Positive Regional Nodes Research Articles

Loss of tight junction proteins (Claudin 1, 4, and 7) correlates with aggressive behavior in colorectal carcinoma.

BackgroundTight junction proteins in the cell organize paracellular permeability and they play a critical role in apical cell-to-cell adhesion and epithelial polarity. Claudins are major integral membrane proteins of tight junctions, especially Claudin 1, 4, and 7, which are known as the impermeability Claudins. In this study, we investigated the importance of loss of Claudin 1, 4, and 7 expression, and their relation to tumor progression in colorectal cancer patients.Material/MethodsLoss of Claudin 1, 4, and 7 expression was examined by immunohistochemical method in 70 patients diagnosed with colorectal cancer. Cases with loss of Claudin expression in <1/3 of tumor cells were classified as mild loss, whereas cases with loss of Claudin expression ≥1/3 of tumor cells were classified as moderate-to-marked loss in order to evaluate the relation between loss of Claudin 1, 4, and 7 expression and clinicopathologic data.ResultsThe severe suppression of Claudin 1, 4, and 7 expression was found to be significantly related to the depth of tumor invasion, positive regional lymph nodes, histological grade, lymphovascular invasion, perineural invasion, and lymphocytic response. Additionally, severity of loss in Claudin 4 expression was found to have a relation with distant metastasis.ConclusionsClaudin 1, 4, and 7 are important building blocks of paracellular adhesion molecules. Their decreased expression in colorectal cancer seems to have critical effects on cell proliferation, motility, invasion, and immune response against the tumor.

Simultaneous modulated accelerated radiation therapy for esophageal cancer: A feasibility study

To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN ±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.

Enhanced miR-182 transcription is a predictor of poor overall survival in colorectal adenocarcinoma patients

Colorectal cancer is the second most frequent cause of cancer-related death in the developed world. Recent studies have tried to associate colorectal cancer with the aberrant expression of several microRNAs. The aim of the present study was the development of a highly sensitive quantitative real-time PCR which can be used to evaluate the miR-182 expression levels in colorectal adenocarcinoma and adjacent non-cancerous tissue specimens and associate them with several clinicopathological characteristics, aiming to examine the prognostic potential of miR-182. Total RNA was isolated from 116 malignant colorectal adenocarcinoma specimens and 60 paired non-cancerous tissues. Then, polyadenylation of 2 μg total RNA by poly(A) polymerase and reverse transcription with suitable oligo-dT-adapter followed. miR-182 levels were quantified by real-time PCR based on SYBR Green chemistry. The results were analyzed by the comparative quantification cycle method and by extensive biostatistical analysis. miR-182 was found to be significantly upregulated in colorectal adenocarcinoma specimens compared to their non-cancerous counterparts (p<0.001). miR-182 expression increases as the histological grade increases (p=0.013). miR-182 overexpression is associated with high depth of tumor invasion, positive regional lymph node status, and advanced TNM stage of patients. Therefore, miR-182 is an unfavorable prognostic marker in colorectal adenocarcinoma, predicting poor overall survival (p=0.007). Most importantly, miR-182 expression retained its unfavorable prognostic significance among patients with well- or moderately differentiated colorectal adenocarcinoma (p=0.006) and among metastasis-free patients (p=0.025). The increased levels of the oncogene-like miR-182 increase the risk for disease progression and predict poor overall survival for colorectal adenocarcinoma patients.

Prognostic factors of primary cutaneus melanoma.

The purpose of this study was to identify tumor characteristics of primary malignant melanoma predictive of sentinel lymph node positive status, and then to determine whether sentinel lymph node status has an impact on recurrence and survival. A total of 100 patients with primary malignant skin melanoma were analyzed. The prospective melanoma database identified patients with histologically confirmed cutaneus melanoma, clinically negative and clinically positive regional lymph nodes with no evidence of distant disease, who had undergone surgery between April 2001 and May 2012. Univariate and multivariate analyses were performed to assess factors that predict sentinel lymph node positive status, recurrence and survival. We identified Breslow's thickness and lymphocytic response as independent predictors of sentinel lymph node status in cutaneous melanoma patients. Sentinel lymph node status was a significant predictor of disease free survival. Despite the limitation, this study confirms Breslow's thickness and tumor lymphocytic infiltration as two factors predictive of sentinel lymph node metastasis in cutaneous melanoma patients. We also found sentinel lymph node status to be the most significant independent predictor of disease free survival and identified sentinel lymph node status as an important variable to consider when estimating the risk of regional recurrence.

