pT1 Tumors Research Articles

Detection of Early Murine Colorectal Cancer by MMP-2/-9-Guided Fluorescence Endoscopy.

Patients with ulcerative colitis are at increased risk for colorectal cancer and endoscopic surveillance is mandatory. Matrix metalloproteinases (MMPs)-2 and -9 activities are increased in malignant colonic mucosa. The aim of the study was to evaluate molecular imaging of MMP-2/-9 by fluorescence endoscopy (FE) for early tumor detection. Colorectal cancer in mice (n = 28) was induced by azoxymethane and dextran sodium sulfate. Twenty-four hours after intravenous injection of a nonpeptidic, Cy5.5-labeled MMP-selective tracer, tumor development was assessed in vivo by white light endoscopy and FE. Topical administration of the tracer was also investigated (after 5 minutes and 24 hours). Colonic tumors were evaluated ex vivo by fluorescence reflectance imaging, immunohistochemistry, Western blot analysis, and zymography. Imaging of MMP-2/-9 expression by FE achieved a significantly higher contrast of the fluorescence signal in colonic adenomas compared with the adjacent nonmalignant mucosa (P < 0.001). Fluorescence reflectance imaging detected a significantly higher tracer uptake in adenoma compared with healthy mucosa (P < 0.001) and revealed a tumor size-dependent increase of tracer uptake (P < 0.01). Topical tracer administration did not facilitate tumor detection. Immunohistochemistry, Western blot analysis, and zymography indicated higher levels of MMP-2 and -9 in high-grade dysplasia and pT1 tumors ex vivo. MMP-2/-9 expression was significantly increased in colorectal neoplasia. FE allows direct visualization of a prognostic parameter (here MMP-2/-9) on a molecular level and may improve the characterization of colorectal lesions and the adenoma detection rate in the future.

Reappraisal of Serosal Invasion in Patients With T3 Colorectal Cancer by Elastic Stain: Clinicopathologic Study of 139 Surgical Cases With Special Reference to Peritoneal Elastic Lamina Invasion

Peritoneal elastic lamina invasion (PELI) has been reported to be an important adverse prognostic factor in pT3 colorectal cancer (CRC). However, the data supporting this contention are limited. To clarify the associations between PELI of pT3 CRC and prognostic significance, 139 consecutive surgical cases of pT3 CRC were examined. One hundred thirty-nine consecutive in-house surgical cases of pT3 CRC between 1993 and 2011 were examined. Thirty consecutive surgical cases of pT4a CRC resected during the same period were examined for comparison. Case selections were restricted to pT3 CRCs with the sections containing the deepest adenocarcinoma invasion partially or entirely covered with the peritoneum. Elastic staining was performed on one section containing the deepest tumor invasion partially or entirely covered with the peritoneum. The associations between the presence of PELI and clinicopathologic factors including prognosis of the patients were examined. Peritoneal elastic lamina invasion was identified in 23.0% (32 of 139) of the pT3 CRCs. PELI was associated with primary site (P = .006), lymph node metastasis (P < .001), lymphovascular invasion (P < .001), recurrence (P = .007), and patient's age (P = .002). The proportions of patients with a 4-year recurrence-free period in those with negative PELI, positive PELI, and pT4a tumor were 90.3%, 66.7%, and 28.9%, respectively (P < .001). Elastic staining is useful to evaluate the serosal invasion of CRC. Positive PELI is a significant predictive factor for lymph node metastasis and recurrence-free survival in patients with pT3 CRC. This indicates that pT3 tumors with PELI should be treated like pT4a tumors.

Impact of age on the biochemical failure and androgen suppression after radical prostatectomy for prostate cancer in chilean men

Aim: The aim of this study was to determine the association of age with the clinicopathological findings, phenotypic expression of circulating prostate cells (CPCs) and micrometastasis, biochemical failure and effect of androgen blockade after radical prostatectomy for prostate cancer in Chilean men. Methods: This is a prospective, observational, single-center study of Chilean men who underwent radical prostatectomy. Three months after surgery, the peripheral blood was collected to analyze the biochemical failure by measuring prostate-specific antigen (PSA) levels in the serum. The blood and bone marrow were collected to detect the presence of CPCs and the bone marrow micrometastasis by checking the expression of PSA, human epidermal growth factor receptor 2 (HER-2), and matrix metalloproteinase 2 (MMP-2) using standard immunocytochemistry. The clinicopathological findings, phenotypic expression of CPCs and micrometastasis, biochemical failure and effect of androgen blockade were analyzed for association with age. Results: In total, 120/338 (36.6%) of patients were ≥ 70 years (older men). A higher frequency of biochemical failure occurred in older men with negative surgical margins, a Gleason score ≥ 8, and pT3 tumors compared to patients vs. 15%) while more older men became castrate resistant (83% vs. 43%). Conclusion: After radical prostatectomy, the older men with pathological features of Gleason score ≥ 8, pT3 tumors, and positive extracapsular extension had higher frequency of biochemical failure and the presence of CPCs. The treatment of androgen blockade was less successful to suppress the disease relapse in the older men than that in the younger man.

