Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study.

BACKGROUND: We previously reported that indocyanine green fluorescence imaging (ICG-FI)-guided laparoscopic lateral pelvic lymph node dissection (LPLND) was able to increase the total number of harvested lateral pelvic lymph nodes without impairing functional preservation. However, the long-term outcomes of ICG-FI-guided laparoscopic LPLND have not been evaluated. The aim of the present study was to compare the long-term outcomes of ICG-FI-guided laparoscopic LPLND to conventional laparoscopic LPLND without ICG-FI. METHODS: This was a retrospective, multi-institutional study with propensity score matching. The study population included consecutive patients with middle-low rectal cancer (clinical stage II to III) who underwent laparoscopic LPLND between January 2013 and February 2018. The main evaluation items in this study were the 3-year overall survival, relapse-free survival (RFS), local recurrence rate, and lateral local recurrence (LLR) rate. RESULTS: A total of 172 patients with middle-lower rectal cancer who had undergone laparoscopic LPLND were included in this study. After propensity score matching, 58 patients were matched in each of the ICG-FI and non-ICG-FI groups. There were no substantial differences in the baseline characteristics between the two groups. The ICG-FI group and non-ICG-FI group included 40 and 38 women and had a median age of 65 (IQR 60-72) and 66 (IQR 60-73) years, respectively. The median follow-up for all patients was 63.7 (IQR 51.3-76.8) months. The estimated respective 3-year overall survival, RFS, and local recurrence rates were 93.1%, 70.7%, and 5.2% in the ICG-FI group and 85.9%, 71.7%, and 12.8% in the non-ICG-FI group (p = 0.201, 0.653, 0.391). The 3-year cumulative LLR rate was 0% in the ICG-FI group and 9.3% in the non-ICG-FI group (p = 0.048). CONCLUSIONS: This study revealed that laparoscopic LPLND combined with ICG-FI was able to decrease the LLR rate. It appears that ICG-FI could contribute to improving the quality of laparoscopic LPLND and strengthening local control of the lateral pelvis. TRIALS REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000041372 ( http://www.umin.ac.jp/ctr/index.htm ).

Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer.

High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes.

Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05).

BACKGROUND: In Japan, S-1 plus cisplatin has been used as first-line therapy for advanced gastric cancer (AGC). Patients with no response to first-line treatment with S-1 often receive a taxane-alone or irinotecan-alone as second-line treatment. However, second-line treatment with S-1 plus irinotecan is widely used in patients with AGC resistant to first-line S-1-based chemotherapy. The goal of this trial was to determine whether the consecutive use of S-1 plus irinotecan improves survival when compared with irinotecan-alone as second-line treatment for AGC. PATIENTS AND METHODS: Patients who had disease progression during first-line S-1-based chemotherapy were randomly assigned to receive S-1 plus irinotecan or irinotecan-alone. The S-1 plus irinotecan group received oral S-1 (40-60 mg/m(2)) on days 1-14 and intravenous irinotecan (150 mg/m(2)) on day 1 of a 21-day cycle. The irinotecan-alone group received the same dose of irinotecan intravenously on day 1 of a 14-day cycle. The primary end point was overall survival (OS). RESULTS: From February 2008 to May 2011, a total of 304 patients were enrolled. The median OS was 8.8 months in the S-1 plus irinotecan group and 9.5 months in the irinotecan-alone group. This difference was not significant (hazard ratio for death, 0.99; 95% confidence interval 0.78-1.25; P = 0.92). Grade 3 or higher toxicities were more common in the S-1 plus irinotecan group than in the irinotecan-alone group. CONCLUSION: The consecutive use of S-1 plus irinotecan is not recommended as second-line treatment in patients who are refractory to S-1-based first-line chemotherapy. ClinicalTrials.gov ID: NCT00639327.

Nutritional management of anastomotic leakage after colorectal cancer surgery using elemental diet jelly.

BACKGROUND/AIMS: Anastomotic leakage is major complication of colorectal surgery. Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage. METHODOLOGY: Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study. RESULTS: Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter. CONCLUSION: Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.

