Low Risk Of Tumor Recurrence Research Articles

Challenging the Requirement to Treat the Contralateral Neck in Cases With >4 mm Tumor Thickness in Patients Receiving Postoperative Radiation Therapy for Squamous Cell Carcinoma of the Oral Tongue or Floor of Mouth.

While treating patients with postoperative radiotherapy (RT) for squamous cell carcinoma of the oral tongue or floor of mouth, we hypothesized a low risk of tumor recurrence in the contralateral neck in the absence of contralateral neck RT when the primary tumor is >1 cm from the midline regardless of tumor thickness (TT) or depth of invasion (DOI)>4 mm. The policy at our institution for many years has been to limit postoperative RT to the ipsilateral side when the primary tumor does not cross the midline, regardless of TT or DOI. We report the rate of isolated contralateral neck failure in this group. We retrospectively reviewed all patients treated with postoperative RT at our institution between 1998 and 2014 for pathologic stage T1-T4 N1-N2b squamous cell carcinoma of the oral tongue or floor of mouth that did not cross the midline and thus were treated with RT limited to the primary site +/- ipsilateral neck. Our study population included 32 patients: 75% with close (<5 mm) or positive margins and 38% with perineural invasion. No patients had a tumor that crossed the midline. TT was ≥4 mm in 75% of patients. DOI was >5 mm in 68% of patients. There were no isolated contralateral neck recurrences with a median follow-up of 5 years. While delivering postoperative RT for oral tongue or floor of mouth cancer with pathologic neck stage N0-2b, the risk of not irradiating the contralateral neck is very low when the primary tumor does not cross the midline, regardless of other factors at the primary site, such as TT and DOI.

The role of programmed death ligand-1 and tumor-infiltrating lymphocytes in breast cancer overexpressing HER2 gene.

The purpose of the study is to investigate the prognostic significance of programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in HER2+ breast cancer (BC). HER2+ BC cases (n=191) were collected between 1996 and 2013. Tissue microarray (TMA) slides were stained with two clones of PD-L1 antibodies (28-8 and 22C3) and the percentage of positive membranous staining was scored. TILs of the full sections were also scored using percentage scale. Clone 28-8 had expression in ≥1% of the tumor cells in 25.7% of the cases, while clone 22C3 in ≥1% of the tumor cells was expressed in 11.5% of the cases. In the multivariate analysis, higher expression of PD-L1 (clone 28-8) in tumor correlated with lower risk of tumor recurrence, with HR of 0.4 (p= 0.033). Higher level of TILs (> 15%) predicts better overall survival (OS) in all patients with HR of 0.35 (p = 0.0046). In the group of patients who were treated with trastuzumab-based adjuvant chemotherapy, lower PD-L1 (clone 28-8) expression in TILs correlated with tumor recurrence (p = 0.034). In the group of patients who were treated with non-trastuzumab-based adjuvant chemotherapy,lower TILs and lower PD-L1 (clone 28-8) expression in tumor had borderline statistical significance in association with tumor recurrence (p = 0.064 and 0.083, respectively). In the group of patients who were treated with trastuzumab-based adjuvant chemotherapy, PD-L1 or TILs was not statistically significant to predict 5-year survival. In the group of patients who were treated with non-trastuzumab-based adjuvant chemotherapy, low TILs (p= 0.009) correlated with 5-year death due to disease. We conclude that PD-L1 may have prognostic significance in HER2+ BCs.

Long-Term Outcome After Liver Transplantation for Hepatocellular Carcinoma Following Yttrium-90 Radioembolization Bridging Treatment.