Recurrence of gastric cancer in patients who are disease-free for more than 5 years after primary resection

Late recurrence of gastric cancer is rare and there are few data on recurrence in patients who are disease free for >5 years after gastrectomy. The aim of this study was to evaluate the predictors and status of tumor recurrence among these patients. Clinicopathologic characteristics, patterns of recurrence, and postrecurrence survival were analyzed in patients who were diagnosed as disease free at 5 years postoperatively and thereafter experienced recurrence. Independent factors associated with the late recurrence were analyzed. Among 1,573 patients who underwent curative surgery from June 1992 to December 2006, 348 patients had recurrence. Of them, 7.6% (n = 25) suffered from late recurrence after 5 years after gastrectomy. Among patients who were diagnosed as disease free at 5 years after surgery, it accounted for 2.8% (25/902). Cases with late recurrence were characterized by more aggressive clinicopathologic features than those without recurrence. The median time to recurrence was 88.8 months (range, 64.8-238.0); of the 25 patients, 18 (72.0%) had recurrence within 8 years after surgery. The most common pattern was peritoneal recurrence (n = 19; 76.0%). The estimated median survival after recurrence was 9.4 months. On multivariate analysis, pT4 classification was the only independent risk factor for late recurrence. There were 185 patients with pT4 tumor who had no recurrence at 5 years after surgery; 19 (10.3%) had late recurrence. pT4 tumor was the only important predictor of late recurrence. Whether extended follow-up for T4 tumors affects survival needs to be demonstrated in more large-scale studies.

Nephron-sparing surgery across a nation - outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit.

To determine the scope and outcomes of nephron-sparing surgery (NSS), i.e. partial nephrectomy, across the UK and in so doing set a realistic benchmark and identify fresh contemporary challenges in NSS. In 2012 reporting of outcomes of all types of nephrectomy became mandatory in the UK. In all, 148 surgeons in 86 centres prospectively entered data on 6 042 nephrectomies undertaken in 2012. This study is a retrospective analysis of the NSS procedures in the dataset. A total of 1 044 NSS procedures were recorded and the median (range) surgical volume was 4 (1-39) per consultant and 8 (1-59) per centre. In all, 36 surgeons and 10 centres reported on only one NSS. The indications for NSS were: elective with a tumour of ≤4.5 cm in 59%, elective with a tumour of >4.5 cm in 10%, relative in 7%, imperative in 12%, Von Hippel-Lindau in 1%, and unknown in 11%. The median (range) tumour size was 3.4 (0.8-30) cm. The technique used was minimally invasive surgery in 42%, open in 58%, with conversions in 4%. The histology results were: malignant in 80%, benign in 18%, and unknown in 2%. In patients aged <40 years 36% (36/101) had benign histology vs 17% (151/874) of those aged ≥40 years (P < 0.01). In patients with tumours of <2.5 cm 29% (69/238) had benign histology vs 14% (57/410) with tumours of 2.5-4 cm vs 8% (16/194) with tumours of ≥4 cm (P = 0.02). In patients aged <40 years with of tumours of <2.5 cm 44% (15/34) were benign. The 30-day mortality was 0.1% (1/1 044). There were major complications (Clavien-Dindo grade of ≥IIIa) in 5% (53/1 044). There was an increased risk of complications after extended elective NSS of 19% (19/101) vs elective at 12% (76/621) (relative risk [RR] 1.54; P < 0.01). Margins were recorded in 68% (709/1 044) of the patients, with positive margins identified in 7% (51/709). Positive surgical margins after NSS for pathological T3 (pT3) tumours were found in 47.8% (11/23) vs 6.1% (32/523) for pT1a, tumours (RR 5.61; P < 0.01). In all, 14% (894/6 042) of the patients underwent surgery for T1a tumours: 55% (488/894) by NSS, 42% (377/894) by radical nephrectomy (RN), and in 3% (29/894) the procedure used was unknown. Major complications after occurred in 4.9% (24/488) of NSS vs 1.3% (5/377) of RN (P < 0.01). Limitations included poor reporting of renal function data and no data on tumour complexity. In its first year, mandatory national reporting has provided several challenging contemporary insights into NSS.

