Clinicopathologic Analysis and Prognostic Factors for Survival in Patients with Operable Ampullary Carcinoma: A Multi-Institutional Retrospective Experience.

Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion (p < 0.001) and lymph node involvement (p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years (p = 0.045), poor performance status (p = 0.048), weight loss (p = 0.045), T3-T4 tumors (p = 0.018), surgical margin positivity (p = 0.01), lymph node involvement (p = 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.007), and poor histological grade (p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.

Prognostic and Predictive Value of NAR Score in Gastric Cancer.

INTRODUCTION: Neoadjuvant treatment is a widely accepted approach for locally advanced rectum cancer. Efforts to explore a surrogate endpoint for clinical trials revealed a new prognostic scoring system which is named as neoadjuvant rectal score (NAR) in patients who received neoadjuvant treatment for rectal cancer. MATERIAL AND METHODS: 88 patients who met inclusion criteria were included in the study. The optimal cutoff value of the NAR score was 17.6 with 71% sensitivity and 63% specificity. Patients with NAR score > 17.6 (n: 48, 54%) were defined as the high-risk group and those with NAR score ≤ 17.6 (n: 40, 56%) as the low-risk group. RESULT: Survival analysis according to the NAR score group (low-risk vs high-risk) revealed that there was a statistically significant difference between groups regarding OS and DFS. The median OS for high-risk patients was 27.3 months (95% CI, 15.0-39.6); it was 76.6 months (47.3-106.0) for low-risk patients (p < 0.0001). The median DFS was 15.1 months (11.8-18.4) for high-risk patients; it was 44.3 months (95% CI, 4.1-84.6) in the low-risk group (p = 0.002). DISCUSSION: As a result, we interpreted our findings as supporting data about the utility of NAR score not only as a surrogate endpoint for the clinical trial of rectal cancer but also as a prognostic marker in patients with gastric cancer who received neoadjuvant treatment.

Prediction of Peritoneal Recurrence in Patients with Gastric Cancer: a Multicenter Study.

PURPOSE: The peritoneum is the common recurrence site of gastric cancer (GC) presenting with worse survival. Although some predictive clinicopathological factors have been identified, there is no comprehensive assessment of peritoneal recurrence risk prediction for patients treated with adjuvant chemotherapy (CR) or chemoradiotherapy (CRT) after surgery. We aimed to predict peritoneal recurrence and develop a new scoring model in GC. METHODS: This retrospective study included 274 GC patients who presented with recurrence after curative gastrectomy followed by adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). Risk factors for peritoneal recurrence were analyzed using the following parameters: age, gender, tumor location and characteristics, and differences between treatment modalities. All parameters were assessed by binary logistic regression analysis to compare the patients with and without peritoneal recurrence. Then, a new risk scoring model was developed. RESULTS: Peritoneal recurrence was observed in 115 (44.1%) patients. Peritoneal recurrence was higher in female gender (odds ratio (OR), 1.93; 1.07-3.49, P = 0.030, 1 point), T4a-b stage (OR, 2.47; 1.14-5.36, P = 0.022, 1 point), poor/undifferentiated (OR, 2.04; 1.31-4.06, P = 0.004, 1 point), and signet cell carcinoma (OR, 2.04; 1.04-4.02, P = 0.038, 1 point) after adjusted for resection and dissection types. The risk scoring model was developed using the related parameters: Peritoneal recurrence rates were 24.6%, 42.6%, and 71.4% for group 1 (0 point), group 2 (1-2 points), and group 3 (3-4 points), respectively. CONCLUSION: Female gender, T4 tumor stage, undifferentiated histopathology, and signet cell type had a tendency to peritoneal recurrence after adjusted for treatment modalities. Patients with 3 or 4 risk factors had an 8.8-fold increased risk for the development of peritoneal recurrence.

Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study.

BACKGROUND: Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown. METHODS: A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL. RESULTS: Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6th month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42-0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39-0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms. CONCLUSIONS: Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).

A rare case: Branch retinal vein occlusion associated with the use of tamoxifen.

