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It currently remains unclear whether stroke volume variation (SVV) before hemodialysis (HD) is an independent predictor of decreased blood pressure (BP) during HD. Fifty-two patients were divided into two groups (Decreased BP during HD group: N = 10, Non-decreased BP group: N = 42). Fractional shortening was lower, and mean arterial pressure (MAP) and SVV were higher in the Decreased BP during HD group. A multiple logistic regression analysis identified low fractional shortening, high MAP, and high SVV as independent predictors of decreased BP during HD. The areas under the ROC curves were as follows: 0.849 for MAP, 0.712 for SVV, and 0.893 for MAP and SVV. Optimal threshold values were 93.0 mm Hg for MAP and 17.3 % for SVV. A multivariate regression analysis identified anemia and a longer dialysis vintage as independently related factors for higher SVV. Our results suggest that high SVV is an independent predictor for decreased BP during HD., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Tumor sensitivity to anticancer drugs such as CPT-11 and platinum derivatives was investigated by assessing Topo-1 and Bax/ERCC-1 expression in patients with stage I/II breast, lung, and gastric cancer who were positive for ONCs, and tumor sensitivity was compared between CPT-11 and platinum derivatives. In the recurrence group (RG) (n=5), immunohistochemistry revealed high expression of Topo-1 in 3 patients (60%) and low expression in 2 patients (40%), while the non-recurrence group (N-RG) (n=17) showed high Topo-1 expression in 3 patients (17.6%) and low expression in 14 patients (82.4%) (not significant; N.S.). High Bax expression combined with low ERCC-1 expression was observed in 2 patients (40%) from the RG and other patterns of expression were seen in 3 patients (60%), while high Bax/low ERCC-1 expression was observed in 3 patients (17.6%) from the N-RG and other patterns were found in 14 patients (82.4%) (N.S.). PCR analysis of Topo-1 expression in the RG (n=4) revealed high expression in 4 patients (100%), while the N-RG (n=5) showed high expression in 3 patients (60%) and low expression in 2 patients (40%) (N.S.). With respect to ERCC-1, PCR analysis of the RG (n=4) also revealed high expression in 4 patients (100%), while the N-RG (n=5) again showed high expression in 3 patients (60%) and low expression in 2 patients (40%) (N.S.). There were significant differences between the expression of high Topo-1 and low ERCC-1 in the RG (p<0.01). These results suggest that tumor sensitivity to CPT-11 may be higher than that for platinum derivatives in patients with node-negative stage I/II breast, lung, or gastric cancer who are positive for ONCs.

This study was designed to examine the relationship between occult neoplastic cells (ONCs) inside and outside harvested lymph nodes (intranodal/extranodal ONCs) and local recurrence in 30 patients who underwent curative resection of primary colorectal cancer. Among 10 patients with colon cancer (Dukes' A=1, Dukes' B=6 and Dukes' C=3), intranodal ONCs were positive in 1 patient (10.0%) and negative in 9 patients (90.0%), while extranodal ONCs were negative in all 10 patients (100.0%). There were no significant differences between the detection of intranodal or extranodal ONCs. Among 20 patients with rectal cancer (Dukes' A=4, Dukes' B=2 and Dukes' C=14), intranodal ONCs were positive in 5 (25.0%) and negative in 15 (75.0%), while extranodal ONCs were positive in 3 (15.0%) and negative in 17 (85.0%). There were no significant differences between the detection of intranodal or extranodal ONCs. These results suggest that patients with rectal cancer and extranodal ONCs should be followed-up carefully as a high-risk group for pelvic local recurrence. However, the prevalence of extranodal and intranodal ONCs was almost similar.

The sensitivity of LN metastases to anticancer drugs such as CPT-11 and platinum agents was investigated by assessing Topo-1 and Bax/ERCC-1 expression in patients who had stage III/Dukes' C colorectal cancer with ONCs. In the recurrence group (RG) (n=21), immunohistochemical expression of Topo-1 was high in 8 patients (38.1%), and low in 13 patients (61.9%), while the non-recurrence group (N-RG) (n=12) showed high expression in 1 patient (8.3%) and low expression in 11 patients (91.7%) (not significant; N.S.). Regarding the immunohistochemical expression of Bax/ERCC-1, high Bax/low ERCC-1 expression was observed in 6 patients (28.6%) from the RG and other patterns of expression were seen in 15 patients (71.4%), while high Bax/low ERCC-1 expression level was observed in 3 patients (25.0%) from the N-RG and other patterns were found in 9 patients (75.0%) (N.S.). PCR analysis of Topo-1 expression in the RG (n=13) revealed high expression in 10 patients (76.9%) and low expression in 3 patients (23.1%), while the N-RG (n=3) showed high expression in 3 patients (100%) and low expression in none (N.S.). With respect to ERCC-1, PCR analysis of the RG (n=13) revealed high expression in 6 patients (46.2%) and low expression in 7 patients (53.8%), while the N-RG (n=3) showed high expression in 2 patients (66.7%) and low expression in 1 patient (33.3%) (N.S.). These results suggest that tumor sensitivity to CPT-11 and platinum derivatives is similar in stage III colorectal cancer patients with ONCs.

