Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer.

PURPOSE: Recently, enzymes of the serine synthetic pathway (SSP) have been suggested as key player in the metabolic adaptation of oncogenesis. We assessed the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired normal tissue (pNT) and the prognostic implications. METHODS: From 2006 to 2010, we included 486 patients with colon cancer who underwent curative surgery at Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated by multiplying intensity by proportion. The final score was classified as follows: 0-2 as negative and 3-12 as positive. RESULTS: During the median follow-up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p < 0.001 for each). The univariate analysis for relapse-free survival revealed that TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However, the expression of TT PDK2 did not represent a prognostic value in multivariate analysis. CONCLUSIONS: In conclusion, PHGDH, PDK1, and PSAT were significantly increased in colonic TT compared with pNT. The prognostic implication of these enzymes needs to be further investigated.

Expression of aquaporin-1, aquaporin-3, and aquaporin-5 correlates with nodal metastasis in colon cancer.

OBJECTIVES: The clinical significance of aquaporin-1 (AQP1), aquaporin-3 (AQP3), and aquaporin-5 (AQP5) expression was analyzed in a large number of patients with colon cancer. METHODS: AQP1, AQP3, and AQP5 expression was investigated based on the immunohistochemistry of tissue microarray specimens from 486 colon cancer patients who underwent curative surgery. Scores were given to the staining intensity and percentage of positive cells, and the staining score was defined as the sum of these scores then used to categorize the AQP expression as negative, weakly AQP-positive, or strongly AQP-positive. RESULTS: A total of 298 (61.3%) patients were identified as strongly AQP1-positive (staining score ≥ 6), while 38 (7.8%) were strongly AQP3-positive and 145 (29.8%) were strongly AQP5-positive. The overexpression of AQP1, AQP3, and AQP5 was significantly correlated with lymph node metastasis in a multivariate logistic analysis (AQP1, p = 0.026; AQP3, p = 0.023; AQP5, p = 0.003). While the multivariate survival analysis, which included age, histology, TNM stage, and CEA level showed that the expression of AQP1, AQP3, and AQP5 had no effect on the overall survival and disease-free survival. CONCLUSIONS: The current study found a significant correlation between AQP1, AQP3, and AQP5 expression and lymph node metastasis in patients with surgically resected colon cancer.

Congenital primary cutaneous anaplastic large-cell lymphoma: a case report.

Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is the second most common type of primary cutaneous T-cell lymphoma. The median age of onset of C-ALCL is 60 years. Presented here is a case of congenital CD30-positive (CD30(+)) primary C-ALCL in a 10-day-old neonate who presented with a large erythematous indurative plaque in the right postauricular area. A systemic workup of the patient excluded other potential causes. The neonate was treated with wide excision, but chemotherapy or radiation therapy was not administered, as the patient's parents did not consent to such treatment. The patient has been monitored for 30 months after excision and there has been no disease recurrence. C-ALCL rarely occurs in children, and to the best of our knowledge, this is the first reported case of a neonate with congenital primary C-ALCL.

Single omental metastasis of renal cell carcinoma after radical nephrectomy: A case report.

BACKGROUND: Renal cell carcinoma (RCC) is the third most common malignancy in the genitourinary tract. The lungs, bone, lymph nodes, liver, and brain are common metastatic sites of RCC. However, there is limited literature on single omental metastasis of RCC. CASE SUMMARY: We present the case of a 44-year-old man with single omental metastasis of RCC after laparoscopic radical nephrectomy. Pathological diagnosis of the resected left kidney revealed pT3a clear cell RCC (Fuhrman grade III). At 6 mo postoperatively, abdominal computed tomography revealed a 12-mm enhancing nodule in the left lower peritoneum. At 7 mo after initial operation, laparoscopic removal of the left omental nodule was performed. The pathological results indicated metastatic clear cell RCC. Currently, the patient is being treated with adjuvant pembrolizumab. CONCLUSION: Omental metastasis of RCC owing to laparoscopic radical nephrectomy is rare. Urologists should be aware of the diverse nature of RCC.

Expression of hMLH1, hMSH2 and hMSH6 in small intestinal carcinomas.

BACKGROUND/AIMS: Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC. METHODOLOGY: A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC). RESULTS: The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status. CONCLUSIONS: The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).