Tamoxifen-induced ocular complications including cataracts, keratopathies, retinopathy, impaired visual acuity, ocular irritation, optical neuritis, and retinal vein occlusion are uncommonly reported in the literature. Herein, we report on a premenopausal patient with right-side breast carcinoma who received adjuvant tamoxifen therapy (20 mg/day) for 1.5 years and developed sudden visual loss. Fundal examination revealed an obstruction in the branch of the retinal vein. The diagnosis was confirmed by fluorescein angiography and optical coherence tomography. Thus, tamoxifen was switched to an aromatase inhibitor. Tamoxifen-induced ocular complications should be kept in mind when visual symptoms are seen in patients undergoing tamoxifen therapy. In such cases, a complete ocular examination should be performed.

Prognostic importance of the albumin to globulin ratio in metastatic gastric cancer patients.

AIM: The aim of this study was to evaluate the prognostic importance of the albumin to globulin ratio (AGR) in terms of overall survival (OS) and progression free survival (PFS) in metastatic gastric cancer patients. METHODS: The patients diagnosed with metastatic gastric cancer between 2009 and April 2016 at the hospital have been studied retrospectively. The clinicopathological characteristics, laboratory, and treatment parameters have been assessed. AGR value has been calculated using the following formula (AGR = serum albumin/total protein - serum albumin). RESULTS: In total, 251 patients were included in the study population. The median value of AGR was 1.206 (range = 0.460-3.130), and the cut-off value was set as 1.20. Based on the cut-off value, 126 patients were categorized in the low AGR group, while the remaining 125 patients were categorized in the high AGR group. ECOG (Eastern Cooperative Oncology Group) performance scores, CEA levels, CA19-9 levels, hemoglobin levels, lactate dehydrogenase levels, and liver metastasis ratios varied significantly between the low and high AGR groups (p < .05). The Kaplan-Meier curve has shown that, compared to the low AGR group, the high AGR group has better OS (12.2 vs 9.3 months, p = .002) and better PFS (8.0 vs 5.7 months, p < .001) rates. The univariate and multivariate analyses also proved that low AGR is an independent bad risk factor in metastatic gastric cancer patients, both in terms of OS (p = .019, Hazard Ratio (HR) = 1.380, 95% Confidence Interval (CI) = 1.055-1.805) and PFS (p = .002, HR = 1.514, 95% CI = 1.164-1.968). CONCLUSION: In metastatic gastric cancer patients, AGR is an independent prognostic factor for OS and PFS. Thus, in this patient group, the low cost albumin and globulin which can be measured with routine clinical practice may be used as an appropriate prognostic tool.

Advanced signet-ring cell carcinoma of the stomach: Clinicopathological characteristics of patients and efficacy of the modified docetaxel, cisplatin, and fluorouracil regimen.

BACKGROUND: The aim of this retrospective study was to investigate the clinicopathological characteristics of patients with signet-ring cell carcinoma (SRCC) of the stomach, and the efficacy of the modified docetaxel, cisplatin, and fluorouracil (mDCF) chemotherapy regimen. PATIENTS AND METHODS: Sixty-five patients diagnosed with metastatic or recurrent SRCC and treated with at least one course of mDCF regimen as the first-line treatment at our hospital July 2007 and January 2015, were included in this study. The mDCF protocol comprised docetaxel at 60 mg/m2/day (day 1), cisplatin at 60 mg/m2/day (day 1), and 5-fluorouracil at 600 mg/m2/day (days 1-5) for every 3 weeks. RESULTS: The median age was 53 years (range, 25-69 years). The most frequent sites of metastasis were the peritoneum (50.8%) and liver (21.5%). The median number of chemotherapy courses was six. In assessing 61 patients for response evaluation, one patient (1.6%) achieved a complete response, and 36 (59.0%) achieved a partial response. Fifteen patients (24.6%) had stable disease and nine (14.8%) had progressive disease. Grades 3-4 hematological toxicity revealed anemia in three (4.6%) patients, thrombocytopenia in two (3.1%), and neutropenia in five (7.7%). Grades 3-4 nonhematological side effects revealed nausea and vomiting in four (6.1%) patients and mucositis in one (1.5%). The overall survival (OS) and progression-free survival (PFS) were 10.4 months (95% confidence interval [95% CI], 8.9-12.0) and 6.1 months (95% CI, 5.1-7.0), respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of 2 and a high pretreatment carcinoembryonic antigen level were statistically significant. CONCLUSIONS: mDCF is an effective regimen in patients with SRCC of the stomach who have ECOG performance score of 0-1 when the PFS, OS, and tumor response rate are considered. Further prospective studies including more patients should be conducted on this subject.

