Mechanical stretch down-regulates expression of the Smad6 gene in cultured rat mesangial cells

Background

Glomerular hypertension aggravates glomerular sclerosis by inducing growth factors, e.g., transforming growth factor-β (TGF-β) to mesangial matrix expansion. Smads are intracellular proteins that transmit signals from TGF-β to nucleus, and Smads are also negatively regulated by inhibitory Smads (I-Smads), Smad6 and Smad7. However, little is known about the role of I-Smads in glomerular hypertension. We studied I-Smad expression in cultured mesangial cells subjected to mechanical stretch as an in vitro model of glomerular hypertension.

Methods

Rat mesangial cells were cultured under cyclic mechanical stretch conditions using the Flexercell Strain Unit. Phosphorylated Smad1 and Smad2 were determined by Western blots. The expression of Smad6 and Smad7 mRNAs was determined by Northern blots. Stretch-mediated I-Smad mRNAs of cells pre-treated with MAPK-ERK kinase inhibitor, U0126, were also determined. Localization of phospho-Smad1, Smad6 and Smad7 proteins in the glomerulus of Dahl salt-sensitive rats was determined by immunohistochemistry.

Results

Stretch stress increased phospho-Smad1 levels, and significantly decreased Smad6 mRNA to 32?% of control, and increased Smad7 mRNA to 136?% of control. U0126 significantly attenuated stretch-mediated decreases in Smad6 mRNA, but had no effect on stretch-mediated increases in Smad7 mRNA. Phospho-Smad1, Smad6 and Smad7 proteins were localized in podocytes and mesangial cells of Dahl rats.

Conclusion

Mechanical stretch increases phospho-Smad1 levels and down-regulates Smad6 mRNA expression in mesangial cells. Stretch-mediated down-regulation of Smad6 is partially involved in ERK1/2 activation. These results indicate that glomerular hypertension might augment Smad1 signaling with concomitant attenuation of Smad6-mediated negative feedback.     

Antegrade and retrograde lymphatico‐venous anastomosis for cancer‐related lymphedema with lymphatic valve dysfuction and lymphatic varix

In healthy people, no retrograde lymph flow occurs because of valves in collecting lymph vessels. However, in secondary lymphedema after lymph node dissection, lymph retention and lymphatic hypertension occurs and valvular dysfunction induces retrograde lymph flow. In this case reported, we focused on retrograde lymph flow and performed retrograde lymphatico‐venous anastomosis (LVA) simultaneously with antegrade LVA. A 67‐year‐old Japanese woman had worsening edema in her right thigh and hip area for 3 years. She had previously undergone extended hysterectomy with lymph node dissection for endometrial cancer 8 years before. Indocyanine green test showed antegrade and retrograde lymph flow. Four LVAs were made in the right medial thigh and right lower abdominal area under local anesthesia. Lymphedema showed rapid improvement within 12 months and compression therapy was not required at 24 months after LVA. Retrograde LVA has a possibility of a more efficacy for secondary lymphedema. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.     

Effect of low loading and joint immobilization for spontaneous repair of osteochondral defect in the knees of weightless (tail suspension) rats

Background Mechanical stimulation has a great influence on articular cartilage regeneration. The objective of this study was to clarify the temporal sequences of spontaneous repair of weightless or immobilized joints. Methods An osteochondral defect was created in the femoral patellar groove of F344 rats. A tail-suspension procedure was performed to control the mechanical environment of the hindlimbs. The experimental knee joints were classified into three conditions: CONT, normal gait; LLB, low load-bearing; LLI, low load and immobilized. The repair processes up to 4 weeks were evaluated histologically. Results The knee defects in the CONT and LLB conditions were repaired to a smooth surface with fibrous tissue and highly developed subchondral bone. The knees in the LLI condition had the lowest reformation rate of subchondral bone, although partial regeneration of hyaline cartilage-like tissue was seen at 4 weeks after the operation. Bulges of fibrous tissue from the defects were observed in the LLI condition. Conclusions These results, combined with our previous report, suggest that dynamic compressive strain stimulates regeneration of the joint surface structures. They also suggest that the contact condition of the defect with surface cartilage may play a role in the hyaline cartilage repair.     