BackgroundBridging treatments are employed in liver transplant waitlist patients with hepatocellular carcinoma (HCC) because of the risk of tumor progression during the waiting time. Radioembolization is mostly employed in the control of large or multifocal HCCs when other locoregional treatment modalities cannot be applied because of the number or size of lesions. The purpose of this study was to evaluate our experience with the use of radioembolization as a bridge to transplantation and its effect on tumor recurrence and survival after liver transplantation.Material/MethodsA retrospective review of 40 consecutive patients with HCC who underwent liver transplantation after radioembolization bridging treatment between January 2007 and December 2015 at the University Hospital Essen, Germany, was performed. Patients’ characteristics, alpha-fetoprotein (AFP) levels, pathologic tumor response, tumor recurrence rate, and survival rates were examined through chart review.ResultsHistopathological examination of the explanted liver specimen revealed complete tumor necrosis in 17 specimens, partial necrosis in 18 specimens, and no significant necrosis in five specimens. Median overall survival was 46 months. Nine patients developed recurrent HCC. Median time from liver transplantation to diagnosis of tumor recurrence was 15 months. There was a trend towards a lower risk of tumor recurrence for patients with complete necrosis on explant specimens. Patients with tumor recurrence demonstrated statistically significantly higher pre- and post-treatment AFP levels (p=0.0234 and p=0.0236) and statistically significantly more frequently microvascular invasion (p=0.0163).ConclusionsHistopathological assessment of explanted livers revealed at least partial necrosis in 87.5% of patients. Patients with successful bridging treatment, i.e. complete necrosis of explant specimens, demonstrate a trend towards a lower risk of tumor recurrence.

The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma.

Different clinical presentations and prognoses have been implied between pancreatic head and body/tail cancers. We aimed to identify the prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). Thirty-two pairs of patients with strictly matched early stage (II) pancreatic head and body/tail cancers were enrolled. The molecular feature of the two subtypes of PDAC was assessed on the level of miRNA expression. Out of the 64 patients, 34 (53.1%) had tumor recurrence after radical resection during the follow-up period (2.3 ± 0.8 years). Both overall and tumor-free survival were significantly higher in the patients with pancreatic body/tail cancer compared with those with pancreatic head cancer. Patient age and tumor location were the independent prognostic factors for tumor recurrence. A remarkably lower expression of miR-501-3p and higher expression of miR-375 were found and were further verified in pancreatic body/tail cancer tissues compared with pancreatic head cancer tissues. The low expression of miR-501-3p was significantly associated with a low risk of tumor recurrence. Both, subcutaneous and orthotopic PDAC mouse models presented highly invasive tumor phenotypes upon up-regulated miR-501-3p expression. An in vitro study showed that miR-501-3p promoted the invasiveness of PDAC cells possibly via suppressing E-cadherin. In summary, at resectable early stage, pancreatic body/tail cancer presents a less malignant phenotype associated with deregulation of miR-501-3p compared with pancreatic head cancer.

Impact of smoking status and cumulative smoking exposure on tumor recurrence of non-muscle-invasive bladder cancer.

To investigate the effect of smoking status, cumulative smoking exposure and smoking cessation on the outcomes of patient with non-muscle-invasive bladder cancer (NMIBC). We collected smoking data from 484 patients with NMIBC who were treated with transurethral resection (TUR); smoking status was categorized as (never smokers vs current smokers vs former smokers). Cumulative smoking exposure was categorized as high smoking exposure (cigarette index≥400) versus low smoking exposure (cigarette index<400). Association with outcomes was examined by multivariable analyses after adjusting for the effects of standard clinicopathologic factors, and the Kaplan-Meier method was used to estimate the effect of smoking status and cumulative smoking exposure on RFS. A total of 168 (34.7%) patients were never smoker, 121 (25%) patients were current smokers, and 195 (40.3%) patients were former smokers. The median follow-up was 25months. By multivariate analysis, pathological grade (p=0.013), history of recurrence (p<0.001), number of tumors (p<0.001) and size of tumors (p=0.013) were significantly associated with tumor recurrence; nevertheless, smoking status did not influence tumor recurrence (p=0.063). Among current and former smokers, cumulative smoking exposure was significantly associated with tumor recurrence (p<0.001), compared to current smokers, patients with smoking cessation ≥10years had a lower risk of tumor recurrence [hazard ratio (HR) 0.456, p=0.007]. Smoking affects the prognosis of patient with NMIBC, which is still controversial; however, among ever smokers, a high cumulative exposure smoking can significantly increase the risk of tumor recurrence. Quitting smoking might be associated with a lower recurrence rate for patients with NMIBC.

Effect of oral antiviral treatment on long-term outcomes of radiofrequency ablation therapy for hepatitis B virus-related hepatocellular carcinoma.

