Extranodal extension in node-positive bladder cancer: the continuing controversy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Although extranodal extension in node‐positive patients may provide prognostic information in certain urological malignancies, contradictory results have been reported in node‐positive patients after radical cystectomy for bladder cancer. We examined whether extranodal extension could have an impact on the outcomes of node‐positive patients who underwent radical cystectomy for bladder cancer in a single large tertiary hospital. We have shown that the presence of extranodal extension was not an independent prognostic factor in node‐positive patients after radical cystectomy and pelvic lymphadenectomy for bladder cancer.

OBJECTIVE

? To examine whether extranodal extension (ENE) has an impact on the outcome of node‐positive patients who underwent radical cystectomy for bladder cancer.

PATIENTS AND METHODS

? Of 543 consecutive patients who underwent radical cystectomy for urothelial carcinoma of the bladder between 1990 and 2007, 112 patients with lymph node metastasis detected on histological examination were evaluated with regard to recurrence‐free survival (RFS) and disease‐specific survival (DSS) based on ENE status.

RESULTS

? The overall 5‐year RFS and DSS rates were 22.3% and 33.8%, respectively. ENE was observed in 41 (36.6%) of the 112 patients. ? The presence of ENE was associated with advanced pathological nodal status (P= 0.004), more positive lymph nodes (P= 0.006), and higher lymph node density (P < 0.001). ? The incidence of positive ENE increased with large positive lymph node diameter (P < 0.001). ? Multivariate analysis showed that lymph node density (hazard ratio (HR) = 2.39, 95% CI 1.09–5.24, P= 0.029; and HR = 3.13, 1.43–6.84, P= 0.004) and use of adjuvant chemotherapy (HR = 1.80, 1.02–3.20, P= 0.041; and HR = 2.07, 1.13–3.79, P= 0.018) were significant predictors of RFS and DSS, respectively. ? After adjustment for other prognostic factors, ENE was not significantly related to RFS (P= 0.825) and DSS (P= 0.961) by multivariate analysis.

CONCLUSIONS

? The presence of ENE was not an independent prognostic factor in node‐positive patients after radical cystectomy for bladder cancer. ? Additional prospective studies are needed to determine the independent prognostic role of ENE.     

Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images

PURPOSE: To determine the accuracy of magnetic resonance (MR) cholangiography for demonstration of the biliary tract and detection of biliary complications in patients who have undergone orthotopic liver transplantation. MATERIALS AND METHODS: Breath-hold half-Fourier rapid acquisition with relaxation enhancement MR cholangiography was performed in 25 patients who had undergone orthotopic liver transplantation. MR cholangiograms were prospectively and independently interpreted by two radiologists for depiction of the biliary tract and ductal anastomosis and for complications (eg, biliary dilatation, stricture, stones). MR cholangiographic findings were correlated with findings from direct cholangiography (n = 24) and surgery (n = 1). RESULTS: MR cholangiography completely demonstrated first-order intrahepatic bile ducts in 23 (92%) patients, the donor extrahepatic bile duct in 25 (100%), the recipient extrahepatic bile duct in 17 of 18 (94%), and the anastomosis in 24 (96%). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of biliary dilatation and stricture were each 100%. Complete interobserver agreement occurred in the detection of biliary dilatation and stricture. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of stones were 100% for one radiologist and 86%, 100%, 96%, 100%, and 95%, respectively, for the other. Both radiologists agreed on the diagnosis of bile duct stones in six of seven cases (kappa = 0.90). CONCLUSION: MR cholangiography enables accurate depiction of the biliary tract and detection of biliary complications in patients with an orthotopic liver transplant.     

Feasibility of Single-Stage Laparoscopic Resection After Placement of a Self-Expandable Metallic Stent for Obstructive Left Colorectal Cancer

BACKGROUND: The present study investigated the feasibility of a single-stage operation consisting of self-expandable metallic stent (SEMS) placement followed by laparoscopic surgery for obstructive left colorectal cancer. METHODS: From July 2002 to March 2007, 17 consecutive patients with primary obstructive left colorectal cancer underwent SEMS placement followed by laparoscopic surgery. Data were collected retrospectively regarding clinicopathological findings, SEMS placement, operative procedures, and perioperative outcomes. Technical success was defined as successful stent deployment across the obstructive lesion, and clinical success as the possibility of performing a single-stage operation without creating a stoma. RESULTS: In the laparoscopic group, the technical success rate was 100% (17/17) and there was no morbidity associated with SEMS placement. The median interval to laparoscopic surgery was 7 (range, 2-11) days, and the procedures included 11 anterior resections, 3 left hemicolectomies, 2 Hartmann's procedures, and 1 subtotal colectomy. All procedures were completed laparoscopically without conversion to open surgery. The median operating time was 178 (range, 93-377) minutes, and the median estimated blood loss was 100 (range, 50-400) ml with no cases requiring intraoperative transfusions. The clinical success rate was 82.4% (14/17), and there was no surgical morbidity other than two patients in whom chyloperitoneum and ileus were controlled by using conservative management. The median postoperative hospital stay was 9 (range, 7-49) days. CONCLUSIONS: A single-stage operation consisting of SEMS placement followed by laparoscopic surgery seems to be a feasible and safe treatment option for obstructive left colorectal cancer.     

