Hideo Terashima

Effects of Platelet-Rich Plasma on Intestinal Anastomotic Healing in Rats: PRP Concentration is a Key Factor

BACKGROUND Few studies have examined the effects of platelet-rich plasma (PRP) on intestinal anastomotic healing. The applied preparation methods and PRP concentrations used in the few studies that have been carried out varied markedly. Therefore, the positive effects of PRP on the anastomotic healing process remain unclear. The aim of this study is to examine the effects of different concentrations of PRP on intestinal anastomotic healing. MATERIAL AND METHODS From SD rat blood, three different concentrations of plasma were prepared: high-concentrated PRP (H-PRP: platelet count 5 × 10(6)/mm(3)), low-concentrated PRP (L-PRP: 2 × 10(6)/mm(3)), and platelet-poor plasma (PPP). Male SD rats underwent proximal jejunal anastomosis and central venous catheterization. Rats were divided into four groups (n = 12 for each group): control, PPP, L-PRP, and H-PRP groups. Two types of PRP and PPP (0.21 mL) were applied to each anastomosis line, with the exception of the control group. Total parenteral nutrition (TPN) solutions were administered (151 kcal/kg/d). Five days after surgery, anastomotic bursting pressure (ABP) in situ and hydroxyproline concentration (HYP) in anastomotic tissue were evaluated. RESULTS The ABP values of control, PPP, L-PRP, and H-PRP groups were 171 ± 20, 174 ± 23, 189 ± 17, and 148 ± 25 mmHg, respectively. The HYP values of each group were 516 ± 130, 495 ± 123, 629 ± 120, and 407 ± 143 μg/g dry tissue. Compared with the other groups, the L-PRP group exhibited a significant increase in both ABP and HYP, while the H-PRP group exhibited a significant decrease in these two variables. As a result, L-PRP was considered to promote anastomotic wound healing, but H-PRP was considered to inhibit it. There was no significant difference between the PPP group and the control group. CONCLUSIONS PRP concentration plays a crucial role in the efficacy of PRP. PRP might exert positive effects on intestinal anastomotic healing in a dose-dependent manner up to a certain level, but adverse effects occur when it is highly concentrated. The essential PRP action appears to be driven by the platelets themselves.

Clinical Results of Proton-Beam Therapy for Locoregionally Advanced Esophageal Cancer

Purpose:To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer.Patients and Methods:The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70–90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62–98 GyE).Results:Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9–30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6–36.3).Conclusion:The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy.ZusammenfassungZiel:Evaluierung der Wirksamkeit und Sicherheit der Protonenstrahlentherapie bei lokoregionar fortgeschrittenem Speiserohrenkrebs.Patienten und Methodik:Es handelte sich um 51 Patienten mit Speiserohrenkrebs, die zwischen 1985 und 2005 mit Protonenstrahlen allein oder kombiniert mit Linac-Photonen behandelt wurden. Bis auf eine Ausnahme hatten alle Patienten ein Plattenepithelkarzinom. Von den 51 Patienten erhielten 33 eine Kombination von Photonen (median 46 Gy) und Protonen (median 36 GyE) als Boost. Die mediane Gesamtdosis der kombinierten Rontgen- und Protonenstrahlung betrug 80 GyE (Spanne 70–90 GyE). Die anderen 18 Patienten wurden ausschlieslich mit Protonenstrahlentherapie behandelt (median 79 GyE, Spanne 62–98 GyE).Ergebnisse:Bei keinem Patienten war eine Behandlungsunterbrechung aufgrund strahleninduzierter Osophagitis oder hamatologischer Toxizitat erforderlich. Die aktuarische Gesamtuberlebensrate der 51 Patienten lag bei 21,1% in 5 Jahren und die mediane Uberlebenszeit 20,5 Monate (95%-Konfidenzintervall 10,9–30,2). Von den 51 Patienten erreichten 40 (78%) innerhalb von 4 Monaten nach Behandlungsende eine komplette Remission und sieben (14%) eine partielle Remission, was eine Ansprechrate von 92% (47/51) ergibt. Die lokale Kontrollrate nach 5 Jahren betrug bei allen 51 Patienten 38,0% und das mediane lokalrezidivfreie Intervall 25,5 Monate (95%-Konfidenzintervall 14,6–36,3).Schlussfolgerung:Die Protonenstrahlentherapie ist eine wirksame Behandlung fur Patienten mit lokal fortgeschrittenem Speiserohrenkrebs. Weitere Studien sind notwendig, um optimale Gesamtdosis, Fraktionierung und die beste Kombination von Protonenstrahlen- mit Chemotherapie zu ermitteln.

