Partial Nephrectomy in the Treatment of Localized Renal Cell Carcinoma — Experience of Taichung Veterans General Hospital

BackgroundPartial nephrectomy has been considered an effective and efficient method in the treatment of localized renal cell carcinoma. Herein, we retrospectively review our experience with partial nephrectomy in the treatment of localized renal cell carcinoma and compared it with patients who received radical nephrectomy.MethodsFrom 1982 to 2005, 35 patients who received partial nephrectomy for localized renal cell carcinoma were enrolled in this study. Ten patients were female (28.6%). The median age was 70 years (range, 42–82 years). Sixteen (45.7%) patients had pathologic T1a tumors; 17 (48.6%) patients had pathologic T1b tumors and 2 (5.7%) patients had pathologic T2 tumor (7 cm). In the meantime, 128 patients who had T1N0M0 renal cell carcinoma and who received radical nephrectomy were assigned to a control group. Thirty-nine patients (30.5%) were female in this group. The median age was 62 years (range, 30–83 years). The tumor characteristics, location, surgical techniques and patient survival were subsequently compared.ResultsThe median tumor size in the partial nephrectomy group was 3.9 cm (range, 1.5–7.0 cm), and it was 4.5 cm (range, 1–6.5 cm) in radical nephrectomy group. The tumor size was smaller in the partial nephrectomy group (p = 0.003). The median follow-up period was 4.38 years (range, 0.05–17.99 years) in the partial nephrectomy group and 5.66 years (range, 0.01–22.25 years) in the radical nephrectomy group. There was no local recurrence or distant metastasis in the partial nephrectomy group. The 5-year overall survival was 85.0% compared with 91.4% in the radical nephrectomy group (p = 0.126). The 5-year disease-specific survival in the partial nephrectomy group was 100%. The postoperative serum creatinine level increased to > 2.0 mg/dL in 5 (14.3%) patients in the partial nephrectomy group, but no patient needed hemodialysis during follow-up.ConclusionFrom our review, partial nephrectomy is safe and provides excellent disease control in the treatment of localized renal cell carcinoma in selected patients. Renal function preservation was observed in the partial nephrectomy group, while the operated kidney showed functioning in the follow-up nuclear medicine survey

Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model

<p>Abstract</p> <p>Background</p> <p>Hedgehog signalling has been implicated in prostate tumorigenesis in human subjects and mouse models, but its effects on transforming normal basal/stem cells toward malignant cancer stem cells remain poorly understood.</p> <p>Methods</p> <p>We produced pCX-shh-IG mice that overexpress Hedgehog protein persistently in adult prostates, allowing for elucidation of the mechanism during prostate cancer initiation and progression. Various markers were used to characterize and confirm the transformation of normal prostate basal/stem cells into malignant cancer stem cells under the influence of Hedgehog overexpression.</p> <p>Results</p> <p>The pCX-shh-IG mice developed prostatic intraepithelial neoplasia (PIN) that led to invasive and metastatic prostate cancers within 90 days. The prostate cancer was initiated through activation of P63⁺basal/stem cells along with simultaneous activation of Hedgehog signalling members, suggesting that P63⁺/Patch1⁺and P63⁺/Smo⁺cells may serve as cancer-initiating cells and progress into malignant prostate cancer stem cells (PCSCs). In the hyperplastic lesions and tumors, the progeny of PCSCs differentiated into cells of basal-intermediate and intermediate-luminal characteristics, whereas rare ChgA⁺neuroendocrine differentiation was seen. Furthermore, in the metastatic loci within lymph nodes, kidneys, and lungs, the P63⁺PCSCs formed prostate-like glandular structures, characteristic of the primitive structures during early prostate development. Besides, androgen receptor (AR) expression was detected heterogeneously during tumor progression. The existence of P63⁺/AR^-, CK14⁺/AR^-and CD44⁺/AR^-progeny indicates direct procurement of AR^-malignant cancer trait.</p> <p>Conclusions</p> <p>These data support a cancer stem cell scenario in which Hedgehog signalling plays important roles in transforming normal prostate basal/stem cells into PCSCs and in the progression of PCSCs into metastatic tumor cells.</p

Differential change in cortical and hippocampal monoamines, and behavioral patterns in streptozotocin-induced type 1 diabetes rats

