The 4-portal technique decreases adverse effects in preoperative radiotherapy for advanced rectal cancer: comparison between the 2-portal and the 4-portal techniques

BACKGROUND: This study evaluated the difference of postoperative complications according to the radiation technique after preoperative radiotherapy for rectal cancer. METHODS: Among 224 patients with rectal cancer who underwent preoperative radiotherapy, 159 patients were treated with the 2-portal technique and 65 patients with the 4-portal technique. Comparison was performed between these 2 groups. RESULTS: The 5-year disease-free survival and local recurrence rate showed no difference between the 2 groups. There was also no difference in postoperative mortality. However, the 4-portal group had a significantly lower morbidity rate of 36.9% than the 2-portal group of 54.1% (P = .02). The rate of major complications that needed reoperation was also significantly lower in the 4-portal group (0%) than the 2-portal group (11.9%) (P = .01). The anastomotic leakage rate was significantly lower in the former (2.8% vs 20.0%, P = .033). CONCLUSION: The 4-portal technique is a better technique than the 2-portal technique for decreasing postoperative complications in preoperative radiotherapy for rectal cancer.     

Prognostic Significance of VEGF Expression in Correlation With COX-2, Microvessel Density,and Clinicopathological Characteristics in Human Gastric Carcinoma

Background Many studies have shown that angiogenesis plays an important role in the process of cancer development and progression. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and cyclooxygenase-2 (COX-2) supports angiogenesis by regulated production of angiogenic factors, including VEGF. The purpose of this study was to examine the expression of VEGF in combination with COX-2 and CD34, their correlation with various clinicopathological factors, and their prognostic significance in human gastric carcinoma. Methods Specimens from 169 patients with different grade and stage gastric carcinoma were investigated by immunohistochemistry for COX-2 and VEGF expression. Tumor microvessel density was assessed with CD34 immunostaining. Correlations between the expression of VEGF, COX-2, CD34, and various clinicopathological factors were studied. The effect of these proteins on patient survival was determined. Results COX-2 and VEGF were positively expressed in 36.7% and 50.3% of the patients, respectively. Positive correlation was found between VEGF and COX-2 and between VEGF and CD34. VEGF expression was correlated with depth of invasion; metastatic lymph nodes; lymphatic and venous invasion; and tumor, node, metastasis system stage. Patients with positive staining for VEGF showed far lower disease-free (64.9% vs. 81.3%) and overall (58.3% vs. 76.9%) survival rates than VEGF-negative patients. In multivariate analysis, only tumor location, depth of invasion, and lymph node metastasis were shown to be independent prognostic factors. Conclusions VEGF expression correlates with angiogenesis and tumor progression and is a valuable prognostic factor in patients with gastric carcinoma.     

Immunosuppressive activity of serum taken from a liver transplant recipient after withdrawal of immunosuppressants

In orthotopic liver transplantation (OLT), tolerance is induced in a certain combination of donors and a recipient in rats and, in some clinical cases, rejection has not occurred in OLT patients after weaning off immunosuppression. However, this mechanism has not yet been elucidated. Among our cases of liver transplantation (LTx), one OLT patient (Patient A) has not required immunosuppressive drugs for the last 5 years, following post-transplant lymphoproliferative disease (PTLD). This patient's serum interleukin-2 levels were undetectable following withdrawal of immunosuppressants. The same serum taken after discontinuing the immunosuppressants inhibited concanavalin A blast cultured cells and up-regulated the IL-4/IFN-gamma gene expression ratio. These results suggested that other proteins were induced following withdrawal of immunosuppressants. Proteomic assay demonstrated 12 differentiated spots exclusive to this patient where immunosuppressants have been discontinued. Haptoglobin, found to have immunosuppressive activity in vitro, may play an important role in the maintenance of drug-free tolerance as a natural immunological suppressor after cessation of immunosuppression. Proteomic analysis will allow us to develop a novel weaning protocol for patients on long-term immunosuppression to avoid major immunosuppressant-related complications.     