The effect of extent of surgery and number of lymph node metastases on overall survival in patients with medullary thyroid cancer.

Total thyroidectomy with central lymph node dissection is recommended in patients with medullary thyroid cancer (MTC). However, the relationship between disease severity and extent of resection on overall survival remains unknown. The aim of the study was to identify the effect of surgery on overall survival in MTC patients. Using data from 2968 patients with MTC diagnosed between 1998 and 2005 from the National Cancer Database, we determined the relationship between the number of cervical lymph node metastases, tumor size, distant metastases, and extent of surgery on overall survival in patients with MTC. Older patient age (5.69 [95% CI, 3.34-9.72]), larger tumor size (2.89 [95% CI, 2.14-3.90]), presence of distant metastases (5.68 [95% CI, 4.61-6.99]), and number of positive regional lymph nodes (for ≥16 lymph nodes, 3.40 [95% CI, 2.41-4.79]) were independently associated with decreased survival. Overall survival rate for patients with cervical lymph nodes resected and negative, cervical lymph nodes not resected, and 1-5, 6-10, 11-16, and ≥16 cervical lymph node metastases was 90, 76, 74, 61, 69, and 55%, respectively. There was no difference in survival based on surgical intervention in patients with tumor size ≤ 2 cm without distant metastases. In patients with tumor size > 2.0 cm and no distant metastases, all surgical treatments resulted in a significant improvement in survival compared to no surgery (P < .001). In patients with distant metastases, only total thyroidectomy with regional lymph node resection resulted in a significant improvement in survival (P < .001). The number of lymph node metastases should be incorporated into MTC staging. The extent of surgery in patients with MTC should be tailored to tumor size and distant metastases.

Merkel cell carcinoma of the hand and upper extremity: Current trends and outcomes

Merkel cell carcinomas represent an uncommon yet aggressive skin cancer. We sought to identify changes in incidence and predictors of outcomes and survival of patients with Merkel cell carcinomas of the hand and upper extremity. The Surveillance, Epidemiology and End Results database was used to identify all patients with Merkel cell carcinomas of the skin located specifically in the hand and upper extremity. Overall, 5211 cases were identified in the period from 1986 through 2009. The age-adjusted incidence of Merkel cell carcinoma of the hand and upper extremity increased from 0.02 cases per 100,000 in 1986 to 0.14 cases per 100,000 in 2009. The mean age of these patients was 75 years and positive regional lymph nodes were identified in 33%. Rate of metastasis was 4.1%. Overall survival for the study cohort was 49%. Multivariate analysis identified tumor size >5 cm, positive regional lymph nodes and metastasis at diagnosis as independent predictors of mortality. The incidence of Merkel cell carcinomas has increased substantially over the study period. Overall survival for Merkel cell carcinomas of the body and hand and upper extremity is related to tumor size and extent of disease at time of clinical presentation. Merkel cell carcinomas of the hand and upper extremity tend to be diagnosed at an earlier stage with lower rates of regional and systemic spread, and subsequently have a higher overall survival rate.

Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer

BackgroundIn colorectal cancer, the involvement of regional lymph nodes with metastasis is an established prognostic factor. The impact of the number of positive nodes on patient outcome with stage IV disease is not well defined. MethodsA retrospective review was performed of 1,421 patients at two tertiary referral centers with stage IV colorectal cancer who underwent primary tumor resection. Associations between regional nodes, lymph node ratio (LNR), and overall survival (OS) from date of diagnosis were analyzed. ResultsThe number of positive regional nodes and LNR correlated with multiple sites of metastases (p < 0.001). Survival was significantly associated with the number of positive nodes and LNR, with a median OS of 43 months with negative nodes, compared to 20 months with ≥7 positive nodes (p < 0.001). The number of regional nodal metastases correlated with OS among 400 patients undergoing resection of liver metastases (p = 0.005) but lost prognostic significance in the subset of 223 patients who underwent hepatectomy with perioperative oxaliplatin- or irinotecan-based chemotherapy (p = 0.48). ConclusionsIn stage IV colorectal cancer, an increasing number of positive regional nodes and LNR correlate with multiple sites of metastases and poorer survival. The number of metastatic regional lymph nodes loses prognostic significance with modern chemotherapy in patients undergoing resection of liver metastases.

Undertreatment of thick head and neck melanomas: an age-based analysis.

To determine U.S. treatment patterns for pathologic staging practices in patients with thick head and neck melanomas (HNM). Patients with thick HNM without clinical evidence of in-transit, regional, or distant metastatic spread at presentation were identified from the Surveillance Epidemiology and End Results database. Treatment trends for patients were summarized, and univariate and multivariate analyses were performed to identify associations between varying practice patterns. A total of 1,230 patients with HNM meeting the inclusion criteria were identified. Surgical staging procedures were utilized in 53.5 %, including both sentinel lymph node biopsy (37 %) and elective neck dissection (16 %). Patients undergoing a surgical staging procedure were younger (64 vs. 77 years, p < 0.001) with smaller tumors (6.3 vs. 6.6 mm, p = 0.008). The rate of occult nodal disease was 22 % in patients undergoing a surgical staging procedure. The presence of a positive regional node in this subgroup of patients was associated with a significant reduction in disease-specific (44 vs. 59 months, p < 0.001) and overall survival (40 vs. 53 months, p < 0.001) on univariate analysis. On multivariate analysis, the presence of a positive node was the most significant factor for reduced overall survival (hazard ratio 2.36, 95 % confidence interval 1.71-3.23) and disease-specific survival (hazard ratio 2.84, 95 % confidence interval 1.99-4.06). Pathologic staging procedures provide independent prognostic information for patients with thick HNM. Despite this, current practice patterns demonstrate underutilization, particularly in elderly patients. Further work is needed to address the barriers to pathologic staging implementation in patients with thick HNM.

Adverse impact of regional lymph node involvement in osteosarcoma

BackgroundMetastatic dissemination in osteosarcoma occurs haematogenously, though regional lymph node involvement is rarely reported. We investigated incidence, patient characteristics and survival for patients with osteosarcoma and regional lymph node involvement at diagnosis. MethodsWe identified 2748 cases of high-grade osteosarcoma with available information regarding regional lymph node involvement in the Surveillance Epidemiology and End Results database from 1973 to 2009. Demographics were compared using chi-squared tests or t-tests. Overall survival was estimated using Kaplan–Meier method and compared with log-rank tests. Multivariate analysis of overall survival was performed using Cox proportional hazards methods. ResultsThere were 74 patients (2.7%) with regional lymph node involvement at diagnosis of whom 19 (0.7%) were pathologically confirmed. Patients with regional node involvement were more likely to have extraskeletal tumours, distant metastases, tumours arising outside the lower extremity (p<0.0001 for all comparisons) and larger tumours (p=0.033). Five-year overall survival in those with and without regional node involvement was 10.9% (95% confidence interval (CI) 4.6–20.4) and 54.3% (95% CI 52.2–56.4; p<0.0001). In multivariate analysis, regional node involvement remained predictive of inferior survival after controlling for differences in metastatic status, age, tumour site and extraskeletal origin (hazard ratio 2.05, 95% CI 1.57–2.67; p<0.0001). Similar survival results were found when the analysis was restricted to patients with pathologically confirmed positive or negative regional lymph nodes. ConclusionThis analysis confirms that regional node involvement is a significant adverse prognostic factor that is independent of metastatic status, extraskeletal origin, age and tumour site.

