Histological variants and lymphovascular invasion in upper tract urothelial carcinoma can stratify prognosis after radical nephroureterectomy.

OBJECTIVES: Patients with histological variants (HV) of bladder cancer have more advanced disease and poorer survival rates than those with pure urothelial carcinoma (UC). Moreover, lymphovascular invasion (LVI) is an important biomarker after RNU in systematic reviews and meta-analyses. Thus, here we investigated the clinical and prognostic impact of HV and LVI in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: Data from 223 UTUC patients treated with RNU without neoadjuvant chemotherapy were retrospectively evaluated. We analyzed differences in clinicopathological features and survival rates between patients with pure UC and those with HV. Conditional survival (CS) analysis was performed to obtain prognostic information over time. RESULTS: A total of 32 patients (14.3%) had HV, with the most common variant being squamous differentiation, followed by glandular differentiation. UTUC with HV was significantly associated with advanced pathological T stage (pT ≥ 3), higher tumor grade (G3), and LVI, compared to pure UC (all P < 0.01). Progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were all significantly worse in the HV group compared to the pure UC group (all, P < 0.001). In multivariable analysis, HV and LVI were independent predictors of CSS and OS. We classified the patients into three groups using these two predictors: low-risk (neither HV nor LVI), intermediate-risk (either HV or LVI), and high-risk (both HV and LVI). Significant differences in PFS, CSS, and OS rates were found among the 3 groups. In CS analysis, the conditional PFS, CSS, and OS rates at 1, 2, 3, 4, and 5 years improved with increased duration of event-free survival. CS analysis revealed that most progression events occurred within 2 years after RNU, and patients with risk factors had worse PFS at all time points. CONCLUSIONS: A risk model using HV and LVI can stratify PFS, CSS, and OS of patients treated with RNU. In addition, CS analysis revealed that HV and LVI were poor prognostic factors over time after RNU.

Prognostic value of Ki67 and p53 in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer: Validation of the cut-off value of the Ki67 labeling index as a predictive factor.

The aim of this study was to evaluate the significance of the Ki67 labeling index and p53 status as prognostic and predictive indicators of operable estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Among 697 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2013, 308 patients with ER-positive and HER2-negative breast cancer were assessed. The results of the multivariate Cox analysis demonstrated that a high Ki67 labeling index was significantly associated with a short recurrence-free interval (RFI) (p=0.004) and was marginally associated with a worse overall survival (p=0.074). A positive p53 status was not associated with worse outcomes. To validate the cut-off values of the Ki67 labeling index for identifying patients who may benefit from additional chemotherapy, prognostic factors were investigated in breast cancer patients treated postoperatively with endocrine therapy alone. Analysis of receiver operating characteristic curves demonstrated that a Ki67 labeling index cut-off of 20.0% was optimal for predicting recurrence among patients who did not receive adjuvant chemotherapy. The 5-year RFIs for patients with Ki67 <20 and ≥20% were 97.2 and 86.6%, respectively (p=0.0244). A high Ki67 labeling index (≥20%) was significantly associated with large tumors (p<0.01), lymph node metastasis (p=0.0236) and positive p53 status (p<0.001). The univariate analysis demonstrated that Ki67 labeling index ≥20%, lymph node metastasis and progesterone receptor negativity were significant worse prognostic factors for RFI (p=0.0333, 0.0116 and 0.0573, respectively). The Ki67 labeling index was found to be a useful prognostic factor in patients with ER-positive and HER2-negative breast cancer and the cut-off values of the Ki67 labeling index for making a decision regarding adjuvant treatment were validated.

Overexpression of hypoxia inducible factor-1 alpha is an independent risk factor for recurrence after curative resection of colorectal liver metastases.

BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is a major regulator of tumorigenesis in hypoxic conditions and therefore represents a potential therapeutic target in colorectal cancer (CRC). Clinical significance of HIF-1α expression in liver metastases has not been elucidated. Therefore, this study aimed to clarify the clinical significance of HIF-1α expression in colorectal liver metastasis (CRLM). METHODS: We retrospectively analyzed 64 patients who underwent curative resection of CRLM from 2000 to 2008. We evaluated HIF-1α expression by immunohistochemical staining and analyzed its association with several clinicopathological characteristics, including vascular endothelial growth factor (VEGF) expression. We analyzed the mutation status of genes involved in CRC (p53, KRAS, BRAF, and PIK3CA). Finally, we compared HIF-1α expression between the primary tumor and the corresponding liver metastases. RESULTS: We found a significant positive correlation between HIF-1α expression in liver metastases and PIK3CA mutation status (p = 0.019). A significant correlation was also observed between the expressions of HIF-1α and VEGF in liver metastases and primary tumors (p = 0.015, 0.024, respectively). High HIF-1α expression in liver metastases was an independent risk factor for recurrence (p = 0.031). CONCLUSIONS: Our results suggest a possible induction of HIF-1α expression by mutant PIK3CA. The expressions of HIF-1α and VEGF in liver metastases significantly correlated with those in the corresponding primary tumor. Overexpression of HIF-1α was an independent risk factor for recurrence after curative resection of CRLM, suggesting that HIF-1α represents an important candidate for the treatment of CRLM in a subset of patients with high HIF-1α expression.

[A case of late recurrent breast cancer that responded to radiation therapy and cisplatin plus pemetrexed therapy].

The patient was a 62-year-old woman who had undergone modified radical mastectomy for right breast cancer 19 years before. She was examined at our hospital for cough and hoarseness. After PET-CT and bronchoscopy, she was diagnosed with stage IIIB non-small cell lung cancer. Radiation therapy and cisplatin plus pemetrexed therapy were effective, and she made a recovery from a life-threatening conditon. During observation, a skin nodule was noticed on her right chest wall, and excisional biopsy revealed a skin metastasis from breast cancer. A transbronchial lung biopsy(TBLB)specimen was reexamined, and the lung lesion was shown to be metastasis from breast cancer. By changing to endocrine therapy, the disease has been effectively controlled.

Inflammatory pseudotumor suspected of lung cancer treated by thoracoscopic resection.

We report a relatively rare surgical treatment for two cases of inflammatory pseudotumors of the lung. In case 1, a 52-year-old male with a history of left chest pain was admitted to our hospital for an abnormal nodule with an irregular margin that was detected in the left upper lung field. The nodule, measuring 15 mm in diameter, was larger than the one observed six months earlier, which had been removed by a thoracoscopic resection. In case 2, a 64-year-old female with a history of chronic cough and hemoptysis was admitted to our hospital, and an abnormal nodule with pleural indentation was detected in the lower left lung field. The nodule, measuring 8 mm in diameter, was also removed by a thoracoscopic resection. In both cases, the histologic examination enabled us to diagnose the lesion as an inflammatory pseudotumor. In general, it is very difficult to differentiate inflammatory pseudotumors from malignant tumors of the lung. The best treatment for inflammatory pseudotumors is usually early and complete surgical resection, since it can lead to improved survival. Therefore, we consider thoracoscopy-aided surgery to be less invasive and more useful than other surgical methods in the diagnosis and treatment of inflammatory pseudotumor of the lung.

Sarcoidosis with multiple organ involvement emerging as Löfgren's syndrome.

A 52-year-old woman was admitted because of high-grade remittent fever, erythema nodosum, and arthritis which had been lasting two months. Antibiotics did not improve her condition. A chest CT scan examination revealed bilateral hilar and mediastinal adenopathy and multiple nodular opacities in the bilateral lungs. The wedge biopsy of the right lower lobe using video-assisted thoracoscopy presented the histological findings of sarcoidosis. Finally, this case fulfilled the criteria of Löfgren's syndrome. Due to the uncovered cardiac involvement, the systemic glucocorticoid therapy had to be initiated. This case suggests that atypical forms of sarcoidosis should be kept in mind as well, when facing cases with unknown fever.