Milan Visnjic

Viral Infection in Renal Transplant Recipients

Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

Characteristics of upper urothelial carcinoma in an area of Balkan endemic nephropathy in south Serbia. A fifty-year retrospective study.

Aims and background Upper urinary tract transitional cell carcinoma, a relatively rare tumor, is up to 100 times more frequent in regions with Balkan endemic nephropathy. Characteristics of transitional cell carcinoma in the endemic South Morava Region in Serbia in the previous 50 years were evaluated. Patients We analyzed 477 cases with pathologically confirmed transitional cell carcinoma who underwent surgery from 1957 to 2006: 91 from endemic, 106 from adjacent and 280 from control settlements. Cases in the study came from 10 endemic villages, 46 adjacent villages, 51 control villages and the city of Nis. Results The increase in number of transitional cell carcinoma from 1957 was followed by a peak between 1967 and 1978 (yearly incidence 21.9 per 100,000) and a slow decrease thereafter to 7.4 (1997–2006). In the control settlements, the increase was steady. Reduced kidney function at surgery was found in 58% of patients from endemic and in 20% from control settlements. Age at surgery has significantly increased from 52.3 and 51.5 (1957–1966) to 70.9 and 66.1 (1997–2006) for endemic and control settlements, respectively. The female sex was predominant in endemic and adjacent settlements and the male sex in control settlements. Transitional cell carcinoma from endemic settlements was of a lower grade in the period from 1957–1986, but in the period from 1987–2006 they were predominantly high grade. Low tumor stage (pTa-pT1) predominated in transitional cell carcinoma from the endemic and adjacent but not the control settlements in the period from 1957 to 1986. However, in the last 20 years, upper urinary tract transitional cell carcinoma stage increased, the highest in the period from 1997 to 2006 in all settlements studied. Conservative surgery was advocated for transitional cell carcinoma in Balkan endemic nephropathy areas up to 1996. Transitional cell carcinoma are now more malignant and more advanced than before, and a less aggressive approach is used only for absolute indications. Conclusions An increased number of transitional cell carcinoma in endemic settlements was observed, markedly decreasing in the last decade. An increasing age and a shorter survival were recorded in patients both from Balkan endemic nephropathy and control settlements. Sporadic cases upper urinary tract transitional cell carcinoma in settlements adjacent to endemic settlements were demonstrated. Free full text available at www.tumorionline.it

Urothelial Cancer Stem Cells

There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs), which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs) raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies.

E-cadherin expression in upper urothelial carcinoma in Balkan Endemic Nephropathy and non-endemic regions.

There is a high incidence of upper urothelial carcinoma (UUC) in regions affected by Balkan Endemic Nephropathy (BEN). The aim of this study was to compare E-cadherin expression in UUC, in regions affected by BEN, and in control rural and city populations free of BEN. Another aim was to determine the influence of some morphological parameters on the E-cadherin status. In the samples of 85 UUC patients, of whom 40 lived in BEN settlements and 45 served as control subjects, immunoreactions were performed using monoclonal anti-human E-cadherin antibody. Aberrant expression of E-cadherin was more frequent in BEN tumors than in control tumors (p<0.01). Decreased E-cadherin expression was linked to high grade and solid growth in control and BEN tumors (p<0.0001 and <0.05 versus p<0.05 and <0.05, respectively), and to the stage in control tumors (p<0.01). However, BEN low grade and low stage tumors showed aberrant expression more often than did control tumors (p<0.05 and <0.005, respectively). In control tumors, using univariate analysis, E-cadherin status was found to be influenced by grade, stage, and tumor growth (p=0.001, 0.017, 0.015, respectively). In the same group, only the grade was significant according to multistep logistic regression analysis (Wald=6.429 and p=0.011). The growth pattern had a predominant influence on E-cadherin expression in BEN tumors (p=0.005). A significant influence on normal membranous or abnormal cytoplasmic expression of E-cadherin in UUC is exerted by tumor grade, stage, growth, and metaplastic change (p=0.002, 0.048, 0.019, 0.011, respectively), but only by tumor grade in the multistep logistic regression model. These results suggest that decreased expression of E-cadherin in BEN tumors may be linked to tumor growth, while expression of E-cadherin in control tumors may be associated with tumor grade.

Extended orbital exenteration in the treatment of advanced periocular skin cancer with primary reconstruction with a galeacutaneous flap.

Extended orbital exenteration includes the removal of orbital contents together with the surrounding orbital wall(s). Skin cancers (basal cell cancer and squamous cell skin cancer) arising in the periorbital region could present as invasive tumours infiltrating the orbit and orbital walls. We describe the treatment of advanced invasive skin cancers of the periorbital region by extended orbital exenteration. A retrospective consecutive series over a nine-year period, included 21 extended orbital exenterations treated in a tertiary referral centre. The margins of excision were clear in 18. Twenty postoperative defects were reconstructed using galea-skin flaps, and one defect was left to heal by secondary intention. Two patients died of their disease during the three-year follow up. The reconstruction with frontal or frontoparietal galea-skin flap is a suitable option. The technique is versatile and simple, and gives acceptable aesthetic results. The operating time is shorter than that required for microvascular reconstructions, and the complication rate is low. The secondary defect can be closed primarily or by skin grafting. Extended orbital exenteration offers the best chances of cure in the treatment of non-melanotic skin cancers that have infiltrated the orbit and orbital walls.

