissection was successfully performed with the robot. The renal pedicle was dissected without any problem, and the artery and vein were individually ligated. Operative time was 200 minutes, anesthesia time was 245 minutes and blood loss was less than 100 ml. Convalescence was uneventful. Histological examination confirmed the preoperative diagnosis. CONCLUSIONS: We report the technical feasibility of robot assisted laparoscopic nephrectomy in humans. Current technology needs further improvement and its actual usefulness for patient treatment must be established by large clinical trials. Technological improvements and future telecommunication networks should open new avenues in surgery, namely remote telesurgery.     

LAPAROSCOPIC BILATERAL HAND ASSISTED NEPHRECTOMY FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: INITIAL EXPERIENCE

PURPOSE: The laparoscopic technique for bilateral nephrectomy in patients with autosomal dominant polycystic kidney disease is technically difficult. The procedure may be more acceptable if alterations to the technique made it safer and easier to perform. We describe our initial experience with, and the feasibility and potential benefits of hand assisted laparoscopic nephrectomy for approaching these large kidneys in patients with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: This approach was successfully applied in 3 patients with end stage renal disease due to autosomal dominant polycystic kidney disease. After obtaining transumbilical pneumoperitoneum ports were placed in the umbilicus (12 mm.), sub-xiphoid in the midline (12 mm.) and subcostal in the midclavicular line on each side (12 mm.). The table was tilted 40 degrees away from the planned side of initial nephrectomy with the patient in the half lateral position. A 7 cm. midline incision was made that incorporated the umbilical port and a commercially available hand assistance device was positioned. One surgeon hand was inserted into the abdomen to serve as a retractor/blunt dissector, while the other operated the electrosurgical instruments. The right hand was inserted for left nephrectomy and the left hand was inserted for right nephrectomy. The laparoscope was passed via the sub-xiphoid port and the instruments were placed through the ipsilateral subcostal laparoscopic port. Nephrectomy was completed and the specimen was removed through the hand port incision by draining the cysts as they were exposed to view via the midline incision. When dissection was difficult, an additional port was placed in the anterior axillary line at the umbilical level. Some cysts were ruptured or aspirated to decrease overall kidney size and make extraction possible via the 6 to 7 cm. midline incision. RESULTS: All procedures were successfully completed. Mean operative time for bilateral hand assisted laparoscopic nephrectomy was 5.5 hours (range 4.5 to 6.6). Estimated blood loss was 200 cc or less. Patients resumed oral intake on postoperative day 1. The mean amount of parenteral analgesics required postoperatively was decreased. Mean hospital stay was 4.3 days but it was 3 days when considering nephrectomy only. Patients returned to normal activity after an average of 2 weeks. There was sustained resolution of preoperative discomfort based on pain analog scales. At 1 month or less all patients recorded absent pain. They uniformly noticed improved preoperative pulmonary and gastrointestinal symptoms CONCLUSIONS: Hand assisted laparoscopic nephrectomy in patients with autosomal dominant polycystic kidney disease makes bilateral nephrectomy a reasonable option. The bilateral procedure may be performed as rapidly as laparoscopic only, unilateral nephrectomy in these cases. The advantages of the hand assisted approach include using tactile sensation to facilitate dissection, rapid blunt finger dissection, hand retraction and the application of immediate tamponade when needed. This procedure provides the benefits of minimal intraoperative blood loss, minimal postoperative pain, brief hospital stay and rapid convalescence in this group of patients at high risk.     