Management of the malignant colorectal polyp: ACPGBI position statement

*Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK, †Torbay Hospital, Torquay, UK, ‡Department of General Surgery, Manchester Royal Infirmary, Manchester, UK, §Royal Infirmary, Glasgow, UK, ¶Department of Histopathology, Royal Bolton NHS Foundation Trust, Bolton, UK, **Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK, ††The Royal Marsden Hospital, London, UK, ‡‡Salisbury NHS Foundation Trust, Salisbury, UK and §§Department of Histopathology, University Hospital of South Manchester, Manchester, UK

P-0262 - Occult Nodal Micrometastases Revealed by the Mrna Marker C-Met and Its Significance in Patients with Recurrent Colorectal Cancer

Background: Colorectal cancer (CRC) is a common cancer that in 25-30% of cases develops recurrence in the absence of positive regional lymph nodes. CRC is the second leading cause of cancer-related deaths in the USA. According to the AJCC the 5-year survival ranges from 90% and 50% according to the stage (I vs. III). Thus, the presence of lymph node metastases represents an important prognostic factor. The standard E&E stain nodal evaluations are inadequate for the detection of micrometastasis, especially when sentinel node technique is performed and intraoperative frozen section examination is required. It has been shown that multilevel sectioning and cytokeratin immunohistochemistry (CK-IHC) may improve sensitivity, showing the presence of micrometastasis (2 mm or less) in 20-25% of patients with negative E&E routine stain. Molecular markers detected using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) based on mRNA marker detection allows rapid detection of occult micrometastases both in bone marrow aspirates and lymph nodes. We hypothesized that patients initially defined as N0 had nodal occult micrometastasis, which can be revealed by CK-IHC or tumor mRNA marker hepatocyte growth factor receptor (c-MET) overexpression. Methods: During postoperative follow-up, 11 patients (8 males, 3 females, median age 59 years) who had undergone colectomy and sentinel node mapping for CRC developed disease recurrence. Intraoperative sentinel node (SLN) evaluation was negative. SLN were examined using CK-IHC and RT-PCR assay was done to assess the presence of c-MET mRNA. Results: CK-IHC was positive in 6 SLN and negative in 5, while c-MET detected micrometastases in 10 SLN out of 11 (chi-square= 3.35, OR = 12, 95%CI 1.11-128.8, p= 0.03). Conclusion: Both CK-IHC and RT-PCR assay to assess c-MET mRNA reveal micrometastases in SNL from patients with CRC, and may help to identify patients at risk of recurrence.

Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma

BackgroundCodon 72 (Arg/Pro), the most frequently studied single nucleotide polymorphism (SNP) of p53 to date, is associated with the ability of the gene to induce cell apoptosis. The PI3K/Akt pathway plays an essential role in the transcriptional activation function of p53, and is an important factor in radiotherapy resistance. The present study was designed to evaluate the prediction of response to radiotherapy based on p53 codon 72 SNP and pAkt expression in biopsy specimens of locoregional nasopharyngeal carcinoma (NPC) before treatment.Materials and methodsIn total, 75 consecutive patients with locoregional NPC were enrolled. The p53 codon 72 SNP was identified from retrospectively collected paraffin-embedded biopsy specimens using Sanger sequencing. Expression patterns of p53, p21, 14-3-3σ, and pAkt proteins were investigated using immunohistochemical analyses. The effects of genetic polymorphisms and protein expression on progression-free survival (PFS) were evaluated using the Cox proportional hazards model, Kaplan–Meier method, and log-rank test.ResultsThe p53 codon 72 Pro/Pro carriers showed lower risk of disease progression (local recurrence and distant metastases) (HR: 0.300; 95% CI: 0.092–0.983; p=0.047). However, this association between the p53 codon 72 polymorphism and PFS was not significant in the pAkt-positive subgroup. No association was observed between protein expression of p53, p21 or 14-3-3σ and p53 codon72 polymorphisms. Notably, positive expression of p53 protein appeared to be correlated with poorer PFS among patients diagnosed as local regional lymph node metastasis (N+) before treatment (p=0.032).ConclusionsThe p53 codon 72 Pro/Pro genotype may be an effective independent prognostic marker for better outcome in patients with locoregional NPC. Based on the current findings, we hypothesize that pAkt weakens the predictive value of p53 codon 72 SNP in NPC. A combination of positive p53 protein expression and local regional lymph node metastasis may additionally be predictive of high risk of disease progression.

