Yusuf Karakas

Metastatic medullary thyroid cancer: a dramatic response to a systemic chemotherapy (temozolomide and capecitabine) regimen.

A 40-year-old male patient presented with increasing serum levels of calcitonin and CEA. He underwent potential curative surgery for medullary thyroid carcinoma, 3 years ago and then 7 months later he had metastasectomy and cervical lymph node dissection for recurrent disease. On admission he had multiple metastatic skin nodules on the chest wall and positron emission tomography–computed tomography revealed multiple visceral metastases as well. The patient had not received any systemic treatment up to that time; therefore, we considered systemic treatment with the new tyrosine kinase inhibitors (vandetanib, cabozantinib, etc). However, since these drugs are only available after cytotoxic chemotherapy, we started temozolomide and capecitabine chemotherapy. After two courses of the treatment all skin nodules disappeared and CEA and calcitonin levels normalized, radiological imaging showed a good partial response.

Effect of vitamin D supplementation on endothelial dysfunction in hemodialysis patients

Introduction: Patients with chronic kidney disease (CKD) commonly experience 25‐hydroxyvitamin D3 (25‐OH‐D3) deficiency, and these patients have a higher incidence of cardiovascular diseases (CVDs) due to endothelial dysfunction (ED). The aim of our study was to investigate the effect of 25‐OH‐D3 deficiency and its supplementation on ED in patients with CKD. Methods: Twenty‐nine uremic patients on dialysis and 20 healthy controls were evaluated for ED by high‐resolution Doppler ultrasonography of the brachial artery. In addition, 25‐OH‐D3‐deficient patients (25‐OH‐D3 < 30 nmol/L) with CKD and healthy controls were evaluated for ED before and after 8 weeks of oral vitamin D (cholecalciferol, 50,000 units) treatment. All subjects were evaluated for percent flow‐mediated dilatation (%FMD), percent endothelium‐independent nitroglycerin‐induced vasodilatation (%NID), and bilateral carotid intima‐media thickness (CIMT). Findings: Patients on dialysis had lower %FMD and %NID 6.11 [2.27–12.74] and 10.96 [5.43–16.4], respectively, than controls 15.84 [8.19–22.49] and 21.74 [12.49–29.4], respectively (P < 0.05). Patients on dialysis had higher left and right CIMT (0.79 ± 0.15 and 0.78 ± 0.14, respectively) than controls (0.60 ± 0.09 and 0.59 ± 0.09, respectively; P < 0.05). In 25‐OH‐D3‐deficient patients with CKD, after vitamin D treatment, %FMD was significantly increased in dialysis patients (10.25 [7.8–12.8]) compared to before supplementation (5.4 [2.77–6.15]; P < 0.001). Discussion: These results indicated that dialysis patients had significantly lower blood 25‐OH‐D3 levels and higher CIMT than healthy subjects. In addition, vitamin D supplementation improved ED and increased %FMD in dialysis patients. Our findings suggest that vitamin D supplementation in dialysis patients might prevent CVD.

Tumor Sidedness and Prognosis in Colorectal Cancer: Is Microbiome the Missing Link?