ObjectivesThis study aimed to investigate the effect of oral antiviral treatment on the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after radiofrequency (RF) ablation.MethodsBetween January 2003 and December 2010, 228 patients without a history of antiviral treatment were treated with RF ablation for a single HBV-related HCC. We divided the patients into two groups, patients who received (n=125) or did not receive antiviral treatment (n=103), based on whether oral antiviral treatment was administered after RF ablation. The median duration of antiviral treatment was 60.1 months. HCC recurrence and overall survival were compared in the two groups in the full cohort and the propensity score-matched cohort.ResultsIn the matched cohort, the probability of HCC recurrence at 5 years was 43.8% for the non-antiviral treatment group and 14.7% for the antiviral treatment group (p<0.001). The probability of overall survival at 5 years was 77.2% for the non-antiviral treatment group and 93.5% for the antiviral treatment group (p=0.002). Multivariable analysis showed that risk factors for HCC recurrence included large tumor size (hazard ratio (HR)=1.30, p=0.022), HBV DNA serum level (HR=1.11, p=0.005), and serum AFP level ≥20 ng/mL (HR=1.66, p=0.005). Overall survival was associated with larger tumor size (HR=1.86, p=0.001) and Child-Pugh Class B (HR=2.13, p=0.019). Oral antiviral treatment after RF ablation was significantly associated with a lower risk of tumor recurrence and death (HR=0.33, p<0.001, and HR=0.44, p=0.004).ConclusionUse of oral antiviral treatment after curative RF ablation was associated with favorable outcomes in terms of tumor recurrence and overall survival in patients with HBV-related HCC.

Tumors of the peripheral nervous system: analysis of prognostic factors in a series with long-term follow-up and review of the literature.

OBJECT Only a few published studies of the surgical treatment of benign peripheral nerve sheath tumors (BPNSTs), malignant peripheral nerve sheath tumors (MPNSTs), and peripheral non-neural sheath tumors (PNNSTs) have analyzed the results and possible prognostic factors using multivariate analysis. The authors report on their surgical series of cases of BPNSTs, MPNSTs, and PNNSTs with long-term follow-up and analyze the role of selected factors with respect to the prognosis and risk of recurrence of these tumors using multivariate analysis. They also review the pertinent literature and discuss their results in its context. METHODS The authors retrospectively reviewed data from cases involving patients who underwent resection of a peripheral nerve tumor between January 1983 and December 2013 at their institution. Of a total of 200 patients, 150 patients (with 173 surgically treated tumors) had adequate follow-up data available for analysis. Pain was assessed using a visual analog scale (VAS), and motor and sensory function were assessed by means of the Louisiana State University grading system. They also analyzed the relationship between tumor recurrence and patient sex, patient age, diagnosis of neurofibromatosis (NF), tumor histopathology, tumor size, tumor location, and extent of resection (subtotal vs gross-total resection), using univariate and multivariate analyses. RESULTS There was a statistically significant improvement in the mean VAS pain score (preoperative 3.96 ± 2.41 vs postoperative 0.95 ± 1.6, p = 0.0001). Motor strength and sensory function were significantly improved after resection of tumors involving the brachial plexus (p = 0.0457 and p = 0.0043, respectively), tumors involving the upper limb (p = 0.0016 and p = 0.0016, respectively), BPNSTs (p = 0.0011 and p < 0.0001, respectively), and tumors with dimensions less than 5 cm (motor strength: p = 0.0187 and p = 0.0021 for ≤ 3 cm and 3-5 cm tumors, respectively; sensory function: p = 0.0003 and p = 0.0001 for ≤ 3 cm and 3-5 cm tumors, respectively). Sensory function showed a statistically significant improvement also in patients who had undergone resection of tumors involving the lower limb (p = 0.0118). Total resection was associated with statistically significant improvement of motor strength (p = 0.0251) and sensory function (p < 0.0001). In univariate analysis, a history of NF (p = 0.0034), a diagnosis of MPNST or PNNST (p < 0.0001), and subtotal resection (p = 0.0042) were associated with higher risk of tumor recurrence. In multivariate analysis (logistic regression analysis), a history of NF (OR 9.28%, 95% CI 1.62-52.94, p = 0.0121) and a diagnosis of MPNST (OR 0.03%, 95% CI 0.002-0.429, p = 0.0098) or PNNST (OR 0.081%, 95% CI 0.013-0.509, p = 0.0077) emerged as independent prognostic factors for tumor recurrence. CONCLUSIONS A total resection should be attempted in all cases of peripheral nervous system tumors (irrespective of the supposed diagnosis and tumor dimensions) because it is associated with better prognosis in term of functional outcome and overall survival. Moreover, a total resection predicts a lower risk of tumor recurrence. Patients with a history of NF and tumors with malignant histology remain a challenge both for neurosurgeons and oncologists due to higher recurrence rates and the lack of standardized adjuvant therapies.

