KNS4/UPEX1: A Type II Arabinogalactan ß-(1,3)-Galactosyltransferase Required for Pollen Exine Development.

Pollen exine is essential for protection from the environment of the male gametes of seed-producing plants, but its assembly and composition remain poorly understood. We previously characterized Arabidopsis (Arabidopsis thaliana) mutants with abnormal pollen exine structure and morphology that we named kaonashi (kns). Here we describe the identification of the causal gene of kns4 that was found to be a member of the CAZy glycosyltransferase 31 gene family, identical to UNEVEN PATTERN OF EXINE1, and the biochemical characterization of the encoded protein. The characteristic exine phenotype in the kns4 mutant is related to an abnormality of the primexine matrix laid on the surface of developing microspores. Using light microscopy with a combination of type II arabinogalactan (AG) antibodies and staining with the arabinogalactan-protein (AGP)-specific ß-Glc Yariv reagent, we show that the levels of AGPs in the kns4 microspore primexine are considerably diminished, and their location differs from that of wild type, as does the distribution of pectin labeling. Furthermore, kns4 mutants exhibit reduced fertility as indicated by shorter fruit lengths and lower seed set compared to the wild type, confirming that KNS4 is critical for pollen viability and development. KNS4 was heterologously expressed in Nicotiana benthamiana, and was shown to possess ß-(1,3)-galactosyltransferase activity responsible for the synthesis of AG glycans that are present on both AGPs and/or the pectic polysaccharide rhamnogalacturonan I. These data demonstrate that defects in AGP/pectic glycans, caused by disruption of KNS4 function, impact pollen development and viability in Arabidopsis.

Long-term functional changes after low anterior resection for rectal cancer compared between a colonic J-pouch and a straight anastomosis.

BACKGROUND/AIMS: We prospectively compared changes in function between colonic J-pouch and straight anastomoses from 1 to 5 years after low anterior resection for rectal cancer. METHODOLOGY: At 1, 3, and 5 years after surgery, functional outcome was compared between 48 patients with J-pouch reconstruction (J group) and 51 with straight anastomosis (S group), using a 17-item questionnaire (overall best, 0; overall worst, 26). Reservoir function was evaluated manovolumetrically. RESULTS: At 5 years, patients with ultralow anastomoses (< or =4 cm from anal verge) had fewer bowel movements during day or night, and less urgency and soiling in the J than S group. At that time, patients with low anastomoses (5 to 8 cm above the verge), had fewer bowel movements at night and less urgency in the J than S group. Manovolumetric results were better in the J than S group for both anastomotic levels. Functional scores improved significantly over time for both anastomotic levels, especially in the S group. Mean scores with ultralow anastomoses were J-group, 5.6 at 1 year vs. 5.3 at 3 years (P = 0.0304) vs. 3.7 at 5 years (P < 0.0001); and S group, 10.2 at 1 year vs. 9.6 at 3 years (P = 0.0063) vs. 7.3 at 5 years (P < 0.0001). Mean scores with low anastomoses were J group, 3.4 at 1 year vs. 3.1 at 3 years (P = 0.0052) vs. 2.1 at 5 years (P = 0.0003); and S group, 5.2 at 1 year vs. 3.8 at 3 years (P < 0.0001) vs. 2.7 at 5 years (P < 0.0001). Manovolumetric results improved overtime in both groups. CONCLUSIONS: Functional outcome improved in the J and especially the S group over 5 years. However, function was better in the J than S group at all time points.

Randomized trial of the efficacy of adjuvant chemotherapy for colon cancer with combination therapy incorporating the oral pyrimidine 1-hexylcarbamoyl-5-fluorouracil.