Prognostic significance of CD44 variant 2 upregulation in colorectal cancer.

BACKGROUND: CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis. METHODS: CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples. RESULTS: CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2(low) group (n=83, 5-OS: 0.88). CONCLUSIONS: CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants.

Perioperative use of a neutrophil elastase inhibitor in video-assisted thoracoscopic oesophagectomy for cancer.

BACKGROUND: This study was undertaken to assess the value of administering perioperative sivelestat sodium hydrate (SSH), a selective neutrophil elastase inhibitor, after video-assisted thoracoscopic oesophagectomy for cancer. METHOD: Thirty-one consecutive patients with thoracic oesophageal cancer selected to undergo video-assisted thoracoscopic oesophagectomy with lymph node dissection between March 2007 and March 2009 were assigned randomly to a treatment group that received SSH intravenously for 7 days from the beginning of surgery (16 patients) and a control group that received saline (15). The primary endpoint was pulmonary function based on the arterial partial pressure of oxygen/fraction of inspired oxygen ratio (P/F ratio) during the first 9 days after surgery. Secondary endpoints included platelet count, serum C-reactive protein (CRP) concentration, plasma neutrophil elastase-α(1)-antitrypsin complex level, duration of mechanical ventilation and systemic inflammatory response syndrome (SIRS), and length of intensive care unit (ICU) and hospital stay. RESULTS: The mean P/F ratio of patients who received SSH was significantly higher than that of the control group on postoperative days 1-5 and 7. Duration of mechanical ventilation and SIRS, and length of ICU stay were significantly shorter in the treatment group. Serum CRP concentration on postoperative day 9 was significantly lower (P = 0·048), platelet counts on days 2, 3 and 5 were higher (P = 0·012, P = 0·049 and P = 0·006 respectively), and the incidence of postoperative acute lung injury was significantly lower following SSH treatment (P = 0·023). CONCLUSION: Perioperative sivelestat may maintain postoperative pulmonary function following video-assisted oesophagectomy.

Effects of an elemental diet to reduce adverse events in patients with esophageal cancer receiving docetaxel/cisplatin/5-fluorouracil: a phase III randomized controlled trial-EPOC 2 (JFMC49-1601-C5).

BACKGROUND: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy. PATIENTS AND METHODS: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1 : 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance. RESULTS: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046). CONCLUSIONS: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.

Risk factors for lymph node metastasis in histologically poorly differentiated type early gastric cancer.

BACKGROUND: We retrospectively evaluated the predictive factors for lymph node metastasis in poorly differentiated early gastric cancer (poorly differentiated tubular adenocarcinoma, signet-ring cell carcinoma, mucinous adenocarcinoma) in order to examine the possibility of endoscopic resection for poorly differentiated early gastric cancer. METHODS: A total of 573 patients with histologically poorly differentiated type early gastric cancer (269 mucosal and 304 submucosal), who had undergone curative gastrectomy, were enrolled in this study. Risk factors for lymph node metastasis were evaluated by univariate and logistic regression analysis. RESULTS: Lymph node metastasis was observed in 74 patients (12.9%) (6 with mucosal cancer and 68 with submucosal cancer). By univariate analysis risk factors for lymph node metastasis were lymphovascular invasion (LVI) (presence), depth of invasion (submucosa), and tumor diameter (> 20 mm), ulcer or ulcer scar (presence), and histological type (mucinous adenocarcinoma). By multivariate analysis, risk factors for lymph node metastasis were LVI, depth of invasion, and tumor diameter. In mucosal cancers, the incidence of lymph node metastasis was 0% irrespective of LVI in tumors smaller than 20 mm, and 1.7% in tumors 20 mm or larger without LVI. In submucosal cancers, the incidence of lymph node metastasis was 2.4% in tumors smaller than 20 mm without LVI. CONCLUSIONS: A histologically poorly differentiated type mucosal gastric cancer measuring less than 20 mm and without LVI may be a candidate for endoscopic resection. This result should be confirmed in a larger study with many patients.

