Cachexia Index in Patients with Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: The cachexia index is a novel biomarker of cancer cachexia. This systematic review and meta-analysis aimed to evaluate the prognostic impact of cachexia index on prognosis after surgery for gastrointestinal cancer. METHODS: In August 2023, we systematically searched PubMed, the Cochrane Library, and Ovid for relevant studies on the oncological outcome after gastrointestinal cancer surgery and analyzed the findings from these studies for meta-analysis. RESULTS: Our systematic and meta-analysis review identified eight studies involving 1876 patients. The number of patients with low cachexia index accounted for 813 patients (43.3%). We found that low cachexia index was associated with worse overall survival (pooled HR, 2.30; 95% CI, 1.85-2.87; z = 7.49; P < 0.001) and disease/relapse/progression-free survival (pooled HR, 1.77; 95% CI, 1.45-2.18; z = 5.50; P < 0.001). CONCLUSION: Our meta-analysis showed that cachexia index was associated with oncological outcome after gastrointestinal cancer surgery. However, the limitations of this meta-analysis should be taken into consideration when interpreting the results.

The role of geriatric nutritional risk index as a predictor for postoperative outcomes in gastrointestinal emergencies.

BACKGROUND: The geriatric nutritional risk index (GNRI) is a simple nutritional and inflammatory marker for older adults. The aim of the present study was to investigate the usefulness of the GNRI in older adults who underwent emergency gastrointestinal surgery. METHODS: This study included 206 older adults who had undergone emergency gastrointestinal surgery. We retrospectively investigated the relationship between the GNRI and postoperative complications. Univariate and multivariate analyses were performed to evaluate risk factors for postoperative complications. We then evaluated the association between GNRI and clinical variables among older adults undergoing emergency gastrointestinal surgery. RESULTS: Postoperatively, all complications occurred in 89 (43%) older adults, infectious in 53 (26%), and non-infectious in 36 (17%). In the multivariate analysis, age (p = 0.016), GNRI (p = 0.012), operative severity (p = 0.003), and operation time (p = 0.003) were independent risk factors for all postoperative complications. While the GNRI (p = 0.049) was an independent risk factor for infectious complications, age (p = 0.035) and bleeding volume (p = 0.035) were independent risk factors for postoperative non-infectious complications. In the low GNRI group, age (p = 0.029), serum C-reactive protein levels (p < 0.001), and proportion of sarcopenia (p < 0.001) were significantly higher, and the length of hospital stay (p < 0.001) was significantly longer than that in the high GNRI group. In Spearman's rank correlation coefficient, the skeletal mass index and the GNRI had a positive correlation (r = 0.415 and p < 0.001). CONCLUSION: The GNRI may be a predictor of postoperative infectious complications in older adults after emergency gastrointestinal surgery, suggesting the usefulness of the GNRI as a nutritional marker and sarcopenia-related parameter. TRIAL REGISTRATION NUMBER: No. 22-16.

Association of Cholinesterase With Postoperative Pneumonia After Gastrectomy for Gastric Cancer.

INTRODUCTION: Cholinesterase is a classical marker that reflects nutritional and inflammatory status. The aim of the present study was to evaluate the association between serum cholinesterase levels and postoperative infectious complications in patients undergoing gastrectomy for gastric cancer. MATERIALS AND METHODS: This retrospective study comprised 108 patients who underwent gastrectomy for gastric cancer. We comprehensively investigated the association between clinicopathological variables and postoperative infectious complications after gastrectomy. Then patients were divided into the cholinesterase-high and -low groups to analyze their clinicopathological variables. Finally, we analyzed the types of infectious complications that were most associated with preoperative serum cholinesterase levels. RESULTS: Twenty-six patients (24%) developed postoperative infectious complications. Multivariate analysis revealed that serum cholinesterase levels (P = 0.026) and N stage (P = 0.009) were independent risk factors for postoperative infectious complications. In particular, the incidence of pneumonia (P = 0.001) was significantly higher in the cholinesterase-low group. Age (P = 0.023), cerebrovascular comorbidities (P = 0.006), serum cholinesterase levels (P = 0.013), and total gastrectomy (P = 0.017) were identified as independent risk factors for postoperative pneumonia. CONCLUSIONS: Preoperative serum cholinesterase levels were associated with postoperative pneumonia after gastrectomy for gastric cancer, suggesting the importance of preoperative nutritional assessment in gastric cancer surgery.