Human amniotic fluid stem cell-derived muscle progenitor cell therapy for stress urinary incontinence.

The most promising treatment for stress urinary incontinence can be a cell therapy. We suggest human amniotic fluid stem cells (hAFSCs) as an alternative cell source. We established the optimum in vitro protocol for the differentiation from hAFSCs into muscle progenitors. These progenitors were transplanted into the injured urethral sphincter and their therapeutic effect was analyzed. For the development of an efficient differentiation system in vitro, we examined a commercial medium, co-culture and conditioned medium (CM) systems. After being treated with CM, hAFSCs were effectively developed into a muscle lineage. The progenitors were integrated into the host urethral sphincter and the host cell differentiation was stimulated in vivo. Urodynamic analysis showed significant increase of leak point pressure and closing pressure. Immunohistochemistry revealed the regeneration of circular muscle mass with normal appearance. Molecular analysis observed the expression of a larger number of target markers. In the immunogenicity analysis, the progenitor group had a scant CD8 lymphocyte. In tumorigenicity, the progenitors showed no teratoma formation. These results suggest that hAFSCs can effectively be differentiated into muscle progenitors in CM and that the hAFSC-derived muscle progenitors are an accessible cell source for the regeneration of injured urethral sphincter.

Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica: comparison of lesional T-cell subsets and investigation of viral associations.

BACKGROUND: Pityriasis lichenoides (PL) exhibits a broad clinical spectrum that includes both acute and chronic forms. The precise biologic mechanisms underlying PL remain unclear. OBJECTIVES: To evaluate the immunohistochemical characteristics of PL and to investigate lesional T-cell subsets and the possible role of viral infection in its pathogenesis. PATIENTS AND METHODS: Samples from 10 patients with PL et varioliformis acuta (PLEVA) and 13 with PL chronica (PLC) were analyzed immunohistochemically. Epstein-Barr virus early regions were assayed by in situ hybridization and T-cell receptor-γ (TCR-γ) gene rearrangements were assayed by polymerase chain reaction (PCR). We also utilized PCR to assay for human herpesvirus-8 (HHV-8) DNA in 51 patients with PL and in 25 controls. RESULTS: Lymphocytes expressing CD8 and T-cell intracellular antigen-1 were more abundant in patients with PLEVA than with PLC, whereas CD4+ lymphocytes and FOXP3-positive regulatory T-cells were more abundant in PLC. HHV-8 DNA was present in 11 of 51 (21.6%) PL patients and 0 of 25 controls. A clonal TCR-γ gene rearrangement was observed in only one patient with PLEVA. CONCLUSIONS: Our data suggests that PL may represent an inflammatory condition induced by various triggering agents, such as HHV-8, rather than a lymphoproliferative disorder. PLEVA, characterized by an acute course with severe symptoms, may indicate a relative lack of regulatory T-cells in comparison with PLC.

Identification of a novel non-invasive biological marker to overcome the shortcomings of PSA in diagnosis and risk stratification for prostate cancer: Initial prospective study of developmental endothelial locus-1 protein.

OBJECTIVE: This prospective study sought to clarify the developmental endothelial locus-1 (Del-1) protein as values of diagnosis and risk stratification of prostate cancer (PCa). DESIGN: From February 2017 to December 2019, a total 458 patients who underwent transrectal ultrasound guided prostate biopsy or surgery of benign prostatic hyperplasia agreed to research of Del-1 protein. We prospectively compared and analyzed the Del-1 protein and prostate specific antigen (PSA) in relation to the patients' demographic and clinicopathological characteristics. RESULTS: Mean age was 68.86±8.55 years. Mean PSA and Del-1 protein was 21.72±89.37, 0.099±0.145, respectively. Two hundred seventy-six (60.3%) patients were diagnosed as PCa. Among them, 181 patients underwent radical prostatectomy (RP). There were significant differences in Del-1 protein between benign and PCa group (0.066±0.131 vs 0.121±0.149, respectively, p<0.001). When we set the cut-off value of del-1 protein as 0.120, in patients with 3≤PSA≤8, positive predictive value and specificity of Del-1 protein (≥0.120) for predicting PCa were 88.9% (56/63) and 93.5% (101/108), respectively. Among 181 patients who underwent RP, there were significant differences in Del-1 protein according to stage (pT2 vs pT3a vs ≥pT3b) (0.113±0.078, 0.171±0.121, 0.227±0.161, respectively, p<0.001) and to Gleason score (6 (3+3) or 7 (3+4) vs 7 (4+3) or 8 (4+4) vs 9 or 10) (0.134±0.103, 0.150±0.109, 0.212±0.178, respectively, P = 0.044). Multivariate analysis showed that PSA, Del-1 protein and high Gleason score (≥9) were the independent prognostic factors for predicting higher pT stage (≥3b). Furthermore, age, PSA and Del-1 protein were independent prognostic factors for predicting significant PCa. CONCLUSION: Patients with PCa showed higher expression of Del-1 protein than benign patients. Del-1 protein increased with the stage and Gleason score of PCa. Collaboration with PSA, Del-1 protein can be a non-invasive useful marker for diagnosis and risk stratification of PCa.