LAPAROSCOPIC LIVE DONOR NEPHRECTOMY: THE PRELIMINARY EXPERIENCE

Background : Recent improvements in video technology and surgical instrumentation have resulted in the application of minimally invasive techniques to many surgical procedures including splenectomy and adrenalectomy. ^{1 , 2} Nephrectomy requires a long flank incision with division of abdominal musculature and possible subcostal nerve damage. Severe postoperative pain and a prolonged recuperative period may result, and the cosmetic outcome may not be satisfactory. A new surgical approach utilizing laparoscopic dissection and delivery of the kidney through a small incision was performed to circumvent these problems. The aim of this paper is to describe the technique of laparoscopic live donor nephrectomy (LLDN) and present the preliminary outcome. Methods : Over the 12-month period between May 1997 and April 1998, 16 donors underwent donor nephrectomy by a laparoscopic approach. The procedure was assessed with regard to its safety, feasibility and advantages over the open method. Results : All the nephrectomies were completed without conversion to an open procedure. The average postoperative pain score on a visual analogue scale of 1–10 was 2 in LLDN. The donors required 36 mg morphine on average over 36 h postoperatively. Postoperative stay averaged 3 days. One donor developed an infective complication along the wound drain tract which settled with adequate drainage and antibiotics. All the removed donor kidneys were transplanted with immediate good function. There were no surgical complications or graft losses. The recipients’ serum creatinine was in the range of 96–181 mmol/L 3 months after transplantation. Conclusions : Significant potential advantages of LLDN include less postoperative pain, shorter hospitalization and decreased recuperative time. This preliminary experience indicates LLDN to be effective in terms of safety and feasibility.     

RENAL CELL CARCINOMA IN CHILDREN: EXPERIENCE AT A SINGLE INSTITUTION IN JAPAN

PURPOSE: We analyzed the presentation, treatment and survival of 4 children with renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the pathological and hospital records of 4 Japanese children diagnosed with renal cell carcinoma at our hospital from 1970 to 1998. RESULTS: In the 1 boy and 3 girls with an average age of 8 years 7 months at diagnosis the most common presenting complaints were gross hematuria in 75% and a palpable abdominal mass in 50%. Computerized tomography revealed characteristic calcification within the tumor in 3 of the 4 patients (75%). In the remaining case the lesion had high density areas with microcalcification, as confirmed by histopathological study. In 2 patients with regional lymph node metastasis calcification was also observed in the metastatic lesions. Disease was stages I to III in 1, 1 and 2 patients, respectively. All patients underwent transabdominal nephrectomy with regional lymphadenectomy. One patient with stage I disease had multiple metastases 15 months later and died of disease 55 months postoperatively. However, the remaining 3 patients received adjuvant interferon therapy and they are without evidence of recurrence a mean of 51.3 months postoperatively. CONCLUSIONS: Calcification within the tumor and/or metastatic lesions or high density areas in the tumor on screening computerized tomography are characteristic findings suggestive of pediatric renal cell carcinoma. Adjuvant therapy with interferon may provide some benefit in select pediatric patients. Further studies of a larger number of pediatric renal cell carcinoma cases may be necessary to establish the optimal diagnostic and therapeutic regimen.     

A POSTOPERATIVE PROGNOSTIC NOMOGRAM FOR RENAL CELL CARCINOMA

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.     

STAGE SPECIFIC GUIDELINES FOR SURVEILLANCE AFTER RADICAL NEPHRECTOMY FOR LOCAL RENAL CELL CARCINOMA

Purpose

We report stage specific followup guidelines based on our evaluation of the pattern of recurrence in 286 patients treated for local N0 or Nx renal cell carcinoma.

Materials and Methods

We retrospectively reviewed the clinical records of 286 patients with pT1 to pT3N0 or Nx renal cell carcinoma who underwent nephrectomy at our center between February 1985 and December 1994. In cases of later metastases the median interval to first metastasis, site of metastasis and method of diagnosis were correlated with the primary lesion stage.

Results

Metastases developed in 68 patients a median of 23 months after nephrectomy. Eight of the 113 patients with pT1 disease had metastases (median time to diagnosis 38 months), while 17 of 64 with pT2 disease and 43 of 109 with pT3 disease had metastases (medians 32 and 17 months, respectively). Of the 92 metastases 59 (64%) were asymptomatic, including 44 detected on routine chest x-rays (32) and blood tests (12). Isolated asymptomatic intra-abdominal metastases were diagnosed by surveillance computerized tomography in only 6 patients (9%). The remaining patients with metastases had associated clinical symptoms and/or abnormal results on interval tests that prompted further diagnostic studies.

