Clinicopathologic study of stage I adenosquamous carcinoma of the lung.

OBJECTIVE: Adenosquamous carcinoma of the lung is a characteristic tumor that has both adenocarcinoma and squamous cell carcinoma components. Adenosquamous carcinoma is reported to have an aggressive clinical course, but its clinicopathological features and prognosis are unclear in the early stage. METHODS: Patients who underwent surgical resection for pathological stage I non-small cell lung cancer between April 2009 and December 2014 were retrospectively reviewed. Preoperative and postoperative data, histologic characteristics and outcomes of patients with adenosquamous carcinoma (n = 40) were compared to adenocarcinoma (n = 598) and squamous cell carcinoma (n = 131) patients. Factors affecting prognosis, particularly on recurrence, were assessed via Cox regression analyses. RESULTS: Patients with adenosquamous carcinoma had a worse prognosis than did patients with adenocarcinoma and squamous cell carcinoma in terms of 5 year overall (66.7%) and recurrence-free survival rates (44.9%), as well as a significantly higher recurrence rate (13/40 patients, 32.5%). Multivariable Cox regression analysis for recurrence-free survival rates revealed that the histology of adenosquamous carcinoma was an independent factor for recurrence (hazard ratio: 2.473, 95% confidence interval: 1.328-3.367; P = 0.0004). High serum carcinoembryonic antigen levels (hazard ratio: 5.962) and vascular invasion (hazard ratio: 4.899) were identified as risk factors for recurrence, and patients with adenosquamous carcinoma tended to have distant relapses, such as in the brain. CONCLUSIONS: Early-stage adenosquamous carcinoma of the lung is a histological type associated with severe prognosis and postoperative recurrence, often in distant sites, in approximately one-third of cases. High serum carcinoembryonic antigen levels and vascular invasion might be risk factors of recurrence.

Bronchial mucosal ablation for bronchial stump closure in right pneumonectomy: a case report.

BACKGROUND: Bronchial fistula is a severe complication of pneumonectomy with a high mortality rate. We previously reported a technique for bronchial closure to prevent bronchial fistula in a canine model. We described that mucosal ablation could result in primary wound healing and involve mucosal tight adhesions histologically. In this paper, the pathologic findings of one patient, who underwent autopsy 4 years after surgery, were reviewed. CASE PRESENTATION: A 70-year-old Japanese man was diagnosed with malignant pleural mesothelioma and underwent right extra-pleural pneumonectomy. The right main bronchus was cut using a scalpel. When closing the bronchial stump, the bronchial mucosa was ablated by electric cautery and sutured manually using 3-0 absorbable sutures. The bronchial fistula was not found after pneumonectomy. Four years after surgery, the patient died of recurrent malignant pleural mesothelioma and underwent autopsy. Macroscopic evaluation showed tight adhesions and white scars on the bronchial stump. Microscopic findings showed few inflammatory cells and α-smooth muscle actin (α-SMA)-positive cells. CONCLUSIONS: The results from this case suggested that bronchial mucosal ablation leads to robust agglutination of bronchial stump over years. This technique is not only simple but also reliable to prevent bronchial fistula.

Gait Reacquisition Rate, Home Outcome Rate, and Gait Prognosis in Patients with Femoral Neck Fractures and Mental Illness - A Multicenter Study.

OBJECTIVE: A total of 183 patients admitted to five hospitals for proximal femoral fractures and psychiatric disorders were examined to determine whether their physical function could be improved by rehabilitation and to identify factors that affected home discharge. METHODS: We conducted surveys to collect data regarding patients' age, sex, type of mental illness, location at time of injury, complications, Charlson Comorbidity Index, Global Assessment of Functioning scale scores, surgical technique, time from surgery to the start of rehabilitation at the target hospital, rehabilitation duration, results of cognitive function tests (e.g., the Mini Mental Status Examination), walking ability before the injury, final walking ability, functional independence measure (FIM) of the patient's activities of daily living at the start and end of treatments, and discharge destinations. RESULTS: The motor function index showed a significant improvement from an average of 36.0 points at admission to an average of 53.0 points at discharge. Overall, 47.9% of patients who were able to walk before injury could regain gait ability. The discharge rate to the patient's home was 15.8%. CONCLUSIONS: The gait reacquisition rate for patients with femoral neck fractures and mental illness admitted to a psychiatric ward was 47.9%, which was lower than that reported in previous studies, but higher than that for dementia patients. Binomial logistic regression analysis identified the following predictive items for home discharge: whether the fracture occurred at home, FIM cognition item scores at admission, and total and motor item scores at discharge. The derived equation had a high hit rate of 80.9%.