Early Postoperative Oral Feeding Accelerates Upper Gastrointestinal Anastomotic Healing in the Rat Model

BackgroundThe benefits of early postoperative oral feeding following colonic anastomosis have previously been demonstrated. However, early postoperative oral feeding in patients with upper gastrointestinal surgery has been avoided because of concerns regarding anastomotic leakage. We investigated whether early postoperative oral feeding was advantageous for upper gastrointestinal anastomosis in comparison to parenteral feeding with a fasting period.Materials and MethodsMale Sprague-Dawley rats were subjected to the same surgical manipulation, i.e., venous catheterization, gastrostomy, and proximal jejunal anastomosis. Rats were divided into two groups: the enteral nutrition (EN) group, which received nutrients via gastrostomy as a substitute for oral feeding, and the total parental nutrition (TPN) group, which was fed via a venous catheter. Identical nutritional solutions were administered to the two groups immediately after surgery. The anastomotic bursting pressure (ABP) and the content of hydroxyproline in the anastomotic tissue were measured 5 days postoperatively.ResultsThe ABP in the EN group was significantly higher than that in the TPN group (214.6 ± 42 versus 149.5 ± 49 mmHg; p < 0.01). The hydroxyproline content in the EN group was also significantly higher (63.5 ± 10 versus 50.5 ± 12 μmol/g dry tissue; p < 0.01).ConclusionsEarly enteral feeding via gastrostomy accelerated jejunal anastomotic healing in comparison to parenteral feeding. This study clearly indicates that early oral feeding after upper gastrointestinal surgery leads to prompt anastomotic healing.

Early Postoperative Oral Intake Accelerates Upper Gastrointestinal Anastomotic Healing in the Rat Model

BACKGROUND In our previous study, we reported that early postoperative oral feeding accelerated upper gastrointestinal anastomotic healing in rats. To investigate its underlying mechanism, we performed in vivo and in vitro experiments. MATERIALS AND METHODS Rats that received proximal jejunal anastomosis were divided into four groups: the enteral nutrition (EN) group were fed via gastrostomy, the total parental nutrition (TPN alone) group were fed via a venous catheter, the TPN + saline group received an additional administration of normal saline solution via gastrostomy, and the TPN + water group received an additional administration of distilled water via gastrostomy. The anastomotic bursting pressure (ABP) and the hydroxyproline content of the anastomotic tissue were measured 5 d postoperatively. In an in vitro setting, the rat gastrointestinal fibroblasts were subjected to uniaxial stretching for 60 min, and the expression of type I and type III collagen mRNA was evaluated. RESULTS The ABP and hydroxyproline content in the EN group, the TPN + saline group, and the TPN + water group were significantly higher than those in the TPN alone group (ABP; 214.6 ± 42, 199.4 ± 36, and 187.3 ± 29 versus 149.5 ± 49 mmHg; P < 0.01, hydroxyproline; 63.5 ± 10, 67.8 ± 13, and 64.1 ± 14 versus 50.5 ± 12 μmol/g dry tissue; P < 0.01). The mRNA levels of type I and type III collagen were increased by stretch stimulation. CONCLUSIONS These results suggest that mechanical loading plays a key role in anastomotic healing. Further investigations are necessary to confirm this suggestion.

