[A case of amelanotic anorectal malignant melanoma mimicking gastrointestinal stromal tumor].

A 56-year-old female patient was admitted, complaining of hematochezia. She was preoperatively diagnosed with poorly-differentiated carcinoma of anorectum with metastases in the lung and mesorectal lymph nodes, and underwent abdominoperineal resection of the rectum. The immunohistochemistry of the rectal tumor showed positive for vimentin and c-kit, and negative for AE1/AE3, S-100, a-SMA, LCA and CD34, which was compatible with gastrointestinal stromal tumor (GIST). Regardless of the administration of imatinib mesylate, multiple metastases in the brain, bone, adrenal glands and inguinal lymph node proceeded in a short term. An excisional biopsy of the inguinal lymph node was performed and immunohistochemistry of the specimen showed positive for S-100, melan-A, HMB45 and tyrosinase. Therefore, we concluded that amelanotic anorectal melanoma (AMM) metastasized to the lymph node, and rechecked the immuno histochemistry of the anorectal tumor. The anorectal tumor showed positive for melan-A, HMB45 and tyrosinase, but negative for S-100. As far as we know, there are few reports of AMM with S-100 negative and c-kit positive. In such cases, making a differential diagnosis between AMM and GIST of the anorectal region can be very confusing.

[A case of advanced gastric cancer with rhabdomyolysis].

We report a patient with advanced gastric cancer with rhabdomyolysis. A 29-year-old man consulted a local doctor complaining of dysphagia and heartburn. He developed rhabdomyolysis that was considered to be caused by administered proton pump inhibitor (PPI). The patient has remained without recurrence for 18 months after operation.

[A case of solitary splenic metastasis from an ovarian cancer 12 years after primary resection].

A 57-year-old woman underwent total hysterectomy and bilateral salpingo-oophorectomy for bilateral ovarian tumors (T1b, N0, M0; Stage I b, serous cystoadenocarcinoma) in May 1994. She received 4 courses of CAP (cyclophosphamide 500 mg/m2+epirubicin 50 mg/m2+cisplatin 60 mg/m2) therapy as adjuvant chemotherapy. An increase of the serum CA125 was detected in December 2006, and abdominal CT revealed a mass in the spleen. Since whole-body FDG-PET-CT showed no evidence of local recurrence of the ovarian cancer or multiple organ metastases, a solitary splenic metastasis from ovarian cancer, even though very rare, was strongly suspected. Splenectomy with distal pancreatectomy was undertaken in December 2007. Histopathological examination revealed poorly-differentiated adenocarcinoma, suggesting the final diagnosis of solitary splenic metastasis from ovarian cancer. Periodic CA125 measurements are considered very important even over 10 years after surgery for ovarian cancer. Once solitary splenic metastasis is diagnosed, surgical resection would be the treatment of choice.

Direct hemoperfusion with polymyxin-B-immobilized fiber columns improves septic hypotension and reduces inflammatory mediators in septic patients with colorectal perforation.

PURPOSE: Although some studies have reported favorable effects of direct hemoperfusion with polymyxin-B-immobilized fiber columns (PMX) for the treatment of septic shock, few studies have demonstrated the efficacy of PMX in studies with a uniform case definition and without any other blood purification techniques. MATERIALS AND METHODS: Fifty-two patients with severe sepsis or septic shock secondary to colorectal perforation were treated with PMX. Hemodynamic alterations and plasma concentrations of endotoxin, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, and IL-10 were evaluated following PMX treatment. RESULTS: We observed a significant reduction in plasma endotoxin in the nonsurvivors immediately after PMX treatment compared to before treatment. Systolic blood pressure was markedly increased and circulating levels of IL-1beta, IL-1Ra, and IL-8 were significantly reduced during a 2-h interval of PMX. CONCLUSIONS: Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.

Circulating concentrations of adiponectin, an endogenous lipopolysaccharide neutralizing protein, decrease in rats with polymicrobial sepsis.