BACKGROUND AND AIMS: The purpose of the present trial was to clarify the efficacy of postoperative adjuvant chemotherapy including an oral fluoropyrimidine anticancer drug, the 1-hexylcarbamoyl-5-fluorouracil (HCFU), for the treatment of colon cancer. METHOD: Patients with clinical stage Dukes' B and C colon cancer, who had been treated surgically, were assigned to a chemotherapy group treated with mitomycin C, 5-fluorouracil (5-FU), and HCFU and to a control group that received no postoperative adjuvant chemotherapy. RESULTS: Of the 1,001 patients registered for the study, 17 (1.7%) were ineligible. The incidence of toxicity was significantly higher in the chemotherapy group than in the control group. However, there were few severe side effects and no deaths related to the treatment. Overall survival showed no significant difference between the groups. The disease-free survival or the recurrence-free intervals was significantly higher in the chemotherapy group than in the control group. The incidence of hepatic recurrence was significantly (P=0.003) lower in the chemotherapy group than in the control group. CONCLUSION: The results of this study demonstrated the efficacy of adjuvant chemotherapy for colon cancer, i.e., combined chemotherapy that included the 5-FU oral anticancer drug HCFU.

Long-term functional outcome of colonic J-pouch reconstruction after low anterior resection for rectal cancer.

PURPOSE: To evaluate the long-term functional outcome of colonic J-pouch reconstruction after low anterior resection (LAR) for rectal cancer in a prospective study. METHODS: We compared the functional outcome of 46 patients who underwent J-pouch reconstruction (J-group) and 49 patients who underwent straight anastomosis (S-group) after LAR for rectal cancer. We evaluated clinical function using a 17-item questionnaire about different aspects of bowel function. Physiologic reservoir function was evaluated by manovolumetry. RESULTS: Among the patients with an ultralow anastomosis (

An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer.

BACKGROUND: Oral carmofur, either as a single or in combination with other chemotherapeutic agents, has been used as adjuvant chemotherapy for curatively resected colon cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with this cancer. The objective of this study was to perform a reappraisal of randomized clinical trials conducted in this regard. METHODS: We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of oral carmofur for curatively resected colon cancer in terms of overall survival (OS) and disease-free survival (DFS). RESULTS: We analyzed individual patient data of three randomized clinical trials, which met the predetermined inclusion criteria. These three trials had a combined total of 2152 patients, carmofur as adjuvant chemotherapy compared with surgery-alone, 5 years follow-up, intention-to-treat-based analytic strategy and similar end points (OS and DFS). In a pooled analysis, 5 year OS rates were 80.4 and 76.4%, and 5 year DFS rates 76.9 and 71.0%, respectively, in carmofur and surgery-alone group. Oral carmofur had significant advantage over surgery-alone in terms of both OS [pooled hazard ratio, 0.82; 95% confidence interval (CI) = 0.68-0.99; P = 0.043] and DFS (pooled hazard ratio, 0.77; 95% CI = 0.65-0.91; P = 0.003). CONCLUSIONS: This individual patient-based meta-analysis demonstrated that oral carmofur significantly improves both OS and DFS in patients with curatively resected colon cancers.

Optimal ligation level of the primary feeding artery and bowel resection margin in colon cancer surgery: the influence of the site of the primary feeding artery.

PURPOSE: In colon cancer surgery, it is recommended that en bloc resection involving extended lymphadenectomy, characterized as a hemicolectomy, be performed by ligating the primary feeding artery at a high position and resecting proximal and distal with 5-cm to 10-cm bowel margins. However, there is little evidence to unequivocally support such extensive lymphovascular resection. METHODS: The distribution of nodal metastases was obtained by the clearing method in 164 patients with colon cancer. RESULTS: For pericolic spread, for pT1 tumors, the distance from the primary tumor to a diseased node was 2.5 cm; for pT2, the distance was less than 5 cm; for 97.0 percent of pT3 tumors and 93.3 percent of pT4 tumors with nodes involved, the distance was less than 7 cm. For central spread, for pT1 tumors, the rate of spread to central nodes was 0 percent; for pT2, the rate of spread was 20.0 percent to intermediate nodes (for tumors more than 5 cm from the feeding artery, the rate for central nodes was 0 percent); for pT3, the rate was 30.6 percent to intermediate nodes and 15.3 percent to main nodes; for pT4, the rate was 44.4 percent to intermediate nodes and 22.2 percent to main nodes. For curative resection cases with pT3 tumors more than 7 cm from the feeding artery, the rate to central nodes was 0 percent. CONCLUSIONS: In T1 tumors, central node dissection is not required, but resection with proximal and distal 3-cm margins are required; in T2, central node dissection that includes the intermediate node should be performed in addition to resection with proximal and distal 5-cm margins. In T3 and T4, central node dissection that includes the main node should be performed in addition to resection with proximal and distal 7-cm margins. However, for T2 more than 5 cm from the primary feeding artery, and for T3 more than 7 cm from the primary feeding artery, proximal and distal resection alone may be adequate.