Among 13 patients with recurrent colorectal cancer (recurrence group: RG), immunohistochemical expression of Topo-1 was high in 4 patients (30.8%) and low in 9 patients (69.2%), while the non-recurrence group (N-RG) (n=8) showed high expression in 1 patient (12.5%) and low expression in 7 patients (87.5%) (NS). Regarding immunohistochemical expression of Bax/ERCC-1, high Bax/low ERCC-1 expression was observed in 6 patients (46.2%) from the RG and other patterns of expression were seen in 7 patients (53.8%), while high Bax/low ERCC-1 expression was observed in 4 patients (50.0%) from the N-RG and other patterns were found in 4 patients (50.0%) (NS). PCR analysis of Topo-1 expression revealed high expression in 9 patients (75.0%) from the RG (n=12) and low expression in 3 patients (25.0%), while the N-RG (n=8) showed high expression in all 8 patients (100.0%) and low expression in none (NS). With respect to ERCC-1, PCR analysis revealed high expression in 7 patients (58.3%) from the RG (n=12) and low expression in 5 patients (41.7%), while the N-RG (n=8) showed high expression in 1 patient (12.5%) and low expression in 7 patients (87.5%) (p<0.05). These results suggest that tumor sensitivity to CPT-11 and platinum derivatives is similar in stage II colorectal cancer patients with ONCs.

We found a substance in culture medium of neonatal pig liver fragments, which suppresses an immune response monitored by (3)H-thymidine incorporation using phytohemagglutinin (PHA)-stimulated lymphocytes. We named it as an immunosuppressive factor (ISF). To purify ISF, ammonium sulfate fractionation, DE52, SP-Sephadex, hydroxyapatite, blue Sepharose, heparin Sepharose and Superdex gel filtration columns were used. Using these purification procedures, ISF was purified 1,254-fold, with 9.2% recovery, from the culture medium of neonatal pig liver fragments, and was identified as arginase by its biochemical characteristics including molecular size, amino acid sequences of digested peptides and expression of arginase activity. The addition of ISF caused to decrease in arginine concentration in culture medium and at the same time DNA synthesis was suppressed dose-dependently, both of which were recovered by the addition of NOHA (N(G)-hydroxy-L-arginine), an arginase inhibitor. In addition, the depletion of arginine in culture medium also led to the inhibition of DNA synthesis. These results led us to the conclusion that immunosuppressive effect of ISF was due to arginase activity that decreased arginine concentration in culture medium, not to another function of ISF.

Among 41 patients with synchronous liver metastases of colorectal cancer, 15 patients underwent synchronous resection of their liver metastases and achieved a median survival time (MST) of 1,441 days (versus 748 days for the 26 patients without resection, p=0.038), a median relapse-free survival time of 652 days (MST not reached), and a recurrence rate in the residual liver of 20% (3/15 patients). The alternating hepatic arterial infusion and systemic chemotherapy showed partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive disease (PD) in 1 case (n=15/26). They had an objective response rate of 40% (6/15), tumor control rate (>/= SD) of 93.3% (14/15), one-year progression-free survival rate of 35.7%, 50% time to progression of 270 days, one-year survival rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3 leucopenia was observed in 2/15 patients (13.3%). These results suggest that the present alternating therapy may become a standard regimen for patients in whom synchronous resection of liver metastases is impossible and patients who have stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or at extrahepatic sites such as the lungs.

This study was designed to prospectively examine whether the presence of occult neoplastic cells (ONCs) in lymph nodes or positive high-risk (HR) criteria were related to the survival of patients with stage II/III colorectal cancer or gastric cancer. The 3-year relapse-free survival (3Y-RFS) rate was calculated for 79 patients who were registered during a 2-year period. The 3Y-RFS rate was 80.5% in patients without ONCs (n=54) and 84.3% in patients with ONCs (n=25; p=0.9089). Among patients who had stage II/III colorectal cancer, it was 89.0% (n=47) and 76.2% (n=15), respectively (p=0.4131). For patients with stage III colorectal cancer alone, it was 80.8% (n=24) and 62.5% (n=9), respectively (p=0.4006). The 3Y-RFS rate was respectively 88.1% and 77.6% for the HR patients (n=31) and low-risk (LR) patients (n=48) with stage II/III colorectal cancer or gastric cancer (p=0.5545). It was respectively 92.3% and 84.3% for the HR patients (n=20) and LR patients (n=42) with stage II/III colorectal cancer (p=0.5073). Also, the rate was respectively 80% and 76.2% for the HR patients (n=7) and LR patients (n=26) with stage III colorectal cancer alone (p=0.9506). These results indicate that the 3Y-RFS rate is lower in ONC-positive patients with stage II/III colorectal cancer, suggesting that ONCs may have an influence on survival.

Among 125 patients with peritoneal dissemination (P1-3) of colorectal cancer, including those with other synchronous metastases, the 5-year overall survival (OS) rate was 13.3% for P1 patients (n=30), 12.8% for P2 patients (n=39), and 1.8% for P3 patients (n=56) (P1 vs. P2, p=N.S.; P2 vs. P3, p=0.02; P1 vs. P3, p=0.001), while the median survival time (MST) was 12.0, 14.1, and 3.1 months, respectively. The 5-year OS rates for patients who had peritoneal dissemination without other metastases were 17.6% (n=17), 12.5% (n=19), and 3.4% (n=28) (P1 vs. P2, p=N.S.; P2 vs. P3, p=N.S.; P1 vs. P3, p=0.039), while the MST was 25.1, 15.1, and 12.5 months, respectively. In the P3 short survival group (SSG; n=13), TS expression was high in 7.7% (1/13) and low in 92.3% (12/13) of tumors, while DPD expression was high in 38.5% (5/13) and low in 61.5% (8/13) of tumors. In the P3 long survival group (LSG; n=15), the corresponding values were 80.0% (12/15), 20.0% (3/15), 33.3% (5/15), and 66.7% (10/15). High TS and low DPD expression was found in only 7.7% (1/13) of the SSG tumors vs. 46.7% (7/15) of the LSG tumors (p=0.028). These results suggest that the prognosis of stage IV colorectal cancer with P3 peritoneal dissemination is extremely poor. In addition, patients fitting the SSG criteria are unlikely to respond to treatment with 5-FU+LV, and may need combination chemotherapy using CPT-11 and/or L-OHP.

