Methylation Changes of Primary Tumors, Monolayer, and Spheroid Tissue Culture Environments in Malignant Melanoma and Breast Carcinoma.

Epigenetic changes have major role in the normal development and programming of gene expression. Aberrant methylation results in carcinogenesis. The primary objective of our study is to determine whether primary tumor tissue and cultured tumor cells in 2D and 3D tissue culture systems have the same methylation signature for PAX5, TMPRSS2, and SBDS. These findings will play an important role in developing in vitro model system to understand the effect of methylation inhibitors on primary tumor tissue. In a previous study PAX5, TMPRSS2, and SBDS genes that we are investigating were reported to be methylated more than 60% in breast cancer and malignant melanoma cell lines. However, these genes have never been studied in primary tumor tissues. Thus, primary tumor tissues of breast cancer and malignant melanoma were first grown in 2D and 3D cultures. Then these two types of tumor tissues and their 2D and 3D cultures were investigated for changes considering methylation levels in PAX5, TMPRSS2, and SBDS genes using real-time polymerase chain reaction. No differences were observed in the primary tissues and culture systems for both PAX5 and TMPRSS2 in malignant melanoma tissues. We found that PAX5 gene was an efficient marker to measure the effects of methylation inhibitors for in vitro systems for malignant melanoma tissue.

Assessment of Anxiety and Depression Status in Turkish Cutaneous Melanoma Patients

Background: Even though anxiety and depression are two mood disorders encountered commonly in cancer patients only few trials have been carried out so far in melanoma patients. The aim of the study was to determine the clinical prevalence of these disorders in Turkish cutaneous melanoma patients and to clarify possible clinicopathological factors influencing them. Material and methods: A total of 100 consecutive outpatient melanoma patients were enrolled and asked to complete the Hospital Anxiety and Depression Scale (HADS) questionnaire immediately after scheduled visits. Results: A total of 24 participants had clinical anxiety and 8 were diagnosed with borderline anxiety. Fifteen were diagnosed with clinical depression and 20 with borderline depression. Prior to melanoma diagnosis the majority of the patients, 93 and 86, were assessed as normal in terms of their anxiety and depression status, respectively (p<0.001). A statistically significant correlation was found between anxiety and depression scores (p<0.001). The patients with advanced disease were significantly more anxious and depressive than those with early stage disease. None of the other socio-demographic parameters was found to be correlated with anxiety and depression status. Conclusions: Because a large group of Turkish melanoma patients, nearly one third of the cohort, was found to be suffering from relevant anxiety and depression, it is of uttermost importance that psychological support and pharmacological intervention for these patients be commenced as soon as possible.

Factors affecting progression-free survival in non-HIV-related Kaposi sarcoma.

BACKGROUND: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS. METHODS: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line. RESULTS: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28-85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 ± 12 versus 41 ± 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 ± 9 versus 54 ± 12 months; p = 0.03). In addition, heavy smoking (≥40 pack-years) had a borderline significance regarding better PFS time (23 ± 24 versus 45 ± 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS. CONCLUSIONS: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and ≥40 pack-years of smoking had better PFS than others.

Is there any effect of first-day usage of a totally implantable venous access device on complications?

BACKGROUND: Our aim was to evaluate whether it is safe to use a totally implantable venous access device (TIVAD) on the day of implantation. METHODS: We investigated data from 1315 cancer patients divided into two groups according to the time interval between TIVAD placement and the first use of the TIVAD to adminster chemotherapy: patients whose devices were used during the first 24 h after placement were enrolled into group 1 and patients whose devices were first used more than 24 h after device placement were enrolled into group 2. RESULTS: Early complications were all related to device insertion and occurred before chemotherapy administration. Infection and venous thrombosis were the most frequent complications during the first 6 months after TIVAD insertion in both groups. However, the frequency of late complications was statistically the same for the two groups. CONCLUSIONS: The early use of TIVADs appears safe. Usage of the catheter for chemotherapy administration during the first 24 h after insertion has no effect on the rate of complications.

