Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia.

Bone marrow-derived stromal cells are associated with gastric cancer progression.

BACKGROUND: The aim of this study was to clarify the role of bone marrow-derived stromal cells (BM-SCs) expressing CD271 in the development of gastric cancer. METHODS: The effect of human BM-SCs on the proliferation and motility of six gastric cancer cell lines, OCUM-2M, OCUM-2MD3, OCUM-12, KATO-III, NUGC-3, and MKN-74, was examined. CD271 expression levels in BM-SCs were analysed by flow cytometry. We also generated a gastric tumour model by orthotopic inoculation of OCUM-2MLN cells in mice that had received transplantation of bone marrow from the CAG-EGFP mice. The correlation between the clinicopathological features of 279 primary gastric carcinomas and CD271 expression in tumour stroma was examined by immunohistochemistry. RESULTS: Numerous BM-SCs infiltrated the gastric tumour microenvironment; CD271 expression was found in ∼25% of BM-SCs. Conditioned medium from BM-SCs significantly increased the proliferation of gastric cancer cell lines. Furthermore, conditioned medium from gastric cancer cells significantly increased the number of BM-SCs, whereas migration of OCUM-12 and NUGC-3 cells was significantly increased by conditioned medium from BM-SCs. CD271 expression in stromal cells was significantly associated with macroscopic type-4 cancers, diffuse-type tumours, and tumour invasion depth. The overall survival of patients (n=279) with CD271-positive stromal cells was significantly worse compared with that of patients with CD271-negative stromal cells. This is the first report of the significance of BM-SCs in gastric cancer progression. CONCLUSIONS: Bone marrow-derived stromal cells might have an important role in gastric cancer progression, and CD271-positive BM-SCs might be a useful prognostic factor for gastric cancer patients.

The impact of the number of occult metastatic lymph nodes on postoperative relapse of resectable esophageal cancer.

Clinical stage II/III esophageal cancer (EC), as defined by the Japanese Classification, relapses at a moderately high rate even after curative resection. The number of lymph node metastases is known to be associated with tumor relapse. Recently, the prognostic significance of occult metastatic lymph nodes (MLNs), as well as that of overt MLNs, has been reported. The aim of this study was to investigate the impact of the total number of MLNs including occult MLNs on postoperative relapse in clinical stage II/III EC. One hundred and five patients with clinical stage II/III EC who underwent esophagectomy accompanied by radical lymphadenectomy at the Department of Surgical Oncology in Osaka City University Hospital between January 2000 and October 2008 were included in this study. Occult MLNs, metastases not detected by hematoxylin-eosin staining, were identified by immunohistochemistry (IHC) using antipancytokeratin antibody AE1/AE3. The clinicopathological features of occult MLNs were compared between the relapse and no relapse groups. A total of 6558 lymph nodes (1357 from two-field dissection and 5201 from three-field dissection) were examined by IHC staining; 362 overt MLNs and 143 occult MLNs were detected. The number of occult MLNs increased in proportion to the International Union Against Cancer pathological (p)N-status and pStage. When the number of occult MLNs was added to the number of pNs, the number of total MLNs was associated with postoperative relapse. With respect to tumor, node, metastasis stage, 6 of 22 patients (27%) who were pathological node-negative converted to node-positive by considering total MLNs. The number of N3 patients with relapse increased markedly with restaging by total MLNs. The number of total MLNs, but not overt MLNs, was an independent prognostic factor on multivariate analysis. These results suggest that occult MLNs were often found, and they were associated with postoperative relapse of resectable esophageal cancer. The total number of MLNs including occult MLNs could contribute to evaluating the precise stage of patients with esophageal cancer.

Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach.