Short-term outcomes of colorectal cancer surgery in patients with dialysis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the effect of dialysis-dependent chronic kidney disease (CKD) on postoperative complications in colorectal cancer surgery. METHODS: In April 2023, we systematically searched PubMed, the Cochrane library, and Ovid for relevant studies on short-term outcomes of colorectal cancer surgery in patients with dialysis and analyzed the findings from these studies for meta-analysis. RESULTS: Our systematic and meta-analysis review identified seven studies involving 50713 patients. We showed that the dialysis group had higher rates of mortality (OR = 4.12, 95%CI: 2.75-6.20, P < 0.001), cardiac complications (OR = 2.45, 95%CI: 1.88-3.21, P < 0.001), and pneumonia (OR = 2.68, 95%CI: 1.83-3.93, P < 0.001). On the other hand, there were no differences in superficial/deep surgical site infection (SSI) (odds ratio [OR] = 1.17, 95%CI: 0.90-1.53, P = 0.230) and organ/space SSI (OR = 1.35, 95%CI: 1.00-1.82, P = 0.053) between the dialysis group and non-dialysis group. CONCLUSION: Our meta-analysis showed that dialysis-dependent CKD was associated with higher rates of mortality, cardiac complications, and pneumonia after colorectal cancer surgery. However, the limitations of this meta-analysis should be taken into consideration when interpreting the results.

Prognostic significance of osteosarcopenia in older adults with colorectal cancer.

Aim: Osteopenia and sarcopenia, features of the aging process, are recognized as major health problems in an aging society. This study investigated the prognostic impact of osteosarcopenia, the coexistence of osteopenia and sarcopenia, in older adults undergoing curative resection for colorectal cancer. Methods: We retrospectively reviewed data of older adults aged 65-98 y who had undergone curative resection for colorectal cancer. Osteopenia was evaluated by bone mineral density measurement in the midvertebral core of the 11th thoracic vertebra on preoperative computed tomography images. Sarcopenia was evaluated by measuring the skeletal muscle cross-sectional area at the third lumbar vertebra level. Osteosarcopenia was defined as the coexistence of osteopenia and sarcopenia. We explored the relationship of preoperative osteosarcopenia with the disease-free and overall survival after curative resection. Results: Among the 325 patients included, those with osteosarcopenia had significantly lower overall survival rates than those with osteopenia or sarcopenia alone (P < 0.01). In the multivariate analysis, male sex (P = 0.045), C-reactive protein-to-albumin ratio (P < 0.01), osteosarcopenia (P < 0.01), pathological T4 stage (P = 0.023), and pathological N1/N2 stage (P < 0.01) were independent predictors of disease-free survival, while age (P < 0.01), male sex (P = 0.049), C-reactive protein-to-albumin ratio (P < 0.01), osteosarcopenia (P < 0.01), pathological T4 stage (P = 0.036), pathological N1/N2 stage (P < 0.01), and carbohydrate antigen 19-9 (P = 0.041) were independent predictors of overall survival. Conclusion: Osteosarcopenia was a strong predictor of poor outcomes in older adults undergoing curative resection for colorectal cancer, suggesting an important role of osteosarcopenia in an aging society.

Prognostic Factors of Bone Metastases From Colorectal Cancer in the Era of Targeted Therapy.

