BACKGROUND: Merkel cell carcinoma (MCC) is an unusual primary neuroendocrine carcinoma of the skin. MCC is a fatal disease, and patients have a poor chance of survival. Moreover, MCC lacks distinguishing clinical features, and thus by the time the diagnosis is made, the tumour usually have metastasized. MCC mainly affects sun-exposed areas of elderly persons. Half of the tumours are located in the head and neck region. METHODS: MCC was first described in 1972. Since then, most of the cases reported, have been in small series of patients. Most of the reports concern single cases or epidemiological studies. The present study reviews the world literature on MCC. The purpose of this article is to shed light on this unknown neuroendocrine carcinoma and provide the latest information on prognostic markers and treatment options. RESULTS: The epidemiological studies have revealed that large tumour size, male sex, truncal site, nodal/distant disease at presentation, and duration of disease before presentation, are poor prognostic factors. The recommended initial treatment is extensive local excision. Adjuvant radiation therapy has recently been shown to improve survival. Thus far, no chemotherapy protocol have achieved the same objective. CONCLUSION: Although rare, the fatality of this malignancy makes is important to understand the etiology and pathophysiology. During the last few years, the research on MCC has produced prognostic markers, which can be translated into clinical patient care.
Background: Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various cancers. The aim of this study was to determinate the prognostic value of the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) in patients with esophageal squamous cell carcinoma (ESCC). Methods: Preoperative NLR and PLR were evaluated in 483 patients undergoing esophagectomy for ESCC from January 2005 to December 2008. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. Receiver operating characteristic (ROC) curves were also plotted to verify the accuracy of NLR and PLR for survival prediction. Results: High preoperative NLR (>= 3.5 versus < 3.5, P = 0.039) and PLR (= 150 versus < 150, P < 0.001) were significantly associated with poor overall survival in multivariate analysis. However, our study demonstrated a better discrimination for the PLR in terms of hazard ratio(HR) than the NLR (HR = 1.840 versus HR = 1.339). Patients with NLR = 3.5 had significantly poorer overall survival compared to NLR < 3.5 (35.4% versus 57.7%, P < 0.001). Patients with PLR = 150 also had significantly poorer overall survival compared to patients with PLR < 150 (32.7% versus 63.5%, P < 0.001). The area under the curve (AUC) was 0.658 (95% confidence interval (CI): 0.610 to 0.706, P < 0.001) for NLR and 0.708 (95% CI: 0.662 to 0.754, P < 0.001) for PLR, indicating that PLR was superior to NLR as a predictive factor in ESCC. Conclusions: Preoperative NLR and PLR were significant predictors of overall survival in patients with ESCC. However, PLR is superior to NLR as a predictive factor in patients with ESCC.
Background: Altered expression of serum microRNAs (miRNAs) have been reported to correlate with carcinogenesis and progression of pancreatic adenocarcinoma (PC), but descriptions of serum exosomal miRNAs in PC are still lacking. This study was designed to evaluate serum exosomal miRNA levels in PC patients and to investigate their relationships with clinicopathologic features and prognosis. Methods: Four miRNAs (miR-17-5p, miR-21, miR-155 and miR-196a) related to PC were selected for examination in our research. Serum miRNA was examined by RT-PCR in a group of 49 patients, including 22 with PCs, 6 with benign pancreatic tumors, 7 with ampullary carcinomas, 6 with chronic pancreatitis and 8 healthy participants. The clinicopathologic data were also collected, and PC patients were classified according to the presence of metastasis, tumor differentiation and advanced stage. Results: There were low expressions of exosomal miR-155 and miR-196a in serum samples of PC patients when U-6 was used as a control. Serum exosomal miR-17-5p was higher in PC patients than in non-PC patients and healthy participants. High levels of miR-17-5p were significantly correlated with metastasis and advanced stage of PC. The serum exosomal miR-21 level in PC was higher than that in the normal and chronic pancreatitis groups, but was not significantly correlated with PC differentiation and tumor stage. Conclusions: There were high expressions of serum exosomal miR-17-5p and miR-21 in PC patients. Examination of serum exosomal microRNA is a useful serum biomarker for PC diagnosis other than serum-free microRNA. It is postulated that exosomal miR-17-5p participates in the progression of PC.
Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. It has been proved to be safe and feasible if performed as an exclusive treatment in patients affected by peritoneal carcinomatosis. The first results in patients treated with PIPAC associated with systemic chemotherapy are presented. Methods: Between June 2015 and February 2016, 57 PIPAC applications with oxaliplatin or cisplatin + doxorubicin every 6 weeks at 37 degrees C and 12 mmHg for 30 min were performed. Forty PIPAC procedures performed in 14 patients were included in this study; thirteen patients were undergoing systemic chemotherapy with a wash-out interval of at least 2 weeks before and 1 week after each PIPAC. Safety, tolerability, and postoperative complications were assessed by collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) 2. Results: Forty PIPAC administrations were performed in 14 patients with no major perioperative complications. CTCAE grades 1 and 2 were observed after six and eight procedures, respectively, for abdominal pain and nausea. Renal and hepatic functions were not impaired; no cumulative renal toxicity was observed after repeated PIPAC procedures in association with systemic chemotherapy. Conclusions: These preliminary data show that the association of PIPAC and systemic chemotherapy does not induce significant hepatic and renal toxicity. It allows inclusion of patients with extraperitoneal disease or at a high risk of developing it. Further studies are needed to assess whether this combination therapy could become part of the standard treatment for peritoneal carcinomatosis.
Background: To investigate the prediction value of preoperative serum alpha-fetoprotein (AFP) level for the prognosis of hepatocellular carcinoma (HCC), by comparing pathological characteristics, recurrence rate and survival rate after hepatectomy. Methods: 108 cases of HCC patients who received liver resection in our hospital from 2005 to 2011 were enrolled in this study. According to preoperative serum AFP level, the patients were divided into AFP 400 ng/mL group, and the clinicopathological and cytopathological features were compared. All the patients were followed up for 24 months, the postoperative recurrence rates and survival rates were compared and analyzed, and the risk factors for HCC postoperative survival rate were studied by multifactor regression analysis. Results: Of the 108 cases of HCC patients, there were 42 cases in AFP 400 ng/mL group. It was shown that cell differentiation degrees (chi(2) = 20.198, P = 0.000) and microvascular invasion rates (chi(2) = 20.358, P = 0.000) were significantly different among the three groups. The AFP = 5 cm) and preoperative serum AFP level (> 400 ng/mL) were closely correlated with HCC postoperative survival rate (P < 0.05). Conclusions: It is shown that preoperative serum AFP level has considerable predictive value for the malignant feature and prognosis of HCC. It is suggested that HCC patients with no contraindication of operation and serum AFP <= 20 ng/mL can benefit most from primary treatment of hepatectomy. While HCC patients with serum AFP higher than 20 ng/mL need comprehensive therapy besides surgical resection and close follow up.
Background: Long noncoding RNAs (lncRNAs) have been proved to play important roles in the tumorigenesis and development of human hepatocellular carcinoma (HCC). The aim of our study is to investigate the expression and function of BRAF-activated noncoding RNA (BANCR) in HCC. Methods: BANCR expression was detected in HCC tissues and cell lines by using quantitative real-time PCR (qRT-PCR). Association between BANCR levels and clinicopathological factors and patient prognosis was also analyzed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometry, and transwell invasion and migration assays were used to investigate the role of BANCR in the regulation of biological behaviors of HCC cells. Results: BANCR expression was remarkably increased in HCC tissues compared with adjacent noncancerous tissues (P < 0.001). BANCR expression in four HCC cell lines was also significantly upregulated (P < 0.05). Clinicopathologic analysis revealed that high BANCR expression correlated with high tumor grade, large tumor size, venous infiltration, advanced tumor, node, and metastasis (TNM) stage, and shorter overall survival. Multivariate regression analysis identified BANCR overexpression as an independent unfavorable prognostic factor (relative risk [RR] 4.245; P = 0.015) in HCC patients. Moreover, BANCR downregulation in Hep3B cells impaired cell proliferation, promoted cell apoptosis, reduced cell invasion and migration, led to downregulated vimentin, and upregulated E-cadherin protein levels. Conclusions: These findings suggested that BANCR may contribute to HCC initiation and progression and would be used as not only a novel prognostic marker but also a potential therapeutic target for this disease.