BACKGROUND: It was recently reported that the transcription factor Forkhead box P3 (FoxP3) is expressed not only in regulatory T cells (Tregs) but also in cancer cells. The aim of this study was to clarify the clinical significance of FoxP3 expression in gastric carcinoma. METHODS: We performed immunohistochemical staining of FoxP3 to examine the association of FoxP3 expression with clinicopathological features of 194 patients with gastric cancer who underwent surgical resection from 2000 to 2010. We also investigated the immunosuppressive function of FoxP3 using gastric cancer cell lines. RESULTS: Immunohistochemical staining indicated FoxP3-positive cells within tumour tissue including both Tregs and tumour cells. Forkhead box P3-positive tumour cells were observed in 79.3% of signet ring cell carcinoma patients, and the expression of FoxP3 showed a significant correlation with lymph node metastasis. We showed that transforming growth factor-ß augmented FoxP3 mRNA expression in cell lines derived from signet ring cell carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown. CONCLUSION: Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma.

The biochemical role of platelet-activating factor in reproduction.

The presence of Co-A independent transacylase activity in amnion cells and the preferential transfer of arachidonic acid to acceptor-ethanolamine plasmalogen provide a satisfactory explanation to the questions raised by the observation that arachidonate-enriched ethanolamine plasmalogen increases in amnion late in gestation without alteration in the total amount of ethanolamine glycerophospholipids. The proposed mechanism also serves as a link between the observed changes in glycerophospholipid composition and the generation of PAF. We have emphasized a role for PAF in fetal lung maturation, the initiation and maintenance of parturition, and in certain complications associated with a premature delivery. Although PAF is known to be the most potent lipid mediator yet described and its importance in reproductive biology is well documented, it is our view that these events cannot be attributed solely to PAF and in all likelihood a number of autacoids participate in these processes.

Apoptosis and thymidylate synthase inductions by 5-fluorouracil in gastric cancer cells with or without p53 mutation.

We studied apoptosis and thymidylate synthase (TS) inductions by 5-fluorouracil (5-FU) in gastric cancer cells with wild-type p53 (MKN-45 and MKN-74) and with mutated p53 (MKN-28 and KATO-III). Apoptotic inductions in MKN-45 and MKN-74 were stronger than those in MKN-28 and KATO-III, suggesting that wild-type p53 may contribute to the induction of apoptosis. After continuous exposure to 0.1 microg/ml of 5-FU for 96 h, no TS induction was obtained in KATO-III, while approximately twice the amount of TS was observed compared to non-treatment cells in MKN-45, MKN-74, and MKN-28. The results of immunohistochemical staining for TS and p53 showed no relation between these two protein expressions in endoscopic biopsy specimens of 25 patients with advanced gastric cancer. These results indicated that p53 status may not play a pivotal role in regulating TS expression. We found no significantly different effects of 5-FU between intermittent (repeat of 24-h continuous infusion and 24-h drug-free) and continuous treatments in either MKN-28 or stem cells (CD34+ hematopoietic progenitor cells) when the same area under the time-concentration curve of 5-FU was administered. The TS induction in MKN-28 cells by intermittent treatment was significantly higher than that by continuous treatment; however, most TSs in both types of 5-FU treatment cells were of the inactive form, i.e., TS bound to FdUMP, a 5-FU metabolite. Therefore, neither intermittent nor continuous treatment appears to induce 5-FU resistance related to the level of increment free TS. In conclusion, our observations suggested that p53 mutation may be associated with apoptotic induction by 5-FU; however, p53 status may not strongly affect TS induction by 5-FU. Intermittent treatment can be replaced with continuous treatment without causing 5-FU resistance.

Changes in glycerophospholipid profile in experimental nephrotic syndrome.

We investigated changes in the glycerophospholipids in kidney tissue and its various intracellular fractions in rats with nephrotic syndrome induced by puromycin aminonucleoside. The ethanolamine plasmalogen, 1-O-alk-1'-enyl-2-acyl-GPE (EP), was increased in kidney tissue obtained from the puromycin-treated animals. A similar increase was found in the mitochondria and endoplasmic reticulum (microsomes) of this tissue. These increases were not found in the liver. Since platelet-activating factor (PAF) is known to be produced in increased amounts in inflammatory disorders, it is suggested that the higher plasmalogen found in rat kidneys during experimental nephrotic syndrome might be derived from increased levels of this autacoid. The increase in PAF may also result in the elevation of plasma PAF-acetylhydrolase (AH) activity observed in these animals.

