Transforming growth factors in urine from patients with primary brain tumors

Urine specimens obtained from 19 patients with primary brain tumors were examined for the activity of transforming growth factors (TGF's). Urine was assayed for TGF's by soft agar colony formation and iodine-125 (125I)-epidermal growth factor (EGF)-binding competition. Two nontransformed cell lines, clonal NRK49F and BALB/3T3 A31-1-1 cells, were used as indicator cells for the soft agar colony assay, while EGF receptor-rich A431 cells were used for 125I-EGF-binding competition assay. Urine samples were dialyzed against acetic acid, then lyophilized, prepared with gel-permeation chromatography, and assayed. All 19 patients and a control group of healthy individuals showed high levels of alpha-type TGF's with low molecular weight (4 to 8 kD) in all urine samples. In addition, alpha-type TGF's of high molecular weight (20 to 50 kD) were detected at high levels in urine from all 10 patients with high-grade astrocytoma; at intermediate levels in urine from one of two patients with low-grade astrocytoma and from two of four patients with meningioma; and at low levels in urine from one of two patients with low-grade astrocytoma, from two of four patients with meningioma, from one patient with oligodendroglioma, from two patients with neurinoma, and from all healthy control individuals. The high level of alpha-type TGF's with high molecular weight detected in urine from patients with high-grade astrocytoma could be useful as a tumor marker.     

Fluid resuscitation of trauma patients: how fast is the optimal rate?

The Advanced Trauma Life Support guidelines recommend an initial rapid infusion of fluid (1-2 L) in trauma and hemorrhage victims as a diagnostic procedure to aid treatment decisions. Although patient response to initial fluid resuscitation is the key to determining therapeutic strategies, the appropriate rate of infusion is not clearly defined. Ninety-nine adult (age >16 years) blunt trauma victims with hypotension were enrolled. Patients were classified into 3 groups according to hemodynamic state after initial fluid resuscitation and requirement of surgical intervention. Total volume and rate of infusion differed significantly between the groups (P < .05). Patients requiring fluid administration at higher rate were all hemodynamically unstable and required immediate surgical intervention. Moreover, rate of infusion was the best predictor of the patients who required immediate surgical intervention. Moderate fluid infusion rate should be considered to allow identification of the patient's response to initial fluid resuscitation.     

Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients

OBJECTIVES: Immature microvessels, which are not covered by pericytes, are irregular and leaky. We hypothesized that tumor cells can penetrate immature microvessels more easily than mature microvessels. In this study, we investigated the maturation of angiogenesis by the immunohistochemical staining of colorectal cancer specimens and determined the correlation between the microvessel count or the maturity of microvessels and clinicopathological variables. METHODS: Ninety-two surgical specimens from our department were used. Double immunostaining of endothelial cells with anti-CD34 antibody and pericytes with anti-alpha-smooth muscle actin antibody was performed. The microvessel density (MVD) and microvessel pericyte coverage index (MPI) as an index of microvessel maturation were evaluated. RESULTS: The MVD showed a significant positive correlation with tumor size, depth of invasion and Dukes' stage. The MPI showed a significant positive correlation with the histological differentiation of the tumor tissues and distant metastasis at the time of operation. The high MVD group (> or =26.0, n = 50) tended to have a poorer prognosis than the low MVD group (<26.0, n = 42) (p = 0.097). Next, the 50 patients in the high MVD group were classified into two subgroups of high MPI (> or =78.1%, n = 25) and low MPI (<78.1%, n = 25). MPI showed a significant negative correlation with hematogenous metastasis, and the low MPI group demonstrated a significantly poorer survival than the high MPI group (p = 0.040). CONCLUSIONS: These findings demonstrate that immature neovascularization was observed in poorly differentiated tumors and was correlated with metastasis, resulting in a poorer prognosis. Taken together, not only microvessel density but also vascular maturation were crucial factors for colorectal cancer patients.     

Pleomorphic carcinoma of the lung producing granulocyte colony-stimulating factor: report of a case

We herein report a case of acute respiratory distress syndrome (ARDS) that appeared to be related to a granulocyte colony-stimulating factor (G-CSF)-producing lung cancer. A 77-year-old man with arterial sclerotic obstruction (ASO) underwent reconstructive surgery of the left femoral artery. He developed ARDS on the 5th postoperative day, which resolved following mechanical ventilation with steroid pulse treatment. Four months later, he was admitted with a fever and right arm pain. Chest computed tomography showed a malignant lesion in the right apical lung, and percutaneous needle biopsy demonstrated adenocarcinoma. Laboratory data revealed neutrophilia with elevated serum G-CSF levels. He underwent a right upper lobectomy with chest wall resection, and administration of sivelestat sodium to treat his postoperative pre-acute lung injury state. Pathology revealed a G-CSF-producing pleomorphic carcinoma. Retrospectively, a tumor shadow was noted on chest X-ray at the time of ARDS just after ASO surgery. The relationship between an abnormal G-CSF level and ARDS was considered, and the implications are herein discussed.     