Number versus distribution in classifying regional lymph node metastases from colon cancer.

BACKGROUND: Metastasis to regional lymph nodes from colon cancer is an important prognostic factor. In the TNM classification, node metastases are classified into three grades based on the number of metastatic nodes. In the Japanese General Rules for Clinical and Pathologic Studies on Cancer of the Colon, Rectum, and Anus (JGR), node metastases are classified into four grades based on the distribution of metastatic nodes. STUDY DESIGN: Based on the findings of node metastases in 164 patients with colon cancer obtained by the clearing method, node classifications by the JGR and TNM classifications were compared. RESULTS: The case distribution by the JGR grading was 41.5% in n (-), 29.3% in n1 (+), 18.3% in n2 (+), and 11.0% in n3 (+) disease. In the TNM classification, the distribution was 23.8% in pN1 and 34.8% in pN2 disease. The 5-year survival rate by the JGR was 98.4% in n (-), 74.3% in n1 (+), 51.2% in n2 (+), and 30.0% in n3 (+) disease; in TNM classification, this rate was 76.0% in pN1 and 45.0% in pN2 disease. CONCLUSIONS: In the classification of regional node metastases from colon cancer, the JGR classification showed a wider range in distribution and 5-year survival rate compared with the TNM system.

Comparison of long-term functional results of colonic J-pouch and straight anastomosis after low anterior resection for rectal cancer: a five-year follow-up.

PURPOSE: Few reports on the long-term functional outcome of colonic J-pouch reconstruction have been published, and data comparing J-pouch and straight reconstruction are contradictory. This prospective study compares the functional outcome of colonic J-pouch and straight anastomosis five years after low anterior resection for rectal cancer. METHODS: Functional outcome was compared in 46 patients with J-pouch reconstruction (J-group) and 48 patients with straight anastomosis (S-group). Clinical status was evaluated with a 17-item questionnaire inquiring about different aspects of bowel function. Reservoir function was evaluated by manovolumetry. The Fisher's exact test and Wilcoxon's rank-sum test were used to compare categoric and quantitative data, respectively. RESULTS: Among patients with an ultralow anastomosis (< or = 4 cm from the anal verge), the number of bowel movements during the day (> or = 5, 4.3 vs. 29.2 percent; P = 0.028) and at night (> 1/week, 4.3 vs. 33.3 percent; P = 0.013) and urgency (4.3 vs. 33.3 percent; P = 0.013) and soiling (21.7 vs. 50.0 percent; P = 0.043) were less in the J-group than in the S-group. Among patients with a low anastomosis (5 to 8 cm from the verge), patients in the J-group had fewer bowel movements at night (> 1/week, 0 vs. 20.8 percent; P = 0.028) and less urgency (0 vs. 20.8 percent; P = 0.028). Reservoir function was better in the J-group than in the S-group in both the ultralow (maximum tolerable volume (mean), 101.7 vs. 76.3 ml; P = 0.004; threshold volume (mean), 46.5 vs. 30.4 ml; P < 0.001; compliance (mean), 4.9 vs. 2.5 ml/cm H2O; P < 0.001) and low-anastomosis (maximum tolerable volume, 120.4 vs. 97.9 ml; P < 0.001; threshold volume, 58.3 vs. 40.8 ml; P < 0.001; compliance, 5.2 vs. 3.1 ml/cm H2O; P < 0.001) groups. CONCLUSIONS: J-pouch reconstruction increased reservoir function and provided better functional outcome than straight anastomosis, even five years after surgery, especially in patients whose anastomosis is less than 4 cm from the anal verge.