Effects of monocular enucleation on receptor binding and innervation pattern of the noradrenergic system in the superior colliculus of the pigmented rat.

To examine visual activity-dependent regulation of the central noradrenergic (NAergic) system, we carried out in vitro autoradiography for alpha2-, beta-adrenergic and NMDA, non-NMDA glutamatergic receptors together with immunohistochemical analysis for dopamine beta-hydroxylase in the major central visual structures, including the lateral geniculate nucleus, superior colliculus (SC), and visual cortex of pigmented rats, that had received monocular enucleation. Beta-adrenergic receptor (beta-AR) binding in the SC contralateral to the enucleated eye was significantly decreased (82%, P < 0.01) following monocular deprivation started at P12 and continued for 2 or 11 weeks. No significant change in beta-AR binding was found in other structures examined. The number of varicosities in NAergic fibers was significantly increased following longer enucleation, i.e. for 11 weeks, in the contralateral SC (197%, P <0.001), whereas that in the ipsilateral SC was reduced (75%, P <0.001). Changes in alpha2-adrenergic, NMDA, and non-NMDA glutamatergic receptor binding were small in these animals. Changes in neither beta-AR binding nor innervation pattern of NAergic fibers were found in one-year-old rats that had received a comparable period of monocular enucleation. Furthermore, neither unilateral ablation of the visual cortex to reduce a different set of major afferents nor neonatal enucleation, which induced anatomical reorganization of the afferents, was found to be effective. These findings suggest that beta-AR binding and innervation pattern of NAergic fibers in the SC are modified only when massive imbalance of retinal afferent activity is imposed during a limited period in early postnatal life (i.e. the sensitive period).

Down-regulation of beta-adrenergic receptor following long-term monocular deprivation in cat visual cortex.

To examine how adrenergic receptor binding is modified by experimental manipulation of sensory afferent, we carried out binding experiments (membrane fraction and in vitro autoradiography) for both alpha 2- and beta-adrenergic receptors in the brain of cats which had been deprived of vision in one eye. In the cerebral cortex of control animals, beta-adrenergic receptor (beta-AR) binding was found to be higher in the occipital regions than in other regions, while alpha 2-AR binding was relatively uniform. Monocular deprivation throughout the postnatal sensitive period (1-7 month of age) significantly decreased beta-AR binding in the visual cortex and lateral geniculate nucleus. Scatchard plot analysis in the visual cortex showed ca. 50% reduction in Bmax and little change in Kd. No significant difference was found in alpha 2-AR binding following monocular deprivation. Similar extent of down-regulation in beta-AR binding was confirmed in all layers of visual cortex using autoradiography.

Serum antisperm antibodies in men with vas deferens obstruction caused by childhood inguinal herniorrhaphy.

OBJECTIVE: To study the incidence of serum antisperm antibodies in patients with vas deferens obstruction caused by childhood inguinal herniorrhaphy. DESIGN: Retrospective. SETTING: Kansai Medical University and Kyoto University Hospital. PATIENTS: Thirteen patients with vas deferens obstruction caused by childhood inguinal herniorrhaphy. MAIN OUTCOME MEASURES: Indirect immunobead test for serum antisperm antibodies. RESULTS: Of 13 patients, 7 (54%) and 2 (15%) tested positive for immunoglobulin (Ig)G and IgA class antisperm antibodies, respectively; all patients tested negative for IgM class antibodies. The incidence of antisperm antibodies was not different between the patients with possible epididymal obstruction and those without epididymal obstruction. CONCLUSIONS: A significant percentage of patients with vasal obstruction caused by infant inguinal herniorrhaphy have serum antisperm antibodies despite the absence of sperm granulomas.

A case of primary Hodgkin's disease of the stomach.

