Prophylactic Effect of Premedication with Intravenous Magnesium on Renal Dysfunction in Preoperative Cisplatin-Based Chemotherapy for Esophageal Cancer.

BACKGROUND: Magnesium premedication is reported to have a significant effect on reducing cisplatin-induced nephrotoxicity in several types of cancer. However, the effectiveness of magnesium administration in reducing nephrotoxicity remains unknown in esophageal cancer, especially regarding neoadjuvant therapy. METHODS: Between January 2017 and January 2019, 105 patients who underwent neoadjuvant chemotherapy followed by surgery were included in this study. Of these patients, 40 received intravenous magnesium premedication (magnesium group), whereas the remaining 65 did not (control group). We investigated the -association between magnesium premedication and chemotherapy-related nephrotoxicity. RESULTS: Baseline characteristics, such as age, body mass index, clinical stage, comorbidity, and pretreatment renal function, were not significantly different -between the magnesium and control groups. Clinical and -pathological responses were similar between the 2 groups. Regarding chemotherapy-related toxicity, there were no significant differences in hematological side effects, such as anemia, thrombopenia, and neutropenia, between both groups. However, nephrotoxicity of grade 2 and higher was significantly less frequent in the magnesium group than in the control group (2.5 vs. 21.5%, p = 0.0026), although there was no significant difference in the incidence of other nonhematological adverse events, such as nausea and diarrhea. Multivariate analysis indicated magnesium premedication and heart disease as independent factors associated with cisplatin-induced nephrotoxicity (p = 0.0026 and p = 0.0424, respectively). CONCLUSION: We showed that intravenous magnesium premedication exerts a protective effect against renal dysfunction in esophageal cancer patients undergoing neoadjuvant chemotherapy including high-dose cisplatin. Large-scale prospective studies are needed to confirm the effect of magnesium premedication on reducing nephrotoxicity in esophageal cancer patients undergoing neoadjuvant therapy.

The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study.

BACKGROUND & AIMS: Neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer (PC) is potentially associated with various toxicities, which can lead to impaired nutritional status. Eicosapentaenoic acid (EPA) can reduce proinflammatory cytokines and positively influence cancer cachexia syndrome. The aim of this study is to clarify the utility of EPA enriched nutrition support during NACRT for PC. METHODS: We randomly assigned 62 patients with PC that received NACRT to either a nutrition intervention (NI) or a normal diet (ND). Patients in the NI group received 2 bottles/day (550 kcal/day) of an EPA-enriched nutrition supplement during NACRT. The primary endpoints were the before-to-after NACRT ratios (post/pre ratios) of skeletal muscle mass and psoas major muscle area (PMA). The secondary endpoints were the post/pre ratios of other nutritional parameters and treatment-related toxicities. RESULTS: Only 14 patients (45.2%) in the NI group consumed more than 50% of the EPA-enriched supplement provided. The post/pre ratio of skeletal muscle mass in the NI group (0.99 ± 0.060) was not significantly different from that of the ND group (0.96 ± 0.079, p = 0.102). However, patients that consumed ≥50% of the EPA-enriched supplement (the good intake group) had significantly higher skeletal muscle mass ratios than patients in the ND group (p = 0.042). The PMA ratio was significantly higher in the NI group (0.96 ± 0.081) than in the ND group (0.89 ± 0.072, p = 0.001). The NI and ND groups were not significantly different in other nutritional parameters or in NACRT-related toxicity. CONCLUSIONS: We found that EPA-enriched intake could potentially improve the nutritional status of patients with PC that received NACRT, but it was difficult for many patients to drink, due to its disagreeable taste. University Hospital Medical Information Network (http://www.umin.ac.jp), registration number UMIN000033589, https://upload.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000038300.

Randomized Controlled Trial of Adjuvant Chemotherapy with Fluoropyrimidines Versus Surgery-alone for Gastric Cancer.