Application of sentinel lymph node biopsy in cutaneous basosquamous carcinoma.

Basosquamous carcinoma of the skin is a relatively rare cutaneous neoplasm that has significant metastatic potential and a metastatic rate greater than that of basal cell and squamous cell carcinoma. We describe the use of lymphatic mapping and sentinel lymph node biopsy in a 63-year-old man after identification of basosquamous carcinoma. Sentinel lymph node biopsy, which is a standard tool to detect regional lymphatic metastasis in cutaneous melanoma, has been rarely employed to detect lymphatic metastasis of basosquamous carcinoma. The approach was successful in detecting a regional lymphatic metastasis of two nodal basins with minor morbidity. Sentinel lymph node biopsy may be useful for certain high-risk lesions of basosquamous carcinoma.

Does incomplete excision of basal cell carcinoma of the eyelid mean tumor recurrence

INTRODUCTION Basal cell carcinoma is the most common tumor of the eyelid. In this region, reconstruction is complex and damage to healthy tissue should be minimal. OBJECTIVE To define the relationship between margin clearance at excision and the recurrence rate of basal cell carcinoma of the eyelid. METHODS This prospective study was conducted with 111 patients submitted to surgery for basal cell carcinoma of the eyelid between 2001 and 2003 and followed up for a period of five years. The patients were evaluated according to age, tumor site, recurrence rate and margin clearance at excision. RESULTS No significant association was found between incomplete tumor excision and recurrence except in patients under 56 years of age, female patients and in the case of tumors of the medial canthus. CONCLUSION A risk of recurrence in incompletely excised basal cell carcinomas of the eyelid was only confirmed in younger patients, females and for tumors of the medial canthus.

Sentinel node biopsy for skin melanoma.

BACKGROUND/AIM Skin melanoma is one of the most malignant diseases with increasing incidence rate. Sentinel node biopsy (SNB) is very important for early detection of metastatic spread. The aim of the study was to analyze the first 40 patients with skin melanoma of 1 to 4 mm Breslow thickness when SNB was indicated. METHODS The patient characteristics, localization of the primary melanoma as well as histology grade were analyzed. SNB with intraoperative radiocolloid and methylene blue dye detection was performed. RESULTS Complication rate after SNB was analyzed and seroma was found in 5% of the patients. The therapeutic node dissection was performed in 10 patients with positive sentinel biopsy. The follow-up lasted two years. In five patients the false negative SNB was defined after the mean time of 11 months and the therapeutic dissection was performed. CONCLUSION SNB in melanoma patients is a useful diagnostic procedure. It is advised for melanoma of 1 to 4 mm Breslow thickness.

Anxiety levels related to the type of therapy for cervical cancer

The aim of this study was to examine the effect of treatment type on anxiety in patients with cervical cancer. Subjects and methods: This prospective study was conducted in 60 patients with cervical cancer treated by radiotherapy. The study was done before treatment, and 3 and 6 months after initial testing. For assessment of anxiety the Hamilton Anxiety Scale (HAM-A) was used.: At baseline, the values of the scale of anxiety in patients who were treated surgically were significantly higher than in patients who had been treated by radiotherapy, but the intensity of anxiety gradually decreased in both groups. In this study, pain and irregular menstrual bleeding were the most important risk factors for the development of anxiety.: Routine assessment should be introduced in clinical practice for the detection and monitoring of anxiety in all patients with cervical cancer, and a psychiatrist should be included in the multidisciplinary team for their treatment.

Sentinel lymph node biopsy in breast neoplasms

BACKGROUND/AIM Sentinel node (SN) is the first draining node from the malignant tumor site. In the last decade, sentinel node biopsy (SNB) has been introduced as an alternative to axillary dissection in breast cancer. I n patients with negative SNB (sentinel node uninvolved with malignancy) axillary dissection is not recommended. The aim of this stady was defining the indications for SNB, and SNB principles, as well as the survey of our first experiences. METHODS In the period from 2004 to 2008, we performed 78 SNBs in 75 patients (72 females, 3 males) with breast cancer. Indications for SNB were T1-2 and N0 lesions according to TNM classification (Tumor, Nodus Methastasis). In all cases, lymphoscintigraphy was done first, and then SNB with double contrast (methylen blue and technetium - Tc-99). In 57 (73%) cases, one SN was confirmed, and in 21 (26.9%) 2 nodes. RESULTS In 58 (74.3%) SNB, SN pathohistology was negative, ie. there were no cancer metastases. In this group of patients, axillary dissection was not done in 47 (81%) SNB. In the remaining 11 (18.9%), lymphonodal dissection level I and II was done after SNB, regardless of the presence or no presence of metastases within SN. All the cases were monitored from six months to one year of the operation and disease progression was not observed. CONCLUSION Sentinel node biopsy is an acceptable method of breast cancer diagnosis and a good alternative to lymphonodal dissection if there are no metastases within SN. The technique is relatively simple, but requires team work of experienced specialists: surgeons, nuclear medicine specialists and anesthesiologists. Our first experiences suggest a high degree of reliability of the method in selected patients and with well trained team of doctors.