Relationship between nutritional status and esophageal fistula formation after radiotherapy for esophageal cancer.

PURPOSE: Chemoradiotherapy and radiotherapy for esophageal cancer sometimes cause esophageal fistulas. Esophageal fistulas often require additional procedures and are associated with a high mortality rate. The present study was conducted to determine the risk factors associated with esophageal fistulas in patients with esophageal cancer. PATIENTS AND METHODS: We reviewed the cases of 206 patients who were treated with definitive radiotherapy for esophageal cancer. The planning dose, which ranged from 44 to 64.8Gy (median: 59.4Gy), was delivered to the primary lesion and regional lymph nodes. Descriptive statistics were calculated, and time-to-event analyses were performed using Cox proportional hazards regression analysis. RESULTS: None of the 68 patients with T1 or T2 esophageal cancer developed esophageal fistulas. Among the 138 patients with T3 or T4 esophageal cancer, esophageal fistulas were detected in 20 (14.5%) patients. Multivariate analysis of the 138 patients with T3 or T4 esophageal cancer revealed low body mass index (BMI) to be an independent risk factor for esophageal fistula formation (P=0.0055). The optimal BMI cut-off value for predicting esophageal fistula formation was 20 kg/m2 (P=0.0121, odds ratio=4.130). CONCLUSION: In patients with esophageal cancer treated with definitive radiotherapy, a BMI below20kg/m2 is a risk factor for esophageal fistula formation. A well-designed randomized controlled trial comparing the incidence of esophageal fistulas between patients with esophageal cancer who do and do not receive nutritional support before radiotherapy is required.

Randomized clinical trial of high versus low inferior mesenteric artery ligation during anterior resection for rectal cancer.

BACKGROUND: The optimal level for inferior mesenteric artery ligation during anterior resection for rectal cancer is controversial. The aim of this randomized trial was to clarify whether the inferior mesenteric artery should be tied at the origin (high tie) or distal to the left colic artery (low tie). METHODS: Patients were allocated randomly to undergo either high- or low-tie ligation and were stratified by surgical approach (open or laparoscopic). The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were duration of surgery, blood loss and 5-year overall survival. RESULTS: Some 331 patients entered the trial between June 2006 and September 2012. The trial was stopped prematurely as recruitment was slow. Seven patients were excluded after randomization but before operation because of procedural changes. High tie and low tie were performed in 164 and 160 patients respectively. The incidence of anastomotic leakage was not significantly different (17·7 versus 16·3 per cent respectively; P = 0·731). The incidence of severe complications requiring intervention was 2·4 versus 5·0 per cent for high and low tie respectively (P = 0·222). In multivariable analysis, risk factors for anastomotic leakage included male sex (odds ratio 4·36, 95 per cent c.i. 1·56 to 12·18) and distance of the tumour from the anal verge (odds ratio 0·99, 0·98 to 1·00). At 5 years there were no significant differences in overall (87·2 versus 89·4 per cent respectively; P = 0·386) and disease-free (76·3 versus 77·6 per cent; P = 0·765) survival. CONCLUSION: The level of ligation of the inferior mesenteric artery does not significantly influence the rate of anastomotic leakage. Registration number: NCT01861678 ( https://clinicaltrials.gov).

Appropriate lymph node dissection for early gastric cancer based on lymph node metastases.

BACKGROUND: Lymph node dissection in patients with early gastric cancer is controversial because lymph node metastases are much less common than in advanced cancer. Therefore, routine extensive lymph node dissection with wide resection of the stomach may be excessive, and an appropriate lymph node dissection procedure in patients with early gastric cancer should be established. METHODS: Retrospectively, 588 consecutive patients with early gastric cancer were analyzed by univariate and multivariate analysis to predict lymph node metastases with clinicopathologic variables. The sites and rates of lymph node metastases for each tumor location were mapped. RESULTS: In early gastric cancer, depth of invasion was an independent predictive factor of lymph node metastases. In cancer confined to the mucosa, however, tumor diameter was the only predictive factor. In contrast, tumor diameter, macroscopic appearance, and histologic type were not predictive factors in early gastric cancers invading the submucosa. In mucosal cancer, metastasis to lymph nodes was confined to the paragastric lymph nodes on the same side of the stomach as the tumor. In submucosal cancer, the incidence of lymph node metastasis was 2% to 17% in group 1 and 1% to 3% in group 2 lymph nodes. CONCLUSIONS: In mucosal cancer, lymph node dissection is unnecessary for tumors measuring less than 30 mm, and limited lymph node dissection with local gastrectomy is appropriate when tumor diameters are 30 mm or greater. In submucosal cancer, gastrectomy with dissection of group 1 and some group 2 lymph nodes should be sufficient to remove all nodal metastases.