Determinants of liquid gastric emptying: comparisons between milk and isocalorically adjusted clear fluids

BACKGROUND Although current preoperative fasting guidelines apply restrictions to drinks containing milk because of delayed gastric emptying, the safe volume of milk that can be consumed up to 2 h before surgery on a theoretical basis has not yet been defined. We aimed to determine whether delayed gastric emptying depended mainly on the total amount of calories irrespective of compositional differences between milk and clear fluids. METHODS We prepared five beverages with a uniform volume (500 ml) and step-wise increments in calories (0, 220, and 330 kcal), comprised mainly of non-human milk, pulpless orange juice, water, and gum syrup. The gastric emptying rate of each beverage was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by eight healthy fasting volunteers. RESULTS The emptying rates of 500 ml of orange juice and 330 ml of non-human milk with 170 ml of water (both were 220 kcal) from the stomach were similar. Furthermore, 450 ml of orange juice with 50 ml of gum syrup and 500 ml of non-human milk (both were 330 kcal) left the stomach at similar rates. The 220 kcal beverages emptied faster than the 330 kcal beverages. CONCLUSIONS There were no significant differences in liquid gastric emptying after drinking equal volumes of either orange juice or milk as long as both had the same amount of calories. Liquid gastric emptying depends chiefly on the total caloric content. CLINICAL TRIAL REGISTRATION UMIN000012537.

A Stand-Alone Synbiotic Treatment for the Prevention of D-Lactic Acidosis in Short Bowel Syndrome

Synbiotics are combinations of probiotics and prebiotics that have recently been used in the context of various gastrointestinal diseases, including infectious enteritis, inflammatory bowel disease, and bowel obstruction. We encountered a patient with recurrent D-lactic acidosis who was treated successfully for long periods using synbiotics. The patient was diagnosed as having short bowel syndrome and had recurrent episodes of neurologic dysfunction due to D-lactic acidosis. In addition to fasting, the patient had been treated with antibiotics to eliminate D-lactate-producing bacteria. After the failure of antibiotic treatment, a stand-alone synbiotic treatment was started, specifically Bifidobacterium breve Yakult and Lactobacillus casei Shirota as probiotics, and galacto-oligosaccharide as a prebiotic. Serum D-lactate levels declined, and the patient has been recurrence-free for 3 years without dietary restriction. Synbiotics allowed the reduction in colonic absorption of D-lactate by both prevention of D-lactate-producing bacterial overgrowth and stimulation of intestinal motility, leading to remission of D-lactate acidosis.

Hyperfractionated Concomitant Boost Proton Beam Therapy for Esophageal Carcinoma

PURPOSE To evaluate the efficacy and safety of hyperfractionated concomitant boost proton beam therapy (PBT) for patients with esophageal cancer. METHODS AND MATERIALS The study participants were 19 patients with esophageal cancer who were treated with hyperfractionated photon therapy and PBT between 1990 and 2007. The median total dose was 78 GyE (range, 70-83 GyE) over a median treatment period of 48 days (range, 38-53 days). Ten of the 19 patients were at clinical T Stage 3 or 4. RESULTS There were no cases in which treatment interruption was required because of radiation-induced esophagitis or hematologic toxicity. The overall 1- and 5-year actuarial survival rates for all 19 patients were 79.0% and 42.8%, respectively, and the median survival time was 31.5 months (95% limits: 16.7- 46.3 months). Of the 19 patients, 17 (89%) showed a complete response within 4 months after completing treatment and 2 (11%) showed a partial response, giving a response rate of 100% (19/19). The 1- and 5-year local control rates for all 19 patients were 93.8% and 84.4 %, respectively. Only 1 patient had late esophageal toxicity of Grade 3 at 6 months after hyperfractionated PBT. There were no other nonhematologic toxicities, including no cases of radiation pneumonia or cardiac failure of Grade 3 or higher. CONCLUSIONS The results suggest that hyperfractionated PBT is safe and effective for patients with esophageal cancer. Further studies are needed to establish the appropriate role and treatment schedule for use of PBT for esophageal cancer.