A case of primary Hodgkin's disease, a lymphocyte-predominant entity, occurring in the stomach is described. The patient was a 37-year-old man who complained of general fatigue. Endoscopic biopsy revealed gastric malignant lymphoma. Subtotal gastrectomy and postoperative chemotherapy following a modified CHOP regimen were performed. The patient has been free of recurrence during a follow-up period of 15 months. The preoperative diagnosis of gastric Hodgkin's disease is difficult. Thus far, of 100 cases of gastric Hodgkin's disease reported in Japan, only 3 were diagnosed correctly preoperatively. We also misdiagnosed our case, as B cell type malignant lymphoma, preoperatively. The final diagnosis of Hodgkin's disease of the stomach was made on the basis of histopathological and immunohistochemical examinations. Hodgkin's disease of the stomach is rare, and there are histologically similar diseases; Ki-1 lymphoma, adult T cell lymphoma, malignant histiocytosis, and infectious monocytosis. Careful diagnosis is essential thus for Hodgkin's disease of the stomach.

Caspase-1 activity as a possible predictor of apoptosis induced by cisplatin in gastric cancer cells.

Recent studies have shown that caspases, which are cystein proteases, elevate endonuclease activity and induce apoptosis. Caspase-1, an interleukin-1beta converting enzyme, has been reported to be related with anti-cancer drug induced apoptosis as well as with caspase-3. To elucidate the caspase-1 activity, which might be a predictor for the effect of chemotherapy, we examined the changes of caspase-1 activity induced after exposure to cisplatin (CDDP) in six gastric cancer cell lines. A high correlation between the 50% inhibitory concentration (IC50) and caspase-1 activity ratio was shown (r=0.83, p=0.041) (caspase-1 activity ratio: the caspase-1 activity of cells at 4 h after CDDP treatment/the caspase-1 activity of untreated cells). Further, we examined the correlation between caspase-1 activity and apoptosis induced by CDDP in two cell lines that have very different CDDP sensitivities; OCUM-2M and OCUM-2M/DDP (IC50; 0. 85+/-0.4 microg/ml and 9.0+/-1.2 microg/ml, respectively). The apoptotic index of OCUM-2M was significantly higher than that of OCUM-2M/DDP (19.8+/-3.8% vs. 4.5+/-1.2%, respectively; p=0.0005). In both cell lines, caspase-1 activity began to increase immediately after exposure to CDDP and peaked at approximately 4 h after cessation of exposure to CDDP, and gradually decreased thereafter. The caspase-1 activity of OCUM-2M was approximately 1.8-times higher than that of OCUM-2M/DDP at 4 h after exposure to CDDP. Taken together, our results indicate that evaluating the changes of caspase-1 activity after exposure to CDDP may be useful to predict apoptosis following CDDP treatment in gastric cancer cells.

Laparoscopic adrenalectomy for pheochromocytoma: a literature review.

Laparoscopic adrenalectomy has become the standard treatment for benign adrenal tumors, providing minimal invasiveness and early recovery. In the case of pheochromocytomas, special attention should be paid perioperatively to prevent excessive hypertension or hypotension. The protocol should include sufficient preoperative medication with alpha 1 blockers, early ligation of the adrenal vein, and minimal handling of the tumor itself. A literature review of 227 laparoscopic adrenalectomies for pheochromocytomas revealed that the perioperative data, including the operative time, blood loss, and hemodynamic status, were similar or slightly better in the laparoscopic procedures as compared to the open procedures, although the convalescence period was significantly shorter in the laparoscopic surgery. The majority of surgeons prefer the transperitoneal approach for pheochromocytomas, although some authors use the retroperitoneal approach successfully. A comparison of the perioperative data from laparoscopic surgeries for pheochromocytomas versus those for other adrenal tumors showed that the former had slightly higher demands to complete the procedure safely. In the treatment of familial pheochromocytoma due to multiple endocrine neoplasia type 2 or von Hippel-Lindau disease, a cortical-sparing adrenalectomy can be safely performed laparoscopically. In conclusion, laparoscopic adrenalectomy is the standard for small pheochromocytomas, with a high success rate when the procedure is performed by experienced surgeons.