Long-term functional outcome of low anterior resection with colonic J-pouch reconstruction for rectal cancer in the elderly.

PURPOSE: Bowel function after low anterior resection for rectal cancer with colonic J-pouch reconstruction is more normal than after conventional straight anastomosis. However, few reports have examined the function of colonic J-pouch reconstruction in the elderly. Good function would obviate the need for colostomy, which is sometimes performed because of concern about fecal incontinence, which increases with age. This study evaluated the function of colonic J-pouch reconstruction in elderly patients aged 75 years or older. METHODS: Functional outcome was compared in 20 patients aged 75 years or older (older group) and 27 patients aged 60 to 74 years (old group) and 60 patients aged 59 years or younger (young group), 3 years after colonic J-pouch reconstruction, using a functional scoring system with a 17-item questionnaire (score range, 0 (overall good) to 26 (overall poor)). RESULTS: The functional scores in the three age groups were satisfactory and similar. Among patients with anastomoses 1 cm to 4 cm from the anal verge, all 17 categories on the questionnaire in the three age groups were similar. Among patients with anastomoses 5 cm to 8 cm from the anal verge, only the use of laxatives or glycerine enemas was more common in the older group than in the old and young group (90 vs. 38.5 percent and 43.3 percent; P = 0.01). CONCLUSIONS: Low anterior resection with colonic J-pouch reconstruction provides excellent functional outcome, including continence, for elderly patients. Colonic J-pouch reconstruction is a highly preferable alternative to permanent colostomy in elderly patients undergoing low anterior resection.

Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.

BACKGROUND: We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT). METHODS: Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2). RESULTS: A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group >> chemotherapy group >> control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups. CONCLUSION: The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).

[Analysis of microsatellite instability and p53 LOH in advanced colorectal cancers--first report of the No. 3 protocol].

In order to establish the most appropriate protocol of adjuvant chemotherapy for colorectal cancers, several cooperative studies have been undertaken by the Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma (KCSGCCC). In the No. 3 protocol of KCSGCCC, several cancer-associated molecular markers were analyzed to investigate a possible correlation with chemosensitivity and/or patient's prognosis. Here, we report the preliminary results of the analysis of microsatellite instability (MSI) and p53 LOH in 559 cases of Stage II, III colorectal cancer. The MSI was detected in 51 cases (9%) and was shown to have a significant correlation with right-sided localization and histology (poorly differentiated, mucinous). p53 LOH was positive in 225 cases (40%) and was shown to have a significant correlation with left-sided localization and histology (well to moderately differentiated). These results might support the concept of 2 distinct pathways of colorectal carcinogenesis, e.g., RER pathway and LOH pathway.

Changes in colorectal cancer during a 20-year period: an extended report from the multi-institutional registry of large bowel cancer, Japan.

