Preoperative oral supplementation support in patients with esophageal cancer.

OBJECTIVE: Surgeries for cancer of the esophagus are still associated with a high rate of postoperative morbidity. There are few reports of perioperative nutritional support for patients undergoing esophageal cancer surgery, and there is insufficient evidence to recommend routine use of immunonutrition in these patients. The aim of this study was to determine whether preoperative immunonutrition positively influences key clinical outcomes such as postoperative infectious complications, mortality, length of hospital stay, and short-term survival in this population. DESIGN AND SETTING: We undertook a retrospective investigation of the effects of preoperative nutritional support on the postoperative course of esophageal cancer surgery at the Department of Gastroenterological Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan. PARTICIPANTS: Fifty-five patients who underwent esophagectomy for esophageal cancer were included in this study. Of the 55 patients, 26 patients consumed a liquid dietary supplement (IMPACT group) before surgery and 29 patients did not (STANDARD group). INTERVENTION: Before surgery, the IMPACT group consumed 750 ml (3 packs)/day of Impact for 5 consecutive days. MEASUREMENTS: The analysis was based on postoperative complications, hospital mortality, length of hospital stay, and short-term survival. RESULTS: Significantly fewer patients developed postoperative infections in the IMPACT group compared with the STANDARD group (p=.007): 4 of 21 patients in the IMPACT group and 10 of 29 patients in the STANDARD group. Either an infectious complication or another complication developed in 8 patients in the IMPACT group and 13 patients in the STANDARD group, with the result that 6 patients in the STANDARD group died of postoperative complications (p=.001). The duration of hospitalization was 34 days in the IMPACT group and 48 days in the STANDARD group; hence, hospitalization was significantly shorter in patients treated with Impact (p=.008). The mean 6-month survival rates for the IMPACT group and the STANDARD group were 92% (24/26) and 72% (21/29), respectively (p=.028). CONCLUSION: Simple preoperative supplementation significantly improved outcome. Administration of the supplemental diet before esophageal surgery appeared to be an effective strategy in reducing infectious complications, mortality, and hospitalization, and improving short-term survival.

Signal intensity of the motor cortex on phase-weighted imaging at 3T.

BACKGROUND AND PURPOSE: It is known that the motor cortex shows hypointensity on T2-weighted images in older patients. The goal of this study was to assess the signal intensity of the motor cortices on the phase-weighted imaging performed with a Windows-based software program that we developed ourselves. MATERIALS AND METHODS: All studies were performed at 3T MR imaging. First, the TE for the phase-weighted image was optimized; the best contrast between the motor and other cortices was obtained with a TE of 40 ms. The study population consisted of 45 healthy subjects (23 females, 22 males; mean age, 32.1 years). The signal intensity of the motor cortices was divided into 3 grades by 2 neuroradiologists in comparison with that of the superior frontal cortex (SFC): In grade I, the motor cortex was isointense to the SFC; in grade II, the motor cortex was slightly hypointense to the SFC; and in grade III, the motor cortex was markedly hypointense to the SFC. RESULTS: The motor cortex was classified as either grade II or III in all subjects older than 20 years of age on the phase-weighted images. Even at 10-19 years of age, the grade II or III appearance was found in 14 (88%) of 16 motor cortices (8 subjects) on the phase-weighted images. CONCLUSION: In adolescents, the motor cortex is hypointense to other cerebral cortices on phase-weighted MR imaging, which probably reflects differences in the concentration of nonheme iron and/or in the tissue architecture.

A case of laparoscopic surgery for blue rubber bleb nevus syndrome.

A 33-year-old woman had presented with some cutaneous and gastrointestinal hemangiomas with iron deficiency anemia three years previously and blue rubber bleb nevus syndrome was diagnosed. Although she had taken an iron supplement for three years, she hoped to discontinue it and underwent laparoscopic surgery for nine gastrointestinal hemangiomas. She was discharged on the ninth postoperative day without any complications. She has been fit without iron deficiency anemia for a year since the operation. Blue rubber bleb nevus syndrome is a rare disease accompanied with cutaneous and gastrointestinal vascular malformations and about 150 cases have been reported. To the best of our knowledge, this is the first report of blue rubber bleb nevus syndrome with small and large intestinal lesions that were treated with laparoscopic surgery.

Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation.

AIM: To demonstrate the antitumour effects of nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), a citrus flavonoid extracted from Citrus depressa Hayata, on human gastric cancer cell lines TMK-1, MKN-45, MKN-74 and KATO-III. MATERIALS AND METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the TdT-mediated dUTP biotin nick-end labelling (TUNEL) method and cell-cycle analysis revealed that nobiletin acted on these cells in several ways, namely by direct cytotoxicity, induction of apoptosis and modulation of cell cycle. The efficacy of combined treatment of nobiletin with a conventional anticancer drug, CDDP, was also examined. Treatment with nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control. CONCLUSIONS: Although the effective dose and administration route of nobiletin require further investigation, our study represents a potential successful linking of this compound with the treatment of gastric cancer.