Infrequent hypermethylation of the PTEN gene in Korean non-small-cell lung cancers.

CpG islands (CGIs) hypermethylation is implicated in the pathogenesis of many cancers, including lung cancer. The phosphate and tension homolog (PTEN) is a tumor suppressor that controls a variety of biological processes including cell proliferation, growth, migration, and death. The defects in PTEN regulation have a profound impact on carcinogenesis. Herein, we have examined the methylation status of the human PTEN gene in 137 primary non-small-cell lung cancers (NSCLCs) by using a methylation-specific PCR and correlated the results with clinicopathological features. Promoter methylation of the PTEN gene was observed in 5.1%, 2.9%, and 0.0% of three different CpG regions, which were localized at -1460 to -1263, -984 to -848, and -300 to -128 nucleotides upstream of the translation start site, respectively. Reverse transcription-PCR and immunohistochemical analysis showed the methylation of the CGI region at -984 to -848 correlated more accurately with PTEN expression. In addition, no significant correlation was found between PTEN methylation and clinicopathological factors, including the survival rates. These findings suggest that promoter methylation is not an important mechanism for PTEN deregulation in NSCLCs from Koreans.

Evaluation of the reversal of multidrug resistance by MDR1 ribonucleic acid interference in a human colon cancer model using a Renilla luciferase reporter gene and coelenterazine.

The reversal effect of multidrug resistance (MDR1) gene expression by adenoviral vector-mediated MDR1 ribonucleic acid interference was assessed in a human colon cancer animal model using bioluminescent imaging with Renilla luciferase (Rluc) gene and coelenterazine, a substrate for Rluc or MDR1 gene expression. A fluorescent microscopic examination demonstrated an increased green fluorescent protein signal in Ad-shMDR1- (recombinant adenovirus that coexpressed MDR1 small hairpin ribonucleic acid [shRNA] and green fluorescent protein) infected HCT-15/Rluc cells in a virus dose-dependent manner. Concurrently, with an increasing administered virus dose (0, 15, 30, 60, and 120 multiplicity of infection), Rluc activity was significantly increased in Ad-shMDR1-infected HCT-15/Rluc cells in a virus dose-dependent manner. In vivo bioluminescent imaging showed about 7.5-fold higher signal intensity in Ad-shMDR1-infected tumors than in control tumors (p < .05). Immunohistologic analysis demonstrated marked reduction of P-glycoprotein expression in infected tumor but not in control tumor. In conclusion, the reversal of MDR1 gene expression by MDR1 shRNA was successfully evaluated by bioluminescence imaging with Rluc activity using an in vivo animal model with a multidrug resistance cancer xenograft.

A rare pericytic tumor of the kidney: The first case in Korea.