Long-Term Oncologic Outcome of an Initial Series of Laparoscopic Radical Prostatectomy for Clinically Localized Prostate Cancer After a Median Follow-up of 10 Years

IntroductionWhen laparoscopic radical prostatectomy (LRP) was introduced as a novel treatment option for prostate cancer, it had to compete with the established open techniques. The short- and intermediate-term oncologic and functional outcomes were encouraging and comparable to those with retropubic radical prostatectomy. However, the long-term oncologic safety for LRP has yet to be fully elucidated. We evaluated the long-term oncologic outcomes of an initial series of patients who had undergone LRP. Patients and MethodsAn initial unselected and consecutive series of 100 patients who had undergone LRP for clinically localized prostate cancer from 1999 to 2001 was identified. The pre-, intra-, and postoperative data were collected. Biochemical recurrence (BCR) was defined as a prostate-specific antigen (PSA) value of ≥ 0.2 ng/mL. The outcome measures were cancer control (CC), BCR-free survival (BCRFS), cancer-specific survival (CSS), and overall survival (OS). ResultsThe mean patient age was 64 ± 7 years, and the mean preoperative PSA level was 9.6 ± 8.3 ng/mL. Of the 100 patients, 79 (79%) had stage pT2 and 15 (15%) had stage pT3 disease. Positive surgical margins were found in 25 patients (25%; 16.4% for pT2 and 40% for pT3). The median follow-up time was 126 months (range, 60-176 months). The 5-year CC rate was 82%. The estimated 10-year BCRFS was 83% and 80% for patients with stage pT2 and pT3 tumors, respectively. The median time to BCR was 52 months (range, 6-144 months). The estimated 10-year CSS and OS was 98% and 93%, respectively. ConclusionOur long-term follow-up data from an initial unselected patient cohort have indicated that LRP offers excellent long-term oncologic control for patients with localized prostate cancer.

Trends in Prevalence of Thyroid Cancer Over Three Decades: A Retrospective Cohort Study of 17,526 Surgical Patients.

IntroductionThyroid cancer (TC) incidence has been increasing in recent years. The aim of this study was to investigate our institution-based estimates of operative volumes for TC over the last three decades.Materials and methodsThis was a retrospective cohort study of patients undergoing thyroid surgery at our institution. Patient characteristics were reviewed in three subgroups: Group I (treated in 1981–1986), Group II (treated in 1987–2002), and Group III (treated in 2003–2012).ResultsTC was diagnosed in 1578/17,526 (9.0 %) thyroid operations. Incidence of TC increased from 3.7 % in Group I to 10.4 % in Group III (p < 0.001). Incidence of papillary TC increased form 40.6 % in Group I to 81.3 % in Group III (p < 0.001). In the latter group, 23.5 % of all papillary TCs were diagnosed in patients with Hashimoto’s disease. Meanwhile, incidence of anaplastic TC decreased from 16.2 % in Group I to 2.1 % in Group III patients (p < 0.001). pT1 tumors were diagnosed in 8.1 % Group I and 54.8 % Group III (p < 0.001), whereas pT4 tumors were identified in 40.5 % Group I, 2.4 % Group II, and 0.84 % Group III subjects (p < 0.001). pT3 tumors were found in 51.6 % Group I, whereas multifocal papillary TCs were found in 15.7 % Group III patients, the latter with a higher prevalence of pN1 stage (p < 0.001).ConclusionsThe following trends in surgical volume for TC were identified throughout the study period: a fivefold increase of thyroid operations for TC, a threefold increase in incidence of papillary TC, and an eightfold decrease in incidence of anaplastic TC. It is of interest that a significant increase in incidence of multifocal papillary TC in young female patients with Hashimoto’s disease was found over time.

Expression of store-operated channel components in prostate cancer: the prognostic paradox