PURPOSE: This study was designed to examine trends of colorectal cancer in relation to age, gender, site, and survival during the past 20 years. METHODS: The multi-institutional registry of the Japanese Society for Cancer of the Colon and Rectum offered 87,695 surgical cases with invasive adenocarcinoma during 1978 to 1997 for analysis. We calculated survival rates and used the Cox's proportional hazard model for cases during 1978 to 1994. RESULTS: The number of cases showed a 2.5-fold increase with consistent male predominance confined to the distal colon and the rectum. Colon cancer in the last five-year period was more likely right-sided for females (odds ratio, 1.26; 95 percent confidence interval, 1.16-1.38) and males (odds ratio, 1.16; 95 percent confidence interval, 1.06-1.25) compared with the first period. Cancers in younger patients were more likely at Stage III to IV in the late 1990s if the cancers were in the distal colon, the rectum (for both genders), or the proximal colon (for females). Survival was improved except for cases with proximal colon cancer of Stage IV. In the multivariate analysis, hazard ratios for death in the postoperative five years were 0.77, 0.59, and 0.66 for proximal colon, distal colon, and rectal cancers, respectively, in the last period as compared with those in the first period [corrected]. Reduced hazard ratio for females was the largest for proximal colon cancer with Stage I to II. CONCLUSION: Although surgical outcome was largely improved, delayed presentation or diagnosis in younger patients remained a problem. Preferential localization in the proximal colon and survival benefit for females should be investigated.

Role of sialyl Lewis X in liver metastasis in view of liver-associated immunity.

BACKGROUND/AIMS: As sialyl Lewis X is a lignad of the selectin family, it has been proposed that sialyl Lewis X-rich colon cancer cells metastasize to the liver by adhesion to selectins on hepatic endothelial cells. However, little is known about the interaction between sialyl Lewis X and hepatic immune cells. We evaluated the role of sialyl Lewis X in liver metastasis in view of liver-associated immunity. METHODOLOGY: RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, which exhibited high metastatic potential to the liver, were used. In an attempt to investigate the underlying basis for the difference in hepatic metastasis formation, we assessed the susceptibility of both cell lines to lysis by hepatic sinusoidal lymphocytes in 51Cr-release assays, and the expression of a number of carbohydrate antigens by both cell lines by flow cytometry. RESULTS: Hepatic sinusoidal lymphocytes mainly consist of natural cytotoxic lymphocytes, including NKT cells. The H4 colonic cancer subclone showed decreased susceptibility to lysis by hepatic sinusoidal lymphocytes, as compared to the parent cell line. In addition, a significant increase of sialyl Lewis X expression was noted in the H4 subclone. Neuraminidase treatment of H4 cells increased their susceptibility to hepatic sinusoidal lymphocyte-mediated killing. Furthermore, rats inoculated with neuraminidase-treated H4 cells produced fewer metastatic nodules in the liver than those inoculated with untreated H4 cells. CONCLUSIONS: Sialyl Lewis X expression in tumor cells reduced their susceptibility to hepatic sinusoidal lymphocyte-mediated killing, and thus, may facilitate the ability of the tumor cells to metastasize to the liver.

Ability of bivariate cytokeratin and deoxyribonucleic acid flow cytometry to determine the biologic aggressiveness of resectable non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to clarify the significance of bivariate cytokeratin and DNA flow cytometry for analysis of the biologic aggressiveness of resectable non-small cell lung cancer. METHODS: In 92 patients who underwent curative operations, the DNA ploidy status and S-phase fractions of the cancer cell populations inside the tumors were analyzed by a cytokeratin gating technique with paraffin-embedded specimens and were correlated with the surgical results. RESULTS: Ninety tumors yielded assessable DNA histograms. DNA diploidy was detected in 25 tumors with a mean S-phase fraction of 14.3% +/- 4.7%, and DNA aneuploidy was detected in 65 tumors with a mean S-phase fraction of 15.1% +/- 7.1%. The 5-year overall and recurrence-free survivals were 73.3% and 70.3%, respectively. Multivariate analysis showed that only TNM staging was a prognostic factor after surgery. There was a negative correlation between the logarithms of S-phase fraction and the disease-free interval for 22 patients with proven recurrence (P =.006). The tumors with high S-phase fractions recurred more rapidly than did those with low S-phase fractions. CONCLUSION: In a bivariate analysis of cytokeratin and DNA flow cytometry in resectable non-small cell lung cancer, the S-phase fraction appeared to be correlated with the disease-free interval. However, DNA ploidy and S-phase fraction were not predictive of either recurrence or survival after operation. Thus DNA flow cytometry may be of limited use for the analysis of the biologic aggressiveness of lung cancer.

