Impact of preoperative docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy on degree of malignant esophageal stenosis.

BACKGROUND: Malignant esophageal stenosis is a common and severe complication of advanced esophageal cancer that can be a serious problem in the continuation of chemotherapy and other anticancer treatments. The impact of chemotherapy regimens on the degree of improvement in esophageal stenosis is unknown. In this study, we focused on the impacts of chemotherapy on the direct anticancer effects, and in the improvement of malignant stenosis. METHODS: Patients who underwent radical esophagectomy after chemotherapy, either adjuvant 5-fluorouracil and cisplatin (FP) or docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen, were included. We assessed the length of the cancerous stenosis, the width of the narrowest segment, and the size of the intraluminal area in the stenotic segment by fluoroscopy, and compared the differences before and after chemotherapy. In addition, we evaluated the dysphagia score (Mellow-Pinkas scoring system) as the evaluation of patients' symptoms. The antitumor effects of chemotherapy were also investigated. RESULTS: A total of 81 patients were enrolled: 50 were treated with FP, and 31 were treated with DCF. The expansion rate in the length of the narrowest part was significantly increased in the DCF group compared with the FP group. Furthermore, the stenosis index (intraluminal stenotic area/stenotic length) was significantly increased in the DCF group compared with the FP group (112% vs 96%, P = 0.038). Dysphagia score after chemotherapy significantly improved in the DCF group compared to the FP group (P = 0.007). The response rates were 60% in the FP group and 67.7% in the DCF group. Effective histopathological response (improvement to grade 2 or 3) was 24% in the FP group and 38.8% in the DCF group. CONCLUSION: DCF therapy is more effective than FP treatment in the improvement of malignant esophageal stenosis.

Effect of Oral Branched-Chain Amino Acids and Glutamine Supplementation on Skeletal Muscle Atrophy After Total Gastrectomy in Rat Model.

BACKGROUND: Sarcopenia is closely related to short-term outcomes of surgery and long-term prognosis. After gastrectomy, a decrease in muscle strength occurs because of insufficient nutrient intake and disturbed digestive function. Branched-chain amino acids (BCAAs) and glutamine (Gln) play vital roles in the signaling pathways regulating protein synthesis and protein degradation. In this study, we investigated the effects of BCAA and Gln supplementation alone or in combination on skeletal muscle atrophy after total gastrectomy in a rat model. METHODS: Male Wistar rats were divided into five groups: (1) sham operation (n = 8); (2) total gastrectomized rats (TG [control group], n = 16); (3) TG with BCAA (TG-B, n = 16); (4) TG with Gln (TG-G, n = 16); and (5) TG with BCAA and Gln (TG-BG, n = 16). In all groups, body weight, muscle weight, and marker for muscle metabolism were examined. RESULTS: Weight gain was significantly greater in the TG-BG group (130.5%) than in the TG group (108.1%) at 15 wk (P < 0.05). The gastrocnemius muscle weight was significantly higher for TG-BG (2.84 g) than for TG (2.44 g) at 15 wk (P < 0.05). Western blotting indicated that atrogin-1 and MuRF1 levels were lower in the TG-BG group than in the TG group but were not suppressed in the TG-B or TG-G group. CONCLUSIONS: In a rodent sarcopenia model induced by TG, the administration of BCAA in combination with Gln more effectively inhibited muscle atrophy than the administration of BCAA or Gln alone.

Preventive effect of oral hangeshashinto (TJ-14) on the development of reflux-induced esophageal cancer.

