Clinical characteristics of struma ovarii

Objective

To evaluate the clinical characteristics of struma ovarii.

Methods

Twenty-five cases of struma ovarii were reviewed retrospectively from June 1994 to April 2007. The presenting clinical, radiologic, and pathologic features of the patients were reviewed.

Results

The mean age of the patients in this study was 45.3 years. The majority was of premenopausal status. Sixteen patients had clinical symptoms such as low abdominal pain, palpable abdominal mass and vaginal bleeding. Although one patient had an abnormal thyroid function test, the laboratory findings normalized after operative treatment. CA-125 levels were elevated in 6 cases. Diagnosis by preoperative imaging studies were 8 dermoid cysts, while only 3 cases were diagnosed as struma ovarii. There were 4 cases of malignant struma ovarii, and no patients with recurrent disease.

Conclusion

Struma ovarii is a rare tumor. The presented clinical, laboratory and radiological findings of patients are very diverse. The diagnosis was confirmed by pathologic findings. The treatment of benign struma ovarii is surgical resection only. The cases of malignant struma ovarii may need adjuvant treatment, but recurrence is uncommon.     

Heart Failure as First Sign of Development of Cardiac Metastases in a Patient with Diagnosis of Papillary Thyroid Carcinoma on Treatment with Tyrosine-Kinase Inhibitors: Differential Diagnoses and Clinical Management

Background

Cardiac metastases from papillary thyroid carcinoma are very uncommon. Their incidence is rising due to improvements in survival and diagnosis; nevertheless, our patient is the fourth case reported up to date. There are no clinical trials available in this scenario. Therefore, treatment choice is made based on clinical experience and case reports; notably, the largest case report series was prior to the approval for using tyrosine-kinase inhibitors in thyroid cancer.

Patient

A 73-year-old lady had dedifferentiated papillary thyroid cancer with ongoing sorafenib. After 9 months on this treatment, she presented with dyspnea and heart failure. Differential diagnosis included infection, progression of disease and cardiotoxicity. After a comprehensive assessment (echocardiography, computed tomography, PET, magnetic resonance), we found progression of lung disease, and the appearance of heart metastases.

Results

After recovering from the basal status, she started on second-line treatment with sunitinib, which was well-tolerated. She achieved stable disease with a decrease in tumor marker levels.

Conclusions

We should include cardiac metastases in the differential diagnosis of heart failure in cancer patients. Magnetic resonance imaging is the gold standard for assessment. Sorafenib is the mainstay of the first-line therapy in metastatic thyroid cancer, achieving long-term disease control with good tolerance. Sunitinib could be a safe second-line treatment option (not cardiotoxicity related) with promising results. Therefore, our report presents a sequence of treatment with tyrosine-kinase inhibitors in metastatic thyroid carcinoma with an encouraging outcome, which deserves further investigation.Key Words: Thyroid cancer, Cardiac metastases, Sorafenib, Sunitinib, Tyrosine-kinase inhibitors, Cardiac magnetic resonance     

Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib

Context

For patients with metastatic papillary thyroid carcinoma (PTC) refractory to radioactive iodine (RAI) treatment, systemic chemotherapy has limited efficacy. Such tumors frequently harbor BRAF V600E, and this alteration may predict responsiveness to vemurafenib treatment.

Objective

We report a metastatic PTC patient refractory to RAI treatment that underwent genomic profiling by next-generation sequencing. The sole genomic alteration identified was BRAF V600E on a near diploid genome with trisomy 1q. With vemurafenib treatment, the patient experienced a dramatic radiographic and clinical improvement, with the duration of an ongoing antitumor response exceeding 23 months.

Design

Hybridization capture of 3,769 exons of 236 cancer-related genes and the introns of 19 genes frequently rearranged in cancer was applied to >50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of a lymph node containing metastatic PTC and was sequenced to a high, uniform coverage of ×616.