Conclusions

We confirmed that the risk of metastatic renal cell carcinoma is stage dependent. Therefore, surveillance protocols should be based on the pathological stage of the primary tumor. We recommend an annual chest x-ray, and serum liver function and alkaline phosphatase level tests for patients with pT1 disease. These studies are indicated beginning at 6 and 3 months for pT2 and pT3 disease, respectively, continuing every 6 months for 3 years and then annually. Surveillance computerized tomography should be performed at 24 and 60 months in patients with pT2 and pT3 disease or earlier when the results of any routine study are abnormal or clinical symptoms are present. Bone and brain surveillance studies should be prompted by site specific symptoms, elevated alkaline phosphatase levels or the diagnosis of metastasis at another site.     

PROGNOSTIC SIGNIFICANCE OF THE 1997 TNM CLASSIFICATION OF RENAL CELL CARCINOMA

PURPOSE: The TNM classification of renal cell carcinoma was recently revised in 1997. The most significant change from the previous edition (1987) is an increase in the size cutoff between T1 and T2 tumors from 2.5 to 7.0 cm. We compared the 1997 and 1987 TNM staging classifications in predicting patient outcome. MATERIALS AND METHODS: A total of 381 patients who underwent nephrectomy for renal cell carcinoma at our hospital between 1968 and 1994 were identified. Mean patient age was 61 years (range 15 to 89) and mean followup was 64.5 months. All pathological slides were re-reviewed in uniform manner and staged using the 1987 and 1997 TNM classifications. The impact of numerous pathological factors and each staging classification on disease specific survival and freedom from progression were statistically analyzed, and Kaplan-Meier survival curves were generated and compared. RESULTS: The 1997 TNM classification resulted in a redistribution of 170 cases previously classified as stage II (T2N0M0) to stage I (T1N0M0) under the new system. Both classifications were strong predictors of survival on univariate and multivariate analyses, and essentially equivalent in the ability to predict patient outcome. However, comparison of survival curves on Kaplan-Meier life tables revealed better separation of survival for stage I (T1N0M0) and stage II (T2N0M0) cases under the 1997 TNM classification, with survival for TNM stage I essentially remaining unchanged. CONCLUSIONS: The 1997 TNM classification of renal cell carcinoma appears to be equivalent to the previous classification in predicting outcome but permits better stratification of cases according to survival and, therefore, may have improved clinical usefulness.     

LAPAROSCOPY-ASSISTED RADICAL NEPHRECTOMY IN COMBINATION WITH MINILAPAROTOMY: REPORT OF INITIAL 7 CASES

We recently developed a new procedure for laparoscopy-assisted radical nephrectomy in combination with minilaparotomy to remove kidneys with renal cell carcinoma. A pararectal incision approximately 7 cm in length was performed from the subcostal region. A 12-mm trocar was placed at the mid-clavicular line at the level of the umbilicus. An 11 -mm trocar was placed at the tip of the rib. Under laparoscopic and trans-minilaparotomic observation, intra-abdominal manipulation was begun. The contents of Gerota's fascia were freed from the surrounding tissues and removed through the abdominal incision. Seven patients have been successfully treated with this procedure. The operating time for this procedure was shorter than the time of laparoscopic nephrectomy. There were none of the adverse hemodynamic or ventilatory effects associated with pneumoperitoneum in this procedure. This procedure also resulted in less postoperative pain and a shorter convalescence period when compared with open nephrectomy.     