AIM: This prospective randomized study compared the survival of patients with stage IB-IIIA gastric cancer treated with surgery alone or surgery followed by adjuvant chemotherapy. PATIENTS AND METHODS: Patients with pathological stage IB-IIIA disease were randomly assigned to the following groups: surgery alone (n=116), or surgery followed by adjuvant chemotherapy with 5-fluorouracil, doxifluridine, or uracil-tegafur for 12 months (n=113). RESULTS: The overall survival rate was 86.1% in the adjuvant group and 78.5% in the surgery-alone group. The overall survival rate did not significantly differ between the adjuvant-chemotherapy and surgery-only groups (p=0.163). In the subgroup analyses, patients with stage II disease and those receiving uracil-tegafur treatment in the adjuvant group showed significantly better prognosis than those in the surgery-alone group (p=0.036 and 0.005, respectively). CONCLUSION: This study did not find a significant survival benefit to be associated with adjuvant chemotherapy with fluoropyrimidines in patients with stage IB-IIIA gastric cancer. However, it may be effective for patients with stage II disease. Additionally, uracil-tegafur is a promising agent for adjuvant chemotherapy of gastric cancer if S-1 is not available because of its toxicity.

Randomized study of the clinical effects of ω-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer.

OBJECTIVES: Omega-3 (ω-3) fatty acids have potential positive effects during chemotherapy, such as body weight maintenance and muscle mass preservation. However, little is known about the effect this supplement might have on reducing chemotherapy-induced toxicities. The aim of this study was to determine the usefulness of ω-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities. METHODS: Sixty-one patients undergoing neoadjuvant chemotherapy for esophageal cancer randomly received ω-3-rich enteral nutrition (EN; n = 31) or ω-3-poor EN support (n = 30) for 15 d during chemotherapy. The daily dosage of ω-3 fatty acids was 900 mg in the ω-3-rich group and 250 mg in the ω-3-poor group. The primary endpoint was the frequency of grade 3/4 neutropenia, and secondary endpoints included other chemotherapy-related adverse events, body weight, and inflammatory markers. RESULTS: The total and dietary intake calories during chemotherapy were equal in both groups. There was no significant difference in the body weight change after chemotherapy between the two groups. There was no significant difference in the incidence of grade 3/4 leukopenia and neutropenia (P > 0.05). However, stomatitis was significantly less frequent in the ω-3-rich group, than in the ω-3-poor group (P = 0.018). Grade 3/4 diarrhea occurred relatively less frequently in the ω-3-rich group than in the ω-3-poor group; however, this difference was not significant (16.1% versus 36.7%, respectively, P = 0.068). Increases in the aspartate aminotransferase and alanine aminotransferase levels were seen significantly less frequently in the ω-3-rich group than in the ω-3-poor group (P = 0.012 and P = 0.015, respectively). CONCLUSIONS: ω-3-rich EN support decreased the frequency of chemotherapy-induced mucosal toxicities, such as stomatitis and diarrhea, and exhibited a hepatoprotective effect during chemotherapy, compared with the ω-3-poor EN support.

[A feasibility study of adjuvant therapy with capecitabine plus oxaliplatin (XELOX) for Japanese patients with advanced colorectal cancer].

We prospectively evaluated the feasibility of XELOX(oxaliplatin 130 mg/m/(2) on day 1 plus capecitabine 1,000 mg/m(2) twice daily on days 1 to 14 every 3 weeks) for adjuvant treatment in 15 patients with stage III/IV (Japanese classification) colorectal cancer and pathological curability A or B after D2-D3 lymph node dissection. Patients were seen at our institute between September 2009 and January 2012. In the current study, no severe adverse events occurred, including hand-foot syndrome greater than Grade 3, as compared with the MOSAIC, NSABP C-07, and NO16968/XELOXA trials. We confirm that XELOX is a feasible treatment option and discuss the benefits of evaluating the safety and efficacy of XELOX in more patients.

[A Patient with Rectal Cancer and Multiple Lung Metastases Treated with XELOX plus Bevacizumab (Bev) Therapy].