Results

A BRAF V600E alteration was identified with no other somatic genomic alterations present within a near diploid tumor genome. The patient initially received vemurafenib at 960 mg twice daily that was reduced to 480 mg twice daily due to rash and diarrhea and has experienced an ongoing antitumor response exceeding 23 months by both PET-CT and dedicated CT imaging.

Conclusions

Genomic profiling in metastatic, RAI-refractory PTC can reveal a targetable BRAF V600E alteration without compounding somatic alterations, and such patients may derive a more prolonged benefit from vemurafenib treatment. Prospective clinical trials are ongoing to confirm our preliminary observation.Key words: Papillary thyroid carcinoma, BRAF V600E, Vemurafenib     

Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model

Background

Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demonstrated that MSCs, upon in vitro priming with anti-cancer drug, become drug-releasing mesenchymal cells (Dr-MCs) able to strongly inhibit cancer cells growth.

Methods

Murine mesenchymal stromal cells were loaded with Paclitaxel (Dr-MCsPTX) according to a standardized procedure and their ability to inhibit the growth of a murine B16 melanoma was verified by in vitro assays. The anti-metastatic activity of Dr-MCsPTX was then studied in mice injected i.v. with B16 melanoma cells that produced lung metastatic nodules. Lung nodules were counted under a dissecting stereomicroscope and metastasis investigated by histological analysis.

Results

We found that three i.v. injections of Dr-MCsPTX on day 5, 10 and 15 after tumor injection almost completely abolished B16 lung metastasis. Dr-MCsPTX arrested into lung by interacting with endothelium and migrate toward cancer nodule through a complex mechanism involving primarily mouse lung stromal cells (mL-StCs) and SDF-1/CXCR4/CXCR7 axis.

Conclusions

Our results show for the first time that Dr-MCsPTX are very effective to inhibit lung metastasis formation. Actually, a cure for lung metastasis in humans is mostly unlikely and we do not know whether a therapy combining engineered MSCs and Dr-MCs may work synergistically. However, we think that our approach using Dr-MCs loaded with PTX may represent a new valid and additive therapeutic tool to fight lung metastases and, perhaps, primary lung cancers in human.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0200-3) contains supplementary material, which is available to authorized users.     

Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology

Background:

Mortality rates in lung cancer patients have not decreased significantly in recent years, even with the implementation of new therapeutic regimens. One of the main problems is that a large proportion of patients present local or distant metastasis at the time of diagnosis. The need for identification of novel biomarkers and therapeutic targets for a more effective management of lung cancer led us to investigate TMPRSS4, a protease reported to promote tumour growth and metastasis.

Material and methods:

In all, 34 lung cancer cell lines were used to evaluate the TMPRSS4 expression. Cell migration and clonogenic assays, and an in-vivo lung metastasis model were used for functional analysis of the TMPRSS4 downregulation in H358, H441 and H2170 cell lines. The TMPRSS4 expression analysis in normal and malignant lung tissue samples was performed by qPCR. Five different microarray-based publicly available expression databases were used to validate our results and to study prognosis.

Results:

The TMPRSS4 knock down in H358, H441 and H2170 cells resulted in a significant reduction in proliferation, clonogenic capacity and invasion. A significant (P<0.05) decrease in the lung colonisation and growth was found when mice were injected with TMPRSS4-depleated H358-derived clones, as compared with controls. Expression of TMPRSS4 showed a >30-fold increase (P<0.001) in tumours in comparison with non-malignant samples. Levels in tumours with squamous cell carcinoma (SCC) histology were found to be significantly higher (P<0.001) than those with adenocarcinoma (AC) histology, which was confirmed in data retrieved from the microarrays. Kaplan–Meier curves demonstrated that high levels of TMPRSS4 were significantly associated (P=0.017) with reduced overall survival in the patients with SCC histology, whereas no correlation was found for the AC histology.

Conclusion:

Our results demonstrate that TMPRSS4 has a role in the lung cancer development. The potential use of TMPRSS4 as a biomarker for lung cancer detection or as a predictor of patient''s outcome warrants further investigation.     