In vitro studies in prostate cancer (PCa) cell lines have suggested a key and complex role of the store-operated channels (SOCs) in major cancer hallmarks, including proliferation, apoptosis, and migration. In the present study, we investigated in vivo the expression of the SOC components transient receptor potential canonical (TRPC) 1, TRPC4, Orai1, and stromal interaction molecule 1 (STIM1), during all stages of PCa progression, and evaluated their prognostic impact in clinically localized cancer (CLC). The expressions of TRPC1, TRPC4, Orai1, STIM1, and the androgen receptor and the proliferation marker Ki-67 were evaluated by immunohistochemistry on tissue microarrays containing samples of normal prostate tissues (n=91), prostatic intraepithelial neoplasia (n=61), CLC surgically treated (n=238), and castration-resistant prostate cancer (CRPC; n=45). All markers significantly increased in CLC compared with normal tissues and (for Orai1 and STIM1) in advanced pT3 tumors compared with pT2. In contrast, their expression decreased in CRPC, particularly for Orai1. In CLC, staining for TRPC1, Orai1 and STIM1 correlated with androgen receptor expression, and TRPC1 status was associated with lower proliferation and longer recurrence-free survival, after adjusting for classical prognostic markers. Although increased SOC expression during PCa progression supports a role in cancer cell migration, the inverse association between TRPC1 and biochemical relapse suggests a protective effect in CLC. Moreover, the dramatic down-regulation of Orai1 in CRPC supports its role in apoptosis at this stage of the disease. These results call for caution when considering SOCs as potential therapeutic targets for PCa.

Treatment mapping of prostate cancer in DVPZ prostate centers in Germany

In prostate centers of the Governing Body of German Prostate Centers (DVPZ, Dachverband der Prostatazentren Deutschlands e.V.) treatment data from 3 university clinics, 21 treatment clinics, 3 private clinics and 330 general practitioners incorporated under 22 certificates are collated, in order to document the quality and type of cross-sectoral and interdisciplinary treatment, in particular of prostate cancer (PCA) patients. This analysis is based on the DVPZ UroCloud data sets from 20 July 2015. The UroCloud reflects the web-based chronological disease development and quality parameters. For the descriptive analysis of particular key figures, available complete data sets were selected. Of the centers 22 held a valid certificate and fulfilled all required case numbers and structural prerequisites at the primary certification or recertification. In three cases a reauditing led to requirements before certification. Since 2005 a total of 9650 PCA patients have been pseudonymized and followed up (41,247 follow-up forms, 4.3 forms per patient). In 2014 the median number of newly documented PCA patients was 61 per center (minimum 7 and maximum 295). Radical prostatectomy (RP) dominated with 4491 (56 %) cases followed by primary hormonal therapy (1210 cases, 15 %), irradiation (809, 10 %) and non-interventional therapy, such as active surveillance (AS) or watchful waiting (WW) in 760 cases (10 %). A prostate-specific antigen (PSA) reduction was documented in 50 % of the patients with a preoperative PSA value > 20, in 60 % of pT4 tumors and in 50 % of patients with a tumor Gleason score of 9-10. A positive incision margin (R+) was found in in 15 % of pT2 stages, 41 % of pT3 stages and 85 % of pT4 stages. A secondary intervention was documented in 6.5 % of RP. The DVPZ certificate reflects the complete spectrum of treatment of PCA patients. The strength of the certificate lies in the documentation of patient development and a simultaneous collation of quality parameters.

The number of metastatic lymph nodes exhibiting poorly differentiated clusters predicts survival in patients with pStage III colorectal cancer.

PurposeMany studies have proposed alternative designations for lymph node (LN) status in colorectal cancer (CRC); however, knowledge of histopathological features in metastatic lymph nodes (MLNs) is limited. This study investigated the clinicopathological significance of poorly differentiated clusters (PDCs) in MLNs.MethodsSlides from 159 patients with pathological Stage III CRC were reviewed. Those with <12 dissected LNs (DLNs) were ineligible. PDCs composed of ≥5 cancer cells lacking full glandular formation and ≥10 PDCs under ×20 objective lens were defined as positive, and the number of MLNs with positive PDCs (MLNs-PDCs) was counted. Results were correlated with patient survival and comparisons made with other indications of LN status.ResultsThe mean numbers of MLNs and MLNs-PDCs were 2.8 and 1.0, respectively, and were moderately and positively correlated with each other. Univariate analysis identified cutoffs of ≥5 MLNs (86 vs. 55 %, p = 0.024), ≥2 MLNs-PDCs (85 vs. 63 %, p = 0.008), and ≥30 % LN ratio (85 vs. 44 %, p = 0.036) to indicate a positive LN status. However, no cutoff for DLNs was obtained. MLNs-PDCs (≥2) were associated with pT4 tumor (p = 0.0035), open surgery (p = 0.016), greater number of MLNs (p < 0.0001), and positive-PDC primary tumor (p < 0.0001). In multivariate analysis, a prognostic model incorporating ≥2 MLNs-PDCs provided the lowest Akaike information criterion value; consequently, both pT4 tumors (p < 0.001) and ≥2 MLNs-PDCs (p = 0.038) were revealed to be significant prognosticators.ConclusionResults showed that applying the number of MLNs-PDCs could improve stratification in pStage III CRC and may be a valuable candidate for LN status.