Cerebral gliomas: prospective comparison of multivoxel 2D chemical-shift imaging proton MR spectroscopy, echoplanar perfusion and diffusion-weighted MRI.

Developments in MRI have made it possible to use diffusion-weighted MRI, perfusion MRI and proton MR spectroscopy (MRS) to study lesions in the brain. We evaluated whether these techniques provide useful, complementary information for grading gliomas, in comparison with conventional MRI. We studied 17 patients with histologically verified gliomas, adding multivoxel proton MRS, echoplanar diffusion and perfusion MRI the a routine MRI examination. The maximum relative cerebral blood volume (CBV), minimum apparent diffusion coefficient (ADC) and metabolic peak area ratios in proton MRS were calculated in solid parts of tumours on the same slice from each imaging data set. The mean minimum ADC of the 13 high-grade gliomas (0.92+/-0.27 x 10(-3) mm(2)/s) was lower than that of the four low-grade gliomas (1.28+/-0.15 x 10(-3) mm(2)/s) ( P<0.05). Means of maximum choline (Cho)/N-acetylaspartate (NAA), Cho/creatine (Cr), Cho/Cr in normal brain (Cr-n) and minimum NAA/Cr ratios were 5.90+/-2.62, 4.73+/-2.22, 2.66+/-0.68 and 0.40+/-0.06, respectively, in the high-grade gliomas, and 1.65+/-1.37, 1.84+/-1.20, 1.61+/-1.29 and 1.65+/-1.61, respectively, in the low-grade gliomas. Significant differences were found on spectroscopy between the high- and low-grade gliomas ( P<0.05). Mean maximum relative CBV in the high-grade gliomas (6.10+/-3.98) was higher than in the low-grade gliomas (1.74+/-0.57) ( P<0.05). Echoplanar diffusion, perfusion MRI and multivoxel proton MRS can offer diagnostic information, not available with conventional MRI, in the assessment of glioma grade.

Artoindonesianin L, a new prenylated flavone with cytotoxic activity from Artocarpus rotunda.

A new prenylated flavone, named artoindonesianin L (1), was isolated from Artocarpus rotunda (Hout) Panzer (Moraceae). Its structure was elucidated as on the basis of spectroscopic evidence. Along with this new compound, four known phenolic compounds were also isolated from this plant and identified as artonins M (2) and E (3), cycloartobiloxanthone (4) and artonin O (5). All these compounds showed significant cytotoxicity against murine P388 leukemia cells.

The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice.

The flavonoid nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), found in Citrus depressa Rutaceae, a popular citrus fruit in Okinawa, Japan, reportedly inhibits the production of pro-matrix metalloproteinase (proMMP)-1, 3, and 9 in rabbit synovial fibroblasts in vitro. In the present study, we demonstrated the inhibitory effects of nobiletin on the proliferation of the cancer cell line, TMK- 1, and its production of MMPs. In the SCID mouse model, we found that nobiletin inhibited the formation of peritoneal dissemination nodules from TMK-1. The enzymatic activity of MMP-9 expressed in culture medium obtained from a co-culture of TMK-1 and mouse fibroblastic cells was inhibited by nobiletin in a concentration-dependent manner. In the SCID mouse model, total weight of dissemination nodules was significantly lower in the treated group compared with the vehicle control group (0.07 g vs. 0.78 g, P = 0.0059). The total number of dissemination nodules was also significantly lower than in the vehicle control group (7.5 vs. 69.3 / body, P = 0.0001). These results suggest that nobiletin may be a candidate anti-metastatic drug for prevention of peritoneal dissemination of gastric cancer.

Isolation and characterization of two new alkaloids, norpandamarilactonine-A and -B, from Pandanus amaryllifolius by spectroscopic and synthetic methods.

Two new alkaloids, norpandamarilactonine-A (1) and -B (2), which have a pyrrolidinyl-alpha,beta-unsaturated gamma-lactone moiety as in the known pandamarilactonine alkaloids, were isolated from the leaves of Pandanus amaryllifolius. Their structures were determined by spectroscopic analysis and total synthesis.

Isolation and bioactivities of constitutents of the roots of Garcinia atroviridis.

Two new prenylated compounds, the benzoquinone atrovirinone (1) and the depsidone atrovirisidone (2), were isolated from the roots of Garcinia atroviridis. Their structures were determined on the basis of the analysis of spectroscopic data. While compound 2 showed some cytotoxicity against HeLa cells, both compounds 1 and 2 were only mildly inhibitory toward Bacillus cereus and Staphylococcus aureus.