Background: Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play essential roles in the occurrence and development of human cancers, including gastric cancer (GC). However, the functional and clinical significance of lncRNAs are still poorly understood. Methods: In this study, the expression of LncRNA HNF1A antisense RNA 1 (HNF1A-AS1) was first examined by lncRNAs microarray analysis in 6 GC tissues, and was then further verified by real-time quantitative reverse transcription PCR (qRT-PCR) both in 3 GC cell lines and 161 cases of GC tissues. We also evaluated the association between HNF1A-AS1 expression and clinicopathological features of patients with GC. Results: LncRNAs microarray analysis results exhibited that HNF1A-AS1 was downregulated in GCs tissues (mean fold change 2.06, p < 0.05), which was further confirmed by qRT-PCR. The results from qRT-PCR showed that the expression of HNF1A-AS1 was not only downregulated in three GC cell lines (AGS, BGC-823, and MKN-45) relative to that in a normal gastric mucosal epithelial cell line (GES-1), but also decreased in GC tissues relative to that in paired adjacent non-neoplastic tissues (low expression, 94 of 161; low expression rate, 58.38 %). Furthermore, low HNF1A-AS1 expression was associated with tumor size/diameter (p = 0.005, multivariate analysis), levels of serum carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), and RRM1 expression in tissue samples (p = 0.028, p = 0.009, and p = 0.006, respectively). Conclusions: Taken together, our data indicate that lncRNA HNF1A-AS1 may be a regulator of GC, and thus, it may have potential as a novel biomarker and treatment target for this type of cancer.
Background: Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer. The aim of this study was to examine the abnormalities of NEAT1 (nuclear paraspeckle assembly transcript 1, also known as MEN epsilon/beta) in gastric adenocarcinomas (GACs). Methods: One hundred thirty-one GAC tissues and matched adjacent normal tissues (ANTs) were collected from patients who undergone surgery. Differences in of NEAT1 expression were examined via quantitative reverse transcriptase PCR (qRT-PCR). WST-1 assay and transwell assay were carried out in vitro to investigate the proliferation and migration of GAC cells with alteration in NEAT1 long non-coding RNA (lncRNA) expression. Results: The expression levels of lncRNA NEAT1 were significantly elevated in GAC tissues (P < 0.001) compared with ANTs. There was also a statistical difference in NEAT1 expression between early and advanced GACs (P = 0.0111). GACs with lymph node metastasis (LNM) expressed higher levels of NEAT1 lncRNA compared with those without LNM (P = 0.004). In the in vitro experiments, the proliferation but not migration of GAC cells was attenuated after NEAT1 knockdown by RNA interference. Conclusions: Expression of NEAT1 lncRNA was enhanced in GACs; and NEAT1 may influence GAC progression by promoting tumor growth.
Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug delivery system able to induce regression of peritoneal metastasis (PM) in the salvage situation. The aim of this study was to determine the clinical characteristics, tumor histology, and extent of disease of the patients having undergone cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after "neoadjuvant" PIPAC. Methods: This study was performed at a single institution, tertiary center. In a prospective registry, retrospective analysis was done. PIPAC indication was restricted to patients in the salvage situation who were not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Results: Nine-hundred sixty-one PIPAC sessions were successfully performed in 406 patients: 21 patients (5.2 %) were scheduled for CRS and HIPEC. Twelve of these patients had a low PCI (mean 5.8 +/- 5.6). The remaining nine patients showed an advanced peritoneal disease (mean PCI 14.3 +/- 5.3) at initial laparoscopy. After repeated PIPAC (mean number of cycles 3.5 +/- 0.9), radiological tumor regression was observed in 7/9 patients and major histological regression was observed in 8/9 patients, so that secondary CRS and HIPEC became possible. Conclusions: PIPAC might be used as a neoadjuvant therapy before CRS and HIPEC in order to improve the outcome of CRS and HIPEC, to select patients with chemosensitive, biologically favorable tumors, to extent the indications of CRS and HIPEC in the presence of diffuse small bowel involvement, and to reduce the extent of cytoreductive surgery.