Prognostic Factors and Clinical Characteristics for Hepatocellular Carcinoma Patients with Benign Enlarged Perihepatic Lymph Nodes: a Single-Center Experience from China

BackgroundThe clinical and prognostic significance of benign perihepatic lymph nodes enlargement (PLNE) from patients with hepatocellular carcinoma (HCC) remains unclear. The objective of this study is to evaluate the relative frequency, incidence and locations of benign PLNE, and the impact on long-term survival of the patients. MethodsA total of 219 consecutive patients who underwent curative resection of HCC between July 2006 and March 2012 in our single institution were divided into two groups according to the presence of PLNE: PLNE group (n = 76), and control group (n = 143). The long-term outcomes were evaluated and compared between the two groups. ResultsThe 1-, 3-, and 5-year recurrence-free survival rates were 77.2, 60.0, and 38.1 % in the PLNE group and 71.3, 42.5, and 25.0 % in the control group (p = 0.080). Corresponding overall survival rates were 96.0, 84.8, 67.1 % and 93.5, 72.4, 46.9 % respectively (p = 0.041). Patients with benign PLNE were associated with a higher rate of centrally located HCCs or tumors adjacent to the major branch of vascular vessels. Multivariate analysis revealed that benign PLNE was an independent positive prognostic factor affecting the overall survival. ConclusionsAccording to our analysis, patients of HCC with benign PLNE after curative resection can be expected to have better long-term survival. It is also associated with a lower risk of tumor recurrence, but not significant. This finding may provide new insights into daily clinical practice and the pathophysiological characteristics of HCC development.

Recurrent Hepatocellular Carcinoma: It's the Virus!

influence the incidence of HCC recurrence, antiviral treatment and preoperative serum HBV DNA were found to have a significant impact on postoperative recurrence and subsequent death. While these results, particularly those of the randomized trial, are exciting and significant, the study has limitations. Inexplicably, the randomization failed to balance important aspects of the two study arms. Patients who were assigned to no antiviral treatment had a significantly higher proportion of incomplete or no tumor encapsulation (73% v 53%), poor differentiation (81 v 62%) and increased serum alpha fetoprotein ( 20 ng/mL, 72% v 57%). On the other hand, patients who were assigned to receive antiviral therapy were enriched with uninodular tumors (88% v 72%), small ( 3 cm) lesions (14% v 6%), and low Barcelona Clinic Liver Cancer stage tumors (0 or A, 88% v 73%), although these differences did not reach statistical significance. These characteristics place patients in the antiviral group at a lower risk of tumor recurrence with a potential for clinical benefits associated with antiviral therapy. A subsequent post hoc multivariable analysis may not necessarily correct the inherent differences between the two arms. As one considers the validity of the conclusion of the study and questions how antiviral therapy may reduce the incidence of HCC, it is

Presentation and surgical results of incidentally discovered nonfunctioning pituitary adenomas: evidence for a better outcome independently of other patients' characteristics

Few data are available on the surgical results in patients with incidentally discovered nonfunctioning pituitary adenoma (NFPA). We investigated the efficacy and safety of surgery in patients with incidentally discovered NFPA. Retrospective analysis of prospectively recorded outcomes. From 1990 to 2011, of 804 consecutive patients undergoing surgery for NFPA, 212 cases had an incidentally discovered tumor (26.4%). Among them, 117 patients were asymptomatic, while 95 had some visual and/or hormonal deficit. The main outcome of the study was to evaluate the frequency of radical resection as judged on the first postoperative neuroimaging study and detection of recurring disease during long-term follow-up. Postoperative residual tumor was detected in 8.9% of patients with asymptomatic incidentalomas as compared with 31.2% of patients with symptomatic incidentalomas (P<0.001) and 41.2% of patients in the control group (P<0.001). Multivariate analysis confirmed that having an asymptomatic incidentaloma was independently associated with a better outcome. The 5-year recurrence-free survival in patients with incidentaloma was 86.8% (95% CI 80.2-92.4%) as compared with 77.9% (95% CI 73.6-82.2%; P<0.01) in the control group. This difference was almost completely due to a lower frequency of relapse in asymptomatic patients. Multivariate analysis confirmed the independent lower risk of tumor recurrence in asymptomatic NFPA. Our study shows for the first time that surgically treated patients with asymptomatic NFPA have a better early and long-term outcome that is independent from all the other demographic, clinical, and morphologic characteristics of the patients.