Secondary sclerosing cholangitis with hemobilia induced by pembrolizumab: Case report and review of published work

A 66‐year‐old man was admitted to our department due to cholestatic liver injury. He had received five cycles of pembrolizumab for small‐cell lung cancer. Imaging showed the possibility of sclerosing cholangitis (SC) with hemobilia. Histologically, CD8⁺ T cells had infiltrated the biliary epithelium of the extrahepatic bile duct. We reached the diagnosis of secondary SC induced by pembrolizumab. Although we treated him with high‐dose corticosteroids, laboratory data showed only a moderate response. Clinicians should recognize that immune checkpoint inhibitors can sometimes cause severe and irreversible SC.     

Glucose transporter expression of intraductal papilloma of the breast detected by fluorodeoxyglucose positron emission tomography

A 40-year-old woman discovered through palpation a tumor in the upper lateral quadrant of the left mammary gland. Mammography, ultrasonography (US), and magnetic resonance imaging (MRI) showed a 10 mm diameter tumor. Fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) showed abnormal accumulation in the detected tumor, and the maximum standardized uptake value was 2.2. The patient underwent tumor resection. The postoperative histopathological finding was intraductal papilloma. The intraductal papilloma showed strong expression of glucose transporter (GLUT)-4 on membrane and/or cytoplasm, and weak expression of GLUT-1 and GLUT-3 by immunohistochemistry. This case suggests that other glucose transporters (e.g., GLUT-4), other pathological factors, and cytokines may have a close relation with ¹⁸F-FDG accumulation in intraductal papilloma more than GLUT-1 or GLUT-3 expression.     

Robotic intragastric surgery: A new surgical approach for the gastric lesion

Background

Intragastric surgery is accepted as a minimally invasive procedure for mucosal or submucosal lesions. Robotic surgery promises to extend the capabilities of the minimally invasive surgeon and many surgical specialties are applying this new technology. However, there is no report of robotic intragastric surgery. We describe the use of the da Vinci^® Surgical System for intraluminal mucosal resection of the stomach.

Methods

We developed our porcine intragastric surgery model using the Tuebingen MIS Trainer. We set a tentative lesion on the posterior wall near the esophagocardiac junction (ECJ) of the stomach and performed mucosal resection of the lesion using the da Vinci Surgical System. We also performed closure of the defect after mucosal resection and subsequent closure of the intentional gastric perforation.

Results

Using our porcine intragastric surgery model, we successfully performed mucosal resection of the tentative lesion. We also smoothly completed closure of the defect and closure of the perforation without any complications. The mean size of the mucosa was 6 cm and the mean duration of the procedure was only 12 min.

Conclusions

The safety and efficacy of robotic intragastric surgery was preliminarily established in this study. However, further studies are needed to prove its practical feasibility in humans using the da Vinci Surgical System to make it an effective operation.

     

A novel 4-oxo-2(E)-nonenal-derived endogenous thiadiazabicyclo glutathione adduct formed during cellular oxidative stress

Cellular oxidative stress causes increased lipid peroxidation with the concomitant formation of DNA and protein reactive bifunctional electrophiles. Glutathione (GSH) detoxifies these bifunctional electrophiles by forming GSH adducts. Several years ago we discovered 4-oxo-2(E)-nonenal (ONE) as a major bifunctional electrophile derived from lipid hydroperoxides. We have now made the unexpected discovery that glutathione-S-transferase (GST)-mediated GSH addition to ONE occurs primarily to C-1 of the alpha,beta-unsaturated ketone rather than to C-3 of the alpha,beta-unsaturated aldehyde. The resulting intermediate rapidly undergoes two intramolecular cyclizations followed by two separate dehydration reactions to provide an unusual thiadiazabicyclo-ONE-GSH adduct (TOG). Quantification of intracellular TOG was performed using stable isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry after the addition of ONE to cells or as an endogenously derived adduct during peroxide-induced oxidative stress. TOG represents the first member of a new class of thiadiazabicyclo GSH adducts that are formed through GST-mediated addition of GSH to reactive intermediates containing the ONE motif during intracellular oxidative stress. ONE formation can potentially result from free radical pathways as well as cyclooxygenase- and lipoxygenase-mediated pathways. Its aldo-keto reductase-mediated reduction product, 4-oxo-2(E)-nonenol (ONO), was also formed and converted to GSH adducts similar to those formed by 4-hydroxy-2(E)-nonenal (HNE). ONO is isomeric with HNE; therefore, protein and peptide adducts ascribed to arise solely from reactions with endogenous HNE will need to be re-appraised.