Background: Autophagy is a cellular pathway that regulates transportation of cytoplasmic macromolecules and organelles to lysosomes for degradation. Autophagy is involved in both tumorigenesis and tumour suppression. Here we investigated the potential prognostic value of the autophagy-related proteins Beclin-1, p62, LC3 and uncoordinated (UNC) 51-like kinase 1 (ULK1) in a cohort of colorectal cancer (CRC) specimens. Methods: In this study, we analysed the immunoexpression of the autophagy-related proteins p62, LC3, Beclin-1 and ULK1 in 127 CRC patients with known KRAS mutational status and detailed clinical follow-up. Results: Survival analysis of p62 staining showed a significant correlation of cytoplasmic (not nuclear) p62 expression with a favourable tumour-specific overall survival (OS). The prognostic power of cytoplasmic p62 was found in the KRAS-mutated subgroup but was lost in the KRAS wildtype subgroup. Survival analysis of Beclin-1 staining did not show an association with OS in the complete cohort. LC3 overexpression demonstrated a slight, though not significant, association with decreased OS. Upon stratifying cases by KRAS mutational status, nuclear (not cytoplasmic) Beclin-1 staining was associated with a significantly decreased OS in the KRAS-mutated subgroup but not in the KRAS wildtype CRCs. In addition, LC3 overexpression was significantly associated with decreased OS in the KRAS-mutated CRC subgroup. ULK1 expression was not correlated to survival. Conclusions: Immunohistochemical analyses of LC3, p62 and Beclin-1 may constitute promising novel prognostic markers in CRC, especially in KRAS-mutated CRCs. This strategy might help in identifying high-risk patients who would benefit from autophagy-related anticancer drugs.
Background: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis. Methods: Tumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues. Results: The mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues (p = 0.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival (p = 0.004) and relapse-free interval (p = 0.013). Conclusions: Our results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer.
Background: The immunological status, consisting of "inflammation status" and "nutritional condition," is important for the survival of patients with various cancers, including non-small cell lung cancer (NSCLC). The neutrophil/lymphocyte ratio (NLR) reflects the inflammation status, and the prognostic nutritional index (PNI) reflects the immunological nutritional condition. In the present study, the correlation between the NLR and the PNI as well as the consistency and magnitude of the prognostic impact of the NLR and the PNI were investigated. Methods: We conducted a retrospective review of data from 334 patients who had undergone a curative resection for NSCLC. The NLR and the PNI were calculated, which was routinely performed before surgery. The correlations between the NLR and the PNI and survival were then evaluated. Results: A clear inverse correlation was observed between the NLR and the PNI. The NLR was associated with sex, smoking history, the CEA level, tumor size, and vascular invasion. The PNI was associated with sex, age, smoking history, tumor size, histological type, tumor differentiation, and vascular invasion. Patients with NLR >= 2.5 had a significantly poorer survival outcome, and patients with PNI < 50 had a significantly poorer survival outcome. A multivariate analysis demonstrated that age, nodal metastasis, tumor differentiation, NLR, and PNI were independent predictors of disease-free and overall survival. Conclusions: Our study demonstrated a significant inverse correlation between the NLR and the PNI, and a high NLR and a low PNI were significantly associated with a poor survival among patients who had undergone a complete resection for NSCLC.