Is serum survivin expression a predictive biomarker in locally advanced gastric cancer patients treated with neoadjuvant chemotherapy?

BACKGROUND: The potential prognostic value of survivin is variably reported depending on the gastric cancer. OBJECTIVE: Evaluation of the prognostic and predictive significance of serum survivin and its relation with survival and treatment response rates in patients with locally advanced gastric cancer (LAGC). METHODS: Serum samples were prospectively collected from 50 patients with newly diagnosed LAGC. Serum samples of 32 healthy subjects were also collected as control groups for survivin levels. Serum survivin levels were evaluated at baseline and after three cycles of neoadjuvant chemotherapy in LAGC patients. RESULTS: Median survivin level was 147 IU/L (range = 4.4-4936) at baseline and was 27 IU/L (range = 4.2-4737) after neoadjuvant chemotherapy. The difference between survivin levels of the control group (26 IU/L, range = 3.8-1430) and pre-treatment patient group was statistically significant (p< 0.001). Clinical response to mDCF regimen was classified as progressive (progressive disease) and non-progressive groups (partial response + stable disease). Baseline survivin levels were similar between patients in progressive and non-progressive groups (p= 0.55). Survivin levels were significantly reduced after chemotherapy in non-progressive group (p< 0.001). In contrast, serum survivin levels increased in a stepwise fashion from baseline to post-chemotherapy in patients with progressive disease (p= 0.06). Patients were divided into low and high survivin groups according to baseline median survivin levels. Median DFS was 12.4 and 14.6 months for low and high groups, respectively (p= 0.18). Moreover, median OS was 14.4 and 24.9 months for low and high group, respectively (p= 0.14). CONCLUSION: It can be suggested that serum survivin can be used as a predictor of response to chemotherapy- but not survival- in LAGC patients receiving neoadjuvant mDCF chemotherapy. However, large multicenter prospective studies are required to confirm these results.

A Modified Epirubicin and Oxaliplatin Plus Capecitabine (EOX) Regimen as a Second- Line Therapy in Patients with Advanced Gastric Cancer

Objective: We aimed to evaluate the effectiveness of an mEOX (modified epirubicin, oxaliplatin plus capecitabine) regimen as second line therapy after failure of mDCF (modified docetaxel, cisplatin plus fluorouracil). Methods: Gastic cancer patients for whom first-line therapy was unsuccessful and who subsequently received mEOX (epirubicin 50 mg/ m2 on day 1, oxaliplatin 85 mg/m² day 1 and capecitabine twice-daily dose of 625 mg/ m2, p.o. for 2 weeks) every 3 weeks until disease progression or unacceptable toxicity, were retrospectively analyzed. Results: The study population comprised 129 cases with a median age of 55 years (range= 27-78), the majority being male (76 %). Most (75.2%) had ≥ 2 sites of metastasis. The median number of chemotherapy courses was five (range= 2­9). Forty-nine achieved a partial response and 33 showed stable disease, resulting in a ORR (overall response rate) of 38% and a DCR (disease control rate) of 63.6%. The most frequent features of grade 3-4 hematological and non-hematological toxicity were neutropenia (8.5%) and nausea/vomiting (5.4%). None of the patients suffered death due to toxicity. The median PFS was 4.7 months (95% CI, 4.1­5.3) and the OS was 7.4 months (95% CI, 6.3­8.5). On multivariate analysis, age ≥ 60 years and ECOG performance status (0-1) were independent prognostic factors affecting PFS and OS. Conslusions: In advanced gastric cancer patients, who progress after first line chemotherapy and have an ECOG performance status of 0-1, mEOX is a well tolerated triple regimen associated with a promising OS and PFS.