Tumor Sidedness and Prognosis in Colorectal Cancer: Is Microbiome the Missing Link? To the Editor We read with great interest the systematic review and meta-analysis by Petrelli and colleagues published in JAMA Oncology.1 Among 1.5 million patients with colon cancer, those with left-sided tumors were shown to have better prognosis and lower risk of death in all stages compared with rightsided tumors. As the authors mention, different embryologic origin and poor histological and genetic features, including a higher rate of diploidy, mucinous histologic findings, microsatellite instability, CpG island methylation, and BRAF mutation in right-sided tumors, and more frequent p53 and KRAS mutations in left-sided tumors might explain the difference in prognosis, but the exact mechanism is not known. Recent studies note that microbiome may also have a role in colon carcinogenesis. Some bacteria are particularly more likely to be involved because the association between cancer and these microorganisms has been repeatedly shown. Differences in the flora of proximal and distal colon may result in a different biology and prognosis for colorectal cancer. For example, Fusobacterium nucleatum, which is a highly invasive, gram-negative anaerobic bacterium, is one of the probable pathogens shown to be associated with colon cancer risk as well as more advanced stage and worse prognosis.2 In a recent study, Mima et al3 assessed 1102 rectal and colon carcinomas and measured the amount of F nucleatum DNA in colorectal tumor tissue using a quantitative polymerase chain reaction assay and equally dichotomized F nucleatum–positive cases (high vs low). The proportion of F nucleatum–high colorectal cancers gradually increased from rectal cancers (2.5% [4 of 157]) to cecal cancers (11% [19 of 178]), with a statistically significant linear trend along all subsites (P < .001). This study shows that microbiome is not uniform throughout proximal and distal colon. Metagenomic analyses of the colon microbiome might show parallel findings of divergent flora between proximal and distal colon and might further illuminate the pathogenesis of sidedness, yielding implications for treatment and prevention.

Real world survival data of a rare malignancy: Anal cancer results in HIV negative patients from Turkey

BACKGROUND/AIMS An organ preservation approach using chemoradiotherapy has been established for anal cancer. This retrospective cohort study aimed to define the clinico-demographic characteristics and outcomes of cases of human immunodeficiency virus (HIV)-negative anal carcinoma during a period of 20 years in a single comprehensive cancer institute. MATERIALS AND METHODS This was a single-center retrospective cohort study of patients who were treated between January 1995 and January 2015. The primary outcome measures that were investigated included overall survival (OS), progression-free survival (PFS), colostomy rates, and colostomy-free survival (CFS). RESULTS A total of 28 patients who were principally treated with standard 5-fluorouracil + mitomycin combination chemoradiotherapy were eligible for analysis. The 3- and 5-year PFS rates were 92.4% and 63%, respectively. The lower T stage was found to be associated with a prolonged PFS (p=0.001). The 3- and 5-year CFS rates were 84.3% and 74.9%, respectively. A longer CFS was observed with lower T stages (p=0.05). At the last follow-up, 75% of the patients with anal cancer were alive, and 71.4% of the patients were disease free. The median OS was not reached with a median follow-up of 54 months (range, 6-115 months). The 3- and 5-year OS rates were 82% and 71.1%, respectively. No late toxicity was observed during the follow-up period. DISCUSSION The short- and long-term prognoses of HIV-negative patients with anal squamous cell carcinoma were good, and low-grade toxicity was rare, thereby demonstrating that these patients can be successfully treated in a real-life setting with favorable outcomes.

Recent advances in the management of pancreatic adenocarcinoma

ABSTRACT Introduction: Pancreatic cancer (PC) demonstrates very poor prognosis and its incidence continues to increase, despite developments in chemotherapy, radiotherapy, and targeted therapies. Surgical resection is currently the only curative approach for PC. The role of radiotherapy in adjuvant and locally advanced PC continues to be increasingly controversial. This review article aims to explore the current knowledge of pancreatic adenocarcinoma, focusing on diagnosis, treatment strategies, and the best supportive care. Areas covered: The current literature on pancreatic adenocarcinoma treatment modalities has been summarized, with a focus on clinical trials and reviews. New treatment strategies and their impact on clinical practice have also been discussed. Expert commentary: Despite many therapeutic developments, only modest improvements in survival rates have been achieved. There is an essential need to increase survival by developing more innovative treatment approaches for patients with PC.