Investigation of surgical technique for bronchial stump closure after lobectomy in animal model.

OBJECTIVE: Bronchial fistulae following lung surgery are associated with high mortality. We examined the histological effects of mucosal ablation as a technique for closing bronchial stumps to prevent bronchial fistulae in an animal model. METHODS: Left lower lobectomy was performed in beagles under general anesthesia. The bronchial stumps were closed using one of the following four methods: (A) manual suturing using 3-0 absorbable sutures, (B) ablation of bronchial mucosa with electric cautery and manual sutures, (C) stapling and reinforcement with manual sutures, or (D) ablation and stapling followed by reinforcement with manual sutures. Bronchial stumps were histologically evaluated on postoperative day 14. RESULTS: No bronchial fistulae were noted in the animals during the observation period. Histologically, there were no adhesions between the bronchial mucosae at the suture and staple lesions in groups A and C. The bronchial mucosae were adherent at the ablation sites in groups B and D. Inflammatory cells, myofibroblasts, and neovascular vessels were abundant around the ablated lesions. CONCLUSIONS: Bronchial mucosal ablation may play a key role in mucosal adhesion and tight union of the bronchial stump.

Reassessment of Right Middle Lobe Lung Cancer: Comparison of Segments 4 and 5 Tumors.

BACKGROUND: The purpose of this study was to elucidate the clinical behavior of right middle lobe lung cancer, with focus on the tumor location. METHODS: We reviewed retrospectively 711 patients who underwent lobectomy or bilobectomy for clinical stage I non-small cell lung cancer (upper lobe, 346; middle lobe, 82; lower lobe, 283). Factors affecting survival were assessed by log rank tests and Cox regression analyses. RESULTS: The prognosis of patients with segment 5 tumors (n = 39) was significantly worse than that of patients with segment 4 tumors (n = 43; 5-year overall survival rates, 69.8% versus 87.6%, p = 0.040; and 5-year recurrence-free survival rates, 58.4% versus 73.0%, p = 0.029). Segment 5 tumors were an independent factor for poor prognosis in multivariable Cox regression analysis, and tended to cause more pathologic mediastinal lymph node metastases than segment 4 tumors (12.8% versus 2.3%, p = 0.097). Compared with tumors in the other lobes, patients with segment 4 tumors demonstrated no significant difference in prognosis; however, patients with segment 5 tumors demonstrated a significantly and outstandingly worse prognosis than patients with other lobe tumors (5-year overall survival rates, 69.8% versus 82.2%, p = 0.020; and 5-year recurrence-free survival rates, 58.4% versus 71.4%, p = 0.0071). CONCLUSIONS: Patients with segment 5 tumors had a worse prognosis than patients with segment 4 and other lobe tumors. We speculate that is because segment 5 tumors cause more metastases to the mediastinal lymph nodes. Tumor location was an important prognostic factor for patients with right middle lobe lung cancer.

Splenic hamartoma associated with thrombocytopenia: A case report.

INTRODUCTION: Hamartomas are rare, benign tumors of the spleen. Few cases of splenic hamartomas associated with thrombocytopenia have been reported. PRESENTATION OF CASE: An asymptomatic 64-year-old man with myelodysplastic syndrome was found to have a splenic tumor. Laboratory tests were significant for thrombocytopenia, with a platelet count of 7.8×104/µL. Ultrasonography showed splenomegaly (10.8×6.6cm), and a hypoechoic splenic mass (8.0×7.0cm). Color doppler ultrasound revealed blood flow within the mass, and the mass density was homogeneous on abdominal computed tomography (CT). Contrast-enhanced CT showed heterogeneous enhancement of the splenic mass during the arterial phase. Positron emission tomography (PET)-CT showed no significant fludeoxyglucose (FDG) accumulation within the mass. The differential diagnosis included splenic hamartoma, splenic hemangioma, splenomegaly associated with extramedullary hematopoiesis, and malignant tumor, including solitary splenic metastasis. A laparoscopic splenectomy was performed due to the possibility of malignancy, the presence of thrombocytopenia, and the risk of splenic rupture. The resected specimen showed a localized, well-demarcated, 8.0×7.0cm splenic mass. Histological examination revealed abnormal red pulp proliferation and the absence of normal splenic structures. The patient's post-operative course was uneventful. His platelet count improved on post-operative day 1 and he was discharged on post-operative day 9. He remained in good health with a normal platelet count one month after surgery. DISCUSSION: Making definitive preoperative diagnosis is difficult in splenic hamartomas. Surgery is necessary for diagnosis when malignancy cannot be ruled out. CONCLUSIONS: Surgery may also improve symptoms of hypersplenism, including thrombocytopenia.