BACKGROUND: Adiponectin is an anti-inflammatory cytokine that is specifically and abundantly produced by adipocytes as a secretory protein. A direct interaction between adiponectin and lipopolysaccharide (LPS) is not fully understood. To elucidate the effects of adiponectin on LPS, we first investigated interactions between recombinant adiponectin and LPS. MATERIALS AND METHODS: Various concentrations of LPS (50, 500, and 5000 pg/ml) and recombinant adiponectin (1, 10, and 100 microg/ml) were incubated for 1 h. The limulus amoebocyte lysate (LAL) activities in the mixture were measured. Interactions between adiponectin (100 microg/ml) and LPS (100 and 300 microg/ml) were also analyzed in Western blotting. Next, we determined plasma adiponectin, tumor necrosis factor-alpha (TNF-alpha), and endotoxin levels at 1.5, 3, and 24 h after onsets of rodent polymicrobial sepsis induced by cecal ligation and puncture (CLP). RESULTS: The incubation with adiponectin significantly and dose-dependently suppressed LAL activity in the mixture compared to control. Western blotting revealed that adiponectin incubated with LPS shifted to a higher mass. In the animal model of sepsis, both plasma endotoxin and TNF-alpha levels after CLP gradually increased and were significantly higher at 3, 24 h compared to those after sham operation. On the contrary, plasma adiponectin levels after CLP gradually decreased and were significantly lower at 3, 24 h compared to those after sham operation. Plasma adiponectin levels were negatively correlated with plasma endotoxin levels (r = -0.77, P < 0.01). CONCLUSIONS: Our results indicate that adiponectin might neutralize LPS in vitro and diminish LPS activity in rats with polymicrobial sepsis. These findings suggest that the anti-inflammatory effects of adiponectin are in part likely because of neutralization of LPS activity.

Magnetic resonance-guided percutaneous microwave coagulation therapy for liver metastases of breast cancer in a case.

Real-time magnetic resonance (MR) imaging enables the application of percutaneous microwave coagulation for high-risk patients with metastatic liver tumours. The tumours, local vessels and bile ducts can be observed clearly in three-dimensional sections and a sufficient surgical margin can be confirmed on the MR image even during the coagulation procedure. MR-guided percutaneous microwave coagulation therapy is effective for treatment of not only primary liver tumours but also metastatic breast cancers in the liver, which are not diffuse but discrete, and difficult to treat with only chemo-and endocrine therapy. We report a 44-year-old Japanese woman who underwent modified radical mastectomy for right breast cancer (T1c N0 M0 Stage I). Three years after the operation, she developed two metastatic liver tumours and was treated by MR-guided percutaneous microwave coagulation, achieving a complete response (CR) without any recurrence for 15 months as of the present. The most beneficial aspect of MR-guided percutaneous microwave coagulation is its safety. It is only minimally invasive and can be repeated. This therapy, therefore promises to prolong the disease free period. Additional clinical trials will be valuable to delineate the effectiveness and safety of MR-guided percutaneous microwave coagulation therapy for controlling the liver metastases of breast cancer.

Laparoscopic cholecystectomy in situs inversus totalis with "inferior" cystic artery: a case report.

A 76-year-old man with known situs inversus totalis presented with left-sided discomfort. Abdominal ultrasonography and CT scan confirmed the diagnosis of a gallstone, as well as, situs inversus; the liver and gallbladder on the left side and the spleen on the right. The biliary system was thought to be left-right reversal, mirror image in the view of drip infusion cholangiogram and MRI. Laparoscopic cholecystectomy was safely performed, despite of unexpected aberrant cystic artery running inferior to cystic duct of situs inversus. Laparoscopic surgeon should be careful for view of reversed relationships and also existence of other anomalies.

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.

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 beta-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.

Open-configuration MR-guided microwave thermocoagulation therapy for metastatic liver tumors from breast cancer.