The patient was a 76-year-old woman who underwent laparoscopic-assisted low anterior resection for rectal cancer. According to the Japanese classification of colorectal carcinoma (8th Edition), the tumor was tub1, ly0, v0, and pStage Ⅰ (pT1bN0M0), Cur A. She received no adjuvant chemotherapy. A chest CT scan obtained 42 months after the surgery revealed 3 lung metastases in the left lung, with the biggest measuring 12 mm; the CA19-9 level was elevated to 72U/mL (normal≦38 U/mL). She declined surgery for the recurrence. She was treated with XELOX plus bevacizumab (Bev) therapy. Before XELOX plus Bev, the 3 lung metastases had enlarged, with the biggest now measuring 15 mm, and the CA19-9 level was elevated to 166 U/mL. After 4 cycles, the lung metastases decreased in size and the CA19-9 level decreased to 4 U/mL. We did not perform pulmonary resection or additional chemotherapy. No progression of the recurrent tumors was detected on CT after 2 years, and the CA19-9 level was within the normal range. XELOX plus Bev therapy may be effective for unresectable pulmonary metastasis from colorectal cancer.

Prognostic Significance of (18)F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET)-Positive Lymph Nodes Following Neoadjuvant Chemotherapy and Surgery for Resectable Thoracic Esophageal Squamous Cell Carcinoma.

PURPOSE: Patients with resectable thoracic esophageal squamous cell cancer (TESCC) and positron emission tomography (PET)-positive lymph nodes (PET-N positive) are likely to have ≥3 pathological lymph node metastases (pLNMs) and show a higher rate of postoperative recurrence despite curative resection than PET-N-negative TESCC patients. We examined the prognostic significance of (18)F-fluorodeoxyglucose uptake into lymph node metastases after neoadjuvant chemotherapy (NAC) for PET-N positive TESCC and aimed to propose the optimal NAC response criteria for these patients. METHODS: Fifty-one patients with PET-N positive TESCC underwent two courses of NAC followed by surgery. Metabolic responses of primary tumors and LNs were prospectively evaluated and associations with clinicopathological data and patient survival assessed by univariate and multivariate analyses. RESULTS: After NAC, 21 patients were post-treatment (post-) PET-N positive and 30 post-PET-N negative. A significantly (p < 0.001) high proportion of the post-PET-N-negative group had ≤2 pLNMs than the post-PET-N positive group (86.7 vs. 28.6 %). The PET-N negative group also had a significantly lower distant metastasis rate (23.3 vs. 75.0 %) and higher 5-year relapse-free survival (RFS) rate (69.0 vs. 20.0 %). Univariate and multivariate Cox's proportional hazard regression analyses identified post-PET-N negative status as the only significant favorable predictive factor for low postoperative recurrence (p = 0.015) independent of the primary tumor response. CONCLUSIONS: PET-N negative status predicts ≤2 pLNMs and longer RFS in resectable TESCC patients even after NAC. Therefore, post-PET-N status, not the effects on the primary tumor, is a critical NAC treatment response criterion for evaluating prognosis and guiding subsequent treatment.

[Irradiation with carbon ions for locally recurrent rectal cancer].

A female patient in her 70s underwent an abdominoperineal resection and bilateral lymph node dissection for advanced lower rectal cancer. The patient did not receive neoadjuvant therapy. In the Japanese classification of colorectal carcinoma (8th Edition), the tumor was a moderately differentiated type 2 adenocarcinoma, and was 4.5 cm in size. Histologically, the tumor was considered to be Stage IIIb (T3N0M0). She received no adjuvant chemotherapy. After 39 months, pelvic computed tomography (CT ) revealed a 29 mm tumor in the right pelvic wall. The patient declined surgery for recurrence so radiotherapy was planned. First, chemotherapy with mFOLFOX6 was administered for 4 courses to reduce tumor size. Consequently, irradiation with carbon ions was given to the site of recurrence at a total dose of 74 GyE in 37 fractions. There were no severe complications. Carcinoembryonic antigen (CEA) level decreased to the lower limit of the normal range from a maximum of 4.9, and no progression of the recurrent tumor was detected on CT for approximately 4 years. Systemic chemotherapy followed by irradiation with carbon ions may be effective for recurrent rectal cancer.

Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling.