Predicting time to ovarian carcinoma recurrence using protein markers

Patients with ovarian cancer are at high risk of tumor recurrence. Prediction of therapy outcome may provide therapeutic avenues to improve patient outcomes. Using reverse-phase protein arrays, we generated ovarian carcinoma protein expression profiles on 412 cases from TCGA and constructed a PRotein-driven index of OVARian cancer (PROVAR). PROVAR significantly discriminated an independent cohort of 226 high-grade serous ovarian carcinomas into groups of high risk and low risk of tumor recurrence as well as short-term and long-term survivors. Comparison with gene expression-based outcome classification models showed a significantly improved capacity of the protein-based PROVAR to predict tumor progression. Identification of protein markers linked to disease recurrence may yield insights into tumor biology. When combined with features known to be associated with outcome, such as BRCA mutation, PROVAR may provide clinically useful predictions of time to tumor recurrence.

Minimally invasive treatment of laparoscopic and endoscopic cooperative surgery for patients with gastric gastrointestinal stromal tumors

To evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery (LECS) for the treatment of gastric gastrointestinal stromal tumors (GISTs). We retrospectively reviewed the data of 69 consecutive patients who underwent LECS, including laparoscopy-assisted endoscopic resection (LAER) and endoscopy-assisted laparoscopic wedge resection (EAWR), for pathologically confirmed gastric GISTs of less than 5 cm in diameter from January 2006 to October 2012. The tumor was located at the upper third of the stomach in 22 patients, the middle third in 38 and the lower third in nine, with a mean tumor size of 2.8 ± 1.6 cm. The operating time was 81.6 ± 31.8 min in the LAER group and 86.3 ± 28.5 min in the EAWR group (P = 0.776). Intraoperative blood loss was 29.8 ± 15.4 mL in the LAER group and 31.4 ± 11.6 mL in the EAWR group (P = 0.561). Most patients had a very low or low risk of tumor recurrence, while six had an intermediate risk of tumor recurrence. The mean length of postoperative hospital stay was 4.6 days. Only two patients had postoperative complications after LECS, both of whom were treated successfully without open surgery. During a median follow-up of 35 months, all patients were disease-free, with no tumor recurrence or metastases. LECS is a minimally invasive and safe alternative approach which can achieve fast recovery and satisfactory short-term outcomes for appropriately selected patients with gastric GISTs.

Prognostic factor for Korean patients with renal cell carcinoma and venous tumor thrombus extension: application of the new 2009 TNM staging system

To study the surgical outcomes of radical nephrectomy with thrombectomy and to determine prognostic factors for survival of Korean patients with renal cell carcinoma (RCC) and venous tumor thrombus. A total of 124 patients with RCC and venous tumor thrombus who underwent radical nephrectomy and thrombectomy were included in this retrospective study. Cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were analyzed retrospectively according to various prognostic factors. The median overall follow-up period for all patients was 29.0 months; the median survival period was 50.0 months. The 2-, 5- and 10-year CSS rates for all patients were 64.2%, 47.1% and 31.7%, respectively. Those for 76 patients (pN0/xM0) without metastasis at presentation were 80.9%, 64.5% and 44.9%, respectively. For all patients, lower body mass index (BMI), higher Fuhrman grade, presence of symptoms, perinephric fat invasion, invasion of inferior vena cava (IVC) wall, lymph node (LN) involvement and distant metastasis at presentation were independent predictors for decreased CSS on multivariate analysis, while thrombus level was not. For non-metastatic patients, lower BMI, presence of symptoms and tumor size were independently associated with decreased CSS. In terms of RFS, lower BMI, presence of perinephric fat invasion were prognostic factors for recurrence. Our data suggest that obesity is independently associated with better survival or lower risk of tumor recurrence in Korean patients undergoing radical nephrectomy with tumor thrombectomy. Also, our results indicate that Fuhrman grade, presence of symptoms, perinephric fat invasion and invasion of IVC wall, LN involvement and distant metastasis at presentation are independent predictors for survival.