Pulmonary metastasectomy in uterine malignancy: outcomes and prognostic factors

Objective

The aim of this study was to investigate outcomes in uterine cancer patients undergoing pulmonary metastasectomy and prognostic factors associated with survival after the procedure.

Methods

A retrospective study was performed in 29 uterine cancer patients who underwent surgical resection of pulmonary metastatic lesions at Samsung Medical Center between June 1995 and December 2011.

Results

Histopathology showed carcinoma in 17 patients (58.6%) and sarcoma in 12 patients (41.4%). Of the 29 patients, 17 (58.6%) had less than three pulmonary metastatic lesions. Eight (27.6%) had symptoms related to lung metastasis. The 5-year survival rate after pulmonary metastasectomy for the entire cohort was 48.2%. On univariate and multivariate analysis, the presence of pulmonary symptoms and more than three lesions of metastasis were associated with poor survival after pulmonary metastasectomy.

Conclusion

Pulmonary metastasectomy for uterine cancer is an acceptable treatment in selected patients. Patients with more than three pulmonary metastatic lesions and pulmonary symptoms related to lung metastasis could expect to have worse prognosis after pulmonary metastasectomy.     

Latency Period until the Development of Thyroid Cancer in Young Patients Submitted to Radiotherapy: Report of 10 Cases

Background

Radiotherapy increases the risk of thyroid cancer (TC); patients submitted to this treatment should undergo a long-term follow-up. Our aim is to describe the features and outcomes of young patients who developed TC after radiotherapy.

Methods

At our center, patients undergoing radiotherapy directly or indirectly involving the thyroid are regularly followed up in order to detect early dysfunction or nodules. Herein, we report the cases of 10 patients who were submitted to radiotherapy and developed TC.

Clinical Findings

Seven patients were irradiated in the neck and 3 in nearby regions. The mean age at the last radiotherapy session was 10 ± 5.5 years. The average time until the appearance of the first thyroid nodule was 14 ± 4.7 years. The mean size increment of the nodules was 2.4 ± 1.6 mm/year. On the first cytology, only 2 results were suspicious of papillary thyroid cancer (PTC). All patients presented a histology of PTC. Eight were in stage I and 2 in stage II. The median follow-up from primary diagnosis to TC and beyond was 20 and 3 years, respectively.

Conclusions

In these patients, cytologies may be difficult to interpret due to persistent benign results. The threshold for surgical indication may be anticipated, considering the increased risk of TC. We report the evolution of these nodules over time, from the end of primary oncological treatment.Key words: Cancer survivors, Radiotherapy, Radiation-related cancer, Thyroid cancer     

Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination with a syngeneic endothelial cell line

Background

Key role of angiogenesis in tumor growth and metastasis based on accumulating evidence and recent progress of immunotherapy have led us to investigate vaccine therapy targeting tumor angiogenesis.

Methods

C57BL/6J mice were vaccinated with a syngeneic endothelial cell line Tpit/E by subcutaneous injection once a week. Prior to ninth vaccination, the mice were challenged with B16/F10 melanoma cells by subcutaneous inoculation on the back for the tumor growth model or by tail venous injection for the lung metastasis model. Development of subcutaneous tumor and lung metastasis was monitored by computed tomography scanning, which enabled accurate evaluation with the minimized sacrifice of mice.

Results

Vaccination with Tpit/E cells inhibited subcutaneous tumor growth and appearance of lung metastasis compared to control. Survival period was elongated in the Tpit/E vaccination in both of the two models. We also obtained hybridomas secreting specific antibodies to Tpit/E cells from a mouse vaccinated with the cells, indicating that specific immune response to the syngeneic endothelial cells was elicited.

Conclusion

These results suggest that vaccination with an autologous endothelial cell line may be effective against melanoma.     