When side effect becomes the effect: Efficacy of capecitabine in refractory psoriasis

Dear Editor, Psoriasis vulgaris (PV) is one of the most common chronic inflammatory skin disorders characterized by hyperproliferation of epidermal keratinocytes. PV substantially affects the quality of life and is associated with disfigurement, and disability (Boehncke & Schon, 2015). Topical agents remain to be the cornerstone of treatment in mild disease. Phototherapy and systemic therapies such as methotrexate, cyclosporine, acitretin are the conventional systemic therapies. Biologic drugs including tumor necrosis factoralfa antagonists, anti-Interleukin (IL)12/23, and anti-IL17 provide a more specific treatment and are indicated for patients who have a resistant disease (Boehncke & Schon, 2015; Kelly, Foley, & Strober, 2015; Kunz, 2009). Here, we present the first case of a psoriatic patient with metastatic gastric cancer whose lesions regressed significantly after capecitabine (Xeloda; Roche Medical) treatment. A 59-year old male presented to our center with newly diagnosed metastatic gastric cancer. He had a history of plaque-type psoriasis for 19 years. He had been treated with infliximab for the last 8 years with complete clinical response. After the diagnosis of gastric cancer, infliximab treatment was terminated, the patient was under follow-up with topical emollients. Of note, in this patient long-term inhibition of tumor necrosis factor alfa may have a role in inducing and evolution of cancer. Docetaxel, cisplatin, and 5-fluorouracil (5-FU) (DCF treatment) was commenced. While he received DCF chemotherapy, 8 mg dexamethasone was administered as a precaution for docetaxel anaphylaxis on the first day of the infusion and no any topical agent was applied for psoriasis during the whole chemotherapy period. He had no psoriatic lesions throughout the treatment period, but the exacerbation of PV was observed after termination of the DCF treatment. After DCF treatment, single-agent capecitabine (1,250 mg/m bid for 14 days, every 3 weeks) treatment was started for gastric cancer. At the beginning of the first cycle of capecitabine, psoriatic lesions were highly active with widespread erythematous scaly plaques involving 70% of the body surface area (Figure 1). At the end of the first cycle, skin lesions of the patient improved significantly (Figure 2). This effect continued in subsequent cycles and capecitabine was well-tolerated. 5-FU is an antimetabolite like methotrexate which is a widely used systemic agent for PV. They are both active at S phase of cell cycle. They are cycle specific and affect mostly rapidly proliferating cells (Parker, 2009). 5-FU interferes with DNA synthesis as well as RNA processing and therefore decreases epidermal proliferation (Ceilley, 2012). It has been used topically or intralesionally for treatment for psoriatic nails. The oral preparation of 5-FU, conversely, has not been used in clinical practice because of unpredictable absorption. 5-FU infusion in a cancer patient which resulted in subsequent erosions and necrosis over the psoriasis plaques similar to methotrexate intoxication is an example to this concern (Wetzig, Beckheinrich, Rytter, & Haustein, 2002).

Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcoma

Leiomyosarcomas (LMS) are rare tumors with poor prognosis owing to the high rate of recurrent and metastatic disease. The combination of doxorubicin (Adriamycin) plus ifosfamide and mesna (AIM) results in moderate response rates of 10%-30%. The aim of this study was to assess the efficacy of the AIM regimen along with multimodality treatment including surgery and radiotherapy in patients with LMS. The clinicopathologic characteristics and outcomes of 51 patients with recurrent or metastatic LMS diagnosed between 2000 and 2014 who received the AIM regimen were analyzed retrospectively. Treatment consisted of ifosfamide 2500mg/m² on days 1-3 (with mesna 2500mg/m² days 1-3, 4-hour i.v. infusion), and doxorubicin 60mg/m² on day 1 (2-hour i.v. infusion), which was repeated every 21 days. The mean age of the patients at diagnosis was 48.9 ± 11.2 years. A total of 42 patients were females (82.4%). The primary tumor site was the uterus in 30 (58.8%) patients. The most common metastatic sites were lung and liver. The median follow-up was 27.9 months (min: 4.3 max: 164.8). The median progression-free survival was 6.7 months (95% CI: 4.1-9.2). The median overall survival (OS) was 24.6 months (95% CI: 16.2-33.0). The overall response rate was 12% (6/51 pts). Response rates were higher in patients with uterine LMS (17%) compared with those with nonuterine LMS (5%); however, the OS times were similar. Surgical intervention for local or distant recurrence was associated with improved median OS (41 vs 16.6 months, P < 0.001). Myelosuppression was the major toxicity of this combination. In our study, the AIM regimen was effective in patients with LMS. Resection of local or distant recurrence was found to improve survival in our study.