Background: The objective of this meta-analysis was to compare the clinical and oncologic outcomes of robotic low anterior resection (R-LAR) with conventional laparoscopic low anterior resection (L-LAR). Methods: A search in the MEDLINE, Embase, and Ovid databases was performed for studies published before July 2014 that compared the clinical and oncologic outcomes of R-LAR and L-LAR. The methodological quality of the selected studies was assessed. Depending on statistical heterogeneity, a fixed or random effects model was used for the meta-analysis. The clinical and oncologic outcomes evaluated included operative time, estimated blood loss, length of hospital stay, rate of conversion to open surgery, post-operative complications, circumferential margin status, and number of lymph nodes collected. Results: Eight studies, including 324 R-LAR cases and 268 conventional L-LAR cases, were analyzed. The metaanalysis showed that R-LAR was associated with a shorter hospital stay (mean difference (MD) = -1.03; 95 % confidence interval (CI) = -1.78, -0.28; P = 0.007), lower conversion rate (odds ratio (OR) = 0.08; 95 % CI = 0.02, 0.31; P = 0.0002), lower rate of circumferential margin involvement (OR = 0.5; 95 % CI = 0.25, 1.01; P = 0.05), and lower overall complication rate (MD = 0.65; 95 % CI = 0.43, 0.99; P = 0.04) compared with L-LAR. There was no difference in operative time (MD = 28.4; 95 % CI = -3.48, 60.27; P = 0.08), the number of lymph nodes removed (MD = -0.63; 95 % CI = -0.78, 2.05; P = 0.38), and days to return of bowel function (MD = -0.15; 95 % CI = -0.37, 0.06; P = 0.17). Conclusions: R-LAR was shown to be associated with a shorter hospital stay, lower conversion rate, lower rate of circumferential margin involvement, and lower overall complication rate compared with L-LAR. There were no differences in operative time, the number of lymph nodes removed, and days to return of bowel function.
Background: In the clinical practice of neoadjuvant chemotherapy, response markers are very important. We aimed o investigate whether tumor markers CEA(carcino-embryonic antigen), CA19-9(carbohydrate antigen 19-9), CA72-4 (carbohydrate antigen 72-4), and CA125(carbohydrate antigen 125) can be used to evaluate the response to neoadjuvant chemotherapy, and to evaluate the diagnosis and prognosis value of four tumor markers in the patients of gastric cancer. Methods: A retrospective review was performed of 184 gastric cancer patients who underwent a 5-Fu, leucovorin, and oxaliplatin (FOLFOX) neoadjuvant chemotherapy regimen, followed by surgical treatment. Blood samples for CEA, CA19-9, CA72-4, and CA125 levels were taken from patients upon admission to the hospital and after neoadjuvant chemotherapy. Statistical analysis was performed to identify the clinical value of these tumor markers in predicting the survival and the response to neoadjuvant chemotherapy. Results: Median overall survival times of pretreatment CA19-9-positive and CA72-4-positive patients (14.0 +/-2.8 months and 14.8 +/-4.0 months, respectively) were significantly less than negative patients (32.5 +/-8.9 months and 34.0 +/-10.1 months, respectively) (P = 0.000 and P = 0.002, respectively). Pretreatment status of CA19-9 and CA72-4 were independent prognostic factors in gastric cancer patients (P = 0.029 and P = 0.008, respectively). Pretreatment CEA > 50 ng/ml had a positive prediction value for clinical disease progression after neoadjuvant chemotherapy according to the ROC curve (AUC: 0.694, 95% CI: 0.517 to 0.871, P = 0.017). The decrease of tumor markers CEA, CA72-4, and CA125 was significant after neoadjuvant chemotherapy (P = 0.030, P = 0.010, and P = 0.009, respectively), especially in patients with disease control (including complete, partial clinical response, and stable disease) (P = 0.012, P = 0.020, and P = 0.025, respectively). A decrease in CA72-4 by more than 70% had a positive prediction value for pathologic response to neoadjuvant chemotherapy according to the ROC curve (AUC: 0.764, 95% CI: 0.584 to 0.945, P = 0.020). Conclusions: Our results suggest that high preoperative serum levels of CA72-4 and CA19-9 are associated with higher risk of death, high pretreatment CEA levels (> 50 ng/ml) may predict clinical disease progression after neoadjuvant chemotherapy, and a decrease (> 70%) of CA72-4 may predict pathologic response to neoadjuvant chemotherapy.