This study was designed to examine the relationship between the presence of occult neoplastic cells (ONCs) in lymph nodes (LNs) and survival in 238 patients with stage I/II LN-negative cancer of the breast, lung, or stomach. In addition, immunohistochemistry for TS and DPD was used to compare the 5-FU sensitivity of the primary tumor in ONC (+) patients. The 5-year relapse-free survival (RFS) rate of 215 ONC (-) patients and 23 ONC (+) patients was 95.2 and 82.6%, respectively (p=0.0107). The 5-year overall survival (OS) rate of the ONC (-) and (+) patients was 97.4 and 77.4%, respectively (p=0.0000). The 6 ONC (+) patients with recurrence showed high and low TS expression in 33.3% (2/6) and 66.7% (4/6), respectively, while high and low DPD expression was observed in 16.7% (1/6) and 83.3% (5/6), respectively. In the 17 ONC (+) patients without recurrence, the corresponding values were 64.7% (11/17), 35.3% (6/17), 29.4% (5/17), and 70.6% (12/17). Patients with a combination of high TS and low DPD expression accounted for 33.3% (2/6) of the ONC (+) patients with recurrence and 52.9% (9/17) of those without recurrence, showing no significant difference between the two groups. These results suggest that ONCs are associated with a lower survival rate and that ONC (+) patients are unlikely to respond to 5-FU+LV therapy.

We studied 42 patients, consisting of 11 stage I/II patients who were node-negative (LN-) and 31 stage II/III patients who were node-positive (LN+). In the LN- patients, detection of occult neoplastic cells (ONCs) in lymph nodes had a sensitivity of 0.0% (0/5), a false-positive (FP) rate of 33.3% (2/6), a specificity of 66.7% (4/6), a false-negative (FN) rate of 100% (5/5), a positive predictive value (PPV) of 0.0% (0/2), and a negative predictive value (NPV) of 44.4% (4/9). In the LN+ patients, the sensitivity of ONCs was 25.0% (5/20), FP rate was 36.4% (4/11), specificity was 63.6% (7/11), FN rate was 75.0% (15/20), PPV was 55.6% (5/9), and NPV was 31.8% (7/22). In LN- patients, positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 20.0% (1/5), FP rate of 16.7% (1/6), specificity of 83.3% (5/6), FN rate of 80.0% (4/5), PPV of 50.0% (1/2), and NPV of 55.6% (5/9). In LN+ patients, these criteria had a sensitivity of 75.0% (15/20), FP rate of 9.1% (1/11), specificity of 90.9% (10/11), FN rate of 25.0% (5/20), PPV of 93.8% (15/16), and NPV of 66.7% (10/15). These results suggest that the high-risk criteria may be useful for predicting recurrence or metastasis in stage II/III lymph node-positive patients with esophageal cancer.

The 5-year overall survival (OS) rates for patients without occult neoplastic cells (ONCs) were 43.0% in stage II (n=15), 52.2% in stage III (n=23), and 48.5% for stages II and III combined (n=38). For ONC-positive patients, the 5-year OS rates were 44.4% in stage II (n=7; p=0.88322), 11.3% in stage III (n=30; p=0.0006), and 17.5% for stages II and III combined (n=37; p=0.0019). Among the ONC(+) recurrence group (75.7%, 28/37), 42.9% (12/28) showed high TS expression in metastatic lymph nodes and 57.1% (16/28) showed low TS expression. In the case of DPD expression, 32.1% (9/28) showed high expression and 67.9% (19/28) showed low expression. Among the ONC(+) non-recurrence group (24.3%, 9/37), 66.7% (6/9) showed high TS expression and 33.3% (3/9) showed low TS expression, while high and low DPD expression was seen in 22.2% (2/9) and 77.8% (7/9), respectively. A combination of high TS and low DPD expression was found in 32.1% (9/28) of the recurrence group vs. 66.7% (6/9) of the non-recurrence group (p=0.070). These results suggest that ONCs are associated with OS. Unlike the non-recurrence group, the ONC(+) patients with recurrence of stage II/III node-positive gastric cancer are unlikely to respond to treatment with 5-FU + LV and may need combination chemotherapy based on L-OHP and/or CPT-11.

In 103 patients without occult neoplastic cells (ONCs) in the lymph node sinuses, the 5-year relapse-free survival (RFS) rate and overall survival (OS) rate were 90.2% and 91.8%, respectively. In 21 patients with ONCs, the 5-year RFS and OS rates were 34.9% and 62.3%, respectively. There were marked differences of survival between the two groups (p=0.0000 and p=0.0003). In the primary tumors of the 21 ONC-positive patients, high and low TS levels were found in 46.2% (6/13) and 53.8% (7/13) of the recurrence group (n=13), respectively. High and low DPD levels were found in 23.1% (3/13) and 76.9% (10/13), respectively. In the non-recurrence group (n=8), high and low TS or DPD levels were found in 75.0% (6/8) and 25.0% (2/8) versus 12.5% (1/8) and 87.5% (7/8), respectively. The percentage of patients with high TS and low DPD levels was 23.1% (3/13) in the recurrence group and 62.5% (5/8) in the non-recurrence group (p=0.07). These results suggest that the presence of ONCs had a clear association with the 5-year RFS and OS rates. The recurrence group of ONC-positive patients with stage II/Dukes' B colorectal cancer was unlikely to be highly responsive to 5-FU-based treatment, thus requiring multi-combination chemotherapy using CPT-11 and/or L-OHP.