Predictors of Lymph Node Metastasis in Western Early Gastric Cancer

BackgroundThe application of endoscopic and local resection for early gastric cancer (EGC) is limited by the risk of regional lymph node (LN) metastasis. We sought to determine the incidence and predictors of LN metastasis in a contemporary cohort of Western patients with early gastric cancer. MethodsSixty-seven patients with pT1 gastric adenocarcinoma underwent radical surgery without neoadjuvant therapy at our institution between 1995 and 2011, and clinicopathologic factors predicting LN metastasis were analyzed. ResultsLN metastases were present in 15/67 (22 %) pT1 tumors, including 1/23 (4 %) T1a tumors and 14/44 (32 %) T1b tumors. Tumor size, site, degree of differentiation, macroscopic tumor sub-classification, perineural invasion status, and depth of submucosal tumor penetration did not predict LN metastasis. The presence of lymphovascular invasion (LVI) and positive nodal status by endoscopic ultrasound (EUS) were the only factors that predicted LN metastasis on multivariate analysis. T1a tumors without LVI had a 0 % rate of positive LN, whereas T1b tumors with LVI had a 64.3 % rate of positive LN. ConclusionsEGC limited to the mucosa, without evidence of LVI, and N0 on EUS, may be considered for limited resection. However, any EGC with submucosal invasion, LVI, or positive nodes on EUS should undergo radical resection with lymphadenectomy.

Pulmonary middle lobectomy for non-small-cell lung cancer: effectiveness and prognostic implications.

The therapeutic value of pulmonary middle lobectomy (PML) has been questioned. PML is currently regarded as a standard form of lobectomy, even so it shares some surgical features with segmentectomies (SEG) more than with lobectomies. The present study's aim was to assess the therapeutic value of PML with respect to other lobectomies (LOBs) and SEGs. A total of 902 consecutive patients who underwent lobectomy or SEG with mediastinal lymph node dissection for Stage I-IIIa non-small-cell lung cancer were analysed. Patients with pT4 tumours and/or pathologically incomplete resection were excluded. PML was performed in 50 patients, SEG in 44 and LOBs were performed in 808. The three study groups were homogeneous, except for gender, pT and grade: females, pT1 and G1 tumours were more frequent in the PML and SEG groups. The lymph node dissection yield was poorer in PML (P < 0.007) and SEG (P < 0.001) groups when compared with LOB group. Five-year overall survival (OS) was 45.3% for PML, 54.0% for SEG and 60.2% for LOB (P = 0.793). When limiting the analysis to G2-3 right-sided tumours, 5-year survival was lower in the PML group than in the LOB group: 41.3 vs 59.0% (P = 0.057). Similar results were found when analysing pT2-3 right-sided tumours: 27.3 vs 57.3% (P = 0.049). Multivariable analysis showed four independent prognostic factors: age (P = 0.001), pathological stage (P < 0.001), gender (P = 0.005) and the type of surgical resection (P = 0.029). PML (hazard ratio, HR = 1.63) and SEG (HR = 1.64) were detrimental in comparison with LOB. After adjusting for baseline differences between groups (propensity score), a trend towards a worse OS in PML group when compared with LOB group was observed (HR = 1.38, P = 0.150). Both the lymphadenectomy yield and prognosis make PML more similar to SEG than lobectomy, especially for pT2-3 or G2-3 tumours.

Erkennungshäufigkeit und Zeitraster bei der Erkennung von Melanomen durch den Patienten selbst und was bedeutet das für den Chirurgen?

Patients play an important role in the detection of their own primary tumor. But how quickly this tumor develops, over how many weeks and months is hardly known, as there is little data available. We have conducted a retrospective survey on N = 127 melanoma patients that underwent sentinel node surgery in our department and asked them whether they noticed a changing skin lesion at the site of the melanoma and if, over which period did they observed the change within the lesion. One forth of the patients did not perceive any lesion at all. The other three quarters noticed the lesion and reported a change, which in one third was taking place quickly, i.e. 0 – 3 months, in another third between 3 – 6 months and in the rest the lesion changed over years. The age and sex distribution was similar in all subgroups. The median tumor thickness was found to be highest in the subgroup with a changing lesion over 3 – 6 months. This subgroup also had the significantly highest number of pT4 tumors and the by far lowest rate of SSM type melanoma. SSM type melanoma was commonest in the lesions that changed over years, whereas nodular melanoma and ulceration was commonest in the lesions that changed over weeks. Looking at the site of the tumors in detail within all groups a comparable pattern was found, which proves that patients, that are unaware of an evolving melanoma do not miss their tumor simply because they cannot detect it at hidden sites. In summary our data shows that melanoma seems to develop very quickly in more than 50% of cases, i.e. within half a year. The most aggressive cases present with a history of mole change between 3 – 6 months. This group has the most advanced tumors. One forth of melanoma patients present with a short history of several weeks changing moles, This subgroup is likely to suffer from NMM type melanoma, a fast vertically growing subtype. This has implications for follow up recommendations for mole patients as well as it emphasizes further the need for early detection campaigns and prompt referral of patients to a mole clinic list respectively prompt appointments for excisional biopsy.

