CD47 (don't eat me signal) expression levels and its relationship with clinicopathologic features in early-stage prostate carcinoma.

BACKGROUND: Prostate cancer is a cancer with poor host immune response and could be defined as a non-T-cell inflamed tumor. Therefore, immunotherapy treatments could not be included in the treatment of prostate cancer until recently. Inadequate antitumoral response is one of the main reasons why tumor cells multiply rapidly and cause lethal results. It was shown that CD47 molecule, which is secreted at high levels by leukemia cells, reduces macrophage-mediated phagocytosis and thus facilitates escape from the antitumoral immune response. The aim of this study was to show don't eat me signaling in prostate carcinoma tissues and its relationship with macrophage polarization. MATERIALS AND METHODS: A total of 263 patients with a diagnosis of prostatic adenocarcinoma after radical prostatectomy between 2015 and 2020 at our institute were included in the study. CD47, CD68, and CD163 expression levels were examined immunohistochemically (IHC) in these tissues. The relationship of these expression levels with unfavorable prognostic factors and survival for prostate carcinoma was investigated. RESULTS: In this study, all the operated prostate carcinoma cases had CD47 expression in tumor tissue, but only 52.5% had a high level of expression. Of 263 prostate cancer tissues, 135 (51.3%) showed high expression of CD68 protein and 189 (71.9%) showed high expression of CD163 protein. There was a statistically strong relationship between CD47, CD68, and CD163. CONCLUSIONS: The CD47 molecule is basically a molecule that inhibits macrophage activation. CD68 is mostly used for macrophage classification, while CD163 is used for tumor-associated macrophage classification. Unlike others, we IHC examined CD47, CD68, and CD163 expressions in the surgical materials of patients who were operated for prostate carcinoma. In addition, we concluded that strong CD47 expression was closely associated with strong CD68 and CD163 expression in all tumor samples. However, a significant relationship between these expression levels and survival could not be demonstrated.

Prevalence of depressive symptoms in elderly cancer patients receiving chemotherapy and influencing factors.

BACKGROUND: Depression is one of the most prevalent causes of distress in the geriatric population. The purpose of this study was to examine the prevalence of depressive symptoms in elderly cancer patients and to determine the possible associated factors. METHODS: Cancer patients 65 years or older and on active chemotherapy completed the Yesavage Geriatric Depression Scale. We examined the relationship of depressive symptoms with age, gender, marital status, educational background, type of cancer, stage of disease, comorbidities, types of treatment for cancer, the duration after diagnosis of cancer, social support, and pain status. RESULTS: The study included 170 patients with a mean age of 71 years, and 47.1% were women. The prevalence of a high depressive symptom score was 19.4%. Of the patients who had a high depressive symptom score based on the Yesavage Geriatric Depression Scale, 18.2% had already been diagnosed with depression and used antidepressants. The mean pain score was significantly higher in patients who had a high depressive symptom score compared to others (P = 0.012). CONCLUSION: The prevalence of depressive symptoms in elderly cancer patients receiving chemotherapy was similar to that in the geriatric population without cancer. It was also consistent with previous studies on elderly cancer population. Pain was found to be a factor related to depressive symptoms. The prevalence of depression may be reduced by pain control. The treatment of depression may both improve the patient's quality of life and enhance their compliance with treatment.

Is advanced age a hesitation for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer?

PURPOSE: The purpose of this study was to assess the feasibility and safety of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients with peritoneal carcinomatosis of colorectal cancer. METHODS: Patients who underwent curative complete CRS and HIPEC for peritoneal carcinomatosis of colorectal cancer with minimum follow-up of 24 months were included in the analysis. Charlson comorbidity index and ECOG performance status were used to evaluate preoperative condition. Patients were tiered into two groups according to age (<65 and ≥65 years). Postoperative morbidity, mortality, recurrence, and overall survival were compared between groups. RESULTS: One-hundred patients were meeting the inclusion criteria. Median age was 56 years (ranging, 20-86). The origin of peritoneal carcinomatosis (PC) was colon in 77 and rectum in 23 patients. There were 31 patients in the elderly group. Mean hospital stay was 1711.8 and 16.814.3 days in young and elderly groups (p=0.937). In young patients, postoperative morbidity was seen in 26 (37.6%) patients versus 9 (29%) patients in elderly group (p=0.272). Mortality was higher in elderly group (n=4, 12.9%) than in the younger group (n=5, 7.2%), but the difference was not statistically significant (p=0.287). Median follow-up was 25 months (ranging, 2-112). Local and/or distant recurrence occurred in 30 (43.4%) patients in the young group and 9 (29%) patients in elderly group (p=0.169). Two-years disease-free survival was similar: 67.1% in the young and 74% in the elderly groups (p=0.713). CONCLUSIONS: CRS and HIPEC offer comparable oncologic outcome in meticulously selected medically-fit elderly patients without increased postoperative morbidity and mortality.