Pulmonary enteric adenocarcinoma.

A 70-year-old man was referred to our department due to abnormal shadows on a chest radiograph. Computed tomography of the chest revealed a 3-cm nodule in the right middle lung lobe, and bronchoscopy revealed adenocarcinoma cells with EGFR mutations. A lung resection was performed. Histological analysis revealed tumors comprising tall columnar cells that were similar to an adenocarcinoma of the sigmoid colon that had been resected 13 years previously. Metastatic colorectal carcinoma was initially considered, but immunohistochemical staining indicated pulmonary enteric adenocarcinoma. Pulmonary enteric adenocarcinoma was first described in 1991, and about 30 cases have since been described in the English literature. However, its concept and etiology are not clear. It is important to distinguish pulmonary enteric adenocarcinoma from metastatic colorectal carcinoma because of obvious differences in therapeutic strategies and prognosis, especially with a past history of colorectal carcinoma. Immunohistochemical and gene mutation analyses seemed to be helpful.

A case of thoracic esophageal cancer with an unusual type of duplicated inferior vena cava.

We describe here a thoracic esophageal cancer with an unusual type of duplicated inferior vena cava. A 58-year-old man was referred to our hospital because a tumor in his lower esophagus had been identified by endoscopy and radiology. Computed tomography scans showed an unusual type of duplicated inferior vena cava characterized by both common iliac veins flowing back into the left-sided inferior vena cava, which drained into the azygos vein, whereas the right-sided one had no drainage. Esophagectomy was performed 3 weeks later after preoperative chemotherapy. Because the patient could have developed thrombosis of the left-sided inferior vena cava and severe hypotension caused by decreased venous return to the heart if the azygos vein had been severed, the azygos vein was preserved. Thus, when performing surgery for thoracic esophageal cancer, the surgeon should check for a duplicated inferior vena cava and preserve the azygos vein if necessary.

Non-small-cell lung cancer prognosis using carcinoembryonic antigen levels in pleural lavage fluid.

OBJECTIVES: The study aimed to evaluate the prognostic significance of carcinoembryonic antigen levels in pleural lavage fluid (p-CEA) in patients with completely resected non-small-cell lung cancer (NSCLC). METHODS: We examined 72 patients who underwent curative surgical resections. Pleural lavage fluid was collected at thoracotomy before lung resection. Pleural lavage cytology and p-CEA were determined. The relationships between p-CEA and clinicopathological factors were analysed. RESULTS: Four patients (5.6%) had positive pleural lavage cytologies. The median p-CEA was 65.2 ng/g protein (range, 0-7331.7). p-CEA was significantly correlated with pleural invasion and CEA levels in serum (s-CEA). Receiver operating characteristic curve analysis identified an optimal cut-off of 38 ng/g protein for p-CEA for predicting recurrence [area under the curve (AUC) = 0.669; sensitivity = 91.7%; specificity = 43.7%; 95% confidence interval (CI) = 0.541-0.796; P = 0.020], whereas this could not be identified for s-CEA (AUC = 0.535; 95% CI = 0.392-0.678; P = 0.629). With a mean follow-up period of 57.5 months, 5-year disease-free survival (DFS) rates were 86.5% for p-CEA ≤ 38 ng/g protein and 47.7% for p-CEA >38 ng/g protein (P = 0.0013). Even for patients with Stage I lung cancer, 5-year DFS rates were 88.2 and 53.8%, respectively (P = 0.017). Multivariate Cox analysis revealed that p-CEA was a significant independent factor for DFS and overall survival. CONCLUSIONS: Intraoperative p-CEA may be a more powerful prognostic determinant than s-CEA for patients with NSCLC.

