Contralateral lymph node metastases in patients with vulvar cancer and unilateral sentinel lymph node metastases.

INTRODUCTION: The risk of contralateral lymph node metastases following unilateral sentinel lymph node (SLN) metastases in patients with vulvar cancer(s) remains to be systematically assessed. MATERIAL AND METHODS: We performed a multicenter, retrospective registry-based study of 476 patients with vulvar cancer. The primary outcome measure was the rate of contralateral non-SLN metastases in the case of positive unilateral SLN. RESULTS: Out of 476 patients with primary vulvar cancer, 202 received SLN biopsy: 58 unilateral and 144 bilateral. Out of 66 patients with unilateral metastatic SLN, 62 (93.9%) received contralateral lymphadenectomy-18 after unilateral and 44 after bilateral SLN biopsy. In the study group, 132 SLN were assessed with a median number of 2 (range 1-4) per patient and 76 of these were positive. Lymph node-positivity was associated with advanced tumor stage, as well as lymph and vascular space invasion. In the group of patients with bilateral inguino-femoral lymphadenectomy, 1004 lymph nodes were resected with a median number of 15 (range 10-29) per patient. After full dissection of the inguino-femoral lymph nodes, no contralateral non-SLN metastases were found. CONCLUSIONS: The risk of contralateral non-SLN metastases in patients with unilateral SLN metastases was low. Therefore, the impact of contralateral lymphadenectomy on patient survival should be investigated in further studies.

The effect of lymph node metastasis on overall survival and disease-free survival in vulvar cancer patients.

OBJECTIVES: To examine the effect of lymphadenectomy on survival in patients with squamous cell vulvar carcinoma. MATERIAL AND METHODS: Patients with squamous cell vulvar cancer who underwent surgery were retrospectively analyzed. All procedures were performed according to current recommendations/standard of treatment. The clinical and pathological features were examined. Sixty-eight patients were studied. The mean age was 64.7 ± 10.9 years. Twenty-three (33.8%) patients had nodal metastasis. Most patients (60.3%) were in stage IB. Adjuvant radiotherapy and chemo-radiotherapy were administered to 33.8% and 25% of the patients, respectively. The median follow-up time was 28.5 (4-183) months. Recurrence occurred in 18 (26.5%) cases. RESULTS: There was no significant difference between node-positive and node-negative patients in terms of age, number of dissected lymph nodes and recurrence. Tumor diameter was significantly higher in the metastatic group. Age and surgical margin positivity were independent prognostic factors for overall survival (OS). Surgical margin positivity and lymph node metastasis had no effect on disease-free survival (DFS). CONCLUSIONS: Our results showed that age and surgical margin positivity were independent prognostic factors for OS. Although surgical margin positivity increased the risk of recurrence in univariate analysis, it was not a significant factor affecting DFS. OS was significantly lower in patients with lymph node metastasis.

Clinical outcomes of muscle invasive bladder Cancer according to the BASQ classification.

BACKGROUND: We evaluated the clinical efficacy and prognosis of muscle-invasive bladder cancer according to the basal/squamous-like (BASQ) classification system based on immunohistochemical staining [CK5/6(+), CK14(+), GATA3(-), and FOXA1(-)]. METHODS: One hundred patients diagnosed with muscle-invasive bladder cancer (cT2-4 N0-3 M0) were included in the study. All patients underwent radical cystectomy after transurethral removal of bladder tumor. Immunostaining was performed for CK5/6, CK14, FOXA1, and GATA3 antibodies on tissue microarray slides, and expression patterns were quantitatively analyzed using a scanning program. RESULTS: The median follow-up time was 77.4 (interquartile range: 39-120.9) months. The mean age of the patients was 65.1 ± 11.2 years. FOXA1 or CK14 expression greater than 1% was respectively positively and negatively correlated with overall survival (OS; p = 0.011 and p = 0.042, respectively), cancer-specific survival (CSS; p = 0.050 for both), and recurrence-free survival (RFS; p = 0.018 and p = 0.040, respectively). For CK5/6+ and GATA3- or FOXA1- expression, 10% CK5/6+ cells were negatively correlated with OS (p = 0.032 and p = 0.039, respectively) and with RFS in combination with FOXA1- only (p = 0.050). CONCLUSIONS: In this study, CK14 expression was associated with a poor prognosis. The new classification system of bladder cancer based on molecular characteristics is expected to helpful tool for the establishment of personalized treatment strategies and associated prediction of therapeutic responses.

Prognostic Factors for Operated Gallbladder Cancer.