5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as a third-line chemotherapy treatment in metastatic gastric cancer, after failure of fluoropyrimidine, platinum, anthracycline, and taxane.

Studies on the effects of third-line chemotherapy (CT) in advanced gastric cancer (GC) patients are still scarce. The aim of this study was to evaluate the efficacy and safety of the modified 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) regimen as a third-line CT in metastatic GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane. After failure of first- and second-line therapies, 42 patients received third-line FOLFIRI (180 mg/m² irinotecan and 400 mg/m² leucovorin administered concomitantly as a 90-minute intravenous (IV) infusion on day 1, followed by a 400 mg/m² 5-fluorouracil IV bolus then 2600 mg/m² continuous infusion over 46 hours), between January 2009 and December 2015. FOLFIRI was administered for a median of 6 cycles (range 4-12 cycles). Eight patients achieved partial response, while 13 patients showed stable disease, resulting in the overall response rate (ORR) of 19% and disease control rate (DCR) of 50%. The most frequent grade 3-4 hematological and non-hematological toxicities were neutropenia (14.2%) and diarrhea (7.1%). The median progression-free survival (PFS) and overall survival (OS) from the start of third-line CT were 3.8 months (95% confidence interval [CI], 3.0-4.5) and 6.8 months (95% CI, 5.6-7.9), respectively. According to the multivariate analysis, two factors were independently predictive of the poor OS: >2 regions of metastasis (relative risk [RR], 2.6; 95% CI, 1.3-5.4) and a high level of carcinoembryonic antigen [CEA] (RR, 3.4; 95% CI, 1.6-7.4). In conclusion, FOLFIRI was well tolerated as third-line CT and showed promising PFS and OS in advanced GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane.

Comparison of Gemcitabine monotherapy with Gemcitabine and Cisplatin combination in metastatic pancreatic cancer: a retrospective analysis.

PURPOSE: Gemcitabine is among the standard first-line agents for the treatment of metastatic pancreatic cancer. However, as the median survival with gemcitabine monotherapy is 6 months, different combinations are being studied for better, prolonged survival. In this multicenter study, we aimed to compare the results of gemcitabine monotherapy with those of gemcitabine and cisplatin combination therapy as first-line treatments for metastatic pancreatic cancer. METHODS: Data of 664 patients diagnosed with metastatic pancreatic cancer between January 2007 and December 2016 from seven oncology centers in Turkey were retrospectively evaluated, and 319 patients with gemcitabine alone (n=138) or gemcitabine and cisplatin combination (n=181) as first-line treatment were included. RESULTS: The median patient age was 62 years (range 42-79), being 60 years (42-75) in the gemcitabine/cisplatin arm and 67 years (52-79) in gemcitabine alone arm. no complete response was observed in either arm, whereas partial response rates were 30.1% in gemcitabine/cisplatin arm and 15.3% in gemcitabine alone arm (p=0.001). median overall survival was 8 months (95% CI:7.7-10.2) and was significantly longer in the gemcitabine/cisplatin arm than in the gemcitabine alone arm (10 vs. 6 months, p=0.004). CONCLUSION: The cemcitabine and cisplatin combination therapy as first-line treatment of metastatic pancreatic cancer yields significantly prolonged survival over gemcitabine monotherapy. In patients with favorable performance conditions, the combination therapy should be preferred.

Clinicopathological and prognostic characteristics in patients with AFP-secreting gastric carcinoma.