BACKGROUND: Various prognostic factors have been reported for bone metastases from different primary tumor sites. However, bone metastases from colorectal cancer are very rare, and the prognostic factors have not been investigated in detail. OBJECTIVE: This study aimed to identify prognostic factors of bone metastases from colorectal cancer. DESIGN: This is a retrospective cohort study using data from a prospectively collected database. SETTINGS: This study was conducted at a single tertiary care cancer center in Japan. PATIENTS: Patients who developed bone metastases from colorectal cancer during the study period among all patients who received initial treatment for colorectal cancer at our hospital between 2005 and 2016 (n = 4538) were included. MAIN OUTCOME MEASURES: Overall survival after diagnosis of bone metastases from colorectal cancer was the main outcome measure. RESULTS: Ninety-four patients developed bone metastases during the study period. The 5-year overall survival rate was 11.0%. Multivariable analysis identified the following independent risk factors associated with poor prognosis: ≥70 years of age at diagnosis of bone metastases (HR, 2.48; 95% CI, 1.24-4.95; p < 0.01), curative surgery not performed as initial treatment (HR, 2.54; 95% CI, 1.24-5.19; p = 0.01), multiple bone metastases (HR, 2.44; 95% CI, 1.30-4.57; p < 0.01), albumin level <3.7 g/dL (HR, 3.80; 95% CI, 1.95-7.39; p < 0.01), CEA ≥30 ng/mL (HR, 1.94; 95% CI, 1.09-3.46; p = 0.02), and less than 3 chemotherapy options remaining at diagnosis of bone metastases (HR, 2.83; 95% CI, 1.51-5.30; p < 0.01). The median survival times for patients with 0-2, 3, and 4-6 risk factors were 25.0, 8.8, and 4.3 months, respectively. LIMITATIONS: The main limitation is the single-center, retrospective design of this study. CONCLUSIONS: Our results may facilitate multidisciplinary decision-making in patients with bone metastases from colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B930 . FACTORES PRONSTICOS DE LAS METSTASIS SEAS DEL CNCER COLORRECTAL EN LA ERA DE LA TERAPIA DIRIGIDA: ANTECEDENTES:Se han reportado varios factores pronósticos para las metástasis óseas de diferentes sitios de tumores primarios. Sin embargo, las metástasis óseas del cáncer colorrectal son muy raras y los factores pronósticos no se han investigado en detalle.OBJETIVO:Identificar los factores pronósticos de las metástasis óseas del cáncer colorrectal.DISEÑO:Estudio de cohorte retrospectivo utilizando datos de una base de datos recolectada prospectivamente.ENTORNO CLINICO:Un solo centro oncológico de atención terciaria en Japón.PACIENTES:Se seleccionaron pacientes que desarrollaron metástasis óseas de cáncer colorrectal durante el período de estudio entre todos los pacientes que recibieron tratamiento inicial para el cáncer colorrectal en nuestro hospital entre 2005 y 2016 (n = 4538).MEDIDA DE RESULTADO PRINCIPAL:Supervivencia general después del diagnóstico de metástasis óseas por cáncer colorrectal.RESULTADOS:Noventa y cuatro pacientes desarrollaron metástasis óseas, lo que representa el 2,0% de todos los pacientes con cáncer colorrectal que comenzaron el tratamiento durante el período de estudio. La tasa de supervivencia global a 5 años fue del 11,0 %. El análisis multivariable identificó los siguientes factores de riesgo independientes asociados con mal pronóstico: edad ≥70 años al momento del diagnóstico de metástasis óseas (hazard ratio 2,48, CI del 95 % 1,24-4,95, p < 0,01), cirugía curativa no realizada como tratamiento inicial (hazard ratio 2,54, CI 95 % 1,24-5,19, p = 0,01), metástasis óseas múltiples (hazard ratio 2,44, CI del 95 % 1,30-4,57, p < 0,01), nivel de albúmina <3,7 g/dL (hazard ratio 3,80, CI del 95 % 1,95 -7,39, p < 0,01), antígeno carcinoembrionario ≥30 ng/mL (hazard ratio 1,94, CI del 95 % 1,09-3,46, p = 0,02) y menos de 3 opciones de quimioterapia restantes al momento del diagnóstico de metástasis óseas (hazard ratio 2,83, 95 % CI 1,51-5,30, p < 0,01). La mediana de los tiempos de supervivencia para los pacientes con 0-2, 3 y 4-6 factores de riesgo fue de 25,0, 8,8 y 4,3 meses, respectivamente.LIMITACIONES:Diseño retrospectivo de un solo centro.CONCLUSIÓN:Nuestros resultados pueden facilitar la toma de decisiones multidisciplinares en pacientes con metástasis óseas de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B930 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

The influence of serum cholinesterase levels and sarcopenia on postoperative infectious complications in colorectal cancer surgery.