Correlation of immunohistochemical p53 labeling index with inhibition rate in chemosensitivity test in gastric and colon cancer.

To determine whether the expression of p53, p21, bcl-2 or Ki-67 in cancer cells is predictive of chemosensitivity, immunohistochemical examination of these factors and chemosensitivity assays were performed on colon and gastric cancer specimens. Chemosensitivity tests were performed using CDDP, 5-FU, MMC, or ADR and inhibition rate (IR) was calculated by MTT assay. Before exposure to anticancer drugs, the samples were investigated immunohistochemically for expression of the above factors and after anticancer drug exposure by TUNNEL staining, for the presence of apoptotic cells. With 5-FU and MMC, the apoptotic index was well correlated with IR, so their effects were related to apoptosis. Moreover, with these two agents, the p53 labeling index (LI) was inversely correlated with IR and p21-LI showed a good correlation with IR. We therefore concluded that immunohistochemical studies for p53 and p21 were useful for predicting the chemosensitivities of colon and gastric cancer to MMC and 5-FU.

Indications for paraaortic lymph node dissection in gastric cancer patients with paraaortic lymph node involvement.

BACKGROUND/AIMS: The surgical results for stage IVb gastric cancer remain very poor. The purpose of the current study is to reveal indications for paraaortic lymph node dissection in stage IVb gastric cancer patients with paraaortic lymph node involvement by analyzing prognostic factors for 3-year survival of stage IVb gastric cancer patients followed by curative B resection. METHODOLOGY: The 3-year survival in clinicopathologic variables were compared by univariate analysis. Using Cox proportional hazards regression model, independent prognostic factors were identified from 11 variables. RESULTS: Overall 5-year survival in stage IVb was 26.5%; mean survival was 19 months. Using univariate analysis, p53 expression significantly influenced 3-year survival. Using Cox proportional hazards regression model, the number of total positive lymph nodes, the number of positive paraaortic lymph nodes, and p53 expression were independent prognostic factors. CONCLUSIONS: In stage IVb, paraaortic lymph node dissection should be indicated in patients with < or = 10 total positive lymph nodes, and < or = 3 positive paraaortic lymph nodes or p53 expression < or = 50%. This indication can be applied according to the preoperative imaging, the staining of p53 by endoscopic biopsy specimens and the intraoperative microscopic evaluation of dissected lymph nodes.

Significance of para-aortic lymph node dissection in advanced gastric cancer.