The aim of the present study was to determine whether there are any clinicopathological or prognostic differences between patients with α-fetoprotein-secreting gastric carcinoma (AFP-SGC) and non-AFP-SGC. Pathological parameters, clinical parameters, and treatment efficacy were compared in patients with AFP-SGC and non-AFP-SGC. In total, 362 patients (53 with AFP-SGC and 309 with non-AFP-SGC) were included in the present study. Patients with AFP-SGC had significantly higher levels of lymphovascular invasion, perineural invasion (PNI), rate of liver metastasis, and stage IV cancer compared with patients with non-AFP-SGC (P<0.05). The median overall survival (OS) rate was 12.6 months in the AFP-SGC group, and 22.1 months in the non-AFP-SGC group (P<0.001). The median OS and disease free survival (DFS) of patients with stage I-III AFP-SGC were 28.1 and 13.4 months, respectively, whereas for patients with non-AFP-SGC, the OS and DFS were 45.3 and 38.0 months, respectively (P=0.01; P=0.02). The median OS for the stage IV AFP-SGC and non-AFP-SGC groups was 9.3 and 11.5 months, respectively (P=0.14). Multivariate analysis of the entire patient group revealed that the Eastern Cooperative Oncology Group (ECOG) performance score of ≥2, lymph node involvement, presence of PNI, high levels of carcinoembryonic antigen, and distant metastasis were significantly correlated with OS. The lymph node involvement, ECOG performance score of ≥2, AFP-SGC type, and weight loss at diagnosis were also significant factors influencing the DFS in the stage I-III group. In conclusion, patients with AFP-SGC had more aggressive clinicopathological features and biological behavior with an increased tendency of liver metastasis compared with patients with non-AFP-SGC. In the near future, AFP may become an important surrogate marker to manage therapies of patients with gastric cancer.

Modified docetaxel, cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study.

AIM: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC). METHODS: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2-6 cycles of mDCF chemotherapy which consisted of docetaxel 60 mg/m2 intravenously (IV) on day 1, cisplatin 60 mg/m2 IV on day 1, and 5-fluorouracil 600 mg/m2 IV for 5 days of continuous infusion, with cycles repeated every 21 days. RESULTS: The most common grade 3-4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3-8.6) and 11.5 (95% CI: 9.4-13.7) months, respectively. CONCLUSIONS: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.

Evaluation of Prognostic Factors and Adjuvant Chemotherapy in Patients With Small Bowel Adenocarcinoma Who Underwent Curative Resection.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. MATERIALS AND METHODS: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan-Meier estimates. RESULTS: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease-free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. CONCLUSIONS: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection.

Small cell carcinoma of the urinary bladder: changing trends in the current literature.

Background Extrapulmonary small cell carcinoma (SmCC), also known as oat cell carcinoma or small cell neuroendocrine carcinoma, is characterized by an aggressive clinical course with early metastasis pattern and a short life expectancy. So far, there is no prospective, data-based case-control study due to its low incidence. The purpose of this paper is to discuss the epidemiology, morphopathology, clinical characteristics, differential diagnosis and treatment of bladder SmCC in the light of the literature. Scope PubMed and American Society of Clinical Oncology Meeting abstracts were searched according to the following keywords: 'extrapulmonary SmCC', 'bladder cancer', and 'therapeutic approach'. The last search was performed on 1 October 2015. Some additional papers were determined by reviewing references of the appropriate articles. Most of the data regarding small cell carcinoma of the urinary bladder (SmCCB) were found to be based on the retrospective trials. Findings Bladder SmCC is more frequent in men and usually appears in the seventh to eighth decades. Macroscopic hematuria is the most common clinical symptom. The diagnosis of SmCCB is performed based on the same criteria determined by the WHO classification for the diagnosis of small cell lung carcinoma (SCLC). Prognosis is closely correlated with the stage at presentation. Although the prognosis of the disease is poor, a long survival can be achieved particularly by radical surgery following neoadjuvant chemotherapy in patients with early stage tumors. Cystectomy is still the current standard local treatment. However, cystectomy alone is not sufficient. Chemotherapy and definitive radiotherapy should be preferred for limited disease in patients who are not candidate for surgery. Conclusion Considering the poor prognosis of the disease, further studies are needed to determine the optimal treatment options and new molecular markers in the way of early diagnosis and favorable outcomes. Prospective, multicenter, randomized studies are required to evaluate the role of neoadjuvant chemotherapy followed either by surgery or radiotherapy.