PURPOSE: The prognosis of gallbladder cancer is poor. Lymph node metastasis and the stage are known to be the strongest prognostic factors for survival. The aim of this study was to determine the importance of complementary surgery and other prognostic factors for survival of operated gallbladder cancer. MATERIAL AND METHOD: We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were diagnosed incidentally during simple cholecystectomy which was performed for benign causes but only 56.4% of them underwent complementary surgery. 51.6% of the recurrence was detected during 18.4 months of follow-up time. R0 resection, T stage, and pathological stage were found to be related with both OS and DFS by univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were also related with DFS. Presence of recurrence, recurrence side, performance score (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis, advanced stage disease, and lymph node metastasis were more common among patients who did not undergo complementary surgery. Adjuvant chemotherapy was given more frequently to patients who undergone complementary surgery group. The multivariate analysis indicated that grade, lymph node metastasis, stage, recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic factors for DFS on the other and only stage was a prognostic factor for OS. CONCLUSION: Our results showed that incidental diagnosis or complementary surgery was not related with DFS or OS but stage was only an independent prognostic factor for both OS and DFS in resected gallbladder cancer.

Chemoradiotherapy for Solitary Skeletal Muscle Metastasis from Oesophageal Cancer: Case Report and Brief Literature Review.

BACKGROUND: The incidence of skeletal muscle metastasis from oesophageal cancer is very low, and the treatment strategy has not been established. CASE REPORT: A 77-year-old man underwent oesophagectomy following neoadjuvant chemotherapy for oesophageal squamous cell carcinoma (CT-pT3 N0 M0, CT-pStage II). Fourteen months after surgery, he became aware of a subcutaneous tumour in his left forearm. Computed tomography and fluorodeoxyglucose positron-emission tomography revealed a 65×75 mm intramuscular nodular lesion with a standardized uptake value of 8.5. Further examination by biopsy strongly suggested this was a solitary metastasis from oesophageal cancer. The patient received chemoradiotherapy with two cycles of 5-fluorouracil combined with cisplatin and radiation. Clinical complete response was confirmed by imaging 7 months after chemoradiation and no recurrence has occurred at 20 months since chemoradiation. CONCLUSION: Radiotherapy or chemoradiotherapy can be an alternative locoregional therapy to surgery for solitary skeletal muscle metastasis.

Loss of PAR-3 protein expression is associated with invasion, lymph node metastasis, and poor survival in esophageal squamous cell carcinoma.

Disrupted cell polarity is a feature of epithelial cancers. The partitioning defective 3 (PAR-3) protein, a key component of the PAR complex that regulates the polarization of cells, is involved in tight junction formation at epithelial cell-cell contacts. Our previous study detected a homozygous deletion of the PAR-3 gene in esophageal squamous cell carcinoma (ESCC) cell lines and frequent copy number loss of the PAR-3 gene in primary ESCC. Here, we aimed to investigate the clinicopathological relevance of altered expression of the PAR-3 protein in primary ESCC. We immunohistochemically analyzed expression of the PAR-3 protein, as well as that of other tight junction proteins, ZO-1 and claudin-1, in 74 primary ESCCs. While the PAR-3 protein was expressed in the cytoplasm of basal cells, it was localized on the plasma membrane of suprabasal cells of normal squamous epithelium of the esophagus. Of the 74 ESCC tumors, 20 (27%), 11 (15%), and 13 (18%) were negative for PAR-3, ZO-1, and claudin-1 proteins, respectively. Negative PAR-3 protein expression, but not negative ZO-1 or claudin-1 expression, was significantly associated with deeper tumor invasion (P<.01), positive lymph node metastasis (P=.03), and advanced tumor stage (P=.01). Patients with PAR-3-negative tumors showed marginally significantly shorter overall survival after surgery than those with PAR-3-positive tumors (P=.053). In conclusion, these results suggest that PAR-3 protein expression is frequently lost in primary ESCC and that loss of the PAR-3 protein is associated with aggressive clinicopathological features of ESCC.

Human papillomavirus detection in fine needle aspiration cytology of lymph node metastasis of head and neck squamous cell cancer.