The detection of significant prostate cancer is correlated with the Prostate Imaging Reporting and Data System (PI-RADS) in MRI/transrectal ultrasound fusion biopsy.

To evaluate the performance of real-time MRI/ultrasound (MRI/US) fusion-guided targeted biopsy (TB) in men with primary and repeat biopsies and correlate the prostate cancer detection rate (CDR) with the PI-RADS score. Analysis included 408 consecutive men with primary and prior negative biopsies who underwent TB and 10-core random biopsy (RB) between January 2012 and January 2015. TB was performed with a real-time MRI/US fusion platform with sensor-based registration. Clinically significant PCa was defined as Gleason score (GS) ≥ 7 or GS 6 with maximal cancer core length ≥ 4 mm for TB and according to Epstein criteria for RB. The overall CDR was 56 % (227/408). The CDR for primary biopsy was 74 % (60/81) and 57 % (67/117), 49 % (62/126), 45 % (38/84) for patients with 1, 2 and ≥ 3 prior negative biopsies. CDRs correlated with PI-RADS 2/3/4/5 were 16 % (5/32), 26 % (29/113), 62 % (94/152) and 89 % (99/111), respectively. The rates of significant tumors in relation to PI-RADS 2/3/4/5 were 60 % (3/5), 66 % (19/29), 74 % (70/94), 95 % (94/99). In 139 (61 %) cases with radical prostatectomy (RP), the rates of ≥ pT3 tumors in correlation with PI-RADS 4 and 5 were 20 % (11/56) and 49 % (32/65). PI-RADS constituted the strongest predictor of significant PCa detection (p < 0.007). Real-time MRI/US fusion-guided TB combined with RB improved PCa detection in patients with primary and repeat biopsies. The CDR was strongly correlated with a rising PI-RADS score, values of 4 and 5 increasing the detection of clinically significant tumors and leading to a higher histological stage after RP.

Multimodality therapy for locally advanced thymomas: A propensity score–matched cohort study from the European Society of Thoracic Surgeons Database

ObjectiveThis study investigated the prognostic impact of multimodality therapies in locally advanced thymomas. MethodsFrom January 1990 to January 2010, clinicopathological, surgical, and oncological features were retrospectively reviewed in a cohort of 370 Masaoka-Koga stage III thymomas (World Health Organization classification A to B3) collected from 37 institutions. A multivariate Cox proportional hazard model was created to identify independent predictors of overall, cancer-specific (CSS), and relapse-free survivals. Furthermore, a propensity score–matching analysis for exposure to adjuvant (AT) therapy was generated. ResultsInduction therapy and AT were administered to 88 (24.9%) and 245 (69.4%) patients, respectively. Overall, 5- and 10-year overall survival, CSS, and relapse-free survivals were 82.8%, 88.4%, and 80.0%, and 68.9%, 83.3%, and 71.5%, respectively. At multivariable analysis performed in the matched cohort, AT was confirmed as the strongest predictive factor for overall survival (hazard ratio, 2.83; 95% confidence interval, 0.88-9.12; P = .08) and CSS (hazard ratio, 4.70; 95% confidence interval, 1.00-22.2; P = .05). Pathologic T classification (according to International Association for the Study of Lung Cancer and International Thymic Malignancy Interest Group TNM staging proposal) was an independent factor for relapse (hazard ratio, 8.69; 95% confidence interval, 1.08-70.04; P = .04). When CSS was adjusted for T classification, AT confirmed a significant survival advantage for pT3 tumors (P = .04). On the other hand, for thymomas larger than 5 cm, stratifying for tumor size and AT did not affect 5-year CSS (P = .17). ConclusionsOur results indicate that AT is beneficial for locally advanced thymomas, mainly for specific pathologic features (pT3 or tumor size smaller than 5 cm). Further larger studies are needed to confirm these data.

Normal Axillary Ultrasound Excludes Heavy Nodal Disease Burden in Patients with Breast Cancer.