Can Steroids plus Surgery Become a First-Line Treatment of Idiopathic Granulomatous Mastitis?

BACKGROUND: The aim of this study is to compare the clinical course of idiopathic granulomatous mastitis (IGM) treated with low-dose oral corticosteroid therapy alone as opposed to treatment with low-dose corticosteroid therapy followed by surgery. PATIENTS AND METHODS: 37 patients were treated with an approach that consisted of methylprednisolone at a dose of 0.5 mg/kg/day followed by wide excision, and 23 patients were treated with an approach that consisted only of methylprednisolone. The treatment efficacy was compared between the two groups. RESULTS: Clinical and radiological regression was reported in all patients with steroid therapy, and the regression rate had a median of 75% (25-100%). No recurrence was observed in patients who were treated with wide surgical excision after steroid therapy during the median follow-up period of 38 (22-78) months. The control group of 23 patients was treated only with steroid therapy, and 7 (30%) of these patients experienced recurrence in the follow-up period (p < 0.001). CONCLUSIONS: Steroid therapy was effective in the treatment of IGM by reducing the lesion size and extent. With regard to the current treatment options available for IGM, surgical excision after steroid therapy seems the better treatment option compared to steroid therapy without surgical excision. This treatment sequence reduces the rate of recurrence.

Successful treatment of triple primary tumor.

INTRODUCTION: The occurrence of multiple primary tumors is rare. Only limited number of cases with triple malignancy have been reported. We report here a rare case of a woman presented synchronous triple tumors, in her lung, breast, skin. PRESENTATION OF CASE: A 56-year-old woman presented with invasive ductal carcinoma of breast, non-small cell lung cancer and malignant melanoma. The patient undergone mastectomy and malignant melanoma tumor excision on-site. After operation stereotactic radiotherapy was given to her lung tumor. Six course of chemotherapy was given to her. She is alive with no progression. DISCUSSION: The patient was diagnosed with melanoma and staging by FDG/PET. There is not any study about routine using PET/CT in the melanoma staging. CONCLUSION: This is a very rare synchronous triple tumor case.

Axillary arch may affect axillary lymphadenectomy.

BACKGROUND: The aim of this study was to identify the axillopectoral muscle anomaly commonly known as Langer's axillary arch, and to understand its importance in surgical procedures of the axilla. PATIENTS AND METHODS: Between 2009 and 2011, 758 patients underwent sentinel lymph node biopsy, axillary dissection, or both. Patients with Langer's axillary arch were identified and assessed retrospectively. The decision to cut or preserve the axillary arch was made based on clinical judgment, and patients were followed-up accordingly to monitor for adverse outcomes. RESULTS: Of the 758 patients who underwent axillary procedures, 9 (1.2%) were found to have a Langer's axillary arch. In 2 patients the arch was cut, and in 7 patients it was preserved. No adverse outcomes were identified in any of the patients upon follow-up. CONCLUSION: Langer's axillary arch is a unique anatomic anomaly of the axillary region that may be problematic due to the potential risks of lymphedema and vascular or nerve compression. It is important for surgeons and radiologists alike to be aware of this anatomic variation in order to properly identify it and respond appropriately based on clinical judgment, and to complete close follow-up of the patient due to the potentially increased risk of adverse outcomes.

The role of antibiotic prophylaxis in totally implantable venous access device placement: results of a single-center prospective randomized trial.

BACKGROUND: This study evaluated whether prophylactic treatment with a cefazolin could prevent infections in patients who had a surgically inserted totally implantable venous access device (TIVAD). METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial comparing wound infection rates in 404 patients (203 received prophylactic cefazolin, 201 received a placebo) undergoing TIVAD insertion. Infections were evaluated 3, 7, 14, and 30 days after discharge and outcomes were compared and analyzed. RESULTS: Groups were well matched for all preoperative variables studied, including comorbid conditions. Superficial surgical site infection developed in 5 patients (2.5%) from the antibiotic group and 6 (3%) from the placebo group (P = .75). One from each group developed deep surgical site infection. Both patients were readmitted and underwent repeated debridement, which eventually resulted in port loss in 1 patient. CONCLUSIONS: We do not recommend the use of prophylactic antibiotics in TIVAD insertion because they will not decrease the already low rate of postoperative infectious complications. Registration number NCT00867295 (http://www.clinicaltrials.gov).