Inguinal lymph node metastasis of seminoma 18 years after initial treatment: a case report

Late relapse of testicular tumor is rare. We report a case of recurrence of seminoma at left inguinal lymph node 18 years after initial treatment. A 63-year-old man had a left orchiectomy for left testicular tumor (T1N0M0) in February 1985, with no past history of scrotal or inguinal surgery. Histological examination revealed seminoma (pT1), and prophylactic radiotherapy (34.2 Gy) to para-aortic and left hemi-pelvic regions was perfomed. In November 2003, the patient presented with left inguinal swelling, and was referred to our hospital with suspicion of metastasis to left inguinal lymph nodes. Serum markers (AFP, hCG, hCGbeta and LDH) were normal. Computerized tomography (CT) showed three masses in the left inguinal region, but no other abnormal mass was detected at chest, abdomen or pelvis. Lymphoidectomy of the left inguinal region was perfomed in January 2004, and the mass revealed to be metastasis of seminoma by histological examination.     

Rectovaginal fistulas after rectal cancer surgery: Incidence and operative repair by gluteal-fold flap repair

BACKGROUND: We investigated the correlation between operative procedures for rectal carcinoma and postoperative rectovaginal fistulas (RVF), and treatment for RVF. METHODS: The medical records of 161 female patients with rectal carcinoma were examined retrospectively with respect to the cause, incidence, and methods of treatment for RVF occurring after rectal cancer operations, and to the outcomes of gluteal-fold flap repairs for RVF. RESULTS: Of the 161 patients, 16 developed RVF clinically. The incidence of RVF was significantly higher in patients who were anastomosed by the double stapling technique (DST) and had concomitant resection of the vaginal wall. No statistical difference was found between the established diverting ostomy group and the no-stoma group. Six patients recovered by the establishment of a diverting ostomy only. The gluteal-fold flap technique was performed for 5 patients. No RVF recurrences were noted in these 5 patients. CONCLUSIONS: The incidence of RVF was higher in the patients who were anastomosed by DST or had concomitant resection of the vaginal wall. Although some RVFs heal with only fecal diversion, for patients in whom RVF is caused by involvement of the vaginal wall in the circular staple or intersphincteric resection, good results are obtained with the gluteal-fold flap repair technique.     

Advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with oral squamous cell carcinoma

Purpose

Hypoxia, a prognostic factor in many types of cancer, can be detected by ¹⁸F-fluoromisonidazole (FMISO) positron emission tomography (PET). It is unclear whether hypoxia reflects the response to chemotherapy in patients with oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET with histological response to preoperative chemotherapy were therefore assessed in patients with OSCC.

Methods

This study enrolled 22 patients with OSCC undergoing preoperative chemotherapy. The T-stages were T2 in 6 patients, T3 in 3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5. Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the maximum standardized uptake value (SUV_max) of FDG- and FMISO-PET and tumor-muscle ratio (TMR) of FMISO-PET were measured. The threshold for the hypoxic volume based on TMR was set at 1.25. The histological response to preoperative chemotherapy was evaluated using operative materials.

Results

FMISO-PET and FDG-PET detected uptake by primary OSCCs in 15 (68 %) and 21 (95 %) patients, respectively, and median SUV_maxs of FMISO- and FDG-PET in the primary site were 2.0 (range, 1.3–3.5) and 16.0 (range, 1.0–32.2), respectively. The median of FMISO TMR was 1.5 (range, 0.99–2.96). There were five cases whose FMISO TMR was less than 1.25. Histological evaluation showed good response to preoperative chemotherapy in 7 patients (32 %) and poor response in 15 (68 %). Good response was significantly more prevalent in patients with negative than positive FMISO uptake (P?P?=?0.04), whereas FDG uptake was not significantly correlated with response to chemotherapy response. Multivariate logistic regression analysis showed that FMISO uptake was an independent significant predictor of response to preoperative chemotherapy (P?=?0.03, odds ratio?=?0.06, 95 % confidence interval?=?0.004–0.759).

Conclusions

An advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with OSCC was observed.     