Background: Endoscopic transsphenoidal surgery has gradually come to be regarded as a preferred option in the treatment of pituitary adenomas because of its advantages of improved visualization and its minimal invasiveness. The aim of this study was to compare and evaluate the outcomes and complications of endoscopic and microscopic transsphenoidal surgery in the treatment of pituitary adenomas. Methods: We performed a systematic literature search of MEDLINE, EMBASE, the Cochrane Library and the Web of Science between January 1992 and May 2013. Studies with consecutive patients that explicitly and fully compared endoscopic and microscopic approaches in the treatment of pituitary adenomas were included. Results: A total of 15 studies (n = 1,014 patients) met the inclusion criteria among 487 studies that involved endoscopic surgery and 527 studies that dealt with microscopic surgery. The rate of gross tumor removal was higher in the endoscopic group than in the microscopic group. The post-operative rates of septal perforation were less frequent in patients who underwent endoscopic surgery. There was no significant difference between the two techniques in the incidence rates of meningitis, diabetes insipidus, cerebrospinal fluid leak, epistaxis or hypopituitarism. The post-operative hospital stay was significantly shorter for the endoscopic surgery group compared with the microscopic surgery group (P 0.05). Conclusions: The present study indicates that the endoscopic transsphenoidal approach is safer and more effective than microscopic surgery in the treatment of pituitary adenomas.
Background: MicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas. Methods: We measured the expression of nine miRNAs (miR-181d, miR-30a-3p, miR-30c, miR-30d, miR-30e-3p, miR-368, miR-370, miR-493-5p, miR-532-5p) in 171 formalin-fixed, paraffin-embedded ovarian tissue blocks as well as six normal human ovarian surface epithelial (HOSE) cell lines using Taqman-based real-time PCR assays. Her-2/neu overexpression was assessed in ovarian carcinomas (n = 109 cases) by immunohistochemistry analysis. Results: Expression of four miRNAs (miR-30c, miR-30d, miR-30e-3p, miR-370) was significantly different between carcinomas and benign ovarian tissues as well as between carcinoma and borderline tissues. An additional three miRNAs (miR-181d, miR-30a-3p, miR-532-5p) were significantly different between borderline and carcinoma tissues. Expression of miR-532-5p was significantly lower in borderline than in benign tissues. Among ovarian carcinomas, expression of four miRNAs (miR-30a-3p, miR-30c, miR-30d, miR-30e-3p) was lowest in mucinous and highest in clear cell samples. Expression of miR-30a-3p was higher in well-differentiated compared to poorly differentiated tumors (P = 0.02), and expression of miR-370 was higher in stage I/II compared to stage III/IV samples (P = 0.03). In multivariate analyses, higher expression of miR-181d, miR-30c, miR-30d, and miR-30e-3p was associated with significantly better disease-free or overall survival. Finally, lower expression of miR-30c, miR-30d, miR-30e-3p and miR-532-5p was significantly associated with overexpression of Her-2/neu. Conclusions: Aberrant expression of miRNAs is common in ovarian tumor suggesting involvement of miRNA in ovarian tumorigenesis. They are associated with histology, clinical stage, survival and oncogene expression in ovarian carcinoma.
Background: The objective of this study is to perform a meta-analysis to evaluate the associations between the BRAF(V600E) mutation status and aggressive clinicopathological features and poor prognostic factors in papillary thyroid cancer. Methods: A literature search was performed within the PubMed, MEDLINE, Web of Science databases, and EMBASE databases using the Medical Subject Headings and keywords from January 2003 to July 2015. Individual study-specific odds ratios and confidence intervals were calculated, as were the Mantel-Haenszel pooled odds ratios for the combined studies. Results: Sixty-three studies of 20,764 patients were included in the final analysis. Compared with wild-type BRAF, the BRAF(V600E) mutation was associated with aggressive clinicopathological factors, including extrathyroidal extension, higher TNM stage, lymph node metastasis, and recurrence, and was associated with reduced overall survival; however, there was no significant association between the presence of BRAF mutation and distant metastasis. Conclusions: BRAF mutations are closely associated with aggressive clinicopathological characteristics and poorer prognosis in papillary thyroid cancer. Accordingly, aggressive treatment should be considered for papillary thyroid cancer patients with BRAF mutation.