Lipocalin 2 promotes lung metastasis of murine breast cancer cells

Background

Lipocalin 2, an iron binding protein, is abnormally expressed in some malignant human cancers and may play an important role in tumor metastasis. However, the roles of lipocalin 2 in breast cancer formation and metastasis have not been clearly shown. This study aimed to investigate the roles of lipocalin 2 in breast tumor metastasis.

Methods

Lipocalin 2 was overexpressed in the metastatic 4T1 murine mammary cancer cells. The effects of lipocalin 2 overexpression on the malignancy of breast cancer cells were examined using cell proliferation assay, migration assay, invasion assay, and soft agar assay in vitro. Tumor formation and metastasis abilities were examined using a well established mouse mammary tumor model in vivo.

Results

Lipocalin 2 overexpression significantly enhanced the migration and invasion abilities of 4T1 cells in vitro, and lung metastasis in vivo. But overexpression of lipocalin 2 in 4T1 cells didn''t affect cell proliferation and anchorage-independent growth in vitro, and primary tumor weight in vivo. Further studies demonstrated that the inhibition of the PI3K/Akt pathway could be a causative mechanism for the promotion of breast cancer migration/invasion induced by lipocalin 2 overexpression.

Conclusion

These results clarified that lipocalin 2 could promote lung metastasis of 4T1 cells through the inhibition of the PI3K/Akt pathway, suggesting that lipocalin 2 was a potential target for therapy of breast cancer.     

The type of metastasis is a prognostic factor in disseminated cervical cancer

Objective

The objectives of this study were twofold: to verify whether the type of metastasis (lymphatic vs. hematogenous) is a prognostic factor, and to identify molecular markers associated with survival in patients with disseminated cervical cancer.

Methods

Between April 1997 and May 2008, 30 patients with disseminated cervical cancer who had supraclavicular lymph node (N=13) or hematogenous metastases (N=17) were initially treated at our institute. We reviewed medical records to extract clinicopathologic variables. For 17 patients with available pathological specimens, we evaluated the association of immunohistochemical staining for metalloproteinase (MMP)-2, vascular endothelial growth factor (VEGF)-A, and laminin V gamma (LAMC)-2 with survival and clinicopathologic variables via a log-rank test and Cox regression analysis.

Results

Patients who had only lymphatic metastasis (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.4 to 19.5) or completed initial treatment (OR, 3.2; 95% CI, 1.1 to 9.9) showed better survival than patients who did not, but none of the molecular markers were associated with survival. Out of 13 patients with only lymphatic metastasis, three patients who had received volume-directed radiation with concurrent chemotherapy had a long-term survival of over two years. However, patients with hematogenous metastasis showed extremely poor prognosis.

Conclusion

The type of metastasis and completion of initial treatment were associated with prolonged survival in patients with disseminated cervical cancer, and over 20% of patients with lymphatic metastasis were salvaged with volume-directed radiation with concurrent chemotherapy. None of the molecular markers were associated with survival in patients with disseminated cervical cancer.     

Difference between papillary and follicular thyroid carcinoma outcomes: an experience from Egyptian institution

Objective

Differentiated thyroid carcinomas (DTCs) are classified into papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). DTCs are analyzed as a single group in clinical studies that investigated the prognostic factors and prognosis of these malignancies. However, the biological behaviors of these carcinomas significantly differ. In the present study, we aimed to detect differences in the outcomes between PTC and FTC in Mansoura University Hospital in Egypt.

Methods

A total of 558 patients with histologically proven thyroid carcinomas from January 2003 to December 2012 were retrospectively enrolled. The clinical and pathological data of patients were reviewed.

Results

Large primary tumor size, lymph node involvement, extrathyroid extension, and distant metastasis were significant poor prognostic factors for overall survival (OS) in old PTC patients. Cox hazard analysis showed that the patient’s age, extra thyroid extension, and distant metastasis were the only independent prognostic factors. In FTC patients, only the distant metastasis and degree of tumor invasion were significant poor prognostic factors in OS univariate analysis. However, these factors were nonsignificant in multivariate analysis. The 10-year OS rates were 97% and 89% for PTC and FTC, respectively (P=0.003). The 10-year disease-free survival (DFS) rates were 77.2% in PTC vs. 65% in FTC (P=0.179).