Liver penetration and gastrobronchial fistula: unusual complication of a peptic ulcer.

The authors present the first case report on a patient with liver penetration and a gastrobronchial fistula from a gastric ulcer. Liver penetration was diagnosed by endoscopy, and the gastrobronchial fistula was noted on a computed tomography scan. An emergent total gastrectomy was performed because of uncontrolled massive gastric bleeding not responsive to conventional treatment. The initial treatment of choice for these patients should be conservative because both complications could potentially have been controlled by H2 blockers and percutaneous drainage of the abscess.

The central role of PAF in necrotizing enterocolitis development.

We have addressed two critical questions concerning NEC development. 1) Why is the neonatal intestine particularly susceptible to necrosis? and 2) Does PAF play a critical role in NEC development? We have found that intestinal tissue of the newborn has the highest specific activity for the acetyltransferase of the de novo pathway. It is suggested that the high capacity of this tissue to synthesize PAF may contribute to the fact that the necrosis of the newborn is more prevalent in this tissue. We have previously reported that dexamethasone lowers the activity of acetyl-CoA:lyso-PAF acetyltransferase in liver and spleen. This hormone also cause an increase in plasma PAF-acetylhydrolase activity and an increased secretion of PAF-acetylhydrolase by various macrophages. It would, therefore, appear that the beneficial effects of glucocorticoids on the prevention of NEC may be due to both increased inactivation of PAF as caused by the increase in PAF-acetylhydrolase as well as a decrease in PAF synthesis. We are presently investigating the effect of glucocorticoids on acetyl-CoA: alkyl-lyso-sn-glycero-3-phosphate acetyltransferase. The reported studies in which NEC was prevented by intravenous infusion of recombinant PAF-acetylhydrolase provides further documentation as to the importance of PAF in the development of NEC. The specific activity of PAF-acetylhydrolase required for protection by dexamethasone was similar. This finding would be suggestive of the fact that the mechanisms by which dexamethasone causes a complete protection against NEC may be mediated by increasing the plasma activity. Other mechanisms have been proposed such as facilitating the maturation of the small bowel. As discussed, other factors such as hypoxia, endotoxins, TNF alpha, and enternal feeding have been suggested to be contributing agents of NEC development. Many of these factors and procedures are known to increase in PAF. We have suggested a mechanism to explain the increase in PAF formation as caused LPS, TNF alpha, and interleukins being the inhibition of the secretion of PAF-AH by macrophages. Our previous reports on the mechanisms involve in the prevention of NEC by glucocorticoids and the reported findings that human recombinant PAF-acetylhydrolase can prevent NEC provide further support for a central role for PAF in NEC development. Furthermore, the presence of a high PAF biosynthetic activity in the neonatal intestine affords an explanation as to why this tissue is highly susceptible to this disease.

Establishment and characterization of the MSKR inbred strain originated from Japanese wild mice (Mus musculus molossinus).

A new inbred strain, MSKR, originated from Japanese wild mice was established in April, 1998. The MSKR mice were 60% of the C57BL/6N inbred mice in the 60-day body weight. Tail length/head-body length and hind-foot length/head-body length of the MSKR mice were significantly smaller than those of the C57BL/6N mice (0.896 vs 1.061, 0.189 vs 0.204), but ear length/head-body length of the MSKR mice was significantly larger than that of the C57BL/6N mice (0.143 vs 0.137). The age of the first parturition and size of the first litter were 63.20 +/- 2.71 days and 6.20 +/- 0.37, respectively, at the 20th and 22nd inbreeding generations. Genetic characterization of the MSKR strain was performed using 34 microsatellite markers, 29 biochemical markers, 9 immunogenetic markers, 3 coat color markers, and mitochondrial DNA RFLP-haplotypes. The result indicated that this newly established inbred strain has some different gene constitution from already known molossinus and common laboratory strains.