In 72 patients without occult neoplastic cells (ONCs) in their lymph node sinuses, the 5-year relapse-free survival (RFS) rate and overall survival (OS) rate were 71.3% and 69.2%, respectively. In 33 patients with ONCs, the 5-year RFS rate and OS rate were 33.9% and 31.3%, respectively. There was a marked difference of survival between the two groups (p=0.0001 and p=0.0003). The metastatic lymph nodes of the 33 ONC-positive patients had high and low levels of thymidilate synthase (TS) expression in 38.1% (8/21) and 61.9% (13/21) of the recurrence group (n=21), respectively, while high and low levels of dihydropyrimidine dehydrogenase (DPD) expression were found in 38.1% (8/21) and 61.9% (13/21), respectively. In the non-recurrence group (n=12), high and low levels of TS or DPD expression were detected in 58.3% (7/12) and 41.7% (5/12) versus 16.7% (2/12) and 83.3% (10/12), respectively. Patients with high TS and low DPD expression accounted for 9.5% (2/21) of the recurrence group and 50.0% (6/12) of the non-recurrence group (p<0.01). These results suggest that ONCs are clearly associated with the 5-year RFS and OS rates. Unlike the non-recurrence group, the recurrence group of ONC-positive patients with Dukes' C colorectal cancer is unlikely to respond well to treatment with 5-FU plus LV and require combination chemotherapy based on CPT-11 and/or L-OHP.

This study compared the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or using 3 criteria to identify high-risk patients among 72 patients who had Dukes' A colorectal cancer with or without proper muscle invasion. Predicting recurrence based on the detection of ONCs had a sensitivity of 40.0% (2/5) and a false-negative rate of 60.0% (3/5), while there was a specificity of 97.0% (65/67) and false-positive rate of 3.0% (2/67), resulting in an accuracy of 68.5%, PPV of 50.0% (2/4), and NPV of 95.6% (65/68). Predicting recurrence based on the presence of at least 2 of the 3 high-risk criteria showed a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5), while it had a specificity of 74.6% (50/67) and a false-positive rate of 25.4% (17/67), resulting in an accuracy of 67.3%, PPV of 15.0% (3/20), and NPV of 96.2% (50/52). These results suggest that a prediction based on ONCs was similar to use of the high-risk criteria, with both methods having a high specificity for recurrence/metastasis of Dukes' A colorectal cancer.

This study was designed to compare the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or using specific criteria to identify patients at high risk of recurrence/metastasis among 105 patients with Dukes' C colorectal cancer. Prediction of recurrence based on the detection of ONCs had a sensitivity of 50.0% (22/44), specificity of 80.3% (49/61), and an accuracy of 65.2%. Prediction of recurrence based on positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 54.5% (24/44), specificity of 83.6% (51/61), and an accuracy of 69.1%. Among the 34 patients with ONCs, prediction of recurrence based on positivity for all 3 high-risk criteria had a sensitivity of 27.3% (6/22), specificity of 91.7% (11/12), an accuracy of 59.5%, and a positive predictive value (PPV) of 85.7% (6/7). These results suggest that the predictive value of ONCs and the high-risk criteria was similar, and that recurrence is likely to occur in patients who fulfill < or =2 of the high-risk criteria. Accordingly, combined use of these parameters may be more effective for the early prediction of recurrence/metastasis to assist in the choice of postoperative systemic chemotherapy.

This study was designed to compare the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or by using high-risk criteria for recurrence/metastasis in patients with Dukes' B colorectal cancer. Prediction of recurrence based on the detection of ONCs had a sensitivity of 59.1% (13/22), a false-positive rate of 7.8% (8/102), a specificity of 92.2% (94/102), and a negative predictive value (NPV) of 91.3% (94/103). Prediction of recurrence based on positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 90.9% (20/22), a false-positive rate of 49.0% (50/102), a specificity of 51.0% (52/102), and an NPV of 96.3% (52/54). Among the 21 patients in whom ONCs were detected, prediction of recurrence based on the presence of all 3 high-risk criteria including ONCs had a sensitivity of 84.6% (11/13) and a positive predictive value (PPV) of 78.6% (11/14). These results suggest that colorectal cancer is unlikely to recur in patients without ONCs, while recurrence is likely in patients who fulfill 2 or more of the high-risk criteria. Accordingly, a combination of these parameters may be useful for the early prediction of recurrence/metastasis to assist in the choice of postoperative systemic chemotherapy.

Prediction of the recurrence of primary breast cancer was attempted by detection of occult neoplastic cells (ONCs) in lymph nodes or by using the high-risk criteria for recurrence/metastasis of gastric and colorectal cancer. The subjects were 70 patients with stage I or II node-negative primary breast cancer. Prediction of recurrence using ONCs had a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5) in the recurrence group, while the specificity was 96.9% (63/65) and the false-positive rate was 3.1% (2/65) in the non-recurrence group. The accuracy of ONCs was 78.5%. Prediction of recurrence based on positivity for at least 2 of the high-risk criteria showed a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5) in the recurrence group, while the specificity was 95.4% (62/65) and the false-positive rate was 4.6% (3/65) in the non-recurrence group. The accuracy of the high-risk criteria was 77.7%. These results suggest that ONCs show the same accuracy as the high-risk criteria for predicting recurrence/metastasis of stage I and II node-negative breast cancer with a high specificity.

This study examined whether detection of occult neoplastic cells (ONCs) in lymph nodes or the high-risk criteria for recurrence/metastasis of colorectal cancer were useful for predicting the recurrence of primary gastric cancer. The subjects were 122 patients with node-negative stage I or stage II primary gastric cancer. Prediction of recurrence using ONCs showed a sensitivity of 25.0% (2/8), specificity of 97.1% (100/103), and accuracy of 61.1% in stage I patients, while the respective values were 75.0% (3/4), 100.0% (7/7), and 87.5% in stage II patients. Prediction of recurrence in patients who fulfilled 2 or more of the high-risk criteria showed a sensitivity of 37.5% (3/8), specificity of 94.2% (97/103), and accuracy of 65.9% for stage I patients, while the respective values were 100.0% (4/4), 85.7% (6/7), and 92.9% for stage II patients. These results suggest that the prediction of recurrence based on the high-risk criteria shows a high sensitivity, specificity, and accuracy in patients of stage II gastric cancer without lymph node metastasis.