Contemporary Strategies in the Management of Hepatocellular Carcinoma

Liver transplantation is the treatment of choice for selected patients with hepatocellular carcinoma (HCC) on a background of chronic liver disease. Liver resection or locoregional ablative therapies may be indicated for patients with preserved synthetic function without significant portal hypertension. Milan criteria were introduced to select suitable patients for liver transplant with low risk of tumor recurrence and 5-year survival in excess of 70%. Currently the incidence of HCC is climbing rapidly and in a current climate of organ shortage has led to the re-evaluation of locoregional therapies and resectional surgery to manage the case load. The introduction of biological therapies has had a new dimension to care, adding to the complexities of multidisciplinary team working in the management of HCC. The aim of this paper is to give a brief overview of present day management strategies and decision making.

Des-γ-carboxy prothrombin and c-Met were concurrently and extensively expressed in hepatocellular carcinoma and associated with tumor recurrence

The aim of this study was to investigate co-expression of des-γ-carboxy prothrombin (DCP) and c-Met in hepatocellular carcinoma (HCC) and its significance in predicting tumor recurrence after surgical resection. Immunohistochemical techniques were used to examine DCP and c-Met expression in HCC samples collected from 153 patients. DCP and c-Met staining were observed in tumor areas in 63.4% (97/153) and 66.7% (102/153) of patients, respectively, and these figures are markedly higher than the rates at which adjacent nontumorous areas tested positive of 13.1% (20/154) and 28.8% (44/153). Furthermore, DCP and c-Met were consistently present or absent in HCC regions in 51.0% (78/153) and 20.9% (32/153) of patients, in adjacent nontumorous regions in 7.2% (11/153) and 65.4% (100/153) of patients, and in whole regions including HCC and adjacent nontumorous regions in 58.2% (89/153) and 19.6% (30/153) of patients. These results indicate that DCP and c-Met usually appeared or disappeared in HCC in a parallel manner. c-Met was found to be related to tumor recurrence in patients with HCC. When combined with DCP, c-Met is more effective at predicting non-recurrence of HCC than c-Met alone. Expression of neither DCP nor c-Met in HCC regions and adjacent regions signified a low rate of tumor recurrence after surgical resection. Results of the current study suggested that DCP and c-Met are commonly and concurrently expressed in HCC and their absence is associated with a low risk of tumor recurrence.

筋層非浸潤性膀胱癌における経尿道的膀胱腫瘍切除術（TURBT）後塩酸ピラルビシン（THP）3日間連続膀胱内注入療法の膀胱内再発に関する検討

We estimated the results of 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) following transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer retrospectively. Through March 1995 to April 2009, a total of 184 patients were instilled 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) (30 mg/40 ml in disinfected distilled water) started within a few hours after TURBT. 184 patients were diagnosed as untreated fresh non-muscle-invasive urothelial bladder cancer with no concomitant carcinoma in situ (CIS), no concurrent upper urinary tract urothelial cancer and no past history of upper urinary tract urothelial cancer. Number of tumors, tumor size, tumor grade and clinical tumor stage were analyzed in relation to tumor recurrence by univariate and multivariate analyses. Median follow-up were 55.1 months. Using EAU guideline on non-muscle invasive urothelial carcinoma of the bladder, 168 patients were classified at intermediate risk of tumor recurrence, 14 patients were at low risk of tumor recurrence and 2 patients were at high risk of tumor recurrence. The shape of non-recurrence rate curve showed two phase decrease pattern, namely, early hasty decrease within 1.5 or two years and late gentle decrease thereafter. The 1, 2, 3, 5-year non-recurrence rate were 82.7%, 75.3%, 72.3% and 67.4% respectively. The 3-year non-recurrence rate of low score group (recurrence score 1-3) at intermediate risk of tumor recurrence was 85.3%. Univariate analysis revealed that number of tumors, tumor grade and clinical tumor stage were related to tumor recurrence (p<0.05). By multivariate analysis, number of tumors and clinical tumor stage were related to tumor recurrence (p<0.05). In patients of low score group at intermediate risk of tumor recurrence without grade 3 urothelial carcinoma and concomitant bladder CIS, 3-day consecutive intravesical instillation of pirarubicine hyorochloride (THP) following TURBT for non-muscle-invasive bladder cancer would be a significant adjuvant therapy. But in patients of high score group at intermediate risk of tumor recurrence, it seemed better to do additional maintenance intravesical chemotherapy or intravesical BCG therapy.