[Duplication of the inferior vena cava with left renal cell carcinoma].

A case of duplication of the inferior vena cava (IVC) with left renal cell carcinoma is presented, and the clinical and radiological significance is discussed. Although computed tomographic (CT) scanning, inferior venacavography and renal venography revealed a sufficient amount of anatomical information, an accidental rupture to the inferior vena cava occurred during the procedure. The patient subsequently required 7 units of blood, and suffered acute hepatitis two months following the blood transfusion. However, no recurrences of renal cell carcinoma and hepatitis have been observed four year after the procedure.

[Complications in urological laparoscopic surgery].

Laparoscopic surgery is often associated with complications which never occur in open conventional surgery. We investigated operative and postoperative complications in urological laparoscopic surgery. From February 1990 to November 1992, 91 laparoscopic operations were performed, including 62 varicocelectomies, 5 pelvic lymphadenectomies, 6 adrenalectomies, 5 simple nephrectomies, 2 radical nephrectomies, 1 staged Fowler-Stephens operation and 10 laparoscopies for cryptorchidism or other disorders. The patients ranged from 3 months to 77 years old. Nine (9.9%) of the 91 patients had complications associated with laparoscopic procedures and 4 (4.4%) of them had major complications. Pneumoextraperitoneum occurred in 3 patients. Two patients, who suffered from preperitoneal insufflation or pneumothorax associated with pneumomediastinum, failed to undergo laparoscopy. A small amount of scrotal emphysema developed in one patient, which subsided within 12 hours. Another patient, who underwent radical nephrectomy and para-aortic lymphadenectomy for left renal cell carcinoma, complained of symptoms due to persistent pneumoperitoneum and subcutaneous emphysema, which subsided 2 weeks after the operation. Respiratory acidosis caused by carbon dioxide absorption, which was difficult to be controlled, occurred in the other two patients; one was an adult male with reduced respiratory function and the other was a 1-year-and-8-month-old child. Bleeding during or after the procedure was another serious complication. Vena caval laceration occurred during right simple nephrectomy for pyonephrosis with renal calculi and was managed with laparotomy. Two patients, one after simple nephrectomy and the other after right adrenalectomy, suffered from postoperative bleeding about 300 ml through the penrose drain, which subsided following a bed rest.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical statistics on in-patients and operations during a 20-year period (1975-1994) at Department of Urology, Kansai Medical University].

The patients, diseases and operations experienced between 1975 and 1994 in our department were statistically analyzed. The numbers of in-patients and operations have been increasing since 1977. During these 20 years, endoscopic surgery has replaced many open surgical procedures. The introduction of extracorporeal shock wave lithotripsy has dramatically changed the therapeutic modality for urolithiasis, and decreased of the necessity of open surgery.

[Chyluria treated with inguinal lymphangiovenous and lymph node-venous anastomosis: a case report].

Stripping and ligation of the renal lymphatics has been a standard operation for patients with chyluria in Japan. However, recently, inguinal lymph node-saphenous vein anastomosis and lymphangiovenous anastomosis in the spermatic cord or the lower limb are introduced as a microsurgical treatment of chyluria with good result from China. We present a case of 50-year-old female with chyluria, which was cured by the lymphatic-venous anastomosis at the groin. The patient had lived in Okinawa, an area of endemic filariasis, till 23 years of age. She noted chyluria for the first time at 28 years of age, when it was treated by irrigation of the renal pelvis with silver nitrate solution. The symptom recurred at 48 years of age, and fatigue developed two months before admission. The conservative treatments including rest, low fat diet and repeated irrigation of the renal pelvis were carried out, but these were ineffective. Therefore, bilateral inguinal lymph node-saphenous vein anastomosis and lymphangiovenous anastomosis in the same wound on the right were performed. The chyluria disappeared five months after the operation. The lymphatic-venous anastomosis at the superficial part of the body may be the surgical procedure of choice, because they are effective, simple, less invasive and less traumatic.