AN ARTICULATING RETRACTOR HOLDER TO FACILITATE LAPAROSCOPIC ADRENALECTOMY AND NEPHRECTOMY

PURPOSE: Minimally invasive surgical approaches to renal and adrenal tumors have gained increasing use. The addition of robotic assistance and mechanical devices has decreased the number of assistants required for these often long cases. We describe an articulating arm retractor holder to aid in liver and spleen retraction during laparoscopic surgery. MATERIALS AND METHODS: The articulating retractor holder consists of 4 components, including a base rod, flexible extension arm, stainless steel precision clamp and table attachment. During laparoscopy the abdomen is visualized using standard approaches. The articulating retractor holder is clamped to the table via the base rod and brought into the surgical field using sterile technique. A retractor is placed intracorporeally to elevate the liver or spleen and the handle is secured in place using the precision clamp. RESULTS: The articulating retractor holder was used in all right and approximately 50% of left laparoscopic cases. Adequate visualization was obtained in all patients. There were no device failures or retractor related complications. CONCLUSIONS: The articulating retractor holder is a useful tool to aid in laparoscopic retraction that should be added to the urologist armamentarium.     

A FEASIBILITY STUDY OF GENE GUN MEDIATED IMMUNOTHERAPY FOR RENAL CELL CARCINOMA

PURPOSE: Gene modified autologous tumor cell vaccines have demonstrated a protective and therapeutic effect in murine tumor model systems. The majority of trials to date have used viral methods of gene transfer for vaccine construction. An alternative approach to transfer genes into tumor cells is to use the gene gun, which is a physical method of gene transfection that produces high levels of gene expression without viral agents. We establish the feasibility of generating cytokine secreting autologous renal tumor cell vaccines for use in gene therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: We obtained 1 cm3 tumor tissue from 12 patients undergoing resection of primary or metastatic renal cell carcinoma. The tumor was disaggregated and placed in culture. The phenotype of the primary renal cell lines was established by microscopy and immunohistochemistry. The 1x10(7) lethally irradiated tumor cells were transfected with plasmid deoxyribonucleic acid containing the human (h) granulocyte-macrophage colony-stimulating factor (GM-CSF) gene under control of a cytomegalovirus promoter using the gene gun. The hGM-CSF production was assayed by enzyme-linked immunosorbent assay in the cell culture media 24 hours after transfection. RESULTS: Of 12 tumor samples 8 grew rapidly to produce a mean of 1.8x10(8) cells after 4 to 5 passages in culture, which was sufficient to produce between 24 and 32 vaccines. Immunocytochemistry confirmed that all cultures were almost exclusively renal tumor cells. Gene gun mediated transfection of lethally irradiated tumor cells resulted in high levels of hGM-CSF production (mean 330 ng./10(6) cells per 24 hours). CONCLUSIONS: We have demonstrated the feasibility of producing cytokine secreting tumor cell vaccines from primary and metastatic human renal tumors, and plan to use this approach in phase I clinical trials of gene therapy for metastatic renal cell carcinoma.     

Hand assisted laparoscopic partial nephrectomy for peripheral and central lesions: a review of 30 consecutive cases

PURPOSE: We reviewed our first 30 hand assisted laparoscopic partial nephrectomies and compared the results of 8 centrally located vs 22 peripherally located tumors. MATERIALS AND METHODS: Tumors were classified by computerized tomography as central (less than 5 mm from the pelvicaliceal system or hilar vessels) or peripheral. The hand assisted technique consisted of mobilization and manual parenchymal compression without vascular occlusion or ureteral stent placement. Argon beam coagulation and a fibrin glue bandage were used for hemostasis. RESULTS: Mean tumor size was 2.6 cm (range 1.0 to 4.7). Mean operative time was 199 and 271 minutes, and estimated blood loss was 240 and 894 ml for peripheral and central lesions, respectively. No case required open conversion. The final diagnoses were renal cell carcinoma in 21 patients, angiomyolipoma in 4, benign or hemorrhagic cyst in 3 and oncocytoma in 2. Initial positive margins were found in 5 of 30 specimens (16.7%) (1 central and 4 peripheral) and all final resection margins were negative. Four central (50%) and 2 peripheral (9.1%) tumor cases required transfusion. Drain creatinine was elevated in 6 patients (20%) postoperatively, of whom 3 had a central and 3 had a peripheral lesion. All responded to conservative management except 1 patient (3.3%) who required stent placement. Postoperative bleeding in a central tumor case required transfusion of 4 units. There were no short-term local recurrences and 1 patient had an asynchronous tumor. CONCLUSIONS: Hand assisted laparoscopic partial nephrectomy is safe with excellent immediate cancer control. Careful dissection and frozen section analysis are mandatory to ensure a negative tumor margin. Blood loss and transfusion rates were higher in patients with centrally located tumors and renal hilar vascular control should be considered for central lesions.     