BACKGROUND: Liver metastases from breast cancer are associated with a poor prognosis, however, local control with microwave thermocoagulation therapy has been used in certain subgroups of these patients in the past decade. In this study, open-configuration magnetic resonance (MR) -guided microwave thermocoagulation therapy was used for metastatic liver tumors from breast cancer, and the efficacy of this treatment was assessed. METHODS: Between June 2000 and April 2004, we used MR-guided microwave thermocoagulation therapy on 11 nodules in 8 patients with metastatic liver tumors from breast cancer. The procedure was carried out under general anesthesia. A 0.5 T open-configuration MR system and a microwave coagulator were used. Near-real-time MR images and real-time temperature images were collected and displayed on the monitor. The MR-compatible thoracoscope was used and combined with MR imaging guidance. Navigation software, a 3D Slicer, was installed and customized. RESULTS: The customized navigation software displayed near-real-time MR images. The percutaneous puncture into the tumors was successful in all cases. No mortality or major complications occurred as a result of the procedures. Five of the 8 patients are alive with new metastatic foci with a mean observation period of 25.9 months. CONCLUSIONS: We developed several devices to allow safe, easy, and accurate MR-guided microwave thermocoagulation therapy of liver tumors. Open-configuration MR-guided microwave thermocoagulation therapy appears to be a feasible method for tumor ablation of metastatic liver tumors from breast cancer.

Invasive ductal carcinoma within a fibroadenoma of the breast.

A rare case of invasive ductal carcinoma within a fibroadenoma of the breast in a 42-year-old woman is reported. The patient had a well-defined mass, measuring 6.0 x 5.0 cm, in the upper lateral quadrant of the left breast. Physical examination suggested fibroadenoma. Ultrasonography and mammography revealed some malignant findings. Needle biopsy demonstrated fibroadenoma. Frozen section revealed invasive ductal carcinoma, scirrhous type, arising in a fibroadenoma; muscle-preserving mastectomy was performed. Only 16 cases of carcinoma within a fibroadenoma of the breast have been reported in the literature in Japan. Carcinoma in a fibroadenoma should be treated on the basis of the therapeutic criteria for ordinary carcinoma.

Hyperoxic condition prevents bacterial translocation and elevation of plasma microorganism components during hemorrhagic shock.

To evaluate the influence of hyperoxic conditions on bacterial translocation (BT) and microorganism components during hemorrhagic shock, rats were divided into a group breathing 100% oxygen and a group breathing room air. The groups were then subjected to hemorrhagic shock. Systemic blood and mesenteric lymph nodes were cultured for BT, and systemic plasma concentrations of microorganism components were measured by the silkworm larvae plasma (SLP) test and the endotoxin test. Hyperoxic conditions prevented both BT and plasma SLP-reactive substance (peptidoglycan and beta-glucan) elevation during hemorrhagic shock. Our findings suggest that hyperoxic treatment might improve host conditions during hemorrhagic shock.

Dendritic cell vaccine immunotherapy of cancer targeting MUC1 mucin.

The use of dendritic cells (DCs) for cancer vaccination is effective in suppressing cancer progression. This is because the DCs play a crucial role in priming tumor-specific immunity efficiently as antigen-presenting cells. In this study, we analyzed the ability of DCs to elicit tumor-specific immunity and clinical effects of DC vaccine immunotherapy targeting MUC1 tumor antigens. DCs from 14 patients with advanced or metastatic breast or lung cancer (9 positive for MUC1 and 5 negative for MUC1) were loaded with MUC1 antigens or tumor lysate and used for therapeutic vaccination. After vaccination, all the MUC1-positive patients acquired antigen-specific immunity whereas only 1 case with MUC1-negative cancer showed the specific immunity. Clinically, marked effects such as reduction in tumor sizes or tumor marker levels or disappearance of malignant pleural effusion were observed in 7 of the 9 MUC1-positive cases. However, MUC1-negative patients did not respond to DC vaccines, with the exception of 1 case with MAGE3-positive lung cancer. Survival of MUC1-positive patients was significantly prolonged in comparison with MUC1-negative patients (mean survival: 16.75 versus 3.80 months, p=0.0101). These data suggest that MUC1 is sufficiently immunogenic to elicit strong anti-tumor immunity as a tumor antigen and that DC vaccines targeting MUC1 are useful for immunotherapy of cancer.

Effect of His-Gly-Lys motif derived from domain 5 of high molecular weight kininogen on suppression of cancer metastasis both in vitro and in vivo.