Sorafenib is a multi-kinase inhibitor applicable to hepatocellular carcinoma (HCC), but its limited therapeutic effects are a major problem to be solved. Here, we show that blockade of ataxia telangiectasia mutated (ATM) improves the antitumor effects of sorafenib. When hepatoma cell lines HepG2 and PLC/PRF/5 were treated with sorafenib plus ATM small inhibitory RNAs, ATM inhibitor KU55933 or caffeine, Akt signaling was suppressed and the cytotoxic effects were significantly potentiated. Moreover, ATM inhibition effectively suppressed the sorafenib-induced cell migration. Taken together, manipulation of ATM activity might be a useful strategy for improving sorafenib treatment of HCC.

Randomized study of clinical effect of enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer.

BACKGROUND & AIMS: Enteral nutrition (EN) is provided for patients with cancer. However, Little is known about the clinical efficacy of EN support during chemotherapy in patients with cancer. METHODS: Ninety-one patients who received neoadjuvant chemotherapy (5-fluorouracil, cisplatin and adriamycin) for esophageal cancer were enrolled to receive either EN (n = 47) or PN (n = 44) at random. The primary endpoint was the incidence of chemotherapy-related toxicities during chemotherapy. RESULTS: Total and dietary intake calories during chemotherapy were equal in the two groups. There were no significant differences in serum albumin level and body weight change after chemotherapy between the two groups. There was no significant difference in tumor response to chemotherapy between the two groups (EN: 51%, PN: 55%, p = 0.886). Leukopenia and neutropenia of grade 3 or 4, defined according to the Common Toxicities Criteria of the National Cancer Institute, were significantly less frequent in the EN group than PN group (leukopenia: 17% vs 41%, p = 0.011, neutropenia: 36% vs 66%, p = 0.005). Lymphopenia and thrombocytopenia tended to be less frequent in the EN group, albeit insignificantly. CONCLUSIONS: Compared with PN support, EN support during neoadjuvant chemotherapy reduced the incidence of chemotherapy-related hematological toxicities in patients with esophageal cancers.

[A case of perianal squamous cell carcinoma attaining a complete response over five years with chemoradiotherapy].

We report a case with perianal squamous cell carcinoma, which showed a complete response more than five years after chemoradiotherapy. A 69-year-old-man was introduced to our hospital for the diagnosis of squamous cell carcinoma [T3 (8.0 × 8.0 cm) N0M0, Stage II]. The patient was treated by chemoradiotherapy, which consisted of 5-FU 750 mg/m²/ day (continuous intravenously) on days 1-5 and 29-33, and mitomycin C 10 mg/m² on days 1 and 29 and radiation at 2 Gy/day for 5 days per week (total dose 60 Gy). The patient tolerated this treatment with no severe adverse effects. Tumor disappeared completely 1 month after this treatment with no adjuvant therapy. The patient has been alive with no sign of recurrence for 6 years.

Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential treatment for hepatitis C.

BACKGROUND: Previously we reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, inhibited hepatitis C virus (HCV) RNA replication. Furthermore, recent reports revealed that the statins are associated with a reduced risk of hepatocellular carcinoma and lower portal pressure in patients with cirrhosis. The statins exhibited anti-HCV activity by inhibiting geranylgeranylation of host proteins essential for HCV RNA replication. Geranylgeranyl pyrophosphate (GGPP) is a substrate for geranylgeranyltransferase. Therefore, we examined the potential of geranyl compounds with chemical structures similar to those of GGPP to inhibit HCV RNA replication. METHODS: We tested geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K(2) and teprenone (Selbex)] for their effects on HCV RNA replication using genome-length HCV RNA-replicating cells (the OR6 assay system) and a JFH-1 infection cell culture system. Teprenone is the major component of the anti-ulcer agent, Selbex. We also examined the anti-HCV activities of the geranyl compounds in combination with interferon (IFN)-α or statins. RESULTS: Among the geranyl compounds tested, only teprenone exhibited anti-HCV activity at a clinically achievable concentration. However, other anti-ulcer agents tested had no inhibitory effect on HCV RNA replication. The combination of teprenone and IFN-α exhibited a strong inhibitory effect on HCV RNA replication. Although teprenone alone did not inhibit geranylgeranylation, surprisingly, statins' inhibitory action against geranylgeranylation was enhanced by cotreatment with teprenone. CONCLUSIONS: The anti-ulcer agent teprenone inhibited HCV RNA replication and enhanced statins' inhibitory action against geranylgeranylation. This newly discovered function of teprenone may improve the treatment of HCV-associated liver diseases as an adjuvant to statins.

