Tsuyoshi Mori

Indocyanine green fluorescence imaging system for sentinel lymph node biopsies in early breast cancer patients.

PurposeThis study presents a new method that enables the detection of sentinel lymph nodes (SLN) with high sensitivity using indocyanine green (ICG) fluorescence imaging.MethodsThis study enrolled 128 patients with clinically node-negative breast cancer. Fluorescence imaging was obtained after ICG was injected into the areola. Subcutaneous lymphatic channels were immediately visible.ResultsLymphatic channels and SLN were successfully visualized in all patients. One lymphatic channel was 60%, two channels were 24%, and three channels were 16%. The number of fluorescence SLN ranged from 1 to 6, and blue-dyed SLN ranged from 0 to 3. In the latter, SLN were not identified in 44 patients. Nineteen patients had pathologically identified lymph node metastases. All of them were recognized by fluorescence imaging, but 8 patients had lymph nodes with metastases were not identified by dye method.ConclusionThis ICG fluorescence imaging technique is feasible and safe for detecting SLN in a less invasive manner than conventional mapping, with real-time observations.

A Possible Role of GLP-1 in the Pathophysiology of Early Dumping Syndrome

Exaggerated plasma concentrations of GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients, resulting in late dumping syndrome. Recently, we showed that GLP-1 elicits the activation of sympathetic outflow. Because sympathetic activation is thought to be a cause of early dumping, we hypothesized that exaggerated GLP-1 may contribute to the pathophysiology of early dumping syndrome. In 11 patients after gastrectomy and 14 controls, blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, GLP-1, glucagon, insulin, and glucose were measured after oral glucose. In gastrectomy patients, GLP-1, norepinephrine, and heart rate peaked 15 to 30 min after oral glucose. Significant positive correlations were found among GLP-1, norepinephrine, and heart rate at 30 min, and these parameters at 30 min were significantly higher in patients with early dumping syndrome. These results suggest that GLP-1 is involved in the pathophysiology of early dumping syndrome.

Spontaneous hematoma of the lateral abdominal wall caused by a rupture of a deep circumflex iliac artery: report of two cases.

Expanding hematoma of the abdominal wall is a rare example of acute abdominal disease. We report two cases of lateral abdominal wall hematoma caused by the rupture of a deep circumflex iliac artery, which is a rare cause of an abdominal wall hematoma. Both patients experienced severe abdominal pain after sneezing or coughing. In both cases, computed tomography (CT) findings suggested that active bleeding was continuing. Emergent angiography was therefore performed, and the hematoma was embolized using Spongel or Microcoils. Ultrasound examinations were repeatedly used to monitor the size of the hematoma. The size of the hematoma and patients pain gradually decreased after embolization. Ultrasound and CT examinations provided useful information for the differential diagnosis of this disease. We conclude that emergent angiography should be performed to control bleeding and avoid any unnecessary surgical procedures in patients with hematoma of the abdominal wall.

Transient receptor potential vanilloid 1 antagonist, capsazepine, improves survival in a rat hemorrhagic shock model.

Objective:To evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in a rat hemorrhagic shock (HS) model using the TRPV1 antagonist, capsazepine (CPZ). Summary Background Data:TRPV1, distributed within the sensory nerve, plays a role in the regulation of cardiovascular functions. TRPV1 may be involved in the cardiovascular responses to HS. Methods:Male rats were anesthetized and HS was induced with the mean arterial pressure (MAP) at 30 mm Hg for 90 minutes. CPZ (5.0 μmol/kg) was administered at 30 minutes after the shock induction, and the 24-hour survival rates were assessed. The MAP, heart rate, and shed blood volume (SBV) were recorded throughout the experiment. Arterial blood gas analysis and the plasma catecholamines levels were measured before and after HS. Double-immunohistochemistry for Fos and tyrosine hydroxylase (TH) was performed in the rostral ventrolateral medulla (RVLM) of the brain. Results:CPZ significantly improved the 24-hour survival rates, which was accompanied by the increase in the MAP and the SBV, a decrease of the plasma catecholamines levels, and attenuation of the severe metabolic acidosis. Furthermore, CPZ reduced the percentage of double-labeled neurons for Fos and TH in the RVLM of the rat brain. Conclusions:TRPV1 may be involved in the regulation of the cardiovascular responses to HS, at least in part, by recruiting catecholaminergic neurons in the RVLM. CPZ appears to induce metabolic compensations, which may be potentially useful in HS.