We have demonstrated previously that kinin-free high molecular weight kininogen, its domain 5 (D5H, Gly402-Lys502), and peptides derived from D5H inhibited vitronectin-mediated migration and invasion of cancer cells in vitro (Kamiyama, F., Maeda, T., Yamane, T., Li, Y. H., Ogikubo, O., Otsuka, T., and Ohkubo, I. (2001) Biochem. Biophys. Res. Commun. 288, 975-980). In this study, we found that the amino acid sequence His-Gly-Lys (HGK) in D5H is the core motif for inhibition of adhesion and invasion of MDA-MB-231 cells in vitro. P-5m (484GHGKHKNK491, Gly484-Lys491), an octapeptide including the HGK motif derived from D5H, and HGK, a tripeptide, inhibited both cell adhesion and invasion in vitro. However, an octapeptide designated P-5m (K487R), in which Lys487 was changed to Arg, did not inhibit either cell adhesion or invasion, and peptides HGR and HGG also had no inhibitory effect. Recombinant GST-D5H expressed in Escherichia coli had a stronger inhibitory effect on cell adhesion and invasion in vitro than did GST-D5H (K487R) in which Lys487 was changed to Arg. Furthermore, P-5m (Gly484-Lys491) peptide clearly suppressed lung metastasis in mice experimentally induced by using B16-F10 cells, but P-5m (G487R) had no effect. These data strongly indicate that both the HGK motif and lysine residue (Lys487) play essential roles in inhibition of cell adhesion and invasion in vitro and in prevention of metastasis of cancer cells in vivo. We tried to identify the HGK motif binding protein on the surface of cancer cells. A 95-kDa surface biotin-labeled membrane protein was specifically detached from GST-D5H by P-5 (His479-Lys493) peptide but not by P-1 (Gly402-Lys420) peptide originating from the N-terminal region of D5H.

Changes in circulating levels of calcitonin gene-related peptide and nitric oxide metabolites in septic patients during direct hemoperfusion with polymyxin B-immobilized fiber.

BACKGROUND/AIMS: This study evaluated the mechanism of hemodynamic improvement in polymyxin B-immobilized fiber (PMX) treatment. METHODS: Fifteen septic patients with endotoxemia and/or gram negative infection were treated with PMX. Plasma concentrations of calcitonin gene-related peptide (CGRP) and nitric oxide metabolites were measured. RESULTS: CGRP and nitric oxide metabolites before treatment were significantly higher than in healthy controls. CGRP had a significantly inverse correlation with diastolic blood pressure and a positive correlation with the Septic Severity Score and the number of failed organs. Systolic and diastolic blood pressure and systemic vascular resistance index increased significantly both immediately after and 24 h after PMX treatment. CGRP decreased significantly 24 h after the treatment. In contrast, there were no significant changes in nitric oxide metabolites. CONCLUSION: PMX treatment improved hemodynamic parameters in septic patients, and CGRP increased with increasing severity of sepsis. We conclude that a decrease in CGRP levels may be related to hemodynamic improvement resulting from PMX treatments.

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 patient's 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.

Obstructive jaundice in a metastatic tumor of the pancreas from breast cancer: a case report.

Metastatic pancreas tumors from breast cancer are comparatively uncommon and patients with this tumor usually remain asymptomatic during their life. A 55-year-old woman presented with obstructive jaundice following mastectomy for invasive ductal carcinoma. We diagnosed obstructive jaundice due to a pancreatic tumor demonstrated on computed tomography and performed percutaneous transhepatic cholangio-drainage. Although the patient recovered from the jaundice, she had exacerbation of pneumonia from which she died. At autopsy, invasive ductal carcinoma was found in the pancreas tumor. Immunohistochemical staining was performed to confirm whether the pancreatic tumor was primary or secondary. Human milk fat globules 1 and 2 and gross cystic disease fluid protein-15, which characteristically exist in normal breast tissue or breast carcinoma, were expressed both in the primary breast tumor and the pancreatic tumor. In contrast, both the anti-estrogen receptor and anti-progesterone receptor antibodies stained positively in the primary breast cancer; however, neither of them was positive in the metastatic pancreatic tumor. We report a rare case of a patient who presented with obstructive jaundice from a pancreatic tumor metastasizing from breast cancer and in whom immunohistochemical staining using the antibodies unique to the mammary gland was effective for the diagnosis of this secondary tumor.