Prostate specific antigen adjusted for transition zone epithelial volume: the powerful predictor for the detection of prostate cancer on repeat biopsy

PURPOSE: The indications for repeat prostate biopsy for persistently increased prostate specific antigen (PSA) in men with prostate cancer never detected on previous biopsy are not clear. In this study we determined that PSA adjusted for transition zone (TZ) epithelial volume is the most powerful predictor for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: Repeat prostate biopsies including additional TZ cores were performed in 75 men with PSA between 4.0 and 10.0 ng/ml. TZ epithelial volume was calculated by multiplying TZ volume by the percent of epithelium, which was measured by morphometric analysis using image analysis computer software. RESULTS: Prostate cancer was detected on repeat biopsy in 19 of the 75 patients. Patients with prostate cancer had a significant smaller percent area of epithelium or glandular lumen than those without cancer. In patients without prostate cancer TZ epithelial volume significantly correlated with total PSA. According to ROC analysis PSA adjusted for TZ epithelial volume had the greatest AUC for cancer detection (0.879). This parameter was able to avoid more than 90% of unnecessary repeat biopsies with 90% sensitivity. Multiple logistic regression analysis showed that PSA complex adjusted for TZ epithelial volume was the significant independent predictor of cancer. CONCLUSIONS: PSA adjusted for TZ epithelial volume is the most powerful predictor of cancer in men who have undergone previous negative prostate biopsies and in whom PSA remains between 4.0 and 10.0 ng/ml.     

Surgical Apgar Score Predicted Postoperative Morbidity After Esophagectomy for Esophageal Cancer

Background

Recently, a simple and easy complication prediction system, the Surgical Apgar Sore (SAS) calculated by three intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has been proposed for general surgery. This study aimed to determine if the SAS could accurately predict perioperative morbidity in patients undergoing esophagectomy for esophageal cancer.

Methods

We investigated 399 patients who underwent esophagectomy at the Kumamoto University Hospital between April 2007 and March 2015. Clinical data, including intraoperative parameters, were collected retrospectively. Patients had postoperative morbidities classified as Clavien–Dindo grade III or more. Univariate and multivariate analyses were performed to elucidate factors that affected the development of complications.

Results

The mean age of the study population was 65.7 years, 357 patients (89.5 %) were male. The frequency of any morbidity was 32.3 %. Univariate analyses showed that the SAS as well as preoperative chemotherapy, volume of bleeding, and reconstruction of organs were associated with morbidities. Multivariate analysis showed that a SAS < 5 was found to be an independent risk factor for morbidities.

Conclusion

The SAS is considered to be useful for predicting the development of postoperative morbidities after esophagectomy for esophageal cancer.

     

Accumulation of Excess Visceral Fat Is a Risk Factor for Pancreatic Fistula Formation After Total Gastrectomy

Background  The effect of obesity on gastrectomy in patients with gastric cancer is controversial. The degree of abdominal fat increases the technical difficulty of abdominal surgery. This study examined the effect of visceral fat on total gastrectomy and risk factors associated with the formation of pancreatic fistula. Methods  Between February 2001 and April 2007, 191 patients with gastric cancer underwent total gastrectomy. The visceral fat area (VFA) was calculated from computed tomography (CT) scans taken at the level of the umbilicus using FatScan Software. Patients were divided into high- (≥100 cm², n = 52) and low-VFA groups (<100 cm², n = 139), and also into high- (≥25 kg/m², n = 47) and low-BMI groups (<25 kg/m², n = 144). Results  Blood loss and incidence of pancreatic fistula were significantly higher in the high- than low-VFA group. However, only blood loss was significantly different between the high- and low-BMI groups. VFA, blood loss, and splenectomy were identified as significant risk factors for pancreatic fistula formation on univariate analysis, and multivariate logistic regression analysis of these factors identified VFA (p = 0.0001) and splenectomy (p = 0.0014) as significant predictors of pancreatic fistula. Conclusions  VFA is a better indicator for pancreatic fistula formation after total gastrectomy than is BMI. Lymph node dissection must be performed carefully, especially in patients with visceral fat accumulation during total gastrectomy with splenectomy.     

Osteosarcoma in a pregnant patient with McCune–Albright syndrome

Malignant transformation of fibrous dysplasia is very rare and has not been previously described in patients with McCune–Albright syndrome in the absence of radiation treatment during gestation. Here, we report a 38-year-old pregnant woman with McCune–Albright syndrome and acromegaly accompanied by osteosarcoma. The patient was in the 6th week of pregnancy, when she visited our hospital. She had multiple fibrous dysplasia, skin pigmentation, and acromegaly. The markedly high bone turnover rate during pregnancy tended to decrease after a normal delivery. Fibrous dysplasia of the lower jaw rapidly increased in the 37th week of pregnancy, and the tumor was surgically resected after delivery. Pathological examination of the resected tumor revealed fibrous dysplasia admixed with osteosarcoma containing chondroblastic and osteoblastic tissue. We firstly reported a case of osteosarcoma in a patient with McCune–Albright syndrome, which rapidly progressed during pregnancy.