Axillary lymph node stage is important in guiding adjuvant treatment for breast cancer. The role of axillary ultrasound (AUS) in axillary staging is uncertain. From an institutional database, all newly diagnosed invasive breast carcinomas from February 1, 2011 to October 31, 2014 were identified; exclusions were for stage IV disease, palpable adenopathy, or receipt of neoadjuvant chemotherapy. AUS findings, categorized as suspicious versus not suspicious, were correlated with the number of nodal metastasis from surgical pathology. The false-negative rate of nonsuspicious AUS for identifying ≥3 lymph nodes positive on final pathology was calculated. A total of 513 cancers were included. Overall, 400 AUSs were not suspicious (78%), and 113 were suspicious (22%). The sensitivity and specificity of AUS for predicting ≥3 nodal metastasis were 71 and 83%, respectively. The false-negative rate for detecting ≥3 nodal metastasis was 4%. False-negative rate was higher for lobular versus nonlobular carcinomas (12.0 vs. 2.3%, p = 0.004) and for pT2-pT4 tumors versus pT1 tumors (8.2 vs. 1.7 %, p = 0.005). Patients with normal axillary physical exam and ultrasound rarely harbor a large nodal disease burden. Randomized trials of sentinel lymph node biopsy versus no axillary surgery in patients with normal AUS must be powered for subgroup analysis of patients with invasive lobular carcinoma and pT2-pT4 tumors. Preoperative identification of nodal metastasis may decrease the need for second surgeries and identify candidates for neoadjuvant chemotherapy. AUS is a noninvasive means of predicting disease burden preoperatively and as such is a powerful tool to individualize treatment plans.

SIGIRR/TIR8, an important regulator of TLR4 and IL-1R–mediated NF-κB activation, predicts biochemical recurrence after prostatectomy in low-grade prostate carcinomas

Single Ig IL-1-related receptor (SIGIRR) is a negative regulator of toll-like receptor 4 and IL-1-mediated activation of nuclear factor κ-light-chain enhancer of activated B cells. The purpose of this study was to qualitatively and quantitatively determine SIGIRR protein expression in human prostate tissues and associate SIGIRR expression with clinical parameters. SIGIRR expression was quantified in glandular prostate tissue using immunohistochemistry and multispectral imaging, and expression was evaluated in relation to clinicopathological features of benign prostatic hyperplasia and prostate cancer (PCa). Subgroupings of low Gleason score (≤ 6 and 3 + 4) and high Gleason score (4 + 3 and ≥ 8) were used for patient outcomes. SIGIRR was predominantly expressed in the cytoplasm and nucleus of the prostatic epithelium with little expression within the stroma. Compared with normal prostate, cytoplasmic SIGIRR expression was similar in benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, PCa, and metastases. A decrease in nuclear expression was found in metastasis samples (P = .04). Changes in SIGIRR expression were not associated with Gleason score, pathological stage, tumor volume, surgical margin status, or serum prostate-specific antigen (P > .05). Nuclear (P = .96) and cytoplasmic (P = .89) SIGIRR expressions were not related to patient outcomes in univariable analysis, but in the analysis of patients with low Gleason scores, high cytoplasmic SIGIRR expression was associated with biochemical recurrence in both univariable (P = .01) and multivariable (hazard ratio, 2.31 [95% confidence interval 1.05-5.06]; P = .04) analyses. Similarly, in multivariable analysis of only low-stage (pT2) tumors, SIGIRR independently predicted biochemical recurrence (P = .009). We conclude that SIGIRR predicts biochemical recurrence in patients with low Gleason score and low pathological stage PCa.

The impact of preoperative axillary ultrasonography in T1 breast tumours.

To (a) determine the diagnostic validity of axillary ultrasound (AUS) in pT1 tumours and whether fine-needle aspiration (FNA) improves its diagnostic performance, and (b) determine the negative predictive value (NPV) of AUS in a simulation environment (cutoff: two lymph nodes with macrometastases) in patients fulfilling American College of Surgeons Oncology Group (ACOSOG) Z0011 criteria. This retrospective multicentre cross-sectional study analysed diagnostic accuracy in 355 pT1 breast cancers. All patients underwent AUS; visible nodes underwent FNA regardless of their AUS appearance. Sentinel node biopsy and axillary lymph node dissection (ALND) were gold standards. Data were analysed considering micrometastases 'positive' and considering micrometastases 'N negative'. The simulation environment included all patients fulfilling ACOSOG Z0011 criteria. Axillary involvement: 22.8 %; AUS sensitivity: 46.9 % (Nmic positive)/66.7 % (Nmic negative); AUS+FNA sensitivity: 52.6 % (pNmic positive)/72.0 % (pNmic negative). In the simulation environment, AUS had 75.0 % sensitivity, 88.9 % specificity and 99.2 % NPV. AUS has moderate sensitivity in T1 tumours. As ALND is unnecessary in micrometastases, considering micrometastases 'N negative' increases the practical impact of AUS. In patients fulfilling ACOSOG Z0011 criteria, AUS alone can predict cases unlikely to benefit from ALND. • AUS+FNA can predict axillary involvement, thus avoiding SNB. • Not all patients with axillary involvement need ALND. • Axillary tumour load determines axillary management. • AUS could classify patients according to axillary load.