Immune Thrombocytopenia Induced by Nivolumab in a Metastatic Non-Small Cell Lung Cancer Patient

phy and cranial magnetic resonance imaging were performed for staging. The tumor was shown to have invaded the third rib, the pleural nodules, and the left hilar region, revealing cT4N1M1a disease. The tumor did not have an EGFR mutation or ALK translocation. The patient progressed after 3 cycles of paclitaxel and carboplatin and was given single-agent nivolumab (3 mg/kg, every 2 weeks). Pre-treatment platelet counts were normal. At the end of the 6th nivolumab infusion, the platelet count suddenly decreased. Nivolumab was subsequently withheld, but the platelets continued to drop to a nadir of 5,000/mm3. However, leukocyte and hemoglobin levels were normal. The patient had no severe bleeding, bruising, or petechiae during this period. A peripheral smear demonstrated reduced platelets, a few giant platelets, and normal leukocytes/erythrocytes. Platelet transfusions were given for 4 weeks. After 5 weeks of persistent thrombocytopenia, a bone marrow biopsy was performed. This revealed hypercellularity and an increased rate of megakaryocytes. Hence, the patient had isolated thrombocytopenia in the absence of other causes and was diag

The Effect of Total Size of Lesions in Multifocal/Multicentric Breast Cancer on Survival

&NA; Multifocal/multicentric (MF/MC) breast cancer was identified about 10% of all breast cancer. Approximately 4000 breast cancer patients were evaluated and it was found that the MF/MC breast cancer was better T stage classified and more predictive according to Tsum which is the sum of the longest diameters of the lesions. This is more prominent in MF/MC patients with low disease burden. Background: In this study, we aimed to assess the prognostic performance of determining the T stage according to the total size of lesions compared with the size of the largest lesion in the breast in patients with multifocal/multicentric (MF/MC) breast cancer. Patients and Methods: The charts of the patients with MF/MC breast cancer who were diagnosed between 2003 and 2014 were reviewed. The T stage of MF/MC tumors was determined according to the largest lesion size (Tmax) as well as the sum of the longest diameters of the lesions (Tsum) in the breast. Results: Multifocal/multicentric tumors were identified in 323 of 3890 patients (8.3%) with breast cancer. Ten‐year rates of overall survival (OS; 75% and 74%; P = .965) and disease‐free survival (DFS; 66% and 61%; P = .817) were similar in patients with unifocal and MF/MC tumors, respectively. When the T stage was determined by summing the sizes of the lesions, the T stage of 67 (20.7%) and 63 (19.5%) patients advanced from T1 to T2 and from T2 to T3, respectively. Thus, the T stage increased in 130 patients (40.2%) according to American Joint Committee on Cancer. Discriminatory ability of Tsum was better than Tmax in terms of OS and DFS, as shown with higher Royston D and Harrel C statistics and Schemper V values. Conclusion: The new T classification proposed in this report stands out as a better predictive classification particularly in patients with low disease burden.

A case of acanthosis nigricans as a paraneoplastic syndrome with squamous cell lung cancer

A 55-year-old man presented with oral mucosal ulcers, blackening of both hands, and hyperpigmentation on axillary, anal, and inguinal regions for the last 3 months, which were all progressive. The patient was referred to the oncology department with the diagnosis of acanthosis nigricans for investigation of an underlying malignancy. He was a smoker. A computed tomography scan of thorax revealed enlarged mediastinal lymphadenopathies and a lesion on the left upper lobe. Fine-needle aspiration biopsy of the mediastinal lesion was consistent with squamous cell carcinoma, and biopsies of the skin and oral mucosal lesion also further confirmed the diagnosis of acanthosis nigricans. After docetaxel and cisplatin chemotherapy, a significant improvement in his skin and mucosal lesions was observed with almost complete resolution of the pulmonary lesion and the mediastinal lymph nodes.