Conclusion

The significant prognostic factors vary between the two types of DTCs. Therefore, PTC and FTC patients need to be analyzed and reported independently. PTC survival is widely and significantly affected by age, extrathyroid extension, and distant metastasis. By contrast, these factors were nonsignificant in FTC, which showed poorer survival than PTC.KEYWORDS : Thyroid cancer, differentiated thyroid, papillary, follicular, Egypt     

The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma

Background:

To elucidate the incidence and mechanisms of sunitinib-induced thyroid atrophy, we investigated serial volumetric and functional changes, and evaluated histological changes of the thyroid gland in metastatic renal cell carcinoma patients who received sunitinib.

Methods:

Thyroid volume (by computed tomography volumetry) and thyroid function were measured at baseline, during the treatment, and at post-treatment periods. Histological evaluation of the thyroid gland was performed in four autopsied patients.

Results:

The median reduction rate in thyroid volume at last evaluation during sunitinib treatment was 30% in all 17 patients. The incidence of hypothyroidism during sunitinib treatment was significantly higher in the high reduction rate group (n=8; more than 50% reduction in volume) than in the low reduction rate group (n=9; less than 50% reduction in volume). Half of the patients in the high reduction rate group exhibited a transient thyroid-stimulating hormone suppression, suggesting thyrotoxicosis during sunitinib treatment. Histological evaluation demonstrated atrophy of thyroid follicles and degeneration of follicular epithelial cells without critical diminution of vascular volume in the thyroid gland.

Conclusion:

Thyroid atrophy is frequently observed following sunitinib treatment and may be brought about by sunitinib-induced thyrotoxicosis or the direct effects of sunitinib that lead to degeneration of thyroid follicular cells.     

Elevated expression of myosin X in tumours contributes to breast cancer aggressiveness and metastasis

Background:

Myosin X (MYO10) was recently reported to promote tumour invasion by transporting integrins to filopodial tips in breast cancer. However, the role of MYO10 in tumours remains poorly defined. Here, we report that MYO10 is required in invadopodia to mediate invasive growth and extracellular matrix degradation, which depends on the binding of MYO10''s pleckstrin homology domain to PtdIns(3,4,5)P3.

Methods:

The expression of MYO10 and its associations with clinicopathological and biological factors were examined in breast cancer cells and breast cancer specimens (n=120). Cell migration and invasion were investigated after the silencing of MYO10. The ability of cells to form invadopodia was studied using a fluorescein isothiocyanate-conjugated gelatin degradation assay. A mouse model was established to study tumour invasive growth and metastasis in vivo.

Results:

Elevated MYO10 levels were correlated with oestrogen receptor status, progesterone receptor status, poor differentiation, and lymph node metastasis. Silencing MYO10 reduced cell migration and invasion. Invadopodia were responsible for MYO10''s role in promoting invasion. Furthermore, decreased invasive growth and lung metastasis were observed in the MYO10-silenced nude mouse model.

Conclusions:

Our findings suggest that elevated MYO10 expression increases the aggressiveness of breast cancer; this effect is dependent on the involvement of MYO10 in invadopodial formation.     

Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion

Background:

Focal adhesion kinase (FAK) is overexpressed in a variety of cancers, such as breast, colon, prostate, ovary, and lung cancers. However, the mechanism by which extracellular matrix fibronectin stimulates lung cancer cell migration and invasion through FAK remains to be investigated.

Methods:

The signalling pathways in fibronectin-mediated lung cancer cell migration and invasion were examined using western blotting. The metastasis function was detected by wound healing, migration and invasion assays. Further, RNA interference and kinase inhibitors were also used to study the downstream signals.