A free radical scavenger, edaravone (MCI-186), diminishes intestinal neutrophil lipid peroxidation and bacterial translocation in a rat hemorrhagic shock model

Objective:To investigate the effects of edaravone, a novel free radical scavenger, on bacterial translocation induced by hemorrhagic shock. Design:Prospective, randomized, unblinded animal study. Setting:Surgical research laboratories of Shiga University of Medical Science. Subjects:Male specific-pathogen-free Sprague-Dawley rats. Interventions:The rats were randomly divided into three groups: conventional saline treatment, edaravone treatment, and sham shock induction. The saline and edaravone groups were subjected to hemorrhagic shock (mean arterial pressure of 30 mm Hg, for 30 or 60 mins). Rats were killed 30 or 60 mins after shock induction. Mesenteric lymph nodes were cultured for determination of bacterial translocation. Systemic plasma silkworm larvae plasma test, which can detect peptidoglycan and &bgr;-glucan, and endotoxin tests were performed. Immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE) was used to assess lipid peroxidation after shock. Measurements and Main Results:The incidence and magnitude of hemorrhagic-shock-induced bacterial translocation to mesenteric lymph nodes were reduced by edaravone. Hemorrhagic-shock-induced increase of plasma silkworm larvae plasma test was also reduced by edaravone. Immunohistochemistry for 4-HNE showed many 4-HNE-positive cells in the lamina propria of the ileum 60 mins after hemorrhagic shock. Double immunohistochemistry revealed that many of these 4-HNE-positive cells were also myeloperoxidase positive. Moreover, the percentage of double-labeled cells with 4-HNE and myeloperoxidase in myeloperoxidase-positive cells was significantly lower in the edaravone group than in the saline group. Conclusions:The present findings suggest that lipid peroxidation of intestinal neutrophils is involved in bacterial translocation during hemorrhagic shock and that edaravone is potentially useful in diminishing bacterial translocation after hemorrhagic shock.

Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct

A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma (LEC), and some of LEC is associated with Epstein-Barr virus (EBV). All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location. Herein, we describe the first case of LEC of the inferior common bile duct. A 68-year-old Japanese man, who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy, was found to have tumors of the common bile duct and pancreas head. Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli. Around the tumor cell nests, dense lymphoplasmacytic infiltration was observed. Focal glandular differentiation (approximately 5%) was also present. These histopathological features corresponded morphologically to LEC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, CK 19 and CA19-9, but negative for CK 20 and Hep Par 1. In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells. Therefore, a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made. Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma, the differences in prognosis between EBV-positive and -negative cases have not yet been established. Therefore, additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.

Diagnostic and predictive value of the silkworm larvae plasma test for postoperative infection following gastrointestinal surgery.

Objective:To determine whether the silkworm larvae plasma (SLP) test is a reliable diagnostic marker of infection in patients with infectious complications following gastrointestinal surgery. Design:Prospective study. Setting:Department of Surgery, University Hospital, Shiga University of Medical Science. Patients:One hundred and twelve adult patients undergoing gastrointestinal surgery Interventions:None. Measurements and Main Results:Thirty-nine of 112 patients developed infectious complications (infected group). Seven patients with sepsis (severely infected group) and 32 patients without sepsis (minor infected group) were observed. The operation time, blood loss, and age were significantly greater in both infected groups than in the noninfected group. The systemic inflammatory response syndrome score on postoperative day (POD) 1 and POD7 was highest in the severely infected group. The increase in C-reactive protein on POD3 and POD7 was significantly higher in both infected groups than in the noninfected group. White blood cell counts on POD7 were elevated significantly higher in the severely infected group than in the other groups. Immediately after surgery, SLP activity significantly increased compared with presurgery in all groups and was significantly higher in the minor and severely infected groups than in the noninfected group. The increased SLP activity returned to preoperative levels in the minor and noninfected groups; however, SLP activity in the severely infected groups remained high throughout the observational period. The most significant factor and time point that predicted infectious complications were the SLP test on POD1; sensitivity 66.7%, specificity 90.4%, positive and negative predictive values 78.8% and 83.5%. The area under the receiver operating characteristic curve for the SLP test was 0.813 ± 0.046. Conclusions:The SLP test appears to be a useful marker of diagnosis and prediction of infectious complications following gastrointestinal surgery. Moreover, the SLP test may be able to evaluate not only the existence but also the severity of infection in surgical patients.