Treatment Guidelines for Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: When Can We Operate or Observe?

Background The objectives of this study were to investigate the clinicopathological features of branch intraductal papillary mucinous neoplasm (IPMN) and to determine safe criteria for its observation. Most clinicians agree that surgical resection is required to treat main duct-type IPMN because of its high malignancy rate. However, no definite treatment guideline (with respect to surgery or observation) has been issued on the management of branch duct type IPMN. Methods We retrospectively reviewed the clinicopathological data of 138 patients who underwent operations for IPMN between 1993 and 2006 at five institutes in Korea. Results Of 138 patients (mean age, 60.6 years; 87 men, 51 women), 76 underwent pancreatoduodenectomy, 39 distal pancreatectomy, 4 total pancreatectomy, and 20 limited pancreatic resection. There were 112 benign cases: 47 adenoma, 63 borderline cases, and 26 malignant cases, with 9 of these being noninvasive and 17 invasive. By univariate analysis, tumor size and the presence of a mural nodule were identified as meaningful predictors of malignancy. By receiver operating characteristic curve analysis, a tumor size of >2 cm was found to be the most valuable predictor of malignancy. When cases were classified according to tumor size and the presence of a mural nodule, the malignancy rate for a tumor ≤2 cm without a mural nodule was 9.2%, for a tumor of ≤2 cm plus a mural nodule was 25%, and for other conditions such as tumor >2 cm, >25%. Conclusions Many branch duct IPMNs are malignant. Surgical treatment is recommended, except in cases that are strongly suspected to be benign or cases that present a high operative risk. Observation is only recommended in patients with a tumor size of ≤2 cm without a mural nodule.     

Cementless alumina-on-alumina total hip arthroplasty in patients younger than 50 years: a 5-year minimum follow-up study

Sixty-seven patients (78 hips) who were younger than 50 years underwent cementless total hip arthroplasty using a porous-coated acetabular cup, an alumina liner, a 28-mm alumina head, and a proximally porous-coated femoral stem. One patient (1 hip) died and 2 patients (3 hips) were lost to follow-up. The remaining 64 patients (74 hips) were followed for 5 to 6 years. Their mean age at the index operation was 37 years. The mean Harris hip score was 94 points at the time of final follow-up. Four patients (4 hips) had mild thigh pain. All acetabular and femoral components were bone-ingrown, and neither pelvic nor femoral osteolysis was identified. No fracture of the ceramic liner or head was identified. Wear of the ceramic components was undetectable in 27 hips in which measurement was possible.     

Porcine PD-L1: cloning, characterization, and implications during xenotransplantation

BACKGROUND: Effective intervention achieved by manipulating cell-mediated xenogeneic immune responses would critically increase the clinical feasibility of xenotransplantation as immediate hyperacute rejections become controllable through genetic modulations of donor organs. Endogenous negative regulatory signals like the programmed death 1 (PD-1)-programmed death ligand 1 (PD-L1) system are candidate targets for the control of cell-mediated xenogeneic immune response. METHODS: A porcine PD-L1 molecule was cloned using RACE (rapid amplification of cDNA ends) technology based on the human PD-L1 sequence. The functional effects of cloned porcine PD-L1 were tested on human CD4(+) T cell activation using porcine PD-L1-transfected bystander cells. Cellular proliferation was monitored by [3H] thymidine incorporation, and human T cell apoptosis was measured by flow cytometry. RESULTS: Porcine PD-L1 (GenBank accession number AY837780) was found to have 73.8% sequence homology with human PD-L1 and to contain two immunoglobulin domains in its extracellular region. Moreover, porcine PD-L1 expressed on Chinese hamster ovary (CHO) cells inhibited human CD4(+) T cell proliferation stimulated with anti-CD3 only or anti-CD3 plus anti-CD28. Percentages of apoptotic activated human T cells increased by over 30% in the presence of porcine PD-L1/CHO cells, and the addition of recombinant human PD-1-Fc fusion proteins during human T cell activation reversed the inhibitory effects of porcine PD-L1. CONCLUSIONS: Cloned porcine PD-L1 showed high sequence homology with human PD-L1 and a similar molecular structure. Moreover, porcine PD-L1 inhibited human CD4(+) T cell activation in human PD-1-dependent manner, and this involved activated T cell apoptosis. The authors suggest that PD-1-PD-L1 might play an important endogenous immune regulatory role during xenogeneic transplantation, and that the effective application of this system would improve transplanted xenogeneic organ survival.     