Epigenetically altered miR-193b targets cyclin D1 in prostate cancer.

Micro-RNAs (miRNA) are important regulators of gene expression and often differentially expressed in cancer and other diseases. We have previously shown that miR-193b is hypermethylated in prostate cancer (PC) and suppresses cell growth. It has been suggested that miR-193b targets cyclin D1 in several malignancies. Here, our aim was to determine if miR-193b targets cyclin D1 in prostate cancer. Our data show that miR-193b is commonly methylated in PC samples compared to benign prostate hyperplasia. We found reduced miR-193b expression (P < 0.05) in stage pT3 tumors compared to pT2 tumors in a cohort of prostatectomy specimens. In 22Rv1 PC cells with low endogenous miR-193b expression, the overexpression of miR-193b reduced CCND1mRNA levels and cyclin D1 protein levels. In addition, the exogenous expression of miR-193b decreased the phosphorylation level of RB, a target of the cyclin D1-CDK4/6 pathway. Moreover, according to a reporter assay, miR-193b targeted the 3’UTR of CCND1 in PC cells and the CCND1 activity was rescued by expressing CCND1 lacking its 3’UTR. Immunohistochemical analysis of cyclin D1 showed that castration-resistant prostate cancers have significantly (P = 0.0237) higher expression of cyclin D1 compared to hormone-naïve cases. Furthermore, the PC cell lines 22Rv1 and VCaP, which express low levels of miR-193b and high levels of CCND1, showed significant growth retardation when treated with a CDK4/6 inhibitor. In contrast, the inhibitor had no effect on the growth of PC-3 and DU145 cells with high miR-193b and low CCND1 expression. Taken together, our data demonstrate that miR-193b targets cyclin D1 in prostate cancer.

Learning Curve of Robotic Radical Prostatectomy

Introduction: Prostate cancer (PrC) is the fifth most common malignancy worldwide and the second most common malignancy in men. Currently, robotic-assisted laparoscopic radical prostatectomy (RARP) has become a popular treatment for localised PrC treatment worldwide. We aimed to assess the learning curve of RARP in our institution. Methods: A total of 391 patients who underwent RARP in our clinic between February 2009 and April 2013 were included in the study. We retrospectively evaluated patient data that were recorded prospectively. The demographic, perioperative, postoperative functional, and oncological results of six surgeons’ patient groups (n=72, n=110, n=103, n=38, n=36, and n=32) and three consecutive series formed by dividing the patient groups of the three surgeons with the highest volume of cases were analysed. Results: There was no significant difference between patient groups with regard to age, American Society of Anesthesiologists score, preoperative International Prostate Symptom Score, International Index of Erectile Function (IIEF) score, number of previously performed operations, prostate-specific antigen levels, clinical stage, biopsy pathology, pathological stage, positive surgical margin (PSM) rate, biochemical recurrence (BCR) rate, potency, and continence rate at postoperative Month 12. When we assessed the three consecutive series of the three highest-volume surgeons we found that, over time, operation time (OT) decreased significantly (p&lt;0.001), blood transfusion rate decreased significantly (p=0.015), estimated blood loss (EBL) decreased (p&gt;0.05), and median IIEF score at 12 months improved significantly (p&lt;0.001) in the series of Surgeon 1; OT decreased significantly (p&lt;0.001), EBL decreased (p&gt;0.05), and median IIEF score at 12 months improved significantly (p=0.01) in the series of Surgeon 2; OT decreased significantly (p&lt;0.001), EBL decreased significantly (p&lt;0.001), and PSM rate decreased and median IIEF scores at 12 months improved (p&gt;0.05 for both) in the series of Surgeon 3. The overall complication rate was 11.7% and 34% of these complications were major ones. The overall blood transfusion rate was 2%. The overall PSM rate was 20.4% (9.3% for pT2 tumours and 44% for pT3 tumours). The overall rate of BCR was 9.4%. Conclusion: In our clinical experience, OT, EBL, and blood transfusion rate seem to decrease during the learning curve of RARP.