Differentiated Thyroid Cancer Presenting with Distant Metastases: A Population Analysis Over Two Decades

Differentiated thyroid cancer (DTC) with distant metastases at presentation is uncommon; the prognosis of patients with this condition is more favorable than for other cancers. Demographic, clinical, and pathologic characteristics are described at a population level; factors associated with long-term disease-specific survival are identified. Patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2009. They were divided into two groups: patients with distant metastases (met-DTC) and patients without distant metastases (DTC) at presentation. Data analyses were performed with chi square tests, ANOVA, Kaplan-Meier analysis, and binary logistic and Cox proportional hazards regression. A total of 1,291 patients with met-DTC at diagnosis and 58,518 with DTC were included. The met-DTC rate was 2.2 %; compared to DTC, met-DTC patients were more often male (22.7 vs 41.3 %, respectively; p < 0.001) and older (mean 48.8 vs 62.7 years; p < 0.001). Patients with met-DTC were more likely not to have had surgery (23.3 vs 2.0 %; p < 0.001) or to have received radiation therapy (RAI) (66.8 vs 46.5 %; p < 0.001). Met-DTC tumors were larger (mean 41.0 vs 20.5 mm; p < 0.001). Independent factors associated with distant metastases were male gender, older age, single status, black and "other" races, follicular and Hurthle cell histology, larger tumors, and positive regional lymph nodes. Disease-specific survival was lower for met-DTC; this has not improved over the past two decades (p = 0.494). Independent factors associated with mortality included patient age ≥ 45 years, single status, follicular and Hurthle cell histologies, tumor size >4 cm, and not receiving surgery and/or RAI. Overall, met-DTC is uncommon. Given the lack of survival improvement observed over the last two decades, novel treatments should be pursued aggressively for this subset of patients.

Up-regulation of miR-182 expression in colorectal cancer tissues and its prognostic value

Accumulating evidences indicate that dysregulated microRNAs (miRNA) are involved in cancer tumorigenesis and progression. In the present study, we evaluated the expression of miR-182 in colorectal cancer and adjacent noncancerous tissues and explored its associations with clinicopathological characteristics and prognosis. Quantitative real-time PCR was used to analyze the expression of miR-182 in 148 pairs of colorectal cancer and adjacent noncancerous tissues. The relationship between miR-182 expression and clinicopathological characteristics in colorectal cancer tissues was estimated using Mann-Whitney U test or Kruskal-Wallis test, as appropriate. We calculated the survival curves and prognostic values of each variable by the Kaplan-Meier method and Cox proportional hazards regression analysis, respectively. The expression of miR-182 was found up-regulated in colorectal cancer tissues compared with adjacent noncancerous tissues (p < 0.001), and its up-regulation was significantly correlated with large tumor size (p = 0.016), positive regional lymph node metastasis (p = 0.008), and advanced tumor-node-metastasis stage (p = 0.020). Furthermore, Kaplan-Meier analysis demonstrated that high miR-182 expression predicted poor survival (p = 0.001), and Cox proportional hazards risk analysis indicated that miR-182 was an independent prognostic factor for colorectal cancer. MiR-182 was up-regulated in colorectal cancer tissues and correlated with adverse clinical characteristics and poor prognosis, indicating that miR-182 might be involved in colorectal cancer progression and could be used as a potential prognostic biomarker and therapeutic target in the management of colorectal cancer.

Staging of ovarian cancer: time to subdivide more?

Staging of ovarian cancer: time to subdivide more?

Neoadjuvant-intensified treatment for rectal cancer: Time to change?