Myelotoxicity of preoperative chemoradiotherapy is a significant determinant of poor prognosis in patients with T4 esophageal cancer.

PURPOSE: Currently, preoperative chemoradiotherapy followed by surgery is the only promising strategy for patients with T4 esophageal cancer. This study retrospectively analyzed the prognostic factors in patients with curatively resected cancer after chemoradiotherapy. PATIENTS AND METHODS: Between September 1989 and December 2003, 42 patients with T4 esophageal cancer received preoperative chemoradiotherapy (CRT) followed by curative surgery. Chemotherapy consisted of 5-fluorouracil/cisplatin (FP) or 5-fluorouracil/adriamycin/cisplatin (FAP). A total dose of 40 Gy of radiation was delivered concurrently. Surgery was scheduled 4 weeks after the completion of CRT. The treatment response was categorized using general criteria. Toxicities of the CRT were assessed according to National Cancer Institute of Common Toxicity Criteria (NCI-CTC). Univariate and multivariate analyses were performed to identify significant prognostic clinicopathological factors. RESULTS: The overall survival rate was 38.4% at 5 years. The toxic grade for leukopenia (grade 0-2/3-4) and pathological effect (grade 3/1-2) were significantly different by univariate analysis (P = 0.03 and 0.05, respectively). Multivariate analysis identified the toxic grade for leukopenia as the only significant and independent determinant of prognosis (P = 0.05). CONCLUSION: In patients with T4 esophageal cancer who receive CRT followed by curatively resection, myelogenic chemotoxicity is a significant prognostic factor.

Lack of fludeoxyglucose F 18 uptake in posttreatment positron emission tomography as a significant predictor of survival after subsequent surgery in multimodality treatment for patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Patients with advanced esophageal squamous cell carcinoma receive neoadjuvant chemotherapy or chemoradiotherapy to improve survival, but benefits are observed only in those with histologic response. Positron emission tomography with fludeoxyglucose F 18 (INN fludeoxyglucose [(18)F]) detects accumulation of glucose analog in viable cancer cells. This study investigated the usefulness of positron emission tomography with fludeoxyglucose F 18 in assessment of response of advanced esophageal squamous cell carcinoma to neoadjuvant treatment to establish new criteria to predict postoperative long-term survival. METHODS: Fifty patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant therapy (chemotherapy 35, chemoradiotherapy 15) underwent positron emission tomography with fludeoxyglucose F 18 before surgical resection in evaluation of posttreatment maximum standardized uptake value, residual tumor size (maximum square area of longitudinal axis), histologic response, and postoperative survival. RESULTS: After treatment, uptake was not noted in 21 patients (posttreatment maximum standardized uptake value < 2.5, negative) but was detected in 29 (> or = 2.5, positive). Residual tumor size ranged from 0 to 54.0 mm(2) for negative results and 55.0 to 676.0 mm(2) for positive, clearly distinguishing histologic major response from nonresponse. The negative group demonstrated significantly higher 5-year cause-specific survival (67.7%) and lower hematogenous recurrence (4.8%) than the 36.5% and 37.0% values in the positive group, (P < .0042 and P = .0083, respectively). Univariate Cox regression analyses identified posttreatment maximum standardized uptake value (cutoff 2.5) as the only preoperative prognostic factor (P = .0071). CONCLUSION: Posttreatment positron emission tomography with fludeoxyglucose F 18 reliably predicted histologic response and postoperative survival in advanced esophageal squamous cell carcinoma. This tool could potentially be used to tailor optimal treatment according to individual responses.

[omega-3 Fatty acid-containing diet (Racol) reduces toxicity of chemoradiation therapy for patients with esophageal cancer].