This study assessed the prediction of gastric cancer recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes, and by using criteria that were developed to identify patients with a high risk of recurrence/metastasis. The subjects were 60 patients of stage II or III gastric cancer with lymph node metastasis. Prediction of recurrence based on the detection of ONCs showed a sensitivity of 33.3% (2/6), specificity of 70.0% (7/10), and accuracy of 51.7% in stage II patients, while the sensitivity was 73.5% (25/34), specificity was 100.0% (10/10), and accuracy was 86.8% in stage III patients. Prediction of recurrence based on the presence of at least 2 high-risk criteria had a sensitivity of 33.3% (2/6), specificity of 100.0% (10/10), and accuracy of 66.7% in stage II patients, while the sensitivity was 82.4% (28/34), specificity was 80.0% (8/10), and accuracy was 81.2% in stage III patients. These results suggest that prediction of recurrence/metastasis soon after surgery using ONCs plus the high-risk criteria can increase the specificity in stage II cancer, and can achieve a sensitivity of 80% or more with a high specificity and accuracy in stage III cancer.

The correlation between detection of occult neo-plastic cells (ONCs) in lymph node sinuses and the recurrence/metastasis of primary breast, lung, esophageal, and gastric cancer was examined. Among patients with Stage I-III cancer treated by radical resection with dissection of at least 10 lymph nodes, 40 patients who suffered recurrence/metastasis within 5 years post-operatively and 94 patients who did not have recurrence within 5 years were randomly selected. A total of 1,340 lymph nodes were subjected to immunohistochemical staining for cytokeratin to identify ONCs. Then the sensitivity, specificity, positive predictive value, and negative predictive value of ONCs were determined for predicting the recurrence of each cancer. These parameters were respectively 40.0, 75.9, 62.4, and 55.8% for breast cancer, while the respective values were 50.0, 77.4, 68.9, and 60.8% for lung, 57.1, 64.3, 61.5, and 60.0% for esophageal, and 68.8, 65.0, 66.3, and 67.5% for gastric cancer. All of the parameters exceeded 65% for gastric cancer. ONCs also showed a high specificity for breast and lung cancer, but both the sensitivity and specificity were low for esophageal cancer.

Among 371 patients with primary colorectal cancer, 54 patients suffered from recurrence/metastasis (recurrence group) and 317 survived without recurrence for at least 5 years (non-recurrence group). The clinicopathological characteristics of the 2 groups were compared and occult neoplastic cells (ONCs) in the lymph node sinuses were detected by cytokeratin immunohistochemistry. There were significant differences of the following factors: venous invasion (v-) vs. (v+) for Dukes' A patients (p=0.0315); harvested lymph nodes (LN) or=15 for Dukes' B patients (p=0.0388); (v-) vs. (v+) (p=0.0059), lymphatic invasion (ly-) vs. (ly+) (p=0.0435) for Dukes' A and B patients combined; D>n vs. D=n (p=0.0033), depth of tumor invasion or=se/a2 (p=0.0329) for Dukes' C patients. When the detection of >or=3 ONCs was defined as positive, the sensitivity, specificity, PPV, and NPV were respectively 77%, 100%, 100% and 71% in Dukes' B patients, as well as 75%, 72%, 73% and 74% in Dukes' C patients. The high-risk groups for recurrence/metastasis were identified by the following criteria: (v+) and (ly+), or=se/a2, and ONCs (+) of those with >or=2 factors for Dukes' C patients (selection rate; approximately 21.2-37.5%). These factors seem to be appropriate for separating patients into high-risk and low-risk groups of colorectal cancer recurrence/metastasis.

We successfully saved a patient with appendicitis followed by necrotizing fascitis. A 77-year-old man with a history of ambulatory treatment for depression underwent an emergency operation because of severe abdominal pain. Laparotomy demonstrated that necrotizing appendicitis was massively extending over the abdominal cavity, involving the right paracolic sulcus and Douglas pouch and posterior surface of the right kidney. Irrespective of the emergency surgery, redness and swelling in the right chest and abdomen, which was noted at the time of admission, was not decreased. Successively, a retension incision was performed under the diagnosis of necrotizing fasciitis. Necrotizing fasciitis is an extremely rare complication of appendicitis, and there were only 10 cases documented. Once necrotizing fasciitis occurs, the mortality rate is high, so that correct diagnosis and prompt debridement are mandatory. Particularly for elderly patients with appendicitis, rapid and accurate diagnosis and treatment are required.

The aim of this study was to investigate whether it was possible to select patients with Dukes' C primary colorectal cancer who had a high risk of metastasis and recurrence. Among 434 patients who underwent surgical resection of primary colorectal cancer, 115 patients (26.5%) had Dukes' C cancer. Among them, 35 patients (30.45%) suffered from metastasis/recurrence postoperatively. Thirty-two patients with recurrence for whom complete follow-up was possible (recurrence group) and 32 patients who survived for at least 5 years without recurrence (non-recurrence group) were compared by immunohistochemical staining of resected lymph nodes for cytokeratin using two antibodies (AE1/AE3 and CAM 5.2). AE1/AE3 staining was positive in 93.85% of the recurrence group versus 68.85% of the non-recurrence group (p=0.0250), while CAM 5.2 staining was positive in 84.45% vs. 53.15%, respectively (p=0.0152). The occult neoplastic cell count (mean +/- SD) in the peripheral lymph node sinuses was 6.28+/-5.17 vs. 2.38+/-3.03 (p=0.0002) in the AE1/AE3-positive patients from the recurrence and non-recurrence groups, while it was 5.13+/-4.84 vs. 1.53+/-2.37 (p=0.0003) in the CAM 5.2-positive patients in each group. Accordingly, the immunohistochemical positivity rate for both AE1/AE3 and CAM 5.2, as well as the occult neoplastic cell count, were significantly higher in the recurrence group. These results suggest that patients with Dukes' C primary colorectal cancer who have a higher risk of recurrence can be selected by immunostaining of resected lymph nodes for cytokeratin.