To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer. Between January 2007 and December 2011, 80 patients with histologically confirmed rectal adenocarcinoma were enrolled. Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes. Patients received intensified combined modality treatment, consisting of neoadjuvant radiation therapy (50.4-54.0 Gy) and infusional chemotherapy (oxaliplatin 50 mg/m(2)) on the first day of each week, plus five daily continuous infusions of fluorouracil (200 mg/m(2) per die) from the first day of radiation therapy until radiotherapy completion. Patients received five or six cycles of oxaliplatin based on performance status, clinical lymph node involvement, and potential risk of a non-sphincter-conserving surgical procedure. Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment; adjuvant chemotherapy treatment was left to the oncologist's discretion and was recommended in patients with positive lymph nodes. After treatment, all patients were monitored every three months for the first year and every six months for the subsequent years. Of the 80 patients enrolled, 75 patients completed the programmed neoadjuvant radiochemotherapy treatment. All patients received the radiotherapy prescribed total dose; five patients suspended chemotherapy indefinitely because of chemotherapy-related toxicity. At least five cycles of oxaliplatin were administered to 73 patients. Treatment was well tolerated with high compliance and a good level of toxicity. Most of the acute toxic effects observed were classified as grades 1-2. Proctitis grade 2 was the most common symptom (63.75%) and the earliest manifestation of acute toxicity. Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three patients (3.75%). Seventy-seven patients underwent surgery; low anterior resection was performed in 52 patients, Miles' surgery in 11 patients and total mesorectal excision in nine patients. Fifty patients showed tumor downsizing ≥ 50% pathological downstaging in 88.00% of tumors. Out of 75 patients surviving surgery, 67 patients (89.33%) had some form of downstaging after preoperative treatment. A pathological complete response was achieved in 23.75% of patients and a nearly pathologic complete response (stage ypT1ypN0) in six patients. An involvement of the radial margin was never present. During surgery, intra-abdominal metastases were found in only one patient (1.25%). Initially, 45 patients required an abdominoperineal resection due to a tumor distal margin ≤ 5 cm from the anal verge. Of these patients, only seven of them underwent Miles' surgery and sphincter preservation was guaranteed in 84.50% of patients in this subgroup. Fourteen patients received postoperative chemotherapy. In the full analysis of enrolled cohort, eight of the 80 patients died, with seven deaths related to rectal cancer and one to unrelated causes. Local recurrences were observed in seven patients (8.75%) and distant metastases in 17 cases (21.25%). The five-year rate of overall survival rate was 90.91%. Using a median follow-up time of 28.5 mo, the cumulative incidence of local recurrences was 8.75%, and the overall survival and disease-free survival rates were 90.00% and 70.00%, respectively. The results of this study suggest oxaliplatin chemotherapy has a beneficial effect on overall survival, likely due to an increase in local tumor control.

Impact of HER2 and PTEN Simultaneous Deregulation in Non-small Cell Lung Carcinoma: Correlation with Biological Behavior

HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. HER2 overexpression (2+/3+ score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03) . Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.

Genitourinary rhabdomyosarcoma: lessons from a developing-world series

ObjectiveThe objective was to retrospectively review a large series of pediatric patients with genitourinary rhabdomyosarcoma from a developing country. MethodsA total of 49 children were treated over a 47-year period (1961-2008). Analysis of the clinical presentation, demographics, surgical records, histological results, and oncological management was performed. The patients were analyzed as a whole and also in 2 separate groups (pre- and post-1992). ResultsThe median age at clinical presentation was 3½ years. The majority (59%) of patients were Intergroup Rhabdomyosarcoma Study group 3, with locally advanced disease at presentation. Twenty (41%) of the 49 patients presented with primary tumors greater than 10 cm in diameter. Sixteen (33%) of the 49 patients had positive regional lymph nodes at presentation. The overall survival of the series was 30 (65%) of 46. The survival for those treated after 1992 in Intergroup Rhabdomyosarcoma Study group 3 was superior (P = .04) to those treated before 1992 (80% vs 56%). ConclusionChildren in this large African series of genitourinary rhabdomyosarcoma present with greater locally advanced disease (node positive and bulky disease) when compared with the developed world. Improvements in the last 2 decades in local surgical and oncological care have led to an improvement in survival in children with locally advanced disease.