BACKGROUND: Prostaglandin E2 is one of the potential products that promotes development of tumors and also is a strong inducer of M2 phenotype macrophages, which contribute to tumor development in the immunosuppressed microenvironment. Hangeshashinto (TJ-14), a Japanese traditional medicine (Kampo medicine), has been reported to be effective in preventing chemotherapy-induced oral mucositis through the reduction of prostaglandin E2. We previously developed a surgical rat reflux model of esophageal cancer and used this well-established animal model to investigate the action of TJ-14 in preventing esophageal cancer. We also assessed the effect of TJ-14 on the downregulation of prostaglandin E2 production, utilizing esophageal squamous cell carcinoma cell line exposed to bile acid. METHODS: An end-to-side esophagojejunostomy was performed for the reflux model. A daily oral diet was subsequently administered, consisting of either diet-incorporated TJ-14 or standard diet as a control group. The rats were killed at 40 weeks after surgery. The incidence of esophageal cancer, Barrett's metaplasia, and proliferative hyperplasia were assessed histologically. CD163, a M2 phenotype macrophage marker, was assessed with immunohistochemistry. Prostaglandin E2 enzyme immunoassay and lactate dehydrogenase assay were performed on chenodeoxycholic acid or gastroesophageal reflux contents exposed to esophageal squamous cell carcinoma cell line. RESULTS: Sixty-seven percent of the controls (n = 12) developed esophageal cancer, but animals that received TJ-14 (n = 10) had a cancer incidence of 10% (P=.007). Barrett's metaplasia was found in 83% of the rats in the control group and 50% of the rats in the TJ-14 indicating a protective tendency of TJ-14 (P=.095). All of the rats developed proliferative hyperplasia. The number of M2 phenotype macrophage were significantly decreased in the TJ-14 group compared to the control group in both Barrett's metaplasia and esophageal cancer lesions. TJ-14 inhibited chenodeoxycholic acid or gastroesophageal reflux content-induced prostaglandin E2 production in esophageal squamous cell carcinoma cell. CONCLUSION: TJ-14 reduced the incidence of reflux-induced esophageal cancer and the infiltration of M2 macrophages in a surgical rat model or suppressed prostaglandin E2 production in esophageal squamous cell carcinoma cell. Further investigation is required regarding the potential clinical use of TJ-14 as an esophageal cancer chemopreventive agent.

[A Case of Spontaneous Esophageal Rupture That Required Operation during Adjuvant Chemotherapy for Transverse Colon Cancer].

A 75-year-old male underwent adjuvant chemotherapy with tegafur uracil(UFT)plus Leucovorin(LV)after surgery for transverse colon cancer(pT3pN0M0, ly1, v2, pStageⅡ). Although he had diarrhea(Grade 3)and vomiting(Grade 2)from day 15, he continued to take the medicine at his own discretion. He visited a hospital because of acute renal failure from severe dehydration. He went into shock after evacuation, and the computed tomography(CT)finding suggested a diagnosis of spontaneous esophageal rupture at the lower esophagus. We made a diagnosis of intrathoracic perforation of the esophagus by using thoracic drainage. Then, we performed an operation for mediastinal drainage via a transabdominal approach and the lesser omentum. He started ingestion from POD36 and transferred to another hospital on POD85. He had no disease recurrence in our outpatient care. We think that the spontaneous esophageal rupture occurred because of the frequent vomiting caused by the continued chemotherapy despite the severe side effects. Treatments must be selected by considering patients' life background and medical compliance, and common guidance in taking medications must be provided to elderly patients at the start of chemotherapy.

The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer.

PURPOSE: The administration of aromatase inhibitors is associated with bone loss in postmenopausal women. We assessed changes in bone mineral density (BMD) from baseline to 60 months of treatment in patients receiving anastrozole as initial adjuvant therapy. METHODS: Postmenopausal women with hormone receptor-positive breast cancer receiving anastrozole as adjuvant therapy at our center since 2004 were enrolled in this study. BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24, 36, 48 and 60 months. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis having a T-score of -2.5 or lower. RESULTS: Fifty-five patients were enrolled in the study between 2004 and 2011, and the mean follow-up period was 53.6 months. Thirty-five patients were administered Bis (risedronate in 27 patients, alendronate in 8 patients). After 6 months of hormone therapy, BMD decreased by 0.5% from baseline at the lumbar spine (LS) and BMD decreased by 1.5% at the femoral neck (FN). However, BMD increased by 1.9% at the LS and BMD decreased by 1.5% at the FN for 60 months of treatment. In patients treated with upfront Bis (n = 19), 5.4% BMD increase from baseline was noted at the LS whereas in those without Bis (n = 21) BMD decreased by 4.3% from baseline within 24 months (P < 0.0001). Fractures were observed in 4 patients (7.3%), and 1 patient (1.8%) had a fragility fracture. CONCLUSIONS: Upfront treatment of Bis with anastrozole significantly increased BMD at the LS and an optimal use of Bis would not increase bone fractures. TRIAL REGISTRATION: UMIN0000017571.