BACKGROUND/AIMS: Since surgical results in advanced gastric cancer remain poor and para-aortic lymph node dissection may contribute to survival, it is useful to determine the significance of para-aortic lymph node dissection. METHODOLOGY: Para-aortic lymph node dissection was provisionally indicated for patients with invasion depth deeper than the subserosal layer. Clinicopathologic variables were retrospectively analyzed using univariate analysis and multivariate analysis to predict para-aortic lymph node metastasis. Similarly, they were analyzed using univariate analysis and the Cox's proportional hazards regression model to estimate the prognostic factor in 120 patients who underwent para-aortic lymph node dissection. Surgical results and post-operative complications were compared between para-aortic lymph node dissection and D2 dissection. RESULTS: Univariate analysis revealed that the mean diameter, the degree of lymph node metastasis, and the invasion depth were significant predictors of para-aortic lymph node metastasis. Multivariate analysis showed that n2 was the only independent predictive factor as to para-aortic lymph node metastasis. Univariate analysis revealed tumor site, tumor diameter, lymph node metastasis, number of positive lymph nodes, INF, and stage were significantly associated with 5-year survival. The Cox's proportional hazards regression model showed that the number of positive lymph nodes and the number of positive para-aortic lymph nodes were independent prognostic factors. Patients with < or = 10 positive lymph nodes in any stage or < or = 3 positive para-aortic lymph nodes in stage IVb had significantly better surgical results. Surgical results for patients who underwent para-aortic lymph node dissection with n2 or invasion depth deeper than the exposed serosa were significantly higher than those in D2. As to post-operative complications, pancreatic fistula and respiratory complications were significantly frequent after para-aortic lymph node dissection. CONCLUSIONS: n2 is helpful in predicting para-aortic lymph node metastasis. Whereas, post-operative morbidity such as pancreatic fistula and respiratory complications after para-aortic lymph node dissection were significantly higher, they were controllable. Para-aortic lymph node dissection should be indicated in advanced gastric cancer patients in which lymph node metastasis is over n2 or invasion depth is deeper than the exposed serosa. But the number of positive para-aortic lymph nodes must be less than three.

Prognostic factors in early gastric cancer.

BACKGROUND/AIMS: Opportunities of observing patients with recurrent early gastric cancer are rare. Assessment of prognostic factors for the recurrence of early gastric cancer is important for determining adequate strategies for managing early gastric cancer. METHODOLOGY: Clinicopathologic variables were compared in 8 patients with and 453 without recurrence who were followed for over 5 years after curative resection. Expression of mutant p53 and Ki-67 was evaluated in 16 patients with n2 or above. RESULTS: Eight patients died of gastric cancer with recurrence. There were no inter-group differences in mean diameter, histologic classification, patterns of infiltrating growth, or cancer-stroma relationship; but macroscopic appearance, depth of invasion, lymphatic invasion, venous invasion and lymph node metastases were significantly more frequent on univariate analysis in those with recurrence. Lymph node metastases was an independent prognostic factor by the Cox proportional hazards regression model. In patients with n2 or above, mutant p53 expression was higher in recurrent than in nonrecurrent cases. CONCLUSIONS: Lymph node metastasis was the only independent prognostic factor for the recurrence of early gastric cancer. The expression of mutant p53 may be an indicator of recurrence in patients with n2 or above.

Changes in clinicopathological findings after portal vein embolization.

BACKGROUND/AIMS: Portal vein embolization is becoming more common as a method of preventing hepatic failure after an extended hepatectomy but its mechanism is not well understood. This clinicopathological study focused on its mechanism. METHODOLOGY: Thirty patients who underwent extended hepatectomy after portal vein embolization were evaluated. Liver volume was measured before and after portal vein embolization, and histological studies were performed to examine morphological changes, morphometric parameters and apoptosis of hepatocytes. RESULTS: The mean volume of the non-embolized lobe grew significantly from 392 to 462 mL after portal vein embolization (P < 0.0001). The hypertrophy ratio of the non-embolized lobe (100 x volume change during portal vein embolization/volume before portal vein embolization, %) was correlated closely with the volume of the non-embolized lobe before portal vein embolization (r = -0.65, P < 0.0001). Histological study showed the embolized lobe hepatocytes to be atrophic, partly necrotic and apoptotic. In the non-embolized lobe, the mean hepatocyte volume was 8686 micron 3 (control: 6544 micron 3) and the mean hepatocyte count was 109 x 10(6)/mL (control: 122 x 10(6)/mL). CONCLUSIONS: The enlargement of the non-embolized lobe was caused by hypertrophy rather than hyperplasia suggesting hyperfunction. The resection of the atrophic embolized lobe, leaving the hypertrophic non-embolized lobe was thought to be less surgically stressful than hepatectomy without portal vein embolization.

[Positive perceptions encouraging continued caregiving at home among family caregivers].