CD147 expression in advanced cutaneous squamous cell carcinoma

CD147 is upregulated in multiple cancer types, but its expression in advanced cutaneous squamous cell carcinoma (SCC) is unknown. Our purpose was to evaluate the expression patterns of CD147 and related monocarboxylate transporters (MCT1, MCT4) to determine their correlation with survival. This is a retrospective cohort study of patients with advanced stage cutaneous SCC of the head and neck who presented to a tertiary care center between 1998 and 2006 (n=50). CD147, MCT1 and MCT4 expression levels were assessed using immunofluorescence analysis of archived tumor samples and correlated with survival and clinicopathologic characteristics. The majority of patients (92%, n = 46) were diagnosed with stage III disease, with 46% (n = 23) having positive regional lymph node metastasis and 8% (n = 4) with distant metastasis. Primary malignancies had an overexpression of CD147 (78%; n = 35), MCT1 (23%; n = 10) and MCT4 (47%; n = 20). In addition, there was a significant relationship between the overexpression of CD147 and node positive disease (p = 0.048). Two- and five-year survival rates were 69 and 61%, respectively. There was a trend toward decreased survival in patients with overexpression of CD147 (p = 0.17), MCT1 (p = 0.11) and MCT4 (p = 0.15). CD147 may represent a biomarker or potential therapeutic target in advanced cutaneous SCC.

Pre-treatment maximal oesophageal wall thickness is independently associated with response to chemoradiotherapy in patients with T3-4 oesophageal squamous cell carcinoma

Combined chemoradiotherapy with or without surgery is frequently performed as a curative treatment in patients with T3-4 locally advanced oesophageal squamous cell carcinoma. Computed tomography (CT) is frequently performed before and after chemoradiotherapy. The aim of this study is to evaluate the utility of the oesophageal wall thickness on CT scans to predict the response to chemoradiotherapy and the treatment outcome in patients with T3-4 locally advanced oesophageal squamous cell carcinoma. Ninety-six patients with T3-4 locally advanced oesophageal squamous cell carcinoma, who were treated with neoadjuvant chemoradiotherapy followed by surgery between 1998 and 2008 at the Kaohsiung Chang Gung Memorial Hospital, were retrospectively reviewed. CT scans before and after chemoradiotherapy were available for 93 patients. Of these 93 patients, 24% (22 of 93) achieved a pathologically complete response (pCR). The measurement of the maximal dimension of the oesophageal wall thickness on CT scans before (pre) and after (post) chemoradiotherapy was performed retrospectively, and correlated with the response to chemoradiotherapy and patients' outcome. The percentage decrease of maximal oesophageal wall thickness after chemoradiotherapy was determined by the formula: [(pre -post)/pre] 100. Pre- and post-chemoradiotherapy maximal oesophageal wall thicknesses were significantly correlated with pCR, but the percent decrease of oesophageal wall thickness after chemoradiothrapy was not. Logistic models showed that pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm was independently associated with response to chemoradiotherapy. For patients with pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm, 91% did not achieve pCR after chemoradiotherapy. Univariate analyses demonstrated that a pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm, T4 disease and positive regional lymph nodes (N stage) were predictive of inferior disease-free survival. In a multivariate comparison, pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm represented an independent adverse prognosticator for disease-specific survival and disease-free survival. Most of the T3-4 locally advanced oesophageal squamous cell carcinoma patients with pre-treatment maximal oesophageal wall thickness ≥20 mm did not achieve pCR after chemoradiotherapy. Thus, oesophgectomy may be considered in advance in this group of patients. Pre-treatment maximal oesophageal wall thickness is of independent prognostic value in patients with T3-4 locally advanced oesophageal squamous cell carcinoma who receive neoadjuvant chemotheradiotherapy.