Results:

In this study, we examined the FAK signalling pathways in relation to calpain-2 and RhoA in fibronectin-mediated lung cancer cell migration and invasion. We found that A549 lung epithelial cells stimulated by fibronectin showed increased phosphorylation of FAK and its downstream targets, Src, ERK1/2, phosphatidylinositol 3′-kinase (PI3K), and Akt. Consistent with this observation, depletion of FAK by siRNA resulted in the inhibition of Src, ERK1/2, PI3K, and Akt activity. In addition, the Src inhibitor, PP2, blocked the phosphorylation of FAK, ERK1/2, PI3K, and Akt. Conversely, inhibition of MEK1/2 using PD98059 reduced the expression of matrix metalloproteinase-9 (MMP9) and calpain-2. The PI3K inhibitor, {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, further blocked the expression of MMP9 and RhoA. Inhibition of both MEK1/2 and PI3K caused reduced cell migration and invasion.

Conclusion:

Our data suggest that fibronectin-mediated activation of FAK that leads to lung cancer metastasis could occur through ERK or PI3K/Akt regulation of MMP9/calpain-2 or MMP9/RhoA activity, respectively.     

Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study

Background:

This study examined the risk of cancer in patients with Hashimoto''s thyroiditis (HT).

Methods:

The Taiwanese National Health Insurance Research Database (NHIRD) was used to identify 1521 newly diagnosed HT patients from 1998–2010, and 6084 frequency-matched non-HT patients. The risk of developing cancer for HT patients was measured using the Cox proportional hazard model.

Results:

The incidence of developing cancer in the HT cohort was 5.07 per 1000 person-years, which was 1.68-fold higher than that in the comparison cohort (P<0.001). Compared with patients aged 20–34 years, patients in older age groups had a higher risk of developing cancer (35–55 years: hazard ratio (HR)=5.96; >55 years: HR=9.66). After adjusting for sex, age, and comorbidities, the HT cohort had HRs of 4.76 and 11.8 for developing colorectal cancer and thyroid cancer, respectively, compared with non-HT cohort. Furthermore, the HT cohort to non-HT cohort incidence rate ratio (IRR) of thyroid cancer was higher in the first 3 years (48.4, 95% confidence interval (CI)=35.0–66.3), with an adjusted HR of 49.4 (95% CI=6.39–382.4).

Conclusion:

Hashimoto''s thyroiditis patients have a higher risk of thyroid cancer and colorectal cancer. The thyroid cancer prevention effort should start soon after HT is diagnosed, while being cautious of colorectal cancer increases with time.     

Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer

Background

Bevacizumab has been increasingly used in combination chemotherapy with paclitaxel for treatment of metastatic or recurrent breast cancer. The aim of this report is to underline possible risks associated with the new combination chemotherapy.

Case Presentation

A 39-year-old woman with recurrent breast cancer was treated with bevacizumab and paclitaxel. Positron emission tomography revealed breast cancer metastasis to the left supraclavicular lymph nodes and right axillary lymph nodes, with no distant metastasis.

Results

After the third cycle of bevacizumab and paclitaxel, the patient developed a bloody bowel discharge. Emergent colonoscopy demonstrated diverticular bleeding on one of the multiple diverticula in the ascending colon. The bleeding point was successfully clipped colonoscopically.

Conclusion

The factors for diverticular bleeding are believed to be non-steroidal anti-inflammatory drugs, constipation, and bevacizumab. We recommend reviewing anamneses for diverticulitis, multiple prior abdominal surgeries, peritoneal carcinomatosis, and regular use of certain drugs.Key Words: Breast cancer, Bevacizumab, Paclitaxel, Adverse effects, Diverticular bleeding, Non-steroidal anti-inflammatory drugs, Opioid analgesics     

Characteristics of thyroid incidentalomas detected by pre-treatment [18F]FDG PET or PET/CT in patients with cervical cancer

Objective

Considering the increased use of [¹⁸F]FDG PET or PET/CT, the clinical significance of thyroid incidentalomas is the subject of controversy. The aim of this study was to determine the incidence of malignancies associated with thyroid incidentalomas detected by pre-treatment PET or PET/CT in patients with cervical cancer.