Objective(s): Diabetes mellitus (DM) is a widespread metabolic disorder worldwide. Clinical physicians have found diabetic patients have mild to middle cognitive dysfunction and an alteration of brain monoaminergic function. This study explored the change in various patterns of behavioral models and brain monoamine function under streptozotocin (STZ)-induced type 1 diabetes.Materials and Methods: We established a type 1 DM model via intravenous injection with STZ (65 mg/kg) in rats. Three weeks after the STZ injection, various behavioral measurements including the inhibitory avoidance test, active avoidance test and Morris water maze were conducted. Finally, all rats were dissected and the concentrations of monoamines and their metabolites in cortex and hippocampus were measured by high performance liquid chromatography with electrochemical detection.Results: We found that STZ induced type 1 diabetes (hyperglycemia and lack of insulin) in rats. STZ-induced diabetic rats had cognitive impairment in acquisition sessions and long-term retention of the active avoidance test. STZ-induced diabetic rats also had cognitive impairment in spatial learning, reference and working memory of the Morris water maze. STZ significantly reduced concentrations of norepinephrine (NE) in the cortex and dopamine (DA) in the hippocampus, but increased concentrations of DA and serotonin (5-HT) in the cortex 35 days after injection. The concentration of 5-HT in the hippocampus was also significantly increased.Conclusion: The data suggested that this cognitive impairment after a short-term period of STZ injection might be related to cortical NE dysfunction, differential alteration of cortical and hippocampal DA function, and brain 5-HT hyperfunction

Therapeutic Potential and Mechanisms of Novel Simple O-Substituted Isoflavones against Cerebral Ischemia Reperfusion

Isoflavones have been widely studied and have attracted extensive attention in fields ranging from chemotaxonomy and plant physiology to human nutrition and medicine. Isoflavones are often divided into three subgroups: simple O-substituted derivatives, prenylated derivatives, and glycosides. Simple O-substituted isoflavones and their glycosides, such as daidzein (daidzin), genistein (genistin), glycitein (glycitin), biochanin A (astroside), and formononetin (ononin), are the most common ingredients in legumes and are considered as phytoestrogens for daily dietary hormone replacement therapy due to their structural similarity to 17-β-estradiol. On the basis of the known estrogen-like potency, these above isoflavones possess multiple pharmacological activities such as antioxidant, anti-inflammatory, anticancer, anti-angiogenetic, hepatoprotective, antidiabetic, antilipidemic, anti-osteoporotic, and neuroprotective activities. However, there are very few review studies on the protective effects of these novel isoflavones and their related compounds in cerebral ischemia reperfusion. This review primarily focuses on the biosynthesis, metabolism, and neuroprotective mechanism of these aforementioned novel isoflavones in cerebral ischemia reperfusion. From these published works in in vitro and in vivo studies, simple O-substituted isoflavones could serve as promising therapeutic compounds for the prevention and treatment of cerebral ischemia reperfusion via their estrogenic receptor properties and neuron-modulatory, antioxidant, anti-inflammatory, and anti-apoptotic effects. The detailed mechanism of the protective effects of simple O-substituted isoflavones against cerebral ischemia reperfusion might be related to the PI3K/AKT/ERK/mTOR or GSK-3β pathway, eNOS/Keap1/Nrf-2/HO-1 pathway, TLRs/TIRAP/MyD88/NFκ-B pathway, and Bcl-2-regulated anti-apoptotic pathway. However, clinical trials are needed to verify their potential on cerebral ischemia reperfusion because past studies were conducted with rodents and prophylactic administration

Combination of Durvalumab and Chemotherapy to Potentially Convert Unresectable Stage IV Penile Squamous Cell Carcinoma to Resectable Disease: A Case Report

Penile squamous cell carcinoma is a rare disease entity with poor overall survival in an advanced stage. Few studies have investigated the role of immunotherapy in advanced penile squamous cell carcinoma. Herein, we report a case of stage IV unresectable penile squamous cell carcinoma presenting with anal bleeding and urethra obstruction who responded dramatically to combination therapy of durvalumab and cisplatin-based chemotherapy. The patient had HPV-positive penile squamous cell carcinoma, cT3N3M0, with concomitant anus squamous cell carcinoma. After 2 months of the combination treatment, almost all bulky inguinal lymph nodes shrank, and the main tumor of the anus and penis responded completely. A durable response was seen 16 months after initiating the combination therapy. This case report highlights the potential role of the combination of immunotherapy and chemotherapy in patients with advanced penile cancer. The promising results of this combination resulted in the conversion of unresectable disease to a potentially curable disease

Mixed Epithelial and Stromal Tumor of the Kidney

A 42-year-old female presented with intermittent left flank pain for 2 years. She developed gross hematuria 1 month prior to seeking help. Intravenous pyelography showed filling defects within the lower portion of the left collecting system and renal pelvis causing hydronephrosis. Abdominal computed tomography revealed a huge cystic heterogenic tumor about 20 cm in largest diameter occupying the entire left kidney. A left radical nephrectomy was performed without complications. The pathology report confirmed the diagnosis of mixed epithelial and stromal tumor of the kidney. From pathologic survey, the spindle cells of this tumor were positive for muscle markers and expressed estrogen and/or progesterone receptors. We suggest that a mixed epithelial and stromal tumor of the kidney should be considered in all cystic renal tumors presenting in perimenopausal women