Recently, it is reported that a omega-3 fatty acid-containing diet (Racol) enhances innate immunity and reduces mucosal damage in the small intestine during chemotherapy. The aim of this study is to examine the effects of a omega-3 fatty acid-containing diet (Racol) on the toxicity of chemoradiation therapy (CRT) for patients with esophageal cancers. Toxicity of CRT was evaluated in 10 patients who took Rakol at a maximum dose of 600 mL/day during CRT, compared with 10 patients who did not take Rakol. Regarding blood toxicity, the decrease of platelets did not differ between the former and the latter. However, the incidence of grade 2~4 neutropenia was lower in the former than in the latter (p=0.0043). With regard to gastrointestinal toxicity, the incidence of grade 2~4 diarrhea was also lower in the former than in the latter (p=0.0118). Moreover, the incidence of grade 2~4 stomatitis/pharyngitis tended to decrease in patients who took Rakol compared with those who did not (p=0.0812). The current results indicated that a omega-3 fatty acid-containing diet (Racol) may be beneficial to patients with esophageal cancers who receive CRT by reducing CRT toxicity.

Liver perfusion chemotherapy for selected patients at a high-risk of liver metastasis after resection of duodenal and ampullary cancers.

OBJECTIVE: To evaluate the prognostic benefit of postoperative liver perfusion chemotherapy (LPC) in patients who undergo curative resection of duodenal and ampullary cancers. SUMMARY BACKGROUND DATA: Both nodal involvement and pancreatic invasion are poor prognostic indicators after curative resection of ampullary or duodenal cancers due to high incidences of liver metastasis. Therefore, we have performed postoperative LPC on a number of such "high-risk" patients. METHODS: During the period of 1990 to 2005, 72 consecutive patients successfully underwent curative (R0) resection of duodenal or ampullary carcinomas at our institution, The Osaka Medical Center for Cancer and Cardiovascular Diseases. Of these 72 patients, 38 were found to have positive nodal involvement and/or pancreatic invasion based on an intraoperative inspection, and of these, 28 were deemed to be suitable candidates for intraoperative catheterization: 1 catheter was placed into the gastroduodenal artery; another into the portal vein (group A). Postoperatively, they received an infusion of 5-fluorouracil (5-FU: 125 mg/d) via each of the 2 catheters for a period of 28 continuous days. The remaining 44 patients (group B) did not receive any other adjuvant therapy. The survival rates and patterns of disease failure were compared between these 2 groups and their subgroups. RESULTS: All 72 patients survived the operation, and all 28 patients in group A completed their courses of LPC without showing any significant adverse signs. Postoperative histopathology was later performed to get a more accurate picture regarding the degree of nodal involvement and/or pancreatic invasion: In group A, 21 patients (group A1) proved positive for nodal and/or pancreatic invasion whereas 7 patients (group A2) proved negative; and in group B, 16 patients proved positive (group B1) whereas 28 proved negative (group B2). Although group A displayed higher incidences of nodal involvement and pancreatic invasion, the 5-year survival rates for the 2 groups varied only slightly. The 5-year survival rate was 70% in group A1, 85% in group A2, 35% in group B1, and 92% in group B2, respectively. The difference between B1 and B2 and the difference between A1 and B1 were statistically significant, and these differences were conclusively found to be attributable to the different incidences of liver metastasis. CONCLUSION: Through this research, both nodal involvement and pancreatic invasion were confirmed to be reliable predictors of liver metastasis after curative resection of ampullary and duodenal cancers. Since LPC was proven to be effective in preventing the postoperative development of liver metastasis, it should be more actively performed for patients with a high-risk of liver metastasis.

Influence of bright light therapy on postoperative patients: a pilot study.

Bright light therapy is a method of maintaining or restoring the natural circadian rhythm by assisting daytime awakening using bright lights. Postoperative delirium is one of the potential complications encountered by patients receiving postoperative care in the intensive care unit (ICU), but there have been no studies on the use of light for the prevention of postoperative delirium. The objective of this study was to examine whether the circadian rhythms of patients after surgery for oesophageal cancer can be adjusted and whether the postoperative delirium crisis rate can be reduced by bright light therapy. The subjects were 11 patients operated on for oesophageal cancer in Osaka University Hospital. After informed consent was obtained, they were divided into a study group and a control group by a random sampling method. After removal of the endotracheal tube, the study group was exposed to light. The light intensity was about 5000lx immediately before the eyes, and the distance from the light source was about 100 cm. The control group was placed in a natural lighting environment after extubation. In both groups, the rhythms of physical activities and autonomic activities were monitored after surgery, and delirium was evaluated. A significant difference was observed in the delirium score between the study group and control group on the morning of day 3 of bright light therapy by the Mann-Whitney U-test (P=0.014). The study group could begin ambulation about 2 days earlier than the control group. Bright light therapy may reduce the rate of postoperative delirium and make early ambulation possible. However, our study involved a very small sample size. We want to increase the sample in the future after having reviewed clinical application methods.