Preoperative parameters, including percent of positive biopsy cores, in predicting pathological findings after radical prostatectomy

OBJECTIVES: We investigated whether preoperative parameters predict pathological stage at radical prostatectomy for patients with clinically localized prostatic cancer. MATERIALS AND METHODS: We studied a total of 160 men with clinically localized prostatic cancer (less than or equal to clinical T2) who underwent radical rertropubic prostatectomy at Wakayama Medical University. Clinical Ts patients are not included in this study. Preoperative parameters include patient age, Body Mass Index, preoperative serum PSA value, biopsy Gleason score, clinical stage, the percent of positive biopsy cores (%PosBx) and the percent of positive biopsy cores on the dominant side (%DomPosBx). Univariate and multivariate analysis were performed to examine the prognostic significance of these preoperative parameters. Significant independent factors were combined to create a table to predict pathologically organ confined disease. RESULTS: Univariate analysis showed preoperative serum PSA value (p< 0.001), biopsy Gleason score (p =0.001), clinical stage (p = 0.026), %PosBx (p= 0.002) and %DomPosBx (p=0.003) were significantly related to the pathological stage. On multivariate analysis, serum PSA value (p< 0.01), biopsy Gleason score (p<0.05) and %DomPosBx (p<0.05) were significant independent predictors of pathological stage. CONCLUSION: We provide two model combinations using preoperative clinical factors, one is a combination of serum PSA and biopsy Gleason score and the other is a combination of serum PSA and %DomPosBx, which define a new preoperative model for predicting pathological organ confined prostatic cancer. These combinations are useful and provide important information for urologists to determine the appropriate treatment strategy for clinically localized prostatic cancer.     

Importance of transition zone biopsies in patients undergoing ultrasound-guided prostate systemic biopsies for the first time

INTRODUCTION: We analyze the efficacy of routine transition zone biopsies in patients undergoing ultrasound-guided systemic prostate biopsies for the first time because of a suspicious digital rectal examination or an elevated serum prostate-specific antigen (PSA) level. PATIENTS AND METHODS: During systemic prostate biopsy two or four additional transition zone biopsies were performed in 192 consecutive patients: in 182 because of a serum PSA concentration >4.1 ng/ml and in 10 because of a suspicious digital rectal examination and a serum PSA level <4.0 ng/ml. RESULTS: The overall prostate cancer detection rate was 37.5% (72/192). In 24 patients (33.3%), cancer was only detected in the peripheral zone, in 3 (4.2%) only in the transition zone, and in 45 (62.5%) in both zones. CONCLUSION: Transition zone biopsies performed at the first time of systemic prostate biopsy seem to have a low efficacy.     

Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury

Emerging data suggest that matrix metalloproteinase-9 (MMP-9) plays a critical role in the pathophysiology of brain injury. However, the regulatory mechanisms involved in vivo remain unclear. In this study, we focus on a mitogen activated protein kinase (MAPK) pathway that may trigger MMP-9 after traumatic brain injury. We aim to show that inhibition of the extracellular signal regulated kinase (ERK) would attenuate MMP-9 levels, reduce blood-brain barrier damage, and attenuate edema after trauma induced by controlled cortical impact in mouse brain. Western blots showed that phospho-ERK was rapidly upregulated after trauma. Treatment with U0126, which inhibits MEK, the kinase upstream of ERK, effectively prevented the activation of ERK. After trauma, gelatin zymography showed an increase in MMP-9. U0126 significantly reduced trauma-induced MMP-9 levels. Correspondingly, U0126 ameliorated the degradation of the tight junction protein ZO-1, which is an MMP-9 substrate, and significantly attenuated tissue edema. At 7 days after trauma, traumatic lesion volumes were significantly reduced by U0126 compared with saline-treated controls. These data indicate that the ERK MAPK pathway triggers the upregulation in MMP-9 after trauma, and further suggest that targeting the upstream signaling mechanisms that regulate deleterious MMP-9 activity may reveal new therapeutic opportunities for traumatic brain injury.     

Mucinous cystic neoplasm of the pancreas presenting with hemosuccus pancreaticus: Report of a case

Hemosuccus pancreaticus (HP) is mostly induced by a ruptured pseudoaneurysm or hemorrhage from a pseudocyst in chronic pancreatitis. We herein report a rare case with HP induced by tumor hemorrhage. The present patient is a 71-year-old woman referred to us with a diagnosis of severe progressive anemia. Endoscopy revealed hemorrhage from the papilla of Vater. Computed tomography showed a multilocular cystic tumor in the tail of the pancreas. The patient underwent a distal pancreatectomy. The histopathological diagnosis was carcinoma in mucinous cystadenoma. No cancer infiltration into the pancreatic duct was detected. Pancreatography of the resected specimen demonstrated an overt communication between the main pancreatic duct and the cystic cavity of the tumor, which was not demonstrated preoperatively by endoscopic retrograde pancreatography. Although the cause of HP is mainly acute or chronic pancreatitis, we should bear in mind that a pancreatic tumor may be a possible cause of HP and that, as such, prompt and proper treatment is mandatory.     