Intrahepatic huge hematoma due to rupture of small hepatocellular adenoma: a case report.

Hepatocellular adenoma sometimes causes intraperitoneal hemorrhage. It is, however, rare for small hepatocellular adenoma to cause intrahepatic huge hemorrhage without intraperitoneal bleeding. Here we describe such a rare case of hepatocellular adenoma with huge intrahepatic hemorrhage in a 25-year-old female, who had taken oral contraceptives for the last 2 weeks. She was admitted to our hospital with a sudden onset of right-upper-quadrant abdominal pain and temporally fell in shock state. Plain CT depicted low density area measuring more than 13 cm in diameter in the right lobe of the liver. Huge tumor was also suggested by abdominal ultrasound, contrast enhanced CT, magnetic resonance imaging (MRI) and angiography. The patient was diagnosed as intrahepatic rupture of hepatic tumor. Because of the risk of re-hemorrhage and malignancy, she underwent right hepatic lobectomy. Histopathologial examination of the resected specimen showed a typical small hepatocellular adenoma with the surrounding huge hematoma in the liver. The case presented here is very rare but seems to be suggestive to the natural course and management of hepatocellular adenoma.

Clinical characteristics of hepatitis B core antibody-positive hepatocellular carcinoma.

The pathology and prognosis of hepatitis B surface antigen (HBsAg)-positive hepatocellular carcinoma (HCC) and hepatitis C virus antibody (HCVAb)-positive HCC is well documented. However, patients with HBsAg-negative/hepatitis B core antibody (HBcAb)-positive HCC are included with non-B non-C disease and have been characterized independently. A series of 125 patients who had undergone hepatectomy for HCC were divided into three groups and compared. The HBsAg group comprised 25 HBsAg-positive patients, the HCV group comprised 70 HCVAb-positive patients, and the HBcAb group comprised 22 HBcAb-positive/HBsAg-negative patients. Eight patients of negative virus markers were excluded in this study. Tumors were larger in the HBcAb group (6.2 cm) than in the HBsAg (4.4 cm) and HCV (3.7 cm) groups. Disease-free 1-, 3-, and 5-year survival rates were, respectively, 75.0%, 57.1%, and 57.1% in the HBcAb group; 60.9%, 41.8%, and 41.8% in the HBsAg group; and 88.0%, 54.0%, and 37.8% in the HCV group. HBcAb-positive HCC patients had larger tumors, but their prognosis was relatively good. Although HBsAg and HCVAb are used for conventional screening of patients with hepatic disorders, we believe that screening is also necessary in patients with positive HBcAb titers for early detection of HCC.

Suppression of T-cell function in gastric cancer patients after total gastrectomy with splenectomy: implications of splenic autotransplantation.

Background. In Japan since the 1960s, patients with gastric cancer have routinely had splenectomy combined with gastrectomy to ensure that lymph node dissection is complete. However, the influence of splenectomy on long-term immunity is unclear.METHODS: Forty-nine gastric cancer patients who underwent total gastrectomy for cure with ( n = 25) and without ( n = 24) splenectomy were assessed for immunologic function, including the proportion of lymphocyte subsets, purified protein derivative from tuberculin (PPD) response, natural killer (NK) activity, and phytohemagglutinin (PHA) response.RESULTS: Peripheral T-cell mediated functions, e.g., PPD and PHA response, were significantly suppressed in patients who underwent gastrectomy with splenectomy compared with those who had gastrectomy alone. Decreased T-cell subsets (CD 3+, 4+, 8+) and increased NK cell subsets (CD 16+, 57+) were observed in patients who underwent splenectomy. Patients who did not undergo splenectomy had immunologic responses within the normal range.CONCLUSIONS: Splenectomy decreased T-cell mediated responses over the long term. As a potential means to co-rrect this T-cell dysfunction in patients with splenectomy, splenic autotransplantation should be considered in future research.