PURPOSE: Cholinesterase is a nutritional marker associated with sarcopenia. The present study evaluated the relationship between cholinesterase and postoperative infectious complications in patients undergoing colorectal resection for colorectal cancer. METHODS: The study involved 231 patients who had undergone colorectal resection for colorectal cancer. We retrospectively investigated the relationship between preoperative serum cholinesterase levels and postoperative infectious complications. Univariate and multivariate analyses were performed to identify independent risk factors for postoperative infectious complications. We then performed stratified analyses to assess the interaction between cholinesterase and clinical variables to predict postoperative infectious complications. RESULTS: In the multivariate analysis, the body mass index (P = 0.010), serum cholinesterase levels (P = 0.005), sarcopenia (P = 0.003) and blood loss (P < 0.001) were independent risk factors for postoperative infectious complications. In stratified analyses, the association between serum cholinesterase levels and postoperative infectious complications differed by the sarcopenia status (Pinteraction = 0.006). CONCLUSION: Preoperative serum cholinesterase levels may be useful for predicting postoperative infectious complications in colorectal cancer surgery. The association differs by the sarcopenia status, suggesting a potential interaction between nutritional markers and sarcopenia.

Evaluation of the Outcome of Local Surgery for Stomal Prolapse.

We reviewed the results of local surgical treatment of stoma prolapse, a long-term complication of stoma construction. Fifteen patients treated for stomal prolapse between 2009 and 2020 at the authors' and affiliated hospitals were included in this study. The treatment comprised local laparotomic stomal reconstruction (LLSR) in nine patients and stapling repair (SR) in six. We compared and evaluated the clinical and surgical information and postoperative complications. Operation time was significantly shorter in the SR group than in the LLSR group: 20 and 53 min, respectively (p = 0.036). The duration of postoperative hospitalization was shorter in the SR group than in the LLSR group: 5.5 and 8 days, respectively; the difference was not significant (p = 0.088). No short-term complications were found in either group. Regarding long-term, postoperative complications, parastomal hernias developed after 2.5 years in one patient in the LLSR group and after 6 months in one patient in the SR group; both patients had histories of parastomal hernia surgery and had relatively high body mass indices. Local surgery for stomal prolapse was minimally invasive and performed safely. In patients with a history of surgery for parastomal hernia, attention must be paid to the potential of parastomal hernia developing as a postoperative complication.

Endoscopic submucosal dissection for the diagnosis and therapy of pedunculated gastric cancer with prolapse into the duodenal bulb: A case report.

INTRODUCTION: Preoperative diagnosis of gastric cancer invasion is not always sufficiently accurate. Diagnostic endoscopic submucosal dissection (ESD) can be performed for the purpose of accurate decision making and to avoid partial treatment vs aggressive over-treatment. We present a patient with the gastric cancer with indeterminate pre-operative diagnosis for depth of the invasion. CASE PRESENTATION: A 70-year-old man presented at our hospital because both anti-Helicobacter pylori (Hp) IGG antibody and serum pepsinogen (PG) levels were classified as positive. Upper gastrointestinal endoscopy was performed, and a large (3.5 cm) pedunculated polyp-shaped gastric cancer with prolapse into the duodenal bulb was found. [fluorine-18]-fluorodeoxy-glucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) imaging showed high 18F-FDG uptake, suggesting the possibility of advanced gastric cancer. Since the pre-operative diagnosis of the cancer invasion was indeterminable, diagnostic ESD was performed. The pathohistological diagnosis was early gastric cancer (33 × 35 × 20 mm, well differentiated tubular adenocarcinoma [tub1], pT1a[M], ly[--], v[--], UL[--], pHM0, pVM0) according to the Japanese classification of gastric carcinoma. DISCUSSION AND CONCLUSION: It was reported that ESD for early gastric cancers that met the expanded criteria was acceptable and should be the standard treatment instead of gastrectomy. The expanded criteria included cancer confined to the mucosa (cT1a), a single primary intestinal-type gastric adenocarcinoma, an ulcer-negative lesion of any size. We reported a case of pedunculated gastric cancer with prolapse into the duodenal bulb that could be treated by ESD. The present case is a good example of diagnostic ESD being used to minimize the damage of gastric cancer treatment.

Hepatic Angiosarcoma Associated with Esophageal Variceal Hemorrhage.

Primary hepatic angiosarcoma is a very rare malignancy with a poor prognosis. Because patients present with no specific symptoms, the cancer can grow undetected and most cases are diagnosed too late for resection. We present the case of a 78-year-old Japanese man admitted to our hospital with massive hematemesis and melena. A total gastrectomy had previously been performed on the patient to treat gastric cancer. Endoscopic injection sclerotherapy was performed to control the bleeding from varices over the anastomosis. Computed tomography revealed the presence of multiple atypical liver nodules in the enhanced image. Histological diagnosis of hepatic angiosarcoma was obtained by percutaneous ultrasound-guided liver biopsy. To our knowledge, this is the first report of a patient with hepatic angiosarcoma and acute variceal hemorrhage.