This study investigated whether it is possible to detect patients who have a high risk of metastasis and recurrence after resection of stage II Dukes' B primary colorectal cancer. Among 434 patients who underwent curative resection of primary colorectal cancer, 167 (38.5%) had Dukes' B cancer. Among them, 19 patients (11.4%) suffered from postoperative metastasis or recurrence. In 17 patients with recurrence who could be followed-up completely (recurrence group) and 17 other patients who survived for at least 5 years without recurrence (non-recurrence group), immunohistochemical staining of resected lymph nodes for cytokeratin (AE1/AE3 and CAM 5.2) was performed. AE1/AE3 was positive in 76.5% and 47.1% of the patients from the recurrence and non-recurrence groups, respectively, while CAM 5.2 was positive in 52.9% and 17.6%, respectively. There were no significant differences of either AE1/AE3 or CAM 5.2 positivity between the groups. However, the occult neoplastic cell count (mean +/- SD) floating in the lymph node sinuses was significantly higher in patients from the recurrence group who were positive for AE1/AE3 or CAM 5.2 than in patients from the non-recurrence group (6.12+/-6.00 vs. 0.59+/-0.71; p=0.0019 and 3.94+/-5.06 vs. 0.29+/-0.69; p=0.0098, respectively). These results suggest that patients with Dukes' B primary colorectal cancer who have a higher risk of recurrence can be selected by immunostaining of resected lymph nodes for cytokeratin.

This study investigated whether the Japanese radical lymph node dissection (J-LND) method was useful for improving the survival and outcome in patients undergoing surgical resection of primary colorectal cancer. The subjects were 434 patients with primary colorectal cancer treated over 17 years. The 10-year survival (10-YS), the number of retrieved and metastatic lymph nodes (LN), the extent of lymph node dissection (D0-D3), and the extent of lymph node metastasis (n0-n4) were compared with Dukes' classification by the Kaplan-Meier curves, log-rank test and multivariate analysis. Patients with a D number larger than their n number (D>n group) were defined as being treated according to J-LND principles, while those with a D number equal to their n number were used as controls (D=n group). Among Dukes' B patients, there was a significant difference of 10-YS between those with retrieval of > or =17 LN or < or =16 LN (p=0.0106). Among Dukes' C patients, a significant difference of 10-YS was observed between those with 1 metastatic node or > or =3 metastatic LN (p=0.0401). A significant difference of 10-YS was also noted between Dukes' C patients with D>n or D=n (p=0.0282). Multivariate analysis showed that retrieval of < or =16 LN (HR=9.051) and intramural invasion (se,si/a2,ai; HR=6.313) were independent determinants of 10-YS in Dukes' B patients, while D=n (HR=2.354) and > or =3 metastatic LN (HR=2.210) were independent determinants in Dukes' C patients. These results suggest that the J-LND method should be performed to retrieve at least 17 nodes when serosal dimpling of the primary tumor is observed during surgery. Effective post-operative adjuvant therapy, such as combination chemotherapy and/or radiotherapy, should be provided for Dukes' C patients with D=n and/or > or =3 metastatic nodes on histopathological examination.

We experienced 12 consecutive cases of complete bowel obstruction due to primary colorectal cancer. Among these patients, temporary loop colostomy (loop C) was performed within the resection zone for the primary tumor in 10 cases, and Hartmann's operation was performed in two cases. The loop C was located in the sigmoid colon in five cases and on the left side of the transverse colon in five cases. The interval until radical resection was from 13 to 35 days (mean: 20 days), the duration of surgery was from 2 h 5 min to 4 h 55 min (mean: 4 h 7 min), and the length of resected bowel ranged from 22.5 cm to 51.2 cm (mean: 29.8 cm). Mild wound infection was observed in two cases. Dukes' clinical stage was as follows: A in 0 case, B in 5 cases, C in 6 cases and D (distant metastasis) in 1 case. We have achieved good results over the past two years without performing standard loop C on the right side of the transverse colon.

Acute appendicitis is usually encountered clinically as acute abdomen. Typical cases are easy to diagnose, but it can sometimes be very difficult to make a diagnosis in atypical cases. We retrospectively studied patients who underwent ultrasonography for right-sided lower abdominal pain suggesting acute appendicitis, and assessed the accuracy of ultrasonic diagnosis. The subjects were 202 patients (100 males and 102 females) aged 6-89 years (mean: 33.3 years). From the ultrasonic findings, appendicitis was classified as follows: 1) catarrhal: a clear layer structure of the appendiceal wall and mucosal edema; 2) phlegmonous: an ill-defined layer structure of the appendiceal wall, moderate enlargement of the apendix, and maximum transverse dimension of > or = 10 mm; and 3) gangrenous: unidentifiable layer structure of the appendiceal wall and marked enlargement to form a mass. The appendix was visualized in 142 of the 202 patients (70.3 %). When the appendix was detected, the sensitivity, specificity and accuracy of ultrasound for making a diagnosis of appendicitis were 97.6%, 82.0 %, 91.5 %, respectively. With regard to assessment of the severity of inflammation, ultrasonic and histologic findings were concordant in 61.2 % of the patients. However, ultrasound was shown to possibly underestimate the extent of inflammation. On the other hand, 11 of the 60 patients with an undetectable appendix (18.3 %) were clinically diagnosed as having appendicitis. The pathologic diagnosis was catarrhal appendicitis in 3 patients and phlegmonous appendicitis in 8 patients. In patients with an undetectable appendix, the possibility of catarrhal or phlegmonous appendicitis should be kept in mind.