The Effect of Metformin on Responses to Chemotherapy and Survival in Stage IV Colorectal Cancer with Diabetes

Metformin is known to lower the risk of cancer and cancer mortality. However, the effect of metformin in stage IV colorectal cancer (CRC) patients with diabetes mellitus (DM) remains unknown. The aim of this study was to evaluate the effect of metformin on tumor response and survival in stage IV CRC patients with DM. We identified 106 patients who were diagnosed with both stage IV CRC and DM (81 patients who underwent palliative chemotherapy and 25 patients who underwent curative resection). Retrospective data of each patient's clinical characteristics, tumor response, and survival rate were compared between two groups of patients who either were or were not administered metformin. For the palliative chemotherapy group, tumor response, change in target lesion size, progression free survival rate, and overall survival rate were not significantly different between the metformin group and the non-metformin group on univariate and multivariate analysis. For the curative resection patient group, metformin use was associated with increased disease free survival on univariate analysis (p=0.012) and multivariate analysis (hazard ratio, 0.024; 95% CI 0.001-0.435; p=0.010), but not with overall survival. Metformin use in stage IV CRC patients with diabetes was shown to be associated with a lower risk of tumor recurrence after curative resection.

Rate of Tumor Growth Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation in Patients Beyond Milan or UCSF Criteria

Background It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC). Methods We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr 3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed. Results Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7–30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P = .001), poorly differentiated tumors (HR 13; P = .039), the presence of microvascular invasion (HR 7.9; P = .001), higher TTV (HR 1.03; P < .001), and faster tumor growth (HR 1.09; P < .001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm 3/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth <1.61 cm 3/mo experienced less recurrence (11% vs 58%; P = .023) than those beyond the Milan criteria with tumor growth >1.61 cm 3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria. Conclusions Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.

High expression of microRNA-15b predicts a low risk of tumor recurrence following curative resection of hepatocellular carcinoma

MicroRNAs (miRNA) have recently been implicated in carcinogenesis and tumor progression. Hepatocellular carcinoma (HCC) is well known for frequent relapses following curative resection. We attempted to identify the miRNAs associated with HCC recurrence. We analyzed miRNA expression profiles in 25 pairs of HCC and adjacent non-tumor liver tissues from HCC patients using miRNA microarray. Out of 449 miRNAs assayed, we identified seven miRNAs associated with HCC recurrence. In particular, the highest ranked miR-15b was negatively correlated with recurrence. MiR-15b inhibitor transfection increased HCC cell proliferation and inhibited TRAIL-induced apoptosis, while miR-15b precursor transfection decreased proliferation and enhanced apoptosis. Bcl-w was identified as a target molecule regulated by miR-15b. These results indicate that miR-15b expression in HCC tissues may predict a low risk of HCC recurrence. In addition, the modulation of miR-15b expression may be useful as an apoptosis-sensitizing strategy for HCC treatment.

Intracranial Schwannomas of the Lower Cranial Nerves

To present our experience in the diagnosis and management of 39 patients with lower cranial nerve schwannomas of the posterior fossa. A retrospective chart review of patient medical records. Tertiary care, academic medical center. All patients with intracranial lower cranial nerve schwannomas treated surgically in our institution between July 1998 and July 2005. A retrosigmoid, transcondylar, or combined approach was used for tumor recurrence. Thirty-nine patients underwent surgical resection, with complete tumor removal in 32, near-total resection in 5 patients, and subtotal tumor excision in 2 patients. Long-term (mean, 8.2 years) magnetic resonance imaging surveillance demonstrated recurrent tumor in 2 of 32 complete resections and slow regrowth in 2 of 7 patients with known residual disease. Only one of these four patients required reoperation. Intracranial schwannomas of the lower cranial nerves are relatively uncommon and may present with subtle or no clinical symptoms. Successful surgical resection with low risk of tumor recurrence can be achieved with the retrosigmoid or transcondylar approach. Morbidity, in this series, was primarily related to lower cranial nerve deficits.