Background: A large number of Asian population studies examined the difference between the 6th and the 7th tumor, node, metastasis (TNM) while it is still poorly validated among Caucasian populations. This is a retrospective study aimed at investigating the efficacy of the 7th edition American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system for gastric cancer focusing on the "N" parameter-related survival for prognostic assessment in gastric cancer patients of a single Western high-volume institution. Methods: From January 2002 to December 2009, the data of 274 patients with gastric cancer who underwent gastric surgery at the 8th General and Gastrointestinal Surgical Centre of the Second University of Naples were analyzed retrospectively. We collected data for patient demographics, tumor characteristics, surgical characteristics, and TNM stage. Particularly, the nodal status, with the number of dissected nodes and metastatic nodes, was reviewed from the pathology records. The same patient dataset was used to stage patients according to both the 6th and 7th edition criteria. Results: Age at surgery, tumor location, histological grade, Lauren's classification subtypes, and 6th and 7th AJCC/UICC N categories were found to have statistically significant associations with overall survival on univariate analysis. In the 6th edition staging system, the Kaplan-Meier plot did not show significant overlapped survival curves: significant differences were found between N0 and N1, P<.001; N1 and N2, P=.04; and N2 and N3, P<.001. On the contrary, in the 7th edition, among all five substages, there were similar survival curves between N categories 2 and 3a (P=.98) with a statistically significant discriminatory ability only between N1 versus N3b and N2 versus N3b (P=.02 and .04, respectively). Conclusions: Based on analysis, we found that several clinicopathological variables, especially histological grade and Lauren's classification, were significant prognostic factors in our database. The 6th and 7th AJCC/UICC N classifications represent significantly independent prognostic factors, and the 6th AJCC/UICC N classification seems to be superior to the 7th AJCC/UICC N classification in terms of uniformity, differentiation, and monotonicity of gradients.
Background: Curative resection of sigmoid colon and rectal cancer includes "high tie" of the inferior mesenteric artery (IMA). However, IMA ligation compromises blood flow to the anastomosis, which may increase the leakage rate, and it is unclear whether this confers a survival advantage. Accordingly, the IMA may be ligated at a point just below the origin of the left colic artery (LCA) "low tie" combined with lymph node dissection (LND) around the origin of the IMA (low tie with LND). However, no study has investigated the detailed prognostic results between "high tie" and "low tie with LND." The aim of this study was to assess the utility of "low tie with LND" on survival in patients with sigmoid colon or rectal cancer. Methods: A total of 189 sigmoid colon or rectal cancer patients who underwent curative operation from 1997 to 2007 were enrolled in this study. The patient's medical records were reviewed to obtain clinicopathological information. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method, with differences assessed using log-rank test. Results: Forty-two and 147 patients were ligated at the origin of the IMA (high tie) and just below the origin of the LCA combined with LND around the origin of the IMA (low tie with LND), respectively. No significant differences were observed in the complication rate and OS and RFS rates in the two groups. Further, no significant difference was observed in the OS and RFS rates in the lymph node-positive cases in the two groups. Conclusions: "Low tie with LND" is anatomically less invasive and is not inferior to "high tie" with prognostic point of view.
Background: The relationship between the number of parathyroid glands preserved and hypoparathyroidism is not well understood. We sought to determine the number of parathyroid glands that need to be preserved to prevent hypoparathyroidism. Methods: We analyzed 454 patients who underwent total thyroidectomy for papillary thyroid carcinoma. We analyzed the frequency of hypoparathyroidism according to the number of parathyroid glands preserved. Results: Incidental parathyroidectomy occurred in 19.8% of the patients; one parathyroid gland in 17.6%, two in 1.5%, and three in 0.7%. Transient hypoparathyroidism was increased when incidental parathyroidectomy occurred (odds ratio 1.83, 95% confidence interval 1.04 to 3.23, P = 0.036) on multivariate regression analysis, but was not influenced by the actual number of parathyroid glands removed. There was no relationship between the number of parathyroid glands preserved and permanent hypoparathyroidism (P = 0.147). Conclusions: Preservation of all parathyroid glands decreases transient hypoparathyroidism compared with when three or fewer glands are preserved, but does not affect permanent hypoparathyroidism. During total thyroidectomy, preserving at least one parathyroid gland with an intact blood supply appears to be sufficient to prevent permanent hypoparathyroidism when autotransplantation is not performed.