A patient was diagnosed as having subacute ileus due to advanced cancer of the descending colon with multiple liver metastases and was treated by palliative left hemicolectomy. He was considered to have Stage IV cancer based on the finding of extensive peritoneal dissemination. Histopathological examination showed that the tumor was moderately differentiated adenocarcinoma. Postoperative palliative chemotherapy was given with 5-FU and LV twice a month as 1 course, and he received a total of 3 courses. As a result, the multiple liver metastases were completely eliminated. However, his liver metastases recurred, so CPT-11 was added to 5-FU and LV for another 3 courses. When bilateral pleural effusions developed about 1 year postoperatively, CPT-11 was changed to CDGP. Jaundice and massive ascites eventually developed, and he died about 1 year and 5 months postoperatively.

Two factors were found in the condition medium of neonatal pig liver fragments, which were capable of stimulating DNA synthesis in primary hepatocytes. They were named hepatocyte proliferation factor (HPF)-1 and HPF-2 and purified 1,025- and 2,580-fold, respectively. Both HPF-1 and HPF-2 seem to be anionic at pH 8.0 judged from the elution pattern of DEAE (DE52) column chromatography. HPF-1 was recovered as a non-adsorbed fraction in blue Sepharose and heparin Sepharose columns, and had a molecular weight of 26-31 kDa as estimated by gel filtration in high salt condition. Purified HPF-1 stimulated DNA synthesis of primary rat hepatocytes, but suppressed that of HepG2 cells. HPF-2 strongly bound to blue Sepharose and heparin Sepharose columns, and had a molecular weight of 71-90 kDa as estimated by SDS-PAGE under non-reduced condition. Purified HPF-2 stimulated DNA synthesis of primary rat hepatocytes dose dependently but did not suppress that of HepG2 cells. From further biological and chemical characteristics studied in this paper, HPF-1 and HPF-2 may be novel stimulating proteins for hepatocyte proliferation, although the possibility that they are already known growth factors can not be excluded without complete purification and its cloning.

Because fluorine-18 fluorodeoxyglucose (18F-FDG) is an excellent tumor-localizing radio-pharmaceutical, a hand-held radiation detection probe capable of localizing an area with high 18F-FDG uptake would make radioguided surgery possible. In this laboratory study, we investigated the capability of a widely used intraoperative gamma probe with a cadmium zinc telluride (CdZnTe) detector for detection of 18F-FDG. For sensitivity tests, an 0.1- ml 18F-FDG preparation was made to act as a point source with radioactivities of 1.0, 2.0, and 3.0micro Ci (37 kBq, 74 kBq, 111 kBq). Relative transmission across the side wall of the probe and sensitivity at each source-to-probe distance were measured. For simulation studies, 2 l of 18F-FDG solution (0.02micro Ci, 0.74 kBq/ml) served as normal background. One ml of 18F-FDG was prepared to simulate tumors with radioactivities of 0.05, 0.1, 0.2, and 0.4micro Ci (1.85 kBq, 3.7 kBq, 17.4 kBq, and 14.8 kBq). The ratios of the radioactive concentration of tumor to that of the background were 2.5, 5, 10, and 20:1, respectively. The tested gamma probe was shown to be sensitive to 18F. The high-energy annihilation radiation was detected from the side wall of the probe despite application of a supplementary collimator. The count rate decreased markedly as the source-to-probe distance increased, owing to the effects of the inverse-square law. In the simulation studies, the probe detected a considerable amount of background activity. However, the measured count rate increased with the increasing source-to-background ratio. In our setting, the probe was capable of distinguishing the 18F-FDG source from the background when the source-to-background ratio was no less than 5:1. To make a surgical application feasible, however, collimation or shielding against high background radiation is necessary.

This is a compilation of the results of preventive intraarterial infusion following resection of hepatic metastasis from colorectal cancer at four surgical centers. The cases studied included two groups: A) 76 patients who underwent normal liver resection only, and B) 78 patients who underwent resection with adjuvant chemotherapy. Methods included: 1) WHF, 50 cases; 2) other methods using 5-FU, 18 cases; and 3) intraarterial infusions other than 5-FU, 10 (2 cases, outcome unknown). Survival rates for groups A and B for 1 and 5 years were 71.2, 18.9% and 91.5, 56.2%, respectively, with the rates for the intraarterial infusion group showing far better results. The 1- and 5-year survival rates in terms of infusion methods were: 1) 90.7% and 64.6%; 2) 94.4% and 39.3%; and 3) 90% and 60%, respectively, showing no remarkable differences between methods. Total doses of 5-FU were (a) less than 5 g, 7 patients (b) 5-15 g, 16 patients (c) 15-30 g, 22 patients (d) greater than 30 g, 23 patients. A comparison of 1- and 5-year survival rates shows (a) 85.7% and 17.1%; (b) 66.5% and 44.3%; (c) 100% and 62.7%; (d) 100% and 66.5%, respectively, with doses (c) and (d) showing markedly better results than the (a) dosage. From this we conclude that the group undergoing intraarterial hepatic infusion had a markedly improved prognosis compared to the group not undergoing any type of adjuvant therapy. Also, groups receiving a dosage of 15 g or greater of 5-FU showed prolonged survival rates.