Methods

We retrospectively reviewed the medical records of patients with cervical cancer who had thyroid incidentalomas detected by pre-treatment PET or PET/CT and were treated at our institute between January 2001 and December 2009.

Results

Of 327 patients who underwent pre-treatment PET or PET/CT, 33 patients had thyroid incidentalomas (10.1%) and 4 patients were diagnosed with thyroid malignancies by percutaneous needle aspiration (PCNA) or surgery. To put it concretely, of 33 patients with thyroid incidentaloma, 16 patients had a diffuse uptake and 17 patients had a focal uptake. Four of 17 patients with focal uptake were diagnosed with thyroid malignancies (23.5%). One patient with a focal uptake had an atypical cell based on PCNA, but did not undergo additional studies. The mean SUV_max of thyroid malignancies did not differ from that of benign thyroid diseases.

Conclusion

Thyroid incidentalomas are frequently detected by pre-treatment PET or PET/CT in patients with cervical cancer. Focal uptake on PET or PET/CT has a high risk of thyroid cancer.     

Prognostic role of lymph node metastasis in early gastric cancer

Objective： To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gaswic cancer （EGC） patients. Methods： We retrospectively observed 226 EGC patients with lymph node resection, and analyzed the associations between lymph node metastasis and clinicopathological parameters using the chi-square test in univariate analysis and logistic regression analysis in multivariate analysis. Overall survival analysis was determined using the Kaplan-Meier and log-rank test. We conducted multivariate prognosis analysis using the Cox proportional hazards model. Results： Of all the EGC patients, 7.5% （17/226） were histologically shown to have lymph node metastasis. The differentiation, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in EGC. The 5- and 10-year survival rates were significantly lower in patients with lymph node metastasis than in those without and the patients also had shorter progress-free survival time. Lymph node metastasis and tumor size were independent prognostic factors for EGC. The status of the lymph nodes was a significant factor in predicting recurrence or metastasis after surgery. Conclusions： The undifferentiated carcinoma and lymphovascular and/or submucosal invasion were associated with a higher incidence of lymph node metastasis in EGC patients, whom need to perform subsequent D2 lymphadenectomy or laparoscopic lymph node dissection and more rigorous follow-up or additional chemotherapy/radiation after D2 gastrectomy for poor prognosis and high recurrence/metastasis rate.     

UHRF1 is a novel diagnostic marker of lung cancer

Background:

Lung cancer is the leading cause of cancer deaths worldwide. As the sensitivity and specificity of current diagnostic markers are not perfect, we examined whether ubiquitin-like with PHD and ring finger domains 1 (UHRF1), which is overexpressed in various cancers but not yet examined in lung cancer in large scale, can be a novel diagnostic marker of lung cancer.

Methods:

Immunohistochemical analysis using surgical specimens obtained from 56 US and 322 Japanese patients with lung cancer was performed.

Results:

The UHRF1 was stained specifically in the nuclei of cancer cells, but not in the other cells. The UHRF1 expression was observed in all histological types of lung cancer, especially in non-adenocarcinomas (non-ADCs), both in the US and Japanese cases. In 322 Japanese non-small cell lung cancer (NSCLC) cases, UHRF1 expression was associated with the histological type (higher in non-ADCs; P<0.00001), gender (higher in male; P=0.00082), smoking (higher in smokers; P=0.00004), pT factor (higher in advanced stage; P=0.00010), and pN factor (higher in cancers with metastasis in regional lymph nodes; P=0.00018). The UHRF1 expression was also associated with poor prognosis for NSCLC patients (P=0.0364). Although UHRF1 overexpression was associated with these malignant indicators, UHRF1 was detectable in half of lung cancer patients in an early pathological stage.

Conclusion:

The UHRF1 is overexpressed in various types of lung cancer from early pathological stage. Therefore, detection of UHRF1 expression in tissue specimens by immunohistochemistry can be useful for diagnosis of lung cancer in all pathological stages.