A new type of stilbene-related secondary metabolite, idenburgene, from Cryptocarya idenburgensis.

A new type of natural product, idenburgene (1), was isolated from Crytocarya idenburgensis, and its unique structure was elucidated. Four known compounds, 3-hydroxy-5-methoxystilbene (2), 2',6'-dihydroxy-4'-methoxydihydrochalcone (3), stigmast-4-ene-3-one, and beta-sitosterol were also isolated and identified.

Artoindonesianin C, a new xanthone derivative from Artocarpus teysmanii.

A new xanthone derivative, artoindonesianin C (1), was isolated from Artocarpus teysmanii, together with two known prenylated flavonoids, cycloartobiloxanthone and artonin J. The structure of artoindonesianin C (1) was determined on the basis of MS and NMR evidence and by comparison with known related compounds.

Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.

The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

[Pathophysiology and diagnosis of ischemic colitis].

Ischemic colitis is the most common manifestation of gastrointestinal ischemia. The presumed etiologies are numerous; however, it typically develops spontaneously. It is classified into the transient type, stricture type, and gangrenous type. The majority of patients with ischemic colitis, excluding the gangrenous type, follow a benign clinical course in the absence of major vasculature occlusion. It usually presents as an acute abdominal illness with bloody diarrhea. Diagnosis is confirmed by colonoscopy and/or barium enema. Nongangrenous ischemic colitis usually requires only conservative therapy, including repeated careful assessment, pain control, and fluid replacement, and is associated with a good prognosis. It may lead to the sequela of persistent segmental colitis or colonic strictures, occasionally requiring surgery. Urgent surgery and high morbidity and mortality rates are hallmarks of the gangrenous type. Special consideration must be given to those patients in whom ischemic colitis develops in the context of colon cancer or obstructive colonic lesions. Successful management of a patient with ischemic colitis requires a high degree of clinical suspicion, early diagnosis, careful follow-up, and prompt recognition of persistent disease.

Intrahepatic interleukin-2 with chemotherapy for unresectable liver metastases: a randomized multicenter trial.

BACKGROUND/AIMS: A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol. METHODOLOGY: Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1 x 10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7 x 10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted. RESULTS: IL-2 combined with chemotherapy produced a higher complete and partial response rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia. CONCLUSIONS: Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.

Chemosensitivity test is useful in evaluating the appropriate adjuvant cancer chemotherapy for stage III non-scirrhous and scirrhous gastric cancers.

A total of 183 cases with gastric cancer was retrospectively analyzed in terms of their chemosensitivity as determined by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay and their survival rates after surgery. After the patients were stratified into scirrhous or non-scirrhous carcinoma groups, they were tested for stage III or IV gastric cancer. In these four cohorts, the patients were categorized into sensitive and insensitive groups determined by the MTT assay. The sensitive group was treated with at least one drug that had been shown to be effective in the MTT assay, and the insensitive group was given a drug that had been shown to be ineffective in the MTT assay. In stage III gastric cancer, the sensitive group showed a favorable survival compared to the insensitive group in scirrhous and non-scirrhous carcinoma, while this difference was diminished in stage IV gastric cancer. There were no survival benefits in the sensitive group in stage III gastric cancer, when they were not treated with adjuvant cancer chemotherapy. These results suggested that MTT assay would be useful in evaluating the appropriate adjuvant cancer chemotherapy for stage III scirrhous and non-scirrhous gastric cancer.

Further evidence for the value of the chemosensitivity test in deciding appropriate chemotherapy for advanced gastric cancer.

BACKGROUND: The chemosensitivity test using the MTT endpoint is useful in predicting chemosensitivity. PATIENTS AND METHODS: One hundred twenty-eight patients with advanced gastric cancer were enrolled in the study, which mitomycin C (MMC), doxorubicin (DXR), 5-fluorouracil (5-FU), and cisplatin (DDP) were used. RESULTS: The corresponding efficacy rates were 12.5% for MMC, 6.3% for DXR, 5.4% for 5-FU and 13.4% for DDP. The overall predictive accuracy was 78% in the patients with measurable lesions. Among the patients without measurable lesions, 21 were treated with a curative operation, and 33 with a non-curative operation. In those patients undergoing curative surgery, the "adapted" group detected by MTT assay survived longer than "non-adapted" cases (p < 0.05). CONCLUSIONS: The present study provides further evidence that the chemosensitivity test may be useful for evaluating appropriate chemotherapy for advanced gastric cancer.