BACKGROUND: Currently, testing on HPV in oropharyngeal squamous cell carcinoma (OPSCC) is performed on histological material. However, in a certain percentage of the cases who present with lymph node metastases no primary tumor can be identified and only fine needle aspiration cytology (FNAC) is available for analysis. OBJECTIVES: Purpose of this study was to assess HPV status on FNAC and to validate it using histological material of the same patients. STUDY DESIGN: Patients with cervical metastasis from OPSCC or cancer of an unknown primary tumor (CUP), diagnosed between 2007 and 2012 were included. In 6 of the 47 patients, no primary tumor could be identified. HPV detection and genotyping was performed in both FNAC slides scrapings and formalin fixed paraffin embedded (FFPE) histological material from the same patients, using the HPV SPF10-LiPA25 assay. HPV PCR analysis on FFPE material was considered the reference standard for HPV status of each case. RESULTS: Compared with HPV negative cases (n=22), significantly more HPV positive cases (n=25) presented initially with cervical metastasis (27% vs 56% respectively; p=0·047). The HPV PCR assay on FNAC material showed a high sensitivity (96%; 95% CI 86.6-97.4) and specificity (100%; 95% CI 85.1-96.7) using the reference standard of HPV PCR analysis on FFPE material of the same patients. CONCLUSION: In this study, testing on HPV in FNAC of cervical lymph node metastases of SCC is validated. It provides a valuable alternative for testing of HPV on histological material from patients with oropharyngeal squamous cell carcinoma or cancer of an unknown primary tumor.

Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study.

This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC.

Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy.

The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS.

Supracricoid partial laryngectomy: oncological and functional results.

PURPOSE: The purpose of this study was to evaluate the oncological and functional results of patients affected by laryngeal squamous cell carcinoma (SCC) and surgically treated by supracricoid partial laryngectomy (SCPL) at the ENT Department of the University Hospital of Ferrara. METHODS: In this retrospective study a total of 155 patients (149 males/l96.1% and 6 females/3.9%), have been included. All patients were treated between January 1st 1998 and December 31st 2010, by SCPL, including 126 cricohyoidopexies (CHP) and 29 cricohyoidoepiglottopexies (CHEP). RESULTS: The overall survival (OS) at 3 and 5 years was 88.77 and 83.24%, respectively and the disease-free survival (DFS) at 3 and 5 years was 84.4 and 81.55%, respectively.The recurrence rate was 17.5%, with local recurrences in 12.1% of the cases, regional in 4.7% and distant metastasis in 0.7% of the cases. Synchronous second primary tumors were 0.7% and metachronous second primary cancers (MSPCs) 5.4%. Removal of nasogastric feeding tube (NGT) or percutaneous endoscopic gastrostomy (PEG) was performed in 98.7% of the patients and lasted 22 days on average after SCPL (range 9-60), while decannulation was performed in all of patients at the 27th day on average after surgery. CONCLUSIONS: Oncological outcomes of this series are consistent with those of the literature, showing that SCPL is an effective and safe procedure in terms of survival rate and disease control. Functional outcomes confirmed that SCPL allows a good organ preservation and recovery of laryngeal functions.

Identification of genes associated with laryngeal squamous cell carcinoma samples based on bioinformatic analysis.

The present study aimed to investigate the differentially expressed genes (DEGs) between laryngeal squamous cell carcinoma (LSCC) samples and non­neoplastic laryngeal squamous cell samples, and the underlying biological mechanism. Gene expression profile data of GSE51985 and GSE10288 were obtained from the Gene Expression Omnibus database. The DEGs between the LSCC and normal samples were identified using the rowtest function in the genefilter package. Hierarchical clustering for DEGs was performed to confirm the distinction between the identified DEGs, and Gene Ontology term and pathway enrichment analyses were performed to determine the underlying function of the DEGs. In addition, protein­protein interaction networks were established to investigate the interactive mechanism of the DEGs. A total of 1,288 upregulated genes and 317 downregulated genes were identified between the LSCC samples and non­neoplastic LSC samples in the GSE51985 dataset, and five upregulated and 26 downregulated genes were identified in the samples from the GSE10288 dataset. The DEGs were clearly distinguished between the LSCC sample and the non­neoplastic LSCC sample by hierarchical clustering. The upregulated genes were predominantly involved in the cell cycle, cell division or focal adhesion, and the 295 upregulated genes formed 374 protein interaction pairs in interaction network analysis. The results revealed that the genes involved in the cell cycle, in cell division or in focal adhesion were associated with the development and progression of LSCC.

Collagen XVII expression correlates with the invasion and metastasis of colorectal cancer.

Collagen XVII has a well-established role as an adhesion molecule and a cell surface receptor located in the type I hemidesmosome of stratified epithelia. Its ectodomain is constitutively shed from the cell surface and suggested to regulate the adhesion, migration, and signaling of cutaneous epithelial cells. Collagen XVII was not previously thought to be expressed by colon epithelial cells. Immunohistochemical analysis of tissue microarray samples of 141 cases of colorectal carcinoma showed that collagen XVII is expressed in normal human colonic mucosa and colorectal carcinoma. In colorectal carcinoma, increased collagen XVII expression was significantly associated with higher TNM stage. It also correlated with infiltrative growth pattern and tumor budding as well as lymph node and distant metastasis. Increased collagen XVII expression was associated with decreased disease-free and cancer-specific survival. Immunofluorescence staining of collagen XVII and its well-known binding partner laminin γ2 chain demonstrated a partial colocalization in normal and tumor tissue. In vitro, the overexpression of murine collagen XVII promoted the invasion of CaCo-2 colon carcinoma cells through Matrigel (BD Biosciences; Bedford, MA). To conclude, this study reports for the first time the expression of collagen XVII in colon epithelium and the association of increased collagen XVII immunoexpression with poor outcome in colorectal carcinoma.

Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone-invasive oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clinical management of bone-invasive feline OSCC.

The oncogenic role of PKCiota gene amplification and overexpression in Chinese non-small cell lung cancer.

BACKGROUND: The atypical protein kinase C isozyme iota (PKCiota) has been proposed as an oncogene based on its transformation property and amplification identified in Caucasian non-small cell lung cancer (NSCLC) patients. Because the geography difference of some genetic aberrance such as EGFR mutations between Caucasian and Asian NSCLC patients has been identified previously, it is important to know whether the PKCiota amplification also occurs in Asian NSCLC patients. METHODS: The PKCiota gene copy number changes and protein expression in Chinese patients samples were detected by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Logistic regression was used to assess the association of PKCiota expression with clinicopathological parameters. siRNA-mediated gene silencing was applied to demonstrate the role of PKCiota in promoting cell growth in PKCiota gene amplified and protein overexpressed cancer cells. RESULTS: The result showed that PKCiota gene was amplified in 20.2% (24/119) of the tested primary tumor samples from Chinese NSCLC patients. Interestingly this gene amplification was highly enriched in squamous NSCLC patients (37.1%, 23/62). Further IHC analysis indicated that PKCiota protein was highly expressed (IHC score 2+ and 3+) in 91.6% (109/119) of Chinese NSCLC tumors. Moreover, the PKCiota gene amplification was also correlated with gender, subtype and distant metastasis. Knockdown of PKCiota gene in the PKCiota gene amplified and protein overexpressed cells led to significant growth inhibition. CONCLUSION: Taken together, our data demonstrate that PKCiota is a potential oncogene and therapeutic target in Chinese NSCLC.

Tumor, node and metastasis classification of lung cancer--M1a versus M1b--analysis of M descriptors and other prognostic factors.

INTRODUCTION: The current edition of the tumor, node and metastasis (TNM) classification of lung cancer (LC) divides the presence of metastasis (M1) into two categories: M1a and M1b, depending on its anatomical location. To assess this new classification, the survival and the M descriptors of LC patients with metastatic disease registered by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery II (GCCB-S-II), were analyzed. METHODS: Non-small cell lung cancer (NSCLC) patients, with M1a or M1b disease, included in the GCCB-S-II, from April 2009 to December 2010, staged in accordance with the prospective staging project protocol of the International Association for the Study of Lung Cancer (IASLC), and with complete TNM staging and follow-up data, were studied. The overall survival associated with each M1 category and each M descriptor, besides other prognostic factors (sex, age, performance status [PS] and others) were analyzed by univariate and multivariate models. RESULTS: 640 NSCLC patients (195 M1a and 445 M1b) were included. M1b tumors had significantly worse survival than M1a tumors (p < 0.001). The prognostic value of M1 category was independent from other prognostic variables such as PS, weight loss, and others. The number of metastatic sites (isolated versus multiple) and the number of lesions (single versus multiple) in patients with isolated metastasis showed prognostic value, especially in those with brain metastasis. CONCLUSION: The current division of the M1 category into two subsets (M1a and M1b) is warranted by their prognostic significance. The number of metastatic sites and the number of lesions in patients with isolated metastasis should be taken into account, because they also have prognostic relevance.

DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma.

BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16. CONCLUSION: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.

Case of metastatic uterine cervical squamous cell carcinoma in the right atrium.

INTRODUCTION: Metastasis of uterine cervical carcinoma to the heart is uncommon and cases with metastasis to the right atrium are especially rare. This type of metastasis occurs in the epicardium and the myocardium in over 90% of cases with a heart metastatic tumor. Most cases of a metastatic tumor in the heart are found by chance during autopsy. CASE REPORT: We present the case of a patient with stage IIa uterine cervical carcinoma who visited our hospital with a chief complaint of arrhythmia 1.9 years after surgical treatment of carcinoma. CT and MRI showed that recurrent metastatic uterine cervical carcinoma had grown from the inferior vena cava upward into the right atrium. CONCLUSION: Although gynecological malignant tumors rarely metastasize to the heart, it is important to consider this possibility in patients with chest symptoms, and to make an early definite diagnosis and give appropriate treatment.