Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone.

Calcium homeostasis is a tightly regulated process involving the co-ordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Neoplasms can alter this homeostasis indirectly through the production of endocrine factors resulting in humoral hypercalcaemia of malignancy. Relatively common with breast and lung cancer, this paraneoplastic condition is most often due to tumour production of parathyroid hormone-related protein and ensuing increased osteoclastic bone resorption. Although control of hypercalcaemia is generally successful, the development of this complication is associated with a poor prognosis. The metastasis of tumour cells to bone represents another skeletal complication of malignancy. As explained in the 'seed and soil' hypothesis, bone represents a fertile ground for cancer cells to flourish. The molecular mechanisms of this mutually beneficial relationship between bone and cancer cells are beginning to be understood. In the case of osteolytic bone disease, tumour-produced parathyroid hormone-related protein stimulates osteoclasts that in turn secrete tumour-activating transforming growth factor-beta that further stimulates local cancer cells. This 'vicious cycle' of bone metastases represents reciprocal bone/cancer cellular signals that likely modulate osteoblastic bone metastatic lesions as well. The development of targeted therapies to either block initial cancer cell chemotaxis, invasion and adhesion or to break the 'vicious cycle' is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.

Prognostic factors for conditional survival in patients with muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy.

Because only a few studies have evaluated conditional survival (CS) in bladder cancer patients, we examined conditional overall survival (OS) and cancer-specific survival (CSS) in these patients after radical cystectomy (RC), and determined which prognostic variables affect CS over time. We reviewed 487 patients treated with RC and pelvic lymph node dissection at our institution between 1991 and 2012. Cox regression models were used to identify the significant prognostic factors for CS depending on clinicopathological characteristics. As survival time increased after RC, conditional OS and CSS rates increased when compared with baseline survival probability. CS more significantly improved in the patients with unfavorable pathologic characteristics. While many variables were associated with survival at baseline, only age was found to be a significant prognostic factor for 5-year conditional OS in all given survivorships. In conclusion, conditional OS and CSS probabilities significantly improved over time, with greater improvements in the cases with unfavorable pathologic features. Moreover, age remained the key prognostic factor for conditional OS estimates from baseline to 5 years after surgery. Our results provide practical survival information to guide adjustments in our current follow-up strategy for bladder cancer patients after RC.

A cyanoacrylate and silastic patch to reduce the risk of opening of the tumor: technical note.

BACKGROUND: Wide surgery is the main factor influencing survival in muscular skeletal tumor. Sometimes the margin can be very thin and the contamination risk can be very high because of manipulation of the mass. MATERIALS AND METHODS: A patch of cyanoacrylate and a silastic mesh are applied on tumor surface. In order to demonstrate the tumor sealing an histologic exam was performed. DISCUSSION: The application of protective patch can decrease the risk of accidental tumor rupture and neoplastic cells spreading.

Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell carcinoma of the bladder can distinguish between residual tumour and post-chemotherapy effect.

INTRODUCTION: Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff). METHODS AND MATERIALS: Twenty-one patients underwent DCE-MRI scans with 2.5s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T2-weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI80s) and plasma perfusion (Fp) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Student's t-test. RESULTS: Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI80s and Fp were significantly higher in areas of residual tumour than Tr-Eff (rSI80s = 2.9 vs 1.7, p < 0.001; Fp = 20.7 vs 9.1 ml/100ml/min, p = 0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI80s), 60% and 86% (Fp), and 75% and 100% when combined. CONCLUSION: DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy.

Immunotoxicologic effects of cyclosporine on tumor progression in models of squamous cell carcinoma and B-cell lymphoma in C3H mice.

Many immunosuppressive drugs are associated with an increased risk of neoplasia, principally non-melanoma skin cancers and B-cell lymphomas. However, only 6 of the 13 immunosuppressive drugs tested in 2 year bioassays increased the incidence of neoplasia. For example, the 2-year bioassays conducted with cyclosporine (CSA), an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, were negative. The purpose of these investigations was to use transplanted tumor models in immunocompetent, syngeneic mice to gain insight into the failure of the 2-year bioassay to show an increased incidence of neoplasia with CSA. C3H HeN mice were used in a battery of assays with a transplanted squamous cell carcinoma (SCC VII cells) or a B-cell, lymphoma (38C13 cells) cells to study effects of CSA on local growth and metastases, experimental metastases, and progression of established metastases. Mice received CSA twice weekly by subcutaneous (SC) injection at doses of 0.5, 5, or 50 mg/kg; controls received the CSA vehicle. CSA had a modest inhibitory effect on SC tumors initiated by 38C13 cells and on intramuscular tumors initiated by SCC VII cells. CSA also decreased the number of lung colonies and decreased the size, growth fraction and vascularity of established lung metastases initiated by SCC VII cells. In contrast, CSA increased progressive growth of metastases to the sentinel lymph node from an intramuscular SCC VII tumor, but had no effect cellular traffic to the node. In conclusion, CSA at doses up to 50 mg/kg did not facilitate tumor progression and it partially inhibited tumor growth, suggesting that suppression of tumor progression may partially explain the failure of CSA to act as a carcinogen in 2 year bioassays.

Port site metastasis after laparoscopic-assisted vaginal hysterectomy for endometrial cancer: possible mechanisms and prevention.

Only 19 cases of metastases at the cannula insertion site after laparoscopy for gynecological malignancy have been reported in the literature. One case has been diagnosed with cervical squamous cell carcinoma, whereas the others have been diagnosed with ovarian cancer and borderline ovarian tumor. We present a novel case of laparoscopy-site abdominal wall metastasis from endometrial cancer after laparoscopic-assisted vaginal hysterectomy (LAVH). The 56-year-old female patient exhibited metastases of an abdominal wall trocar site and a perineal site after undergoing LAVH and laparoscopic-assisted (LA) bilateral pelvic lymph node sampling as well as LA para-aortic lymph node sampling for treating endometrial carcinoma, surgical staging IIIC, G3. The interval between the surgical extirpation of endometrial carcinoma and diagnosis of the tumor recurrence was 6 months, suggesting that overmanipulation of the diseased organ during laparoscopic surgery may have resulted in tumor spillage, intraperitoneal dissemination, and wound contamination. Although this procedure has been proven beneficial to patients with benign disease or early-stage gynecologic malignancies, laparoscopic-assisted vaginal hysterectomy may not be efficacious to eradicate advanced gynecological malignancy.

Unexpected gallbladder cancer and laparoscopic surgery.

Case histories of three patients who underwent laparoscopic cholecystectomy for unexpected gallbladder cancer are reviewed. Port-site recurrence was observed in two of them. In one patient whose abdominal wall recurrent tumor was excised, a new recurrence developed, but after the reexcision she is symptom-free 10 months after the last procedure. The surgeon has to be aware of the fact that the survival rate can be doubled in stage pT2 if cholecystectomy is followed by extended radical operation. Only gallbladder cancer in stage pT1 does not need further procedure, except for excision of port sites. In case of uncertain diagnosis preoperative frozen section is recommended. Port-site recurrence does not mean an incurable stage of the disease or a sign of diffuse metastases. Even after reexcision of abdominal wall metastasis patients might be free from other detectable recurrences.