The manner of the inflammation-boosting effect caused by acute hyperglycemia secondary to overfeeding and the effects of insulin therapy in a rat model of sepsis

BACKGROUND The aim of the study was to investigate both the inflammation-boosting effect and the metabolic stress induced by acute hyperglycemia secondary to overfeeding with excessive glucose infusion and the effects of insulin therapy on those events in a rat model of sepsis. MATERIALS AND METHODS Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham operation. Preestablished continuous intravenous glucose infusion was initiated immediately after surgery. First, rats with CLP-inducing sepsis were divided into three groups on the basis of the target blood glucose (BG) levels: high glucose (HG) group (overfed, >300 mg/dL), moderate glucose group (moderate hyperglycemia, 200-300 mg/dL), and no glucose group (100-150 mg/dL). The sham group received the same glucose infusion as that of the HG group. BG and plasma interleukin (IL) 6 levels were monitored over time. All rats were sacrificed 9 h after surgery to evaluate lung histology and measure hepatic total glutathione and malondialdehyde contents. Based on the results, the high glucose and insulin (HI) group was added to septic groups as a model of insulin therapy, in which insulin with the same HG dose as that in the HG group was administered to maintain moderate hyperglycemia. RESULTS BG level in all groups remained in the preestablished target range throughout the experiment. Plasma IL-6 level in all septic groups increased in a time-dependent manner, whereas that in the sham group with moderate hyperglycemia hardly increased. Nine hours after CLP, plasma IL-6 level in the HG group rose to 7407.5 ± 1987.3 pg/mL, which was three times higher than that in the other septic groups. There was no significant difference among moderate glucose, no glucose, and HI groups, in which BG level remained constant at <300 mg/dL. The HG group showed the worst consequences of lung injury and oxidative stress in the liver, which were completely stable in HI group. CONCLUSIONS Acute severe hyperglycemia in critical illness might excessively boost the existing systemic inflammatory response in a threshold-based manner. Insulin therapy under overfeeding could strongly inhibit such a boosting effect and oxidative stress in the liver.

A comparison of gastric emptying of soluble solid meals and clear fluids matched for volume and energy content: a pilot crossover study

We previously demonstrated that the gastric emptying time of different liquids with the same volume mainly depended on their energy content, regardless of differences in composition. In this crossover study, we investigated whether the same applies when soluble solid foods are ingested with water. Ten healthy volunteers ingested one of five test diets consisting of two test meals (Calorie Mate® 100 and 200 kcal) and three test solutions (water and glucose solutions of 100 and 200 kcal), each given in a volume of 400 ml, and then underwent ultrasonography to measure the gastric antral cross‐sectional area every 10 min for 120 min. The gastric emptying time was defined as the time for the antral cross‐sectional area to revert to its initial value. When test diets with the same energy content were ingested, the gastric emptying curves were nearly identical, regardless of whether the original form was solid or liquid. The median (IQR[range]) gastric emptying times of Calorie Mate® of 100 kcal with water vs. isocaloric glucose solution were 65 (60–78 [50–80]) vs. 65 (60–70 [50–80]) min (p = 0.58), and for Calorie Mate® of 200 kcal with water vs. isocaloric glucose solution they were 100 (93–108 [90–120]) vs. 105 (90–110 [90–120]) min (p = 0.54). The median (IQR [range]) for water was 40 (30–40 [30–50]) min. Energy content may be a critical determinant of the gastric emptying time when ingesting soluble solid diets with water.

Organizing Pneumonia as the First Clinical Manifestation of Early Stage Rheumatoid Arthritis Determined by Hand Joints Synovitis Using Magnetic Resonance Imaging

We report the case of a 50-year-old man who presented with organizing pneumonia (OP) as the first manifestation of rheumatoid arthritis (RA). He experienced repeated episodes of pneumonia, which did not respond to several antibiotics. The lymphocyte dominant cell increase in the bronchoalveolar lavage fluid on chest computerized tomography suggested OP. Although he did not present with articular symptoms, magnetic resonance imaging (MRI) revealed synovitis of the hand joints without joint erosion, suggesting that this was a case of early stage RA. The MRI may be a useful diagnostic tool in asymptomatic patients with early stage RA.