Perioperative Allogeneic Blood Transfusion Is Associated With Surgical Site Infection After Abdominoperineal Resection—a Space for the Implementation of Patient Blood Management Strategies

Allogeneic blood transfusion (ABT) has been reported as a major risk factor for surgical site infection (SSI) in patients undergoing colorectal surgery. However, the association of ABT with SSI in patients undergoing abdominoperineal resection (APR) and total pelvic exenteration (TPE) still remains to be evaluated. Here, we aim to elucidate this association. The medical records of all patients undergoing APR and TPE at our institution in the period between January 2000 and December 2012 were reviewed. Patients without SSI (no SSI group) were compared with patients who developed SSI (SSI group), in terms of clinicopathologic features, including ABT. In addition, data for 262 patients who underwent transabdominal rectal resection at our institution in the same period were also enrolled, and their data on differential leukocyte counts were evaluated. Multivariate analysis showed that intraoperative transfusion was an independent predictive factor for SSI after APR and TPE (P = 0.004). In addition, the first–operative day lymphocyte count of patients undergoing APR, TPE, and transabdominal rectal resection was significantly higher in nontransfusion patients compared with transfusion ones (P = 0.026). ABT in the perioperative period of APR and TPE may have an important immunomodulatory effect, leading to an increased incidence of SSI. This fact should be carefully considered, and efforts to avoid allogeneic blood exposure while still achieving adequate patient blood management would be very important for patients undergoing APR and TPE as well.Key words: Colorectal cancer, Abdominoperineal resection, Surgical site infection, Allogeneic blood transfusion, Patient blood managementPostoperative surgical site infection (SSI) is one of the most frequent complications associated with various surgical procedures, and it results in adverse outcomes, including longer hospital stay, higher health care costs, and increased surgical mortality.¹ It is one of the most frequent nosocomial complications, accounting for almost one fifth of all health care–associated infections.² Colon surgery and rectal surgery are associated with higher SSI rates compared with most other abdominal procedures, with 5% to 25% of colon and rectal surgery patients developing incisional and organ/space SSI.^3–5 Moreover, the incidence of overall SSI was reported to be higher in rectal surgery patients (17%–28%) than in colonic surgery patients (9%–23%),^3,5,6 with especially higher overall SSI rates observed in patients undergoing abdominoperineal resection (APR; 12%–51%).^7–9 These are attributed to the high infection rates of the perineal wound, reported to be as high as 21%.¹⁰ Thus, the incidence of SSI associated with APR should be the highest among the various abdominal operative procedures.Various risk factors for postoperative SSI in colorectal surgery were reported previously. Open surgery,^10–12 perioperative allogeneic blood transfusion (ABT),^4,10,12 and prolonged operation time^4,9 have been found to be risk factors for SSI in a number of studies. Although several preceding reports have investigated the risk factors for SSI associated with APR, the reported independent risk factors varied among the studies. Although a number of studies have reported on the role of ABT as a strong risk factor for incisional SSI in colorectal surgery,^13,14 only one study has investigated on its relevance to the onset of incisional SSI after APR procedure; but this study failed to demonstrate a significant association. Presently, therefore, the role of ABT as a potential risk factor for incisional SSI in APR remains to be elucidated, and doing so will be very important for the implementation of measures to achieve patient blood management in this group of patients.In this study, we aimed to elucidate the risk factors for SSI in patients receiving APR, especially focusing on ABT.     

Autologous bone‐marrow‐derived mesenchymal stem cell transplantation into injured rat urethral sphincter

Objectives: To evaluate the functional and histological recovery by autologous bone‐marrow‐derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters. Methods: BMSC were harvested from female Sprague–Dawley retired breeder rats for later transplantation. The cells were cultured, and transfected with the green fluorescence protein gene. The urethral sphincters were injured by combined urethrolysis and cardiotoxin injection. One week after injury, the cultured BMSC were injected autologously into the periurethral tissues. Controls included sham‐operated rats and injured rats injected with cell‐free medium (CFM). Abdominal leak point pressures (LPP) were measured before and after surgery during the following 13 weeks. The urethras were then retrieved for histological evaluation. The presence of green‐fluorescence‐protein‐labeled cells and the regeneration of skeletal muscles, smooth muscles, and peripheral nerves were evaluated by immunohistochemical staining. Results: LPP was significantly reduced in the injured rats. It increased gradually after transplantation, but there was no significant difference between the BMSC and CFM groups. In the BMSC group, transplanted cells survived and differentiated into striated muscle cells and peripheral nerve cells. The proportions of skeletal muscle cells and peripheral nerves in the urethra were significantly greater in the BMSC group compared to the CFM group. Conclusions: Despite a clear trend towards recovery of LPP in BMSC‐transplanted urethras, no significant effect was detected. Further study is required for clinical applications for the treatment of stress urinary incontinence.