INTRODUCTION: A pericytic tumor is a group of mesenchymal neoplasm found in superficial tissues and only rarely described in viscera. The family of pericytic tumors includes glomus tumors and variants, myopericytoma including myofibroma, and angioleiomyoma etc. The renal pericytic tumor is extremely rare, and only few comprehensive discussions about this entity have been done. PRESENTATION OF CASE: A 58-year-old man was transferred to our institute with suspicions of renal cell carcinoma. The kidney dynamic computed tomography scan showed a 3 cm sized solid mass in the upper pole of the right kidney. Laparoscopic radical nephrectomy was performed due to the deep-seated mass. Pathological result confirmed that the kidney mass was renal pericytic tumor. DISCUSSION: Although general biological behavior of published renal pericytic tumors is likely to be benign, the clinicopathologic experiences are very limited. Therefore, we should evaluate the malignant potential of the entity according to the parameters proposed for soft tissue tumors, including tumor location, tumor size, growth pattern, cellularity, cytological atypia, and mitotic figures with atypical forms. The current case shows several worrisome features, including an extremely rare tumor location, partially infiltrative growth, and a mildly increased proliferating index, which resulted in it being classified as an uncertain malignant potential. CONCLUSION: We described the first case of renal pericytic tumor, addressing uncertain malignant potential, in a Korean male, which would be a distinct mesenchymal neoplasm differentiating from other groups of perivascular tumor families based on histological and immunohistochemical features.

Epigenetic inactivation of Homeobox A5 gene in nonsmall cell lung cancer and its relationship with clinicopathological features.

Promoter methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. Homeobox A5 (HOXA5) is a master regulator of the morphogenesis and cell differentiation to be implicated as a tumor suppressor gene in breast cancer, but its role in lung cancer is still unknown. In this study, we have investigated the methylation status of the promoter region of the HOXA5 gene in nonsmall cell lung cancers (NSCLCs) using nested and standard methylation-specific PCR (MSP) and correlated the methylation status with clinicopathological features. With standard MSP analysis, HOXA5 methylation were found in 113 (81.3%) of 139 NSCLCs and 72 (51.8%) in their corresponding nonmalignant lung tissues. RT-PCR and immunohistochemical analysis showed that HOXA5 methylation correlates with gene expression. Moreover, in the patients with stage I disease, HOXA5 methylation was more frequent in smokers than in never-smokes (P = 0.01). There was no influence of HOXA5 methylation on survival in all NSCLCs or at stages II-IV. However, in the patients with stage I disease, HOXA5 methylation was associated with a borderline significantly worse survival (P = 0.09). These findings suggest that downregulation of the HOXA5 gene by aberrant promoter methylation occurs in the vast majority of NSCLCs and that it may play a role in the pathogenesis of NSCLC. Additional studies with larger sample sizes are required to evaluate the prognostic value of HOXA5 methylation in patients with stage I NSCLC.

Intrarenal ectopic adrenal tissue and renal-adrenal fusion: a report of nine cases.

Intrarenal ectopic adrenal tissue and renal-adrenal fusion are rare findings in the adult population. We reviewed seven cases of intrarenal adrenal tissue and two cases of renal-adrenal fusion. Patients ranged in age from 35 to 75 years (mean 55). Ectopic adrenal tissue was identified at the superior pole of the kidney in all but one case, which was located in the mid-portion of the kidney. Ectopic adrenal tissue varied in its growth from subcapsular lesions that were plaque-like (n=3), wedge-shaped (n=2), or spherical (n=1) to irregular nests deep in the renal parenchyma (n=1). In all nine cases, the adherent and intrarenal adrenal tissue was composed of adrenal cortical tissue, with no adrenal medullary tissue present. In six cases, adrenal tissue focally extended into renal parenchyma in an infiltrative manner. Of the nine cases, two were diagnostic problems for the contributing pathologists. In one case, intrarenal adrenal tissue mimicked low-grade clear cell renal cell carcinoma. In another case, an adrenocortical adenoma adherent to the kidney resembled renal invasion by adrenocortical carcinoma. This study summarizes key morphological features of intrarenal ectopic adrenal tissue and renal-adrenal fusion along with histological pitfalls and its differential diagnoses.

Clinical significance of the De Ritis ratio for detecting prostate cancer in a repeat prostate biopsy.