Surgical completeness of robotic thyroidectomy: a prospective comparison with conventional open thyroidectomy in papillary thyroid carcinoma patients

Background

Using the da Vinci^® robotic system, surgeons can complete secure thyroidectomy without noticeable neck scarring. This study compared the surgical completeness of transaxillary robotic thyroidectomy (RT) with conventional open procedures (OT) in treating papillary thyroid carcinoma (PTC) patients.

Materials and methods

From April 2009 through February 2011, 94 PTC patients underwent total thyroidectomy with central compartment neck dissection (CCND) at Yonsei University College of Medicine. All patients received 1.1 GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBS), and diagnostic WBS (DxWBS) 1 year later. We prospectively compared patient clinicopathologic characteristics and surgical completeness between the two groups.

Results

Fifty-one patients underwent OT and 43 underwent RT. Mean age was significantly younger in the RT group. Tumor size, capsular-invasion frequency, multifocality, bilaterality, and central nodal metastasis were not different between the two groups. The number of retrieved nodes during CCND did not significantly differ between the groups. There was no significant difference between the OT and RT groups in stimulated thyroglobulin levels acquired during TxWBS and DxWBS. The RAI uptake ratios at TxWBS were significantly higher in the RT group compared with the OT group; however, follow-up DxWBS showed no difference in RAI uptake ratios. Also, the ablation success rate was similar between the two groups. There were no abnormal findings in follow-up neck ultrasonography in either group.

Conclusion

Remnant thyroid tissue ablation after transaxillary RT was successfully managed by 1.1 GBq RAI. RT showed similar surgical completeness versus conventional OT, and provides a safe and feasible surgical option for PTC patients.     

Fracture of the coracoid process with acute subscapularis tear without shoulder dislocation

Coracoid process fracture is an uncommon injury and can be easily missed. An associated acute subscapularis tear is still rare. Herein, we describe a 61 year old male who fell from a 2 meter height (stair case) and presented with isolated coracoid process fracture with acute subscapularis tear without dislocation of (R) shoulder joint. The plain x-rays, CT scan and MR arthrography comprised the diagnosis. He was operated upon with reattachment of subscapularis to lesser tuberosity and conjoint tendons to pectoralis major. At 6 mo followup he had good range of motion and his MRI revealed complete healing.     

Potential of Oncostatin M to accelerate diabetic wound healing

Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti‐inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full‐thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left‐side wounds (n = 10) and phosphate‐buffered saline was applied on the two right‐side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM‐treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds.     

Wound‐healing effect of adipose stem cell‐derived extracellular matrix sheet on full‐thickness skin defect rat model: Histological and immunohistochemical study

The potential use of extracellular matrix (ECM) as a source of wound dressing material has recently received much attention. The ECM is an intricate network of various combinations of elastin, collagens, laminin, fibronectin, and proteoglycans that play a key role in stimulating cell proliferation and differentiation. We evaluated the efficacy of an ECM sheet derived from human adipose tissue as a wound dressing material to enhance healing. We prepared a novel porous ECM sheet dressing scaffold from human adipose tissue. in vitro analysis of the ECM sheets showed efficient decellularisation; absence of immunostimulatory components; and the presence of a wide number of angiogenic and bioactive factors, including collagen, elastin, and proteoglycans. To evaluate in vivo efficacy, full‐thickness excisional wounds were created on the dorsal skin of a rat, and the ECM sheets; secondary healing foam wound dressing, Healoderm; or a conventional dressing were applied to each wound site. Photographs were taken every other day, and the degree of reepithelialisation of the wounds was determined. Application of an ECM sheet dressing enhanced the macroscopic wound‐healing rate on days 4, 7, and 10 compared with that in the control group. Microscopic analysis indicated that the reepithelialisation rate of the wound was higher in the ECM group compared with that in the control group; the reepithelialisation rate was better than that of the secondary healing foam wound dressing. Moreover, a denser and more organised granulation tissue was formed in the ECM sheet group compared with that in the secondary healing foam wound dressing and control groups. The ECM sheet also showed the highest microvessel density compared with the secondary healing foam wound dressing and control groups. Based on these data, we suggest that a bioactive ECM sheet dressing derived from human adipose can provide therapeutic proteins for wound healing.