[Salvage surgery for the T4 esophageal cancer following downstaging by neoadjuvant chemoradiotherapy].

The standard modality of the treatment for the patients with T4 esophageal cancer, whose prognosis still remains quite poor, is not established yet. Salvage surgery for the T4 esophageal cancer following downstaging by neoadjuvant chemo-radiotherapy has become to be available. During the period from 1992 to 96, 30 patients with the suspected T4 esophageal cancer underwent chemoradiotherapy, which consisted of two courses of CDDP/5-FU with-sequential or concurrent 50-60Gy radiotherapy. Among them eleven patients became to be resectable by means of thoracotomy and laparotomy and pathological CRs were obtained in either primary lesions or lymph nodes. The longest survival term following surgery is 36 months. Three patients died of cancer recurrence including the organ metastasis and one died from pyothorax without cancer due to severe immunosuppression attributable to chemoradiation. Our results warrants further studies of neoadjuvant chemoradiotherapy for the patients with T4 esophageal cancer.

T2 shortening in the visual cortex: effect of aging and cerebrovascular disease.

PURPOSE: To evaluate the effect of aging and cerebrovascular disease on T2 shortening in the visual cortex at MR imaging. METHODS: MR images of 72 neurologically normal subjects (45 men and 27 women, 35 to 92 years old) and 32 (13 men and 19 women, 54 to 92 years old) with cerebrovascular disease were evaluated retrospectively. On T2-weighted spin-echo images, the signal intensity of the visual, motor, and sensory cortices was divided into three grades and compared with the signal intensity of the frontal subcortical white matter. RESULTS: Decreased signal intensity (grade III) was rarely seen in the visual and sensory cortices of the neurologically normal subjects who were less than 60 years old. The signal intensity of the motor cortex decreased rapidly after the age of 50 years. At 61 to 70 years of age, 53% of these subjects had grade III intensity, and at age 71 years or older, 94% had reached grade III. The frequency of progression from grade I to grade III was lower in the visual cortex than in the motor cortex; 22% of these subjects had grade III appearance at age 61 to 70 years, and at age 71 years older, 56% had reached grade III. In patients with cerebrovascular disease who were older than 60 years of age, the frequency of grade III signal intensity in the visual cortex was almost equal to that in the neurologically normal subjects. CONCLUSIONS: T2 shortening in the visual cortex is frequently seen in neurologically normal older persons. These findings are compatible with a previously reported histochemical study of normal iron deposition in the visual cortex. Cerebrovascular disease has no effect on T2 shortening in the visual cortex.

Motor activity of refashioned colorectoanus in patients with total colonic aganglionosis.

An ano-recto-sigmoid colon pressure study was designed to evaluate the characteristics of the motor activity of refashioned colorectoanus in patients with total colonic aganglionosis (TCA) in comparison to patients with rectosigmoid Hirschsprung's disease (HD) and healthy children (HC), and to elucidate the pathophysiology of the pulled-through ileum, with aganglionic colon as an onlay patch, in coordination with the anal sphincter. The study group consisted of six patients with TCA, six with HD who underwent endorectal colonic pull-through, and six HC. Pressure studies were performed using a triple-lumen catheter; recording sites were 15 and 9 cm from the anal verge, and at the anal canal. The following were measured and compared: (1) anal canal pressure profile, (2) resting pattern of activity at the refashioned colorectum and anal canal, and (3) changes in motor activity after stimulation with cold water and glycerin. The motor activities of the refashioned colorectoanus of TCA and HD patients differed greatly from those of HC. All six HC had no isolated high-amplitude contraction (IHAC) in the colorectum during the 45-minute study period; they complained of a strong urge to defecate after glycerin enema and actually did so. In contrast, IHAC appeared 2.0 +/- 1.3 times per 10 minutes, with maximal amplitude of 60.3 +/- 24.9 cm H2O in TCA, and 5.6 +/- 3.7 per 10 minutes with maximal amplitude of 79.5 +/- 11.7 cm H2O in HD. After glycerin enema, IHAC increased to 0.5 +/- 0.2 per minute and 69.3 +/- 44.6 cm H2O in TCA and to 0.8 +/- 0.4 per minute and 93.0 +/- 12.8 cm H2O in HD. Defecation was postponed for more than 10 minutes in two HD and all TCA patients. The mean motility index per minute was least for TCA patients (76.9 +/- 98.2); it was 406.5 +/- 197.1 (P < .05) for HD patients and 159.2 +/- 84.2 (P < .01) for HC. TCA patients had the lowest amplitude of maximal resting anal pressure, and hypoactivity of the colorectum during rest and after stimulation; this suggests that motor dysfunction involves even the ganglionic ileum, concomitant with suppressed signals to the higher integrating center for defecation.