Erdafitinib-Induced Bilateral Multifocal Serous Retinal Detachments and Severe Dry Eye Related Unilateral Peripheral Ulcerative Keratitis in a Patient with Metastatic Urothelial Carcinoma.

Background: A case of bilateral multifocal serous retinal detachments and dry eye complicated with unilateral peripheral ulcerative keratitis (PUK) during erdafitinib therapy is described. Case description: A 76-year-old male underwent a baseline examination two months after initiating 8 mg erdafitinib therapy (April 2023) due to metastatic urothelial carcinoma. Left subfoveal serous retinal detachment was observed initially but the treatment was resumed as he was asymptomatic. In May 2023, bilateral multifocal subretinal fluid pockets were identified, and the patient was still asymptomatic. However, in June 2023 he complained of bilateral redness and a stinging sensation in his right eye. Bilateral severe dry eye and right PUK were diagnosed. He was prescribed dexamethasone eye drops and sodium hyaluronate artificial tears for both eyes. One week later corneal staining decreased, and progression of PUK ceased. Erdafitinib therapy was discontinued in June 2023 due to the planned transurethral prostatectomy. By July 2023, after discontinuation of the drug and administration of the topical treatment, the dry eye improved and the PUK became inactive. There was also resolution of subretinal fluid pockets in the right eye and a reduction of subretinal fluid pockets in the left eye. After the reinitiation of erdafitinib therapy, serous retinal detachments recurred in both eyes in September 2023, but both corneas remained stable with topical low-dose dexamethasone, cyclosporine-A and artificial tear usage. Conclusion: Erdafitinib therapy may lead to concurrent anterior and posterior segment complications. Multidisciplinary monitoring is crucial for patients undergoing erdafitinib therapy to prevent possible visual disturbances. LEARNING POINTS: Erdafitinib, a tyrosine kinase inhibitor of fibroblast growth factor receptors 1 to 4, is administered for the treatment of locally advanced, unresectable or metastatic urothelial carcinoma but however is fraught with several systemic and ocular side effects.Concurrent anterior and posterior segment ocular involvement could be encountered in patients undergoing erdafitinib therapy.Maintaining a high level of suspicion and closely monitoring for potential ocular complications through collaborative efforts is essential for all patients undergoing erdafitinib therapy.

Endogenous Endophthalmitis Caused by Aspergillus lentulus in an Immunocompromised Patient with Lung Cancer

A 78-year-old man with a history of lung cancer, chemotherapy, radiotherapy, and coronavirus disease 2019 infection experienced visual deterioration of two-weeks' duration in his right eye. There was multifocal, yellowish-white retinitis foci, vascular engorgement, and scattered intraretinal hemorrhages extending from posterior pole to retinal periphery in the right eye, whereas the left eye was normal. Intravitreal vancomycin, ceftazidime, clindamycin, and dexamethasone were given for endogenous endophthalmitis initially. Vitreous culture confirmed the presence of Aspergillus lentulus, and he was treated with intravitreal amphotericin-B and voriconazole injections together with systemic amphotericin-B, voriconazole, posaconazole, and micafungin therapy. During follow-up, vitreoretinal surgery was performed because of rhegmatogenous retinal detachment, and he received one additional cycle of chemotherapy due to recurrence of the cancer. Although the retina was attached, enucleation was eventually required due to painful red eye. Atypical squamous cells beneath the neurosensory retina suggesting metastasis were noted on histopathological examination. Timely ocular examination is crucial for any immunocompromised patient having ocular symptoms. High level of suspicion for a fungal etiology is a must in these patients.

The effect of octreotide, an analog of somatostatin, on bleomycin-induced interstitial pulmonary fibrosis in rats.

In this study, octreotide (OCT), a synthetic somatostatin analog, was tested for its beneficial effects in the prevention of interstitial pulmonary fibrosis (IPF) induced by bleomycin (BLM) in rats by histological examination and by evaluating tissue OH-proline levels. Thirty male Wistar rats were divided randomly into three groups: group I: intratracheal (i.t.) BLM (7.5 mg/kg, single dose) + saline solution [0.9% NaCl, subcutaneously (s.c.), once-daily for 7 days]; group II: i.t. BLM (7.5 mg/kg, single dose) + OCT acetate (82.5 µg/kg, s.c., once-daily for 7 days); and the control group. At the end of the 7 days, lung tissues were excised and examined by histopathological methods. Levels of tissue hydroxyproline (OH-proline) were determined. BLM administration resulted in prominent histopathologic findings, such as diffuse alveolar damage and interstitial pulmonary fibrosis, as well as a significant increase in OH-proline level, as compared to controls. OCT application explicitly attenuated the histopathologic changes to a significant extent. OCT decreased paranchymal fibrosis and structural deformities in BLM-induced lung fibrosis. These results suggest that OCT administration to rats with BLM-induced IPF has a protective effect. Further studies are necessary to reveal the molecular mechanism(s) of OCT-induced protective effect.