RENAL CELL CARCINOMA IN BOTH MOIETIES OF CROSSED FUSED ECTOPIA

Crossed fused renal ectopia is an uncommon condition and cases of malignant tumours in such anomalies are exceedingly rare. The first case where simultaneous involvement of both moieties and perirenal fat by tumour occurred is reported here. A comparison of the appearances of radiological investigations with the anatomical specimen is presented, as is a literature review of this topic.     

LAPAROSCOPIC REPAIR OF RENAL ARTERY ANEURYSM

PURPOSE: We describe technical considerations of the laparoscopic repair of a renal artery aneurysm. MATERIALS AND METHODS: A 57-year-old woman presented with a 3 cm. aneurysm of the distal left main renal artery at its bifurcation. Using a purely laparoscopic 4-port transperitoneal technique the aneurysm was completely mobilized from its location behind the renal vein. Its 3 feeding vessels were controlled individually with bulldog clamps. The aneurysm sac was bivalved and precisely trimmed to conform with the diameter of the main renal artery. Vascular reconstruction was performed with running freehand laparoscopic suturing and intracorporeal knot tying using 4-zero polypropylene suture. RESULTS: Warm ischemia time was 31 minutes, total operative time was 4.2 hours, blood loss was 100 cc and hospital stay was 2 days. Postoperatively renal scan showed improved perfusion and renal arteriography confirmed adequate repair of the aneurysm. CONCLUSIONS: Laparoscopic repair of the renal artery aneurysm is feasible. To our knowledge we present the initial clinical report of laparoscopic renovascular surgery in the literature.     

T CELLS ACTIVATED IN VITRO AS IMMUNOTHERAPY FOR RENAL CELL CARCINOMA: CHARACTERIZATION OF 2 EFFECTOR T-CELL POPULATIONS

PURPOSE: Effector T cell populations generated using 2 methods of in vitro activation are currently being tested in separate clinical trials as immunotherapy for patients with advanced cancer, including renal cell carcinoma. To determine the most appropriate method of activation for cancer immunotherapy in vitro antitumor activity of the 2 effector T-cell populations were compared. METHODS AND METHODS: The effector T-cell populations were generated concurrently by activation of peripheral blood mononuclear cells from patients with advanced renal cell carcinoma or other cancer using soluble anti-CD3 monoclonal antibody (3T cells) or anti-CD3 and anti-CD28 monoclonal antibodies immobilized on beads (3/28T cells). After 14-day culture the phenotype and functional activity of the cells were tested. RESULTS: Fold expansion of CD4(+) cells for 3T cultures was lower than for 3/28T cultures but expansion of CD8(+) cells was similar for both cultures. Expression of CD69 was higher on 3T cells. 3T and 3/28T cells exhibited similar ability to kill various human tumor cell lines. Although both effector T-cell populations produced Th1-type cytokines upon re-stimulation, 3T cells secreted a higher level of interferon-gamma and tumor necrosis factor-alpha compared with 3/28T cells. Intracellular cytokine analysis demonstrated that the percent of cells producing interferon-gamma was higher in CD4(+), CD8(+), CD25(+), CD69(+) and CD45RO(+) 3T cells compared with 3/28T cells. CONCLUSIONS: These data suggest that 3T cells may have increased efficacy as immunotherapy for patients with cancer due to higher levels of tumoricidal cytokine production than 3/28T cells.