Septic acute renal failure.

Acute renal failure (ARF) is the rapid loss of the renal filtration function, which is characterized by metabolic acidosis, high potassium levels, a body fluid imbalance, and so on. The overall mortality rate of ARF is about 45%; however, the mortality rate of sepsis-induced ARF is about 70%. In addition, sepsis is the most common trigger of ARF. Little is known about the pathogenesis of septic ARF, although renal hypoperfusion and ischemia have been proposed as being central. Blood purification therapies for septic ARF include the elimination of pathogenesis, such as endotoxin or mediators that contribute to ARF, and renal replacement therapy (RRT). The adsorption of endotoxin with direct hemoperfusion using polymyxin-B immobilized fiber makes the urinary output increase, while also improving renal function. It would seem logical to initiate RRT earlier rather than later, especially in rapidly developing symptomatic oliguric renal failure with metabolic derangement. Continuous RRT (CRRT) has an advantage over intermittent RRT in that it provides greater hemodynamic stability, easier fluid removal and greater flexibility in providing parenteral nutrition as a result of a greater control over the fluid balance. CRRT may be able to reduce chronic dialysis dependence. Patients with sepsis and ARF are hyper-catabolic. Some studies have suggested that increased doses of dialysis improve survival in patients who are hypercatabolic and have ARF. The increase in the ultrafiltration rate may, however, be associated with some difficulties, namely cost and labor. The mechanisms of septic ARF therefore need to be further elucidated and the potential of RRT in improving the mortality associated with ARF needs to be established.

The Kampo Medicine Goshajinkigan Prevents Neuropathy in Breast Cancer Patients Treated with Docetaxel

BACKGROUND Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. MATERIALS AND METHODS Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. RESULTS The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was 2.7 ± 2.2. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was 4.9 ± 2.4. CONCLUSIONS Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.

Association between Reduction of Plasma Adiponectin Levels and Risk of Bacterial Infection after Gastric Cancer Surgery

Background and Purpose Infections are important causes of postoperative morbidity after gastric surgery; currently, no factors have been identified that can predict postoperative infection. Adiponectin (ADN) mediates energy metabolism and functions as an immunomodulator. Perioperative ADN levels and perioperative immune functioning could be mutually related. Here we evaluated a potential biological marker to reliably predict the incidence of postoperative infections to prevent such comorbidities. Methods We analyzed 150 consecutive patients who underwent elective gastric cancer surgery at the Shiga University of Medical Science Hospital (Shiga, Japan) from 1997 to 2009; of these, most surgeries (n = 100) were performed 2008 onwards. The patient characteristics and surgery-related factors between two groups (with and without infection) were compared by the paired t-test and χ2 test, including preoperative ADN levels, postoperative day 1 ADN levels, and ADN ratio (postoperative ADN levels/preoperative ADN levels) as baseline factors. Logistic regression analysis was performed to access the independent association between ADN ratio and postoperative infection. Finally, receiver operating curves (ROCs) were constructed to examine its clinical utility. Results Sixty patients (40%) experienced postoperative infections. The baseline values of age, American Society of Anesthesiologists physical status, total operating time, blood loss, surgical procedure, C-reactive protein (CRP) levels, preoperative ADN levels, and ADN ratio were significantly different between groups. Logistic regression analysis using these factors indicated that type 2 diabetes mellitus (T2DM) and ADN ratio were significantly independent variables (*p<0.05, ** p<0.01, respectively). ROC analysis revealed that the useful cutoff values (sensitivity/specificity) for preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 8.81(0.567/0.568), 0.76 (0.767/0.761), 405 g (0.717/0.693), 342 min (0.617/0.614), and 8.94 mg/dl (0.583/0.591), respectively. Conclusion T2DM and ADN ratio were independent predictors of postoperative infection and ADN ratio was the most useful predictor for postoperative infection.