What Is Your Choice for Androgen Deprivation Therapy in Metastatic Prostate Carcinoma: Surgical or Medical?

OBJECTIVE: At the time of diagnosis, approximately 16.5% of prostate cancer patients are metastatic. The main framework of metastatic prostate cancer treatment is androgen deprivation therapy, which is performed surgically or medically. The aim of this study is to evaluate the attitudes of medical oncologists and urologists about orchiectomy as androgen deprivation therapy. MATERIAL AND METHODS: A total of 387 physicians working in the Departments of Urology (n=217) and Medical Oncology (n=170) were included in this descriptive study. Data were collected through an electronic survey. RESULTS: Only 7.5% of participants indicated that they offered surgical castration to their patients. Urologists preferred surgical castration more than oncologists for the treatment of metastatic castration-sensitive prostate carcinoma (P=.003). The reasons why medical oncologists preferred surgical castration less are that it is an invasive procedure, has risk of morbidity and mortality, high cost of hospitalization, and may cause deterioration of the patient's body image (P < .05). CONCLUSION: This study showed that physicians were less likely to perform orchiectomy as an androgen deprivation therapy. Although the most important reason for this is the patient preference, the biased presentation of treatment options to patients, the lack of knowledge of physicians about orchiectomy, and the effect of the pharmaceutical industry should also be kept in mind.

Evaluation of hereditary/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey.

Breast cancer, a worldwide leading cause of cancer in women, may occur in familial cases. Germline mutations in BRCA1/2 genes are responsible for 15% of the familial cases. With the power of next generation sequencing (NGS) analysis, it is possible to analyze genes related to hereditary susceptibility to breast cancer and investigate the genetic etiology more thoroughly. In this study, we investigated 30 genes identified frequent pathogenic alleles in Turkish population. The study includes 495 unrelated individuals diagnosed with breast cancer who are selected for genetic testing according to NCCN criteria for hereditary breast cancer. All patients were analyzed by NGS for BRCA1/2 genes. Deletion/duplication investigation by Multiplex ligation-dependent probe amplification (MLPA) and massive sequencing of 30 breast cancer-related genes (Oncorisk Gene Panel) were performed in a stepwise manner. BRCA1/2 variants are the most frequent pathogenic variants which are found in 45 of 495 (9.1%) patients. Four previously unreported, novel, pathogenic variants of BRCA2 gene are identified. In four cases, exonic deletions of BRCA1/2 genes are determined and there is no duplication of these genes. NGS panel investigation involving other moderate-high risk genes contributed genetic diagnosis in an extra 39 out of 419 (9.3%) cases. Our study presents the cost effectiveness of the gene panel approach. We suggest that gene panels should be the first-tier genetic testing for hereditary breast cancer and MLPA analysis of BRCA1/2 genes should be investigated as a complementary method of NGS analysis.

Ghrelin and obestatin expression in oral squamous cell carcinoma: an immunohistochemical and biochemical study.

The underlying molecular mechanism of carcinogenesis in oral squamous cell carcinoma (OSCC) is poorly understood and appears to be controlled on many genetic, environmental, and hormonal factors. Obestatin and ghrelin, two recently discovered hormones, are co-expressed in endocrine cells. The purpose of this investigation was to examine the immunohistochemical features of OSCCs in relation to the tissue concentration of ghrelin and obestatin. The association between OSCC and Epstein Barr Virus (EBV) status was also explored. The expression of ghrelin and obestatin was examined by immunohistochemistry and immunoassay in oral biopsy specimens: 10 benign squamous epithelial cell samples, 10 microinvasive squamous cell carcinomas, and seven well-differentiated and seven poorly differentiated OSCCs. The presence of EBV was evaluated in these samples using immunohistochemistry. The concentrations of ghrelin and obestatin in tissue homogenates were measured by RIA and ELISA, respectively. Squamous cell carcinomas and benign tissue samples were positive for anti-EBV antibody, and obestatin and ghrelin were shown to be co-expressed in all stratified squamous epithelium samples. Expression of ghrelin and obestatin was decreased or absent in OSCCs in relation to the invasiveness of the carcinoma; ghrelin and obestatin levels in cancerous tissue homogenates were lower than in benign tissue homogenates. These results indicate that the concentrations and distribution of immunoreactive obestatin and ghrelin might be helpful in distinguishing OSCC from benign tumors. Maintaining normal levels of these hormones might be required for regulation of normal cell division. However, detailed studies will be required for better understanding of the complex mechanism of carcinogenesis relating to OSCCs.

Malignancies diagnosed during pregnancy and treated with chemotherapy or other modalities (review of 27 cases): multicenter experiences.

BACKGROUND: Cancer is the second leading cause of death in women of reproductive age. The most common tumors diagnosed during pregnancy are breast and cervix cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, leukemias, and malignant melanoma. The aim of therapy in pregnancy is to give optimal treatment to the mother without harm to the fetus. In the first trimester, organogenesis continues, so chemotherapy should not be given