Prognostic impact of the primary tumor location based on the hilar structures in non-small cell lung cancer with mediastinal lymph node metastasis.

The status of mediastinal lymph node metastasis is one of the main factors determining the treatment strategy for non-small cell lung cancer (NSCLC), but the primary tumor location is not considered crucial in the tumor-node-metastasis (TMN) classification at present. The aim of this study was to estimate the prognostic value of the primary tumor location on the basis of the hilar structures in NSCLC with mediastinal lymph node metastasis. We retrospectively reviewed the cases of 337 consecutive patients who underwent surgical resection for NSCLC between 1995 and 2004, divided the pN2 NSCLC cases (n=40) into central- and peripheral-type tumors according to the distance of the primary tumor from the first branch of the extrapulmonary bronchus, and compared the surgical outcomes between these tumor groups. Eighteen and twenty-two cases were classified as central- and peripheral-type tumors, respectively. The 5-year survival rate was significantly better for patients with central-type tumors than peripheral-type tumors (51.5% vs. 21.2%, P=0.034). The location-specific prognostic tendency was noted irrespective of the presence (n=13) or absence of skip metastasis. In a multivariate Cox analysis of the N2 NSCLC cases, the primary tumor location was a significant (P=0.026) prognostic factor for overall survival. In conclusion, evaluation of the primary tumor location based on the hilar structures is useful to predict the prognosis in N2 NSCLC.

Fibrinogen/thrombin-based collagen fleece (TachoComb(R)) promotes regeneration in pulmonary arterial injury.

OBJECTIVES: To repair unexpected damage of the pulmonary artery (PA) during thoracic surgery, fibrinogen/thrombin-based collagen fleece (TachoComb(®) [TC]) can be applied as a haemostatic material. The progression of vessel restoration with TC has not been elucidated. In this study, we investigate details of the healing process with TC after PA injury using a canine model. METHODS: Left thoracotomy was performed on female beagles under general anaesthesia. PA injury was induced and repaired using TC. Repair sites were histologically evaluated 2, 4 and 8 weeks after surgery (n = 3 in each group). RESULTS: Haemostasis of PA injury was achieved promptly after TC application. After surgery, no bleeding was found in the thoracic cavity, and no repair sites revealed stenosis, thrombi or false aneurism formation. Two weeks after surgery, inflammatory cells had infiltrated around the vascular defect, and vascular endothelium had regenerated on the innermost surface of TC applied to the defect. At Week 4, elastic and smooth muscle fibres had begun to extend into the defect between the endothelial layer and collagen fleece. By Week 8, elastic fibres and smooth muscle had completely regenerated in the medial layer. The adventitial layer had also fully regenerated. CONCLUSIONS: Haemostasis of injured PA using TC was safe and reliable. TC provided a mechanical scaffold on which vascular regeneration occurred. Three layers reconstructed in the PA defect were identical to those in normal structures.

Radical hybrid video-assisted thoracic segmentectomy: long-term results of minimally invasive anatomical sublobar resection for treating lung cancer.

We analysed the results of radical segmentectomy achieved through a hybrid video-assisted thoracic surgery (VATS) approach that used both direct vision and television monitor visualization at a median follow-up of over 5 years. Between April 2004 and October 2010, 102 consecutive patients able to tolerate lobectomy to treat clinical T1N0M0 non-small cell lung cancer (NSCLC) underwent hybrid VATS segmentectomy in which we used electrocautery without a stapler to divide the intersegmental plane detected by selective jet ventilation in addition to the path of the intersegmental veins. Curative resection was achieved in all patients. The median surgical duration and blood loss during the surgery were 129 min (range, 60-275 min) and 50 ml (range, 10-350 ml), respectively. The complication rate was 9.8% (10/102) with the most frequent being prolonged air leak, and there was no case of in-hospital death or 30-day mortality post procedure. Five and seven patients developed locoregional and distant recurrences, respectively. The overall and disease-free 5-year survival rates were 89.8% and 84.7%, respectively. Radical hybrid VATS segmentectomy including atypical resection of (sub)segments is a useful option for clinical stage-I NSCLC. The exact identification of anatomical intersegmental plane followed by dissection using electrocautery is critical from oncological and functional perspectives.