[A case of refractory inguinal lymphorrhea cured by lipiodol lymphangiography].

We report a case of inguinal lymphorrhea cured by Lipiodol lymphangiography. The patient was a 80-year-old female who underwent an abdomino-perineal resection with lateral pelvic lymph node dissection and inguinal lymph node extraction for anal canal cancer. Histologically, the tumor was a poorly differentiated adenocarcinoma and considered to be stage IV (a2, n3 (+), P0, H3, M (-), cur C) in the Japanese classification of colorectal cancer. We recognized a lot of lymph node metastases in dissected lateral pelvic lymph node and inguinal lymph node. By hepatic arterial infusion using 5-FU (1250 mg/body weekly), the liver metastases had a complete response after 15 courses. She noticed a left inguinal lymph node swelling and an elevation of serum CEA level (79.5 ng/mL) was observed. There was no evidence of recurrence except left inguinal lymph nodes. She underwent a left inguinal lymph node dissection. Serous discharge from a surgical site persisted despite of conservative therapy such as compression. She received lymphangiography using 8 mL of Lipiodol from left dorsum of foot. We found three lymph ducts heading to left groin and observed a lot of Lipiodol leakage from ducts. We determined not only the site of leakage but we also confirmed a gradual decrease and a complete stop of lypmphorrhea in 7 days after lymphangiography. Slight lymph edema of left lower extremity appeared but gradually relieved. Lymphangiography using Lipiodol helps determine the site of leakage and may be an effective therapeutic modality for treating refractory lymphorrhea.

Neoadjuvant chemotherapy followed by salvage surgery: effect on survival of patients with primary noncurative gastric cancer.

The prognosis for gastric cancer patients who undergo noncurative resection is extremely poor. This study evaluated the effects of neoadjuvant chemotherapy for primary noncurative gastric cancer. Thirty-four patients with biopsy-proven noncurative gastric cancer were treated with either of two neoadjuvant chemotherapies: FEMTXP (5-fluorouracil, epirubicin, methotrexate, cisplatin) or THP-FLPM (pirarubicin, 5-fluorouracil, leucovorin, cisplatin, mitomycin C). Noncurability was determined by conventional staging procedures, staging laparoscopy, and exploratory laparotomy. After chemotherapy the resectability of the tumors was reassessed. Patients who were judged to be candidates for curative resection underwent salvage surgery. Of the final 33 patients, 8 (24.2%) showed a major response [0 complete response (CR), 8 partial response (PR)]. In three patients the second laparoscopy revealed disappearance of the peritoneal metastasis. Of the 33 patients, 14 (42.4%) underwent salvage surgery, including 8 curative resections (2 curability A, 6 curability B). Pathologic examinations revealed a grade 2 response in eight patients but no grade 3 response. Univariate analysis showed the following to be significant prognostic factors: histology type (differentiated type vs. undifferentiated type; p = 0.035), T4 as a noncurative factor (T4 vs. T3 or less; p = 0.025), clinical response (PR + no change vs. progressive disease; p = 0.002), and salvage surgery (resected vs. unresected; p = 0.001). Among these factors, salvage surgery was found to be the only independent prognostic factor by multivariate analysis, with a relative risk of 0.253 and a 95% confidence interval of 0.066 to 0.974. The treatment was well tolerated. Major toxicities of WHO grade 3 or more were leukopenia in 20 (60.6%), gastrointestinal toxicities in 5 (15.2%), renal toxicities in 2 (6.1%), and alopecia in 1 (3.0%). In conclusion, neoadjuvant chemotherapy is effective for primary noncurative gastric cancer when salvage surgery can be performed. A chemotherapy regimen with a higher complete response rate would improve the prognosis of this dismal disease even more.