Colonic stenosis caused by infection of an intraperitoneal access port system: a rare complication of intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis.

BACKGROUND: Intraperitoneal (i.p.) chemotherapy is garnering attention as an effective treatment for gastric cancer with peritoneal metastasis. We report the case of a patient who developed colonic stenosis caused by infection of an i.p. access port system during i.p. chemotherapy. It was difficult to differentiate whether the extrinsic colonic stenosis arose from a catheter infection or peritoneal metastasis of the gastric cancer. CASE PRESENTATION: A 66-year-old Japanese man underwent total gastrectomy for gastric cancer. Because the intraoperative findings revealed peritoneal metastasis, a port system was implanted for subsequent i.p. chemotherapy. Two months after initiation of chemotherapy, he complained of vomiting and abdominal pain. A computed tomography scan revealed marked thickening of the sigmoid colon wall adjacent to the catheter of the i.p. access port system. A barium enema demonstrated extrinsic irregular stenosis of the sigmoid colon. Although it was difficult to distinguish whether infection or peritoneal metastasis had caused the colonic stenosis, we removed the port system to obtain a therapeutic diagnosis. Coagulase-negative staphylococci were detected by catheter culture. The wall thickening and stenosis of the sigmoid colon completely resolved after removal of the port system. CONCLUSIONS: We report the case of a rare complication in association with an i.p. access port system. Infection of the port system should be considered as a differential diagnosis when colonic stenosis adjacent to the catheter is observed during i.p. chemotherapy.

Effects of KTP laser irradiation, diode laser, and LED on tooth bleaching: a comparative study.

OBJECTIVE: This in vitro study examines the whitening efficacy of a light-emitting diode (LED), a diode laser, and a KTP laser irradiation in dental bleaching by analyzing the change in color achieved from the treatment, the temperature increase induced in the pulpal cavity, as well as enamel microhardness measurement after treatment. BACKGROUND DATA: Bleaching techniques achieved significant advances with the use of coherent or incoherent radiation sources to activate the bleaching agents. METHODS: A hydrogen peroxide bleaching agent, Hi-Lite, was stimulated with an LED, a 980-nm diode laser at 0.8 W, or a 532-nm KTP laser at 1.0 W for 30 sec on 64 extracted human incisors. During irradiation, the temperature in the pulpal cavity was monitored. The color change was evaluated using the CIE L*a*b* color space measurement system, and Vikers enamel microhardness was tested after treatment. RESULTS: A mean total color difference value (DeltaE*) greater than 5.0 was obtained in each group. KTP-laser-induced bleaching gave a significantly higher DeltaL* (8.35) after treatment (p < 0.01). Neither LED nor the two lasers produced significant differences in the enamel microhardness after treatment (p > 0.01). Mean maximal pulpal temperature rise was 2.95 degrees C for LED, 3.76 degrees C for KTP laser, and 7.72 degrees C for diode laser, respectively. CONCLUSION: The results of this study suggest that KTP laser is effective at providing brighter teeth. According to the conditions used in this study, the LED and KTP laser induced a safer pulpal temperature increase when assisted with Hi-Lite bleaching gel.

Thermographical and morphological studies of Er,Cr:YSGG laser irradiation on root canal walls.