Difference in prognostic significance of maximum standardized uptake value on [18F]-fluoro-2-deoxyglucose positron emission tomography between adenocarcinoma and squamous cell carcinoma of the lung.

OBJECTIVE: This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. METHODS: We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n = 132) or squamous cell carcinoma (n = 44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. RESULTS: The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P< 0.001). Analyses of receiver operating characteristic curves identified an optimal maximum standardized uptake value cutoff value to predict recurrence of 3.7 for adenocarcinoma, whereas such an indicator could not be identified for squamous cell carcinoma. Although 2-year disease-free survival rates were 70.2% for maximum standardized uptake value ≤6.95 and 59.3% for maximum standardized uptake value >6.95 (P = 0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P < 0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P < 0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P = 0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P = 0.001). CONCLUSIONS: Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung.

Induction of gamma delta T cells using zoledronate plus interleukin-2 in patients with metastatic cancer.

A loss of human leukocyte antigen (HLA) expression in clinical tumors is one of their escape mechanisms from immune attack by HLA-restricted effector cells. In this study, the induction of HLA-unrestricted effector cells, gamma delta T cells, using zoledronate (ZOL) and interleukin (IL)-2 in vitro was investigated in patients with metastatic cancer. Peripheral blood mononuclear cells (PBMCs) from 10 cancer patients (8 colorectal and 2 esophageal) with multiple metastases and ascites lymphocytes from 3 cancer patients (1 gastric and 2 colorectal) were stimulated with varied concentrations of ZOL plus 100 U/ml IL-2 for 48 hr followed by culturing with IL-2 alone for 12 days. Lymphocyte proliferative responses were determined using 3H-TdR uptakes and interferon (IFN)-gamma production was evaluated using enzyme-linked immunosorbent assay. Surface phenotyping was performed using flow cytometry. Cytotoxic activity of effector cells was determined using 51Cr-releasing assay. It was found that proliferative responses of PBMCs were significantly stimulated with ZOL plus IL-2 when compared with IL-2 alone, showing 200 to 500-fold expansions for 2 weeks, although ZOL alone induced no response. The optimal concentration of ZOL was 1-5 microM. Ascites lymphocytes could also be stimulated with ZOL plus IL-2. The proliferative responses were remarkable in patients whose PBMCs could produce high levels of IFN-gamma during an initial 48-hr stimulation using ZOL plus IL-2. Removal of an adherent cell fraction before the induction augmented the proliferative responses in patients who otherwise had low-grade proliferative responses. Generated cells comprising approximately 90 or 20% in PBMCs from healthy donors or cancer patients, respectively, expressed gamma delta-type T-cell receptor. Gamma delta T cells showed high cytotoxic activity against CD166-positive TE12 and TE13 cancer cells but not against CD166-negative MKN45 cells. The cytotoxic activity against TE13 cells was augmented when target cells were pre-treated overnight with ZOL. These results suggest that ZOL in the presence of IL-2 can efficiently stimulate the proliferation of gamma delta T cells, which have cytotoxic properties against cancer cells. The use of zoledronate-activated killer (ZAK) cells should be encouraged in possible adoptive immunotherapy trials for patients with incurable cancer.

Targeting of CD4+CD25high cells while preserving CD4+CD25low cells with low-dose chimeric anti-CD25 antibody in adoptive immunotherapy of cancer.

The CD4+CD25high regulatory T (Treg) cells have been demonstrated to negatively modulate anti-tumor immune responses in cancer patients. In this study, effects of low dose anti-CD25 antibody (Ab) to attenuate Treg cells were investigated in cancer patients in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) from cancer patients were cultivated in vitro in the presence of a high-affinity chimeric anti-CD25 Ab (basiliximab). The CD4+CD25high population, interferon-gamma (IFN-gamma) production and FOXP3 expression were analyzed using flow cytometry (FCM), enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, respectively. During in vivo studies, basiliximab was administered intravenously on day 1, followed by AIT using autologous activated lymphocytes on day 8, and the treatment cycle was repeated. Subjective and objective effects were observed, and patients' PBMCs were subjected to FCM and RT-PCR analysis. In vitro analysis revealed that a low concentration of 0.01 microg/ml basiliximab reduced almost all of CD4+CD25high cells, but less of the CD4+ CD25low cells, and augmented IFN-gamma production of activated PBMCs. FOXP3 mRNA expression of PBMCs was not affected with or without basiliximab. An in vivo study of 9 metastatic cancer patients (7 colorectal and 2 esophageal) demonstrated no subjective or objective adverse effects, even under repeated administration of basiliximab. The results suggested that low-dose basiliximab can safely be administered repeatedly, and can target CD4+CD25high Treg cells whilst relatively preserving CD4+CD25low activated T cells. The host conditioning with low-dose basiliximab may augment the efficacy of AIT for cancer using activated autologous lymphocytes.

Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class I-matched allogeneic tumor cells.

A 29-year-old female breast cancer patient with multiple bone metastases (HLA-A2) was treated with adoptive transfer using autologous peripheral blood mononuclear cells (PBMCs) activated with the HLA-A2-matched allogeneic GC022588 gastric cancer cell line and interleukin-2 plus an immobilized anti-CD3 antibody culture system. The relief of bone pain in parallel with a decrease of serum carcinoembryonic antigen levels was obtained just after the administration of GC022588-activated effector lymphocytes, and a good quality of life was accomplished for 4 months. The GC022588-activated effector lymphocytes included 44% CD4+, 77% CD8+, and 26% CD4+CD8+ phenotypes, and expressed 25% killing activity against GC022588 stimulator cells at an E/T ratio of 50:1. T cell receptor (TCR) usage analysis for the effector cells showed oligoclonal expression of TCRVbeta1, 3, 9, and 11, especially TCRVbeta5.2, 12, 13.1 and 17, and their killing activity was significantly inhibited in the presence of anti-TCRalphabeta antibody and anti-TCRVbeta12 antibody. SSCP analysis revealed clonotypic bands of TCRVbeta12. These results suggest that shared antigens exist between breast and gastric adenocarcinomas. Allogeneic tumor cells can stimulate PBMCs to generate effector cells with selected TCRCDR3 usages that recognize tumor antigens. These effector lymphocytes may be good candidates for the adoptive immunotherapy of cancer.

Postoperative immunosuppression cascade and immunotherapy using lymphokine-activated killer cells for patients with esophageal cancer: possible application for compensatory anti-inflammatory response syndrome.

Immunological parameters were measured in order to elucidate a postoperative immunosuppression mechanism in transthoracic esophagectomy for patients with esophageal cancer. Moreover, lymphokine-activated killer (LAK) cells were transferred just after the surgery to overcome the postoperative immunosuppression. Fifteen consecutive patients who underwent transthoracic esophagectomy were subjected to the postoperative measurement of immunological parameters. Ten patients who underwent open cholecystectomy served as controls. Heparinized venous blood was obtained pre- and postoperatively, and serum levels of cytokines IL-6 and IL-10 and immunosuppressive acidic protein (IAP) were measured. Peripheral blood lymphocytes were harvested and analyzed by flow cytometry for phenotype detection and by a mixed lymphocyte reaction for detecting concanavalin (Con)-A-induced or -non-induced suppressor activity. Another 29 consecutive patients who underwent transthoracic esophagectomy were randomly enrolled in a postoperative immunotherapy trial either with or without lymphokine-activated killer cells. It was found that, in the esophagectomy group, IL-6 and IL-10 increased postoperatively and peaked on day 1, followed by an increase in IAP, peaked again on day 4, with a profound decrease in helper and cytotoxic T-cell subsets, followed by increases in Con-A-induced (on day 7 or later) and spontaneous (on day 10) suppressor activities. These changes were minimal in the cholecystectomy group. LAK cell transfer restored the postoperative decrease in the helper and cytotoxic T-cell population, and there was a trend of reduction for postoperative remote infection such as pneumonia and surgical site infection in the LAK therapy group. Taken together, we would like to propose the existence of a postoperative immunosuppression cascade consisting of increases in cytokines and immunosuppressive proteins, decreases in helper and cytotoxic T-cell populations, and the development of suppressor T-cell activities in surgery for esophageal cancer. Postoperative adoptive transfer of LAK cells may be a novel clinical application in surgery for esophageal cancer as a means of treating this postoperative immunosuppressive condition that may be identical to the status of compensatory anti-inflammatory response syndrome (CARS).