A comprehensive review of the role of the hedgehog pathway and vismodegib in the management of basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer. Most cases of BCCs are treated with only optimal surgical resection. However, unresectable, locally advanced or metastatic tumors might have potential to progress. In this patient group, there is no standardized treatment approach. Vismodegib is a new selective inhibitor of the hedgehog (Hh) pathway. This manuscript is aimed to review the efficacy of the Hh pathway inhibitor vismodegib in BCC patients with locally advanced or metastatic disease. SCOPE: Vismodegib showed positive results in clinical studies. A computerized search of the PubMed and American Society of Clinical Oncology Meeting abstracts was performed, by searching for the following keywords: 'vismodegib', 'pathway', 'inhibitor', and 'targeted therapies for BCC'. The last search was done on 1 September 2014. Most of the vismodegib data depend on phase I and II trials. FINDINGS: Preclinical and clinical studies have shown that Hh pathway activation occurs in BCC. In BCC patients the role of chemotherapy is not completely known. Although conventional chemotherapies like cisplatins increase the response rate in BCC, improvement in overall survival and progression free survival were not demonstrated. Results of both phase I and phase II studies have shown that vismodegib is a potential new treatment strategy for patients with locally advanced and metastatic BCC. As in previously published phase I trials, in the ERIVANCE BCC study the primary endpoint, objective response rate, significantly increased by 43% and 30% in patients with locally advanced and metastatic BCC, respectively. Because of the promising results in phase I and II trials, vismodegib was approved by the Food and Drug Administration (FDA) in the treatment of patients with BCC who are not suitable for surgery or radiotherapy or with relapsed locally advanced disease following surgery or metastatic disease. CONCLUSION: Recent trials have shown that vismodegib has produced promising activity in patients with locally advanced and metastatic BCC. The ongoing studies with vismodegib in other solid tumors and BCC will shed light on more certain treatment pathways.

Treatment Approaches in 102 Elderly Patients With Non-Small Cell Lung Cancer.

BACKGROUND: The life expectancy and presence of co-morbidities cause reservations in treatment decisions for elderly patients with cancer. In this study, we retrospectively evaluated 102 patients who are considered as middle-old aged (aged 75 - 84) by gerontologists. METHODS: Medical records of patients were reviewed. One hundred and two patients with a diagnosis of non-small cell lung cancer (NSCLC) whose follow-up ended with death between March 2006 and May 2013 were examined. RESULTS: The median age at diagnosis was 77 (75 - 85) years. Thirty-three patients (67.6%) were over 80 years old. The number of patients with metastasis was 57 (55.8%). Forty-two (41.2%) patients had stage IIIA and IIIB disease. Fifteen of the metastatic patients (26.3%) were given chemotherapy, while 12 of the non-metastatic patients (26.6%) were given chemotherapy. Of the non-metastatic patients, 25 (55.6%) were treated with radiotherapy, and five (11.1%) were treated with chemotherapy. The median duration of follow-up was 4 (1-55) months. Progression-free survival (PFS) was 4 months in non-metastatic patients, and 3 months in metastatic patients. Overall survival (OS) was 4 months. OS rates for 1 and 2 years were 10% and 2%. CONCLUSION: Chemotherapy and radiotherapy may be administered even to patients of this age group. The beneficial effect of chemotherapy in patients with metastasis on OS is an important finding of our study.

A rare case: Hallucination associated with pazopanib.

Diarrhea, hyperglycemia, anemia, depigmentation of the hair, and rash are common side effects of tyrosine kinase inhibitors. Neurological side effect like hallucination due to pazopanib is exceptionally rare in literature cases. Herein, we reported a case of hallucination related to pazopanib in a patient with renal cell carcinoma. A 47-year-old male patient with renal cell carcinoma developed repetitive hallucinations on the following days of pazopanib initiation. There was no other significant finding in the differential diagnosis of hallucination. Neurological symptoms disappeared after termination of pazopanib. We aimed to emphasize that neurological side effect like hallucination may rarely occur during the treatment of pazopanib and take note that physicians should be aware of this infrequent side effect in the patients treated with pazopanib.