Modification of approach for totally implantable venous access device decreases rate of complications.

BACKGROUND: The aim of this study was to analyze the potential utilization of external jugular vein (EJV) cutdown approach for totally implantable venous access device (TIVAD) placement. METHODS: This is a prospective, non-randomized, observational, uni-institutional study. All patients (n = 451) were first subjected to attempted subclavian vein (SV) percutaneous approach. If SV percutaneous approach was unsuccessful after multiple puncture in group A and maximum two puncture in group B, an ipsilateral EJV cutdown approach was attempted. RESULTS: Four hundred four patients (89.6%) underwent TIVAD placement via SV percutaneous approach. Of those 47 patients in which SV percutaneous approach was not successful, 8 patients in group A and 39 patients in group B, TIVAD was placed via ipsilateral EJV cutdown approach. The average of operative time was 17.9 +/- 8.5 min in group A and 18 +/- 7.3 min in group B (P > 0.05). The early complications of group A were significantly higher than that of group B (P = 0.02). CONCLUSIONS: TIVAD placement by the SV percutaneous approach is safe and fast, and its success rate is very high. By avoiding the immediate complications associated with the percutaneous approach, the EJV cutdown has to be considered a valid, safe, and suitable alternative when the SV percutaneous approach unsuccessful after two needle puncture.

Malignant melanoma in Turkey: a single institution's experience on 475 cases.

BACKGROUND: This study was performed to determine the characteristics and the clinical outcomes of patients with cutaneous melanoma in Turkey. METHODS: The medical records of patients between 1991 and 2003 at Institute of Oncology were retrieved from the cancer registry. RESULTS: Of the 475 adult cases with complete staging procedure, the incidence of localized (stages I-II) disease was 301 (63.4%), and followed by node involved (stage III) and metastatic (stage IV) disease with the incidence of 117 (24.6%) and 57 (12.0%), respectively. The median age of patients was 50 years (17-104 years) and male/female ratio was 1.1. Of 206 patients (43.4%) the diseases were located on extremities, 150 (31.6%) on the trunk, and 102 (21.5%) on the head and neck region. In cases with early/node negative stage, stage distribution was identical. The superficial spreading type was the commonest histology (52.2%). The Breslow thickness distributed equally, whereas tumor invasion aggregated mainly at Clark level III and IV. Half of the lesions were ulcerated and with low mitotic potential. In cases with the node involved stage, the majority of patients had only one lymph node involved. In metastatic patients, two thirds had distant metastases including lung metastases and half of them had single metastatic region. With the median follow-up of all patients of 5.2 years, the median overall survival of all patients was 62.2 months and the 5-year overall survival was 50.5%. Overall survival was significantly negatively correlated with male (P<0.001), advanced stages (P<0.001) and old ages (P=0.005). The five-year survival rates of patients with stages I-II and III disease were 63.6% and 36.6%, respectively. Nodular histology subtype, deeper Breslow tumor depth, extensive invasion, presence of ulceration, advanced stage, presence of relapse, being male and elderly patient, presence of visceral recurrence, and high mitotic activity were found to be associated with poor prognosis for overall survival in localized disease. The median survival of metastatic patients was 9.9 months and 1-year overall survival rate was 32.7%. Unresponsiveness to chemotherapy, visceral metastasis, multiple metastases and not given chemotherapy were the poor prognostic factors for overall survival. CONCLUSION: The descriptive and prognostic factors in Turkey are similar to those in Western countries.

Penile metastasis of cutaneous malignant melanoma: a true hematogenous spread?: Case report and review of the literature.