Background/aims: Due to the anatomical location of the pancreas, sufficient drainage of a pancreatic necrosis by laparotomy may be unsatisfactory., Methods: CT and helical CT have provided extremely useful information on the surgical treatment of necrotic pancreatitis. The retroperitoneal approach (RPA) allows direct and complete removal of necrotic tissues., Results: RPA was used to treat 8 patients with infected pancreatic necrosis. Excision of necrotic tissues was effective and could minimize the complications often associated with laparotomy such as bleeding and intestinal injuries., Conclusion: By CT and helical CT, three-dimensional images of pancreatic necrosis are obtained. These investigations have greatly facilitated RPA, which has advantages over laparotomy in the treatment of infected pancreatic necrosis.

Two hundred eleven cases, 27.1%, of multiple primary cancers of esophagus and other organs were found in 778 cases of esophageal cancers which were treated in our institution. Among them, double cancer accounted for 92.9%, triple cancer accounted for 6.6% and quadruple cancer for 0.5%. As for the other organ of esophageal double cancer. 59.9% of them were head and neck, 25.1% were stomach, 4.9% were colon and rectum, and remaining included liver, breast, lymphoma lung kidney etc. Head and neck cancers consisted with hypopharynx, tongue, larynx, oral floor and gingiva regarding incidence in its order. For discovering of double cancer in esophagus and other organs, 1. head and neck, stomach, colon and rectum, lung, liver etc. should be investigated preoperatively in the patients of esophageal cancer, 2. Esophagus should be examined preoperatively in the patients of these cancers, 3. Screening of esophageal cancer should be performed in the patients of high risks of esophageal cancer. As for the multiple primary cancer of esophagus and other organs, the balance of treatment should be considered to take the priority of the cancer limiting the prognosis.

It is well known that total parenteral nutrition (TPN) causes atrophy of the intestinal mucosa, resulting in degeneration and atrophy of the gut-associated lymphoid tissues (GALT). This study was conducted to examine the suppressive effect of TPN on GALT in rats. Rats that received TPN alone for 2 weeks, i.e., the TPN group, showed a decreased number of Peyer's patches and thoracic duct lymphocytes (TDL), as well as atrophy. Conversely, those treated with TPN in combination with polysaccharide K (PSK) at a daily dose of 1000 mg/kg for 2 weeks, i.e., the PSK group, showed increases in the number of Peyer's patches and TDL and improvement in the TDL subsets compared with the TPN group. Immunohistological examination of the changes in immunocytes in GALT using monoclonal antibodies revealed increases in the production of the major histocompatibility complex (MHC)-I and (MHC)-II, helper T cells, and interleukin 2 (IL-2). These findings indicate that PSK improves GALT suppression induced by TPN.

Total parenteral nutrition (TPN) causes atrophy of the intestinal mucosa, resulting in the degeneration and atrophy of gut associated lymphoid tissues (GALT). This suppressive effect of TPN on GALT was examined using rats. In rats receiving TPN for 2 weeks, a decrease and atrophy of Peyer's patches and a decrease in thoracic duct lymphocytes (TDL) were observed. Daily oral administration of 1000 mg/kg PSK to the rat in the TPN group corrected the number and size of Peyer's patches, and the number of TDL and its subsets were also improved compared with the TPN group. Diminution of the S-IgA of bile and portal venous blood was noticed during TPN in rats. But the groups PSK administrated were increased the amount of S-IgA in bile and portal venous blood. The immune plasma cells in the Peyer's patches were observed, the number of the MHC-class II, T helper, and IL-2 (T CGF) positive cells were decreased in the TPN group compared with control group (PSK group). It has been concluded, therefore, that PSK is effective for improving GALT inhibition caused by TPN.

Microsatellite instability or replication error seems to be related to defective DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2, which have been identified as causative genes of hereditary nonpolyposis colorectal cancers (HNPCC). Recently, it was reported that mutations at the simple repeated sequences in the transforming growth factor-beta type II receptor (TGF-beta RII) gene occurred in replication error-positive colorectal cancers. To determine genetic alterations in familial gastric cancers (FGC, we examined replication error using eight microsatellite DNA markers, and screened mutations in the hMSH2, hMLH1 and TGF-beta RII genes in six cases from four FGC kindreds. Moreover, hMTH1, a human homolog of the bacterial mutT gene, was also screened. Four of six (67%) cancers showed the replication error-positive phenotype, indicating that microsatellite instability is highly associated with not only HNPCC, but also FGC. No germline mutation was found in the whole coding sequences of hMSH2 and hMTH1, or in the conservative regions of hMLH1 in any patient, while one cancer DNA showed a somatic mutation at codon 682 (threonine to alanine) in hMSH2. No alteration was found at the small repeated sequences in TGF-beta RII in FGC tumor DNA. These results indicate that the carcinogenetic process of FGC may be different from that of HNPCC.

The effect of the proteoglycan biologic response modifier, PSK, on lymphocyte subsets was investigated in normal rats. Six-week-old male SPF Wistar-Imamichi rats were fed a diet containing 2% PSK. Peripheral blood lymphocytes (PBL), thoracic duct lymphocytes (TDL), and those existing in the thymus, spleen and Peyer's patches were collected for analysis of subsets of T cells, helper/inducer T (Th) cells, suppressor/cytotoxic T (Ts) cells and B cells compared with those of the control group. In the PBL, differential and absolute counts of T and Th cells were lower in the group fed PSK (the PSK group) than the control group. There was no difference in Ts cells between the groups, and the PSK group showed a higher B-cell differential count. In the case of TDL, the PSK group showed greater absolute counts of T and Th cells than the control group. In tissue lymphocytes, differential T and Th cell counts were significantly greater in the PSK group than the control group, as observed first in Peyer's patches and later in the spleen. No differences between the groups were observed in these counts in the thymus. Changes in body distribution of T and Th cells induced by PSK treatment first appeared in lymphocytes in Peyer's patches, followed by PBL and TDL, and those in the spleen. No such changes were observed in the thymic lymphocytes.