Improvement of QOL and Immunological Function With Lentinula Edodes Mycelia in Patients Undergoing Cancer Immunotherapy: An Open Pilot Study.

Context • Combined treatment with an extract of Lentinula edodes mycelia (LEM) and chemotherapy has been reported to improve quality of life (QOL) and immunological function in cancer patients. However, those effects have not been elucidated for patients receiving cancer immunotherapy. Objective • The present study intended to investigate the effects of oral LEM on QOL and immunological function in cancer patients receiving immunotherapy. Design • The research team designed an open-label, single-armed pilot study. Setting • The study took place at Bio-Thera Clinic, a facility associated with Tokyo Women's Medical University in Tokyo, Japan. Participants • The participants were 10 cancer patients undergoing cancer immunotherapy at Bio-Thera Clinic. Intervention • The participants received either dendritic cell (DC)-based cancer vaccine therapy or CD3-activated T-lymphocyte (CAT) therapy as immunotherapy. They received the immunotherapy only for the first 4 wk of the study, and then oral LEM (1800 mg/d) was added for the next 4 wk. Outcome Measures • Preintervention and at 4 and 8 wk after the start of the study, participants completed a QOL survey, and immunological parameters were measured. Results • Participants' QOL symptom scores increased (ie, worsened) by 5.1 ± 1.7 during the first 4 wk of treatment when they were receiving immunotherapy only, but it decreased (ie, improved) by -2.5 ± 1.6 during the next 4 wk when the immunotherapy was combined with the LEM, P < .05. The measurement of the immunological parameters during the 4 wk of immunotherapy combined with LEM showed that the amount of interferon-γ (IFN-γ) produced in the peripheral blood tended to increase as compared with that during the first 4 wk of immunotherapy only. The rise in IFN-γ was correlated with changes in several regulatory T cells (Tregs) (ie, forkhead box P3 [FOXP3]+/cluster of differentiation 4 [CD4]+ and transforming growth factor beta [TGF-ß]). Conclusions • The findings suggest that a combined treatment of LEM and immunotherapy might improve QOL and immunological function in cancer patients.

Fever-range whole-body heat treatment stimulates antigen-specific T-cell responses in humans.

Increase in body temperature has been thought to play an important role in the regulation of immune responses, although its precise mechanisms are still under investigation. Here, we examined the effects of physiologically relevant thermal stress on the cytokine production from human peripheral T cells. Volunteers were heated using a whole-body hyperthermia device, the rectal temperature was maintained above 38.5 °C for more than 60 min, and peripheral blood mononuclear cells (PBMCs) were obtained before and after the treatment. When T cells were stimulated with anti-CD3/CD28 antibodies, marked increases in the production of interferon-γ (IFN-γ) and interleukin-2 were observed in PBMCs prepared immediately after and 24h after the treatment. Similarly, enhanced production of IFN-γ in response to the tuberculin purified protein derivative or antigenic viral peptides was also observed immediately after and 24h after the treatment. Fluorescence photo-bleaching analyses showed heat-induced increase of membrane fluidity in T cells, which probably enables them to induce rapid and efficient cluster formation of molecules involved in antigen recognition and signal transduction for T-cell stimulation. We concluded that physiologically relevant thermal stress could efficiently modify T-cell responsiveness to various stimuli, including enhanced responses to specific antigens.

[Evaluation of quality of life and immune function in cancer patients receiving combined immunotherapy and oral administration of lentinula edodes mycelia extract].

UNLABELLED: Lentinula edodes mycelia extract(LEM) may mitigate the immunosuppression caused by regulatory T cells(Tregs), and it is therefore expected that LEM will be useful with cancer immunotherapy. In this study, we evaluated the quality of life (QOL) and immune function in cancer patients receiving a combination of immunotherapy and oral administration of LEM. METHODS: Ten patients who had received cancer immunotherapy were enrolled. They received cancer immunotherapy alone for the first 4 weeks, and were then administered LEM (1,800 mg/day) with cancer immunotherapy for the next 4 weeks. QOL scores and immune parameters were evaluated at weeks 0, 4, and 8. RESULTS: The total score for QOL was improved during the period with LEM administration compared to the period with immunotherapy alone. Interferon (IFN)-γ secretion from peripheral blood cells was increased during the period with LEM administration. The change in IFN-γ secretion in the LEM administration period possibly correlated with changes in the Treg population. CONCLUSION: Oral administration of LEM may improve QOL and immunity in patients receiving cancer immunotherapy.