OBJECTIVE: This study was performed to investigate the temperature rises on root surfaces and morphological changes on root canal walls of extracted human teeth after irradiation by erbium, chromium: yttrium, scandium, gallium, garnet (Er, Cr:YSGG) laser and to evaluate the efficiency in removing smear layer and debris from the prepared root canal walls in vitro. BACKGROUND DATA: No report on Er, Cr:YSGG laser effects under various conditions and specific tips for endodontic treatments has been reported. METHODS: Sixty extracted human teeth with single and straight root were used in this study. The teeth were prepared at 1 mm short of the apical foramen by a conventional technique using K-files. Fifty-four specimens were irradiated by Er, Cr:YSGG laser at the output powers of 2 W, 3 W, and 5 W for 7 sec with three fiber tips (200, 320, and 400 microm diameters). Temperature changes were recorded thermographically. All teeth were examined by light microscopy or scanning electron microscopy (SEM). RESULTS: Thermographic study showed that the average temperature rises on root surfaces were less than 8 degrees C. Observation by light microscopy revealed the ablation at the apical stop, and that by SEM indicated that laser irradiation at 5 W using a fiber tip with 400 microm diameter was efficient for removing smear layer and debris without carbonization or melting. CONCLUSIONS: The results of this study suggested that the temperature rises during Er, Cr:YSGG laser irradiation at the parameters used in this study are minimal to cause the damage on periodontal and bone tissues. Moreover, it was suggested that it is efficient to remove smear layer and debris without causing any carbonization and melting.

Comparative study of carious dentin removal by Er,Cr:YSGG laser and Carisolv.

OBJECTIVE: The present study aimed to compare carious dentin removal by air turbine, Carisolv and erbium,chromium:yttrium,scandium,gallium,garnet (Er,Cr:YSGG) laser, and examine morphological changes before and after these caries removal techniques under light microscopy and scanning electron microscopy (SEM). BACKGROUND DATA: Although there have been numerous studies on removing caries by Er,Cr:YSGG laser, none has compared Er,Cr:YSGG laser and Carisolv, or reported on the usage of DIAGNOdent as a diagnostic tool particularly for advanced caries in in vitro experiments. MATERIALS AND METHODS: Sixty extracted human teeth diagnosed as advanced caries were divided into three groups based on the treatment received, namely air turbine, Carisolv, and Er,Cr:YSGG laser groups. Each group was sub-divided into two in order to examine the results with or without finishing using nylon brush, 15% ethylene diamine tetraacetic acid (EDTA) or low-power laser, respectively. After evaluation by DIAGNOdent, specimens were observed under light microscopy or SEM. RESULTS: Light microscopic observations varied considerably in the three treatment groups. SEM revealed that the surfaces treated by air turbine were very smooth, but with substantial debris. The Carisolv group exhibited a very rough surface with a thick smear layer, while the Er,Cr:YSGG group demonstrated smooth undulations with little smear layer and debris. Among the finishing techniques, the laser group demonstrated the best efficiency. DIAGNOdent scores supported the results of light microscopy. CONCLUSION: These results suggest that caries removal by Er,Cr:YSGG laser is very effective even without finishing and DIAGNOdent is useful for diagnosing advanced caries in in vitro experiments.

Dual subcellular distribution of cytochrome b5 in plant, cauliflower, cells.

Subfractionation studies showed that cytochrome b(5) (cyt b5), which has been considered to be a typical ER protein, was localized in both the endoplasmic reticulum membrane (ER) and the outer membrane of mitochondria in cauliflower (Brassica olracea) cells and was a component of antimycin A-insensitive NADH-cytochrome c reductase system in both membranes. When cDNA for cauliflower cyt b5 was introduced into mammalian (COS-7) and yeast cells as well as into onion cells, the expressed cytochrome was localized both in the ER and mitochondria in those cells. On the other hand, rat and yeast cyt b5s were specifically localized in the ER membranes even in the onion cells. Mutation experiments showed that cauliflower cyt b5 carries information that targets it to the ER and mitochondria within the carboxy-terminal 10 amino acids, as in the case of rat and yeast cyt b5s, and that replacement of basic amino acids in this region of cauliflower cyt b5 with neutral or acidic ones resulted in its distribution only in the ER. Together with the established findings of the importance of basic amino acids in mitochondrial targeting signals, these results suggest that charged amino acids in the carboxy-terminal portion of cyt b5 determine its location in the cell, and that the same mechanism of signal recognition and of protein transport to organelles works in mammalian, plant, and yeast cells.