Purpose: We evaluated factors predicting a positive repeat biopsy result in patients with an initial negative prostate biopsy result. Materials and Methods: This study included 124 patients in whom prostate cancer (PCa) was not detected in the initial transrectal ultrasound-guided prostate biopsy and who underwent repeat biopsy from January 2011 to December 2017. Patients without PCa in both initial and repeat prostate biopsies were designated as group 1 (n=82), and those in whom PCa was detected on a repeat prostate biopsy were designated as group 2 (n=42). Among group 2 patients, 6 had insignificant PCa according to the Epstein criteria and were combined with group 1 patients to make up group A (n=88). Patients with significant PCa were categorized as group B (n=36). We compared clinicopathologic characteristics between the groups. Results: Multivariate analysis showed that age (p=0.018) and detection of atypical small acinar proliferation (ASAP) or ≥3 cores of high-grade prostatic intraepithelial neoplasia (HGPIN) (p=0.011) on the initial biopsy were predictive factors for a positive result on a repeat biopsy. When we compared group A and group B, age (p=0.004) and the De Ritis ratio (p=0.024) were significantly higher in group B in the multivariate analysis. Conclusions: Age and the detection of ASAP or ≥3 cores of HGPIN on the initial biopsy were associated with detection of PCa on a repeat biopsy. Age and the De Ritis ratio were found to be predictive factors for the detection of clinically significant PCa on a repeat biopsy.

ZNF492 and GPR149 methylation patterns as prognostic markers for clear cell renal cell carcinoma: Array­based DNA methylation profiling.

The present study aimed to identify novel methylation markers of clear cell renal cell carcinoma (ccRCC) using microarray methylation analysis and evaluate their prognostic relevance in patient samples. To identify cancer­specific methylated biomarkers, microarray profiling of ccRCC samples from our institute (n=12) and The Cancer Genome Atlas (TCGA) database (n=160) were utilized, and the prognostic relevance of candidate genes were investigated in another TCGA dataset (n=153). For validation, pyrosequencing analyses with ccRCC samples from our institute (n=164) and another (n=117) were performed and the potential clinical application of selected biomarkers was examined. We identified 22 CpG island loci that were commonly hypermethylated in ccRCC. Kaplan­Meier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, Kaplan­Meier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G protein­coupled receptor 149 (GPR149), was significantly associated with shorter time­to­progression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression. Similarly, the methylation status of these two genes was significantly associated with poor outcomes in the independent external validation cohort. Collectively, the present study proposed that the novel methylation markers ZNF492 and GPR149 could be independent prognostic indicators in patients with ccRCC.

A Novel Orally Active Inverse Agonist of Estrogen-related Receptor Gamma (ERRγ), DN200434, A Booster of NIS in Anaplastic Thyroid Cancer.

PURPOSE: New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy-refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERRγ) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC50 = 0.006 µmol/L), selective, and orally available ERRγ inverse agonist for NIS enhancement in ATC. EXPERIMENTAL DESIGN: We sought to identify better ERRγ-targeting ligands and explored the crystal structure of ERRγ in complex with DN200434. After treating ATC cells with DN200434, the change in iodide-handling gene expression, as well as radioiodine avidity was examined. ATC tumor-bearing mice were orally administered with DN200434, followed by 124I-positron emission tomography/CT (PET/CT). For radioiodine therapy, ATC tumor-bearing mice treated with DN200434 were administered 131I (beta ray-emitting therapeutic radioiodine) and then bioluminescent imaging was performed to monitor the therapeutic effects. Histologic analysis was performed to evaluate ERRγ expression status in normal tissue and ATC tissue, respectively. RESULTS: DN200434-ERRγ complex crystallographic studies revealed that DN200434 binds to key ERRγ binding pocket residues through four-way interactions. DN200434 effectively upregulated iodide-handling genes and restored radioiodine avidity in ATC tumor lesions, as confirmed by 124I-PET/CT. DN200434 enhanced ATC tumor radioiodine therapy susceptibility, markedly inhibiting tumor growth. Histologic findings of patients with ATC showed higher ERRγ expression in tumors than in normal tissue, supporting ERRγ as a therapeutic target for ATC. CONCLUSIONS: DN200434 shows potential clinical applicability for diagnosis and treatment of ATC or other poorly differentiated thyroid cancers.

Residual tumor potentially left behind after local ablation therapy in prostate adenocarcinoma.