Separation methods of T cells, natural killer, and dendritic cells from peripheral blood of cancer patients using interleukin-2 and functional analysis of natural killer cells after separation.

We aimed to induce three different immune cell subsets from a single blood sample from cancer patients to target different biological characters of cancer cells. In the presence of 6000 IU/ml IL-2, natural killer (NK) cells adhere to plastic. By using this ability, we could separate dendritic cells, T cells, and NK cells from peripheral blood mononuclear cells. The cultured NK cells demonstrated higher nonspecific cytotoxicity against tumor cell lines than did the T cells. Furthermore, adherent NK cells demonstrated higher cytotoxicity than nonadherent NK cells, although there was no difference between adherent and nonadherent NK cells in natural cytotoxicity receptors (NKp30, NKp44, NKp46) and NKG2D expression. With these results, we confirmed that we could induce dendritic cell, T cell, and higher cytotoxic NK cells from a single blood draw, and this methodology facilitates to the use of these cells for clinical grade conditions.

[Combined cell therapy by using dendritic cells, T-cells and NK cells to human polymorphic cancer].

Although an expression of MHC molecules and tumor associated antigens of the cancer are not uniform, we consider that the cancer immunotherapy for some specific tumor antigens cannot correspond to molecular biological varieties of the cancer. Consequently, we tried to develop a method to separate dendritic cells (DC), T-cells and natural killer (NK) cells from peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers. PBMC were separated by centrifugation on Ficoll-Hypaque gradients from peripheral blood obtained from healthy volunteers. After separating these cells, the cells were put into a plastic flask, and we isolated monocyte fraction (dendritic cells), NK cell fraction and T-cell fraction one after another by the difference in its ability to adhere to a plastic flask. We analyzed surface markers and activation states of these groups. We could induce dendritic cells from the monocyte fraction, CD3-activated T-cells (CAT) from the T-cell fraction, and adherent lymphokine activated-killer cells (A-LAK) from the NK cell fraction. Therefore, we indicate the possibility of the combined cell therapy with three immune cell fractions in which we can induce from the same blood at once.

[Preparation of NK-enriched LAK cells--their potential cytotoxic and ADCC activities].

We examined several culture methods to induce proliferation of natural killer (NK) cells from peripheral blood mononuclear cells (PBMC). In the presence of IL-2, a remarkable proliferation of NK cells was observed when PBMC were co-cultured with MMC-treated K562, which is known as a highly sensitive in vitro target cell for the NK assay. Addition of OK-432 or TNF-alpha and IL-1 beta also induced marked NK proliferation in a dose dependent manner. These NK-enriched lymphokine activated killer (LAK) cells showed highly cytotoxic activities against various MHC class I positive or negative tumor cells. They also showed potent ADCC activities against Herceptin-coated SK-BR-3, a HER2/neu positive breast cancer cell line. These results indicated that NK-enriched LAK cells are potent effector cells, and suggested novel therapeutic strategies for nonspecific immunotherapy as well as target immunotherapy in combination with anticancer antibodies, such as Herceptin.

[Phenotypical analysis of effector cells on nonspecific cancer cell therapy].

In the present study, we examined the contributions of lymphocyte subpopulations in lymphokine activated killer (LAK) activity. LAK cells prepared from peripheral blood mononuclear cells (PBMC) of healthy donors showed highly cytotoxic activities against target tumor cells. When CD16 and CD56 positive cells in LAK cells were depleted by magnetic cell sorting, their cytotoxic activities were dramatically decreased. In contrast, little change was observed by the depletion of CD3 positive cells, suggesting that CD16 and/or CD56 positive populations, but not CD3 positive populations, including natural killer (NK) cells are the major cell types involved in LAK activity. Indeed, NK-enriched LAK cells prepared by culturing PBMC with IL-2 and OK-432 showed a more potent LAK activity than conventional LAK cells and CD3-activated T cells. These results suggest that selective expansion and activation of CD16 and CD56 positive cells in LAK cells is a useful strategies to improve their anti-tumor potential in nonspecific immunotherapy, and possibly in combination therapy with other target immunotherapies as well.