Penile involvement has been implicated as a metastatic site in several tumors; approximately 300 cases have been reported. Of these, only two cases showed cutaneous melanoma as the primary site. Our patient presented with a painless mass on the penile shaft together with other distant metastases. A magnetic resonance image demonstrated two sites of deposit in the subcutaneous tissue on the radix penis, and fine needle aspiration cytology of the mass confirmed the presence of melanoma cells. The patient died of systemic disease without any further treatment for penile involvement. This unusual involvement is presented with a review of the related literature.

Sentinel lymph node biopsy for the staging of anal melanoma: report of two cases.

Primary melanoma of the anal region is a rare pathological entity and its prognosis is generally poor. The aim of this report is to demonstrate the feasibility of the sentinel lymph node (SLN) procedure with combined technique in patients with anal melanoma. We report of two cases with anal melanoma that had wide local excision of the primary lesion and was referred for further evaluation. After diagnostic metastatic work-up, SLN procedure consisted of a combination of preoperative lymphoscintigraphy with technetium-99m nanocolloid injected around the tumor, and intraoperative detection of SLN with gamma probe (combined technique) was performed. In addition, patent blue dye was injected at the periphery of the tumor to facilitate direct identification of the blue-stained lymph node. In the first case, SLN identified both inguinal and iliac lymph node basins, both of which were histologically negative on both frozen and paraffin sections. In the other case, SLN removed from the inguinal lymph node basin showed micrometastasis by paraffin section. In both cases SLN procedure with combined technique was performed sufficiently without significant complications. Consequently, we suggest that SLN procedure with combined technique is also a useful technique in malignant melanomas similar to other anal canal cancers.

Intermediate dose interferon alpha in adjuvant treatment for high-risk melanoma: a single institution's experience.

Interferon is widely used as the most effective agent in the adjuvant therapy of patients with melanoma. However, little is known about the effect of intermediate dose interferon (IDI) in adjuvant therapy. We conducted this study to determine whether intermediate doses of interferon-alpha 2 could be beneficial for these patients. A series of 84 melanoma patients with high-risk relapse potential (stage II-III) after excisional biopsy were enrolled for adjuvant therapy with IDIs, either IFN-alpha 2a, 9 MU or IFN alpha 2b, 10 MU per day, subcutaneously, for 1 yr consisted of an induction period (5 d/wk for 4 wk) followed by 48 wk of same dose administered three times per week. The median follow-up was 25.9 mo with range 4-90.4 mo. Thirty-three (39%) patients had progressed; 18 (55%) of them while on treatment. The median (range) time of the failure occurrence was 9.1 mo (1.7-47.3 mo). Distribution of failure site was identical and the majority of the recurrences were found as single metastasis. For distant metastasis-free interval, mean (+/- SE) value was 28.8+/-3.6 mo; 1- and 2-yr survival rates were 87.8+/-5.7% and 61.6+/-9.3%, respectively. Twenty-two deaths were observed. Five-year survival rates of progression-free survival and overall survival were 50% and 60%, respectively. Generally, the treatment was found well-tolerated; drug-induced dose reduction or treatment discontinuation due to toxicity was minimal. Severe toxicity was rare. In conclusion, the small number of patients and the short follow-up does not permit any conclusion. However, the preliminary data seem to show that treatment with IDI was usually well tolerated with low toxicity of the patients during the adjuvant therapy.

Different manifestations of malignant melanoma in the breast: a report of 12 cases and a review of the literature.

BACKGROUND: The breast is associated with a large number of diseases. Besides being the host of many benign and malignant tumors, breast skin and parenchyma are also metastatic sites for various tumors such as leukemia, lung cancer and melanoma. METHODS: Malign melanoma has different manifestations in the breast. All these manifestations are important not only as initial presentations of the disease, but also as indicators of the progression period of the disease. RESULTS: This study reports on 12 cases of cutaneous malignant melanoma in breast skin and tissue. Nine of these cases are primary cutaneous melanomas, while the others are breast metastases from a distant site cutaneous melanoma. In two of the nine primary cutaneous melanomas in-transit metastasis to the breast developed during the follow-up period. CONCLUSIONS: In this paper, the diagnostic and surgical approach to primary and metastatic melanoma of the breast, and the importance of the breast during the follow-up period are reviewed.

Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in patients with malignant melanoma.

Degradation of basement membranes and extracellular matrix is an essential step in cancer invasion and metastasis. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in this step. The present study was conducted to investigate the levels of MMP-3 and TIMP-1 in serum of patients with malignant melanoma and the relationship to tumor progression and known prognostic parameters. Seventy patients with cutaneous malignant melanoma were investigated. Serum samples were obtained on first admission before any adjuvant and metastatic treatment was given or follow-up of patients. Serum TIMP-1 and MMP-3 levels were determined by the solid-phase sandwich ELISA (Oncogene Science Inc.) method. The elevation of serum MMP-3 and TIMP-1 levels between the patients with malignant melanoma and healthy controls were not significantly different (p > 0.05). The serum levels of MMP-3 were significantly different in males and females (p = 0.001) and serum TIMP levels were influenced by age (p = 0.047). Except for the ulceration status of the tumor, serum levels of MMP-3 and TIMP-1 were not related to the known prognostic factors such as tumor histology, localization, stage of the disease, Breslow thickness, Clark invasion, mitosis, TIL, and regression of tumor (p > 0.05). In patients with ulceration positive, the serum levels of MMP-3 were higher (p = 0.04) and TIMP-1 were lower (p = 0.008) than those in patients without ulceration. No significant relationship was found between serum levels of MMP-3 and TIMP-1. In conclusion, these results suggest that neither of the serum levels of MMP-3 and TIMP-1 could be a good indicator of invasion and metastasis nor can be recommended as a tumor marker in the management of melanoma patients owing to lack of sensitivity and specificity. However, much research still continues in this field and exciting new knowledge will ultimately emerge.

Effects of amifostine on healing of microvascular anastomoses, flap survival, and nerve regeneration with preoperative or postoperative irradiation.

Amifostine is an organic thiophosphate compound, which has both cytoprotective and radioprotective effects. An experimental study was undertaken to investigate the effects of its use on reconstructive surgery in cancer treatment. One hundred and twenty guinea pigs were divided into three equal groups to investigate flap survival and healing, patency of microvascular anastomoses, and nerve regeneration, respectively. The groups were subdivided in such a way that they were given either preoperative or postoperative radiotherapy, with or without amifostine treatment. Macroscopic and planimetric examination, light and electron microscopy, and histomorphometric analyses were performed to evaluate flap survival and healing, patency of arterial anastomoses, and nerve regeneration. Although flap survival rates were not affected, significantly better flap healing was observed in the postoperative radiotherapy subgroup with amifostine treatment. However, amifostine treatment did not result in a statistically significant difference in terms of anastomotic patency and nerve regeneration with either preoperative or postoperative radiotherapy.

Detection of circulating melanoma cells by a two-marker polymerase chain reaction assay in relation to therapy.

Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanin biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination in evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.

Totally implantable venous-access ports: local problems and extravasation injury.

Totally implantable venous-access ports (TIVAPs) are valuable instruments for long-term intravenous treatment of patients with cancer, but implantation and use of these devices are each associated with complications. In addition to the perioperative problems, long-term complications can arise; these can be classified in five categories-catheter malfunction, catheter-related venous thrombosis, catheter-related infection, port-related complications, and extravasation injury. Such complications reduce the benefits of reliable access to the venous system in patients with malignant tumours. The vast majority of such disadvantages are attributable to inexpert handling of ports and, therefore, should be avoidable. TIVAP placement procedures and TIVAP complications are discussed in this review, with special emphasis on local problems and extravasation injuries. To obtain maximum benefit from TIVAPs, all health-care personnel must be familiar with the use and routine maintenance procedures of the devices and treatment options for catheter-related complications.