PURPOSE: We examined contralateral prostate cancer potentially left behind by focal therapy. MATERIALS AND METHODS: We investigated 100 completely embedded radical prostatectomy specimens in which needle biopsy predicted limited disease (less than 3 positive cores, 50% or less involvement of any positive core, Gleason score 6 or less) and all positive needle cores were unilateral. Clinical stage was T1c in 85 and T2a in 15 cases with the palpable lesion on the positive biopsy side. RESULTS: There was 1 positive core in 66 cases. On average 13.9% of each positive core was involved with tumor. The mean number of separate tumor nodules per radical prostatectomy was 2.9. In 65 radical prostatectomy specimens there was some tumor contralateral to the positive biopsy side. Total tumor volume in the radical prostatectomy contralateral to the positive biopsy side averaged 0.2 cm(3) (largest 1.3). In 23 cases contralateral tumor volume was greater than biopsy positive side tumor volume. There were 13 cases in which more than 0.5 cm(3) cancer was contralateral to the positive biopsy and 7 with predominantly anterior tumor. Volume contralateral to positive biopsy side could not be predicted by the number of positive cores (1 vs 2) or maximum percent of the core involved. Gleason pattern 4, extraprostatic extension or positive margins were seen contralateral to the positive biopsy side in 13, 1 and 2 cases, respectively. CONCLUSIONS: In a highly selected population with limited unilateral biopsy cancer, tumor contralateral to the positive biopsy side at radical prostatectomy is typically small. However, 20% of radical prostatectomy specimens had some contralateral adverse pathology in terms of size, extraprostatic extension, grade or margins.

Oncological and functional outcomes following robot-assisted laparoscopic radical prostatectomy at a single institution: a minimum 5-year follow-up.

Background: To evaluate mid-term oncological and functional outcomes in patients with prostate cancer treated by robot-assisted laparoscopic radical prostatectomy (RALP) at our institution. Methods: We retrospectively reviewed the medical records of 128 patients with prostate cancer who underwent RALP at our institution between February 2008 and April 2010. All patients enrolled in this study were followed up for at least 5 years. We analyzed biochemical recurrence (BCR)-free survival using a Kaplan-Meier survival curve analysis and predictive factors for BCR using multivariate Cox regression analysis. Continence recovery rate, defined as no use of urinary pads, was also evaluated. Results: Based on the D'Amico risk classification, there were 30 low-risk patients (23.4%), 47 intermediate-risk patients (38.8%), and 51 high-risk patients (39.8%), preoperatively. Based on pathological findings, 50.0% of patients (64/128) showed non-organ confined disease (≥T3a) and 26.6% (34/128) had high grade disease (Gleason score ≥8). During a median follow-up period of 71 months (range, 66-78 months), the frequency of BCR was 33.6% (43/128) and the median BCR-free survival was 65.9 (0.4-88.0) months. Multivariate Cox regression analysis revealed that high grade disease (Gleason score ≥8) was an independent predictor for BCR (hazard ratio=4.180, 95% confidence interval=1.02-17.12, p=0.047). In addition, a majority of patients remained continent following the RALP procedure, without the need for additional intervention for post-prostatectomy incontinence. Conclusion: Our study demonstrated acceptable outcomes following an initial RALP procedure, despite 50% of the patients investigated demonstrating high-risk features associated with non-organ confined disease.

The Combination of Periostin Overexpression and Microvascular Invasion Is Related to a Poor Prognosis for Hepatocellular Carcinoma.

BACKGROUND/AIMS: Periostin is an extracellular matrix protein and is known to be related to the metastatic potential and prognosis of cancer. However, few studies have investigated the expression level of periostin and its association with prognoses in hepatocellular carcinoma. Therefore, we analyzed periostin overexpression in hepatocellular carcinoma and its implication for prognoses. METHODS: We evaluated 149 patients who underwent surgical resection between 2006 and 2010. Tissue microarrays were constructed from hepatocellular carcinoma tissue and adjacent nontumor tissue, and immunohistochemistry was performed. RESULTS: A high periostin level was observed more frequently in cases of multiple tumors (odds ratio [OR], 2.826; 95% confidence interval [CI], 1.224 to 6.527; p=0.013), positive microvascular invasion (OR, 2.974; 95% CI, 1.431 to 6.181; p=0.003), and advanced stage disease (OR, 3.032; 95% CI, 1.424 to 6.452; p=0.003). Patients with high periostin expression had significantly (p=0.002) lower overall survival rates than those with low periostin expression (90.3%, 66.1%, and 56.2% vs 97.7%, 85.1%, and 77.5% at 1, 3, and 5 years). CONCLUSIONS: We found that a combination of periostin overexpression and microvascular invasion in hepatocellular carcinoma was correlated with a poor prognosis and can be a good prognostic marker for hepatocellular carcinoma.