PURPOSE: Few data are available on factors encouraging continued caregiving at home, especially in relation to positive perceptions of caregiving and the care burden. This study was conducted to explore this question. METHODS: We collected data from forty caregivers using Visiting nursing station, with structured interviews conducted at home. RESULTS: 1. Sixty-five percent of caregivers had positive perceptions of the worth and enjoyment of their work in caregiving. 2. Encouraging continued caregiving was associated with positive perceptions and these are relatively independent of the care burden. 3. Caregivers who had high encouraging continued caregiving were spouses or children of the clients. They had positive attitude to caregiving, an intention to use social services and satisfaction in caregiving. 4. Events from which caregivers felt worth and enjoyment in their work were improvement of client's health conditions, gratitude in client response, learning of care skills and strengthening bonds of family relationship. CONCLUSION: The findings suggest it is important to approach caregivers for the positive perceptions, rather than simply by decreasing burden.

[Clinical evaluation of granisetron hydrochloride for nausea and vomiting induced by oral anticancer drugs].

We investigated the antiemetic effect, safety and usefulness of granisetron hydrochloride tablets on nausea and vomiting induced by oral anticancer drugs used in chemotherapy for gastric cancer and colorectal cancer. In the present trial, oral administration of granisetron hydrochloride was performed during 5 days after nausea or vomiting. 1) Clinically, the effective rate of granisetron hydrochloride (the percentage of cases in which the drug was assessed as "Remarkably effective" or "Effective") was more than 75% on each day of administration. There were no adverse events or abnormal laboratory tests. 2) In terms of usefulness, granisetron hydrochloride was rated "Extremely useful" or "Useful" in 17 out of 23 cases (78.2%). The above results have shown that granisetron hydrochloride tablets, administrated orally once daily at a dose of 2 mg, have an excellent antiemetic effect, and that this is a safe and useful drug.

Effects of hEGF (MG111) on gastric mucosal potential difference in rats.

hEGF (GMG111) given i. v. significantly and dose-dependently suppressed the reduction in gastric mucosal potential-difference (PD) induced by 30% ethanol in rats. Pretreatment with indomethacin did not affect its effect, thereby suggesting that endogenous prostaglandins will not be involved in the mechanism of action of MG111. These results indicate that MG111 protects the weakening of "gastric mucosal barrier". The PD was significantly reduced when MG111 was given i. v. at 20 micrograms/kg. This reduction caused by MG111 was not affected by pretreatment with atropine, hexamethonium, propranolol, and phentolamine.

[Changes in gastric mucosal glycosidases and thiobarbituric acid reactants induced by burn stress in obstructive jaundice rats].

To elucidate the pathogenesis of acute gastric mucosal lesion (AGML), burn stress was loaded in rats with and without obstructive jaundice. The activation of gastric mucosal glycosidases (beta-N-acetyl-D-glucosaminidase (NAG), beta-glucuronidase (BG)), which were released into the cytoplasm as a results of instability of the lysosomal membrane, was studied biochemically, enzymatically and histochemically after burn stress with and without obstructive jaundice. The latent enzyme activity calculated by NAG or BG, which represented the stability of lysosomal membrane, was lowest at 2-3 hour after burn stress in both groups. In other words, the degree of activation of the glycosidases was highest at 2-3 hour after burn stress. The latent enzyme activity calculated by NAG decreased significantly (p < 0.05) at 1 hour after burn stress in obstructive jaundice group compared with the non-obstructive jaundice group. The staining of NAG before burn stress was observed in mucus neck cell and surface epithelial cell in granular shape and it was observed diffusely after burn stress, especially in obstructive jaundice group. The changes in staining of BG was similar to NAG. Before activation of glycosidases, the thiobarbituric acid reactants, which are considered products of lipid peroxidation, increased promptly at 30 min after burn stress in both groups. Ulcer index increased gradually after burn stress and the significance was found between in the obstructive jaundice group and in non-obstructive jaundice group at 3 hour after burn stress. It's concluded that obstructive jaundice accelerated the fragility of lysosomal membrane after burn stress and these change were considered to be the reasons of frequent occurrence of AGML.