A case of acute hepatic insufficiency treated with novel plasmapheresis plasma diafiltration for bridge use until liver transplantation.

A patient with acute hepatic insufficiency induced by a drug presented to our institution, and we performed a novel plasmapheresis that we call plasma dia-filtration (PDF). The patient was a 36 year old woman. She underwent 11 sessions of PDF for a duration of about 9 h for each procedure using the Evacure EC-2A filter together with 20 units of fresh frozen plasma and dialysate simultaneously. Serum levels of total bilirubin and prothrombin time were significantly improved after she underwent each procedure. However, after the third procedure the levels returned to the same level as on the previous day. Encephalopathy improved after the first procedure, and this improvement was maintained until the ninth procedure. The patient prepared to undergo liver transplantation after the tenth procedure because of the development of hepatic coma, but she died of respiratory insufficiency before undergoing the procedure. Accordingly in this case, PDF worked to maintain liver function in acute liver failure and may act as bridge therapy until the patient can undergo liver transplantation.

Enzyme histochemistry is useful to assess viability of tumor tissue after microwave coagulation therapy (MCT): metastatic adenocarcinoma treated by lateral segmentectomy after MCT.

We report on a case of metastatic adenocarcinoma of liver that was removed and examined histochemically after microwave coagulation therapy (MCT). The patient was a 65-year-old woman who had a metastatic tumor in the liver (S3) after high anterior resection due to a rectal adenocarcinoma and received MCT against the tumor. One month after MCT, multiple metastatic tumors were detected by abdominal computed tomography (CT) scan. As it was difficult to control them by MCT alone, we performed lateral segmentectomy. To assess the effects of microwave ablation on cellular viability of metastatic tumor, we used enzyme histochemistry for acid phosphatase (AcP), which is positive in macrophages infiltrating in the tumor. In a part of the ablated area of resected liver, there was remaining neoplastic tissue of which the morphology was maintained in H&E staining. This was found to be microwave-fixed non-viable tissue because no enzyme activity of AcP was detected in the infiltrating macrophages. This case report suggests that enzyme histochemistry was useful to assess the effect of MCT, enabling us to distinguish fixed cells from viable cells.

Bacterial translocation and peptidoglycan translocation by acute ethanol administration.

BACKGROUND: We examined bacterial translocation (BT) by acute ethanol administration, using a peptidoglycan detecting system. METHODS: Rats were given 20% (v/w) ethanol (10 ml/kg body weight), and heparinized samples of portal blood were collected at specific time points after administration. Plasma peptidoglycan, beta-glucan, and endotoxin concentrations of portal blood were measured. The rats were divided into three groups: a 20% ethanol group (20ET group), a 5% ethanol group (5ET group), and a control group. The groups were given 10 ml/kg body weight of either 20% (v/w) ethanol (20ET group), 5% (v/w) ethanol (5ET group), or distilled water (control group). Femoral arterial blood, portal blood, mesenteric lymph nodes (MLNs), spleen, and liver were cultured to assess BT. Plasma peptidoglycan, beta-glucan, and endotoxin concentrations of femoral arterial blood and portal blood were measured. RESULTS: The plasma peptidoglycan concentration of portal blood was significantly increased 24 h after the administration of 20% ethanol. There was no significant difference in the incidence and magnitude of viable BT to the MLNs, spleen, and liver among any of the groups at this time point. The rate of plasma peptidoglycan positivity and the plasma peptidoglycan concentration were increased significantly in the portal blood of the 20ET group 24 h after administration. CONCLUSIONS: Peptidoglycan was translocated into the portal blood by acute administration of 20% ethanol. Our findings suggest that viable bacterial flora may translocate from the intestine under the influence of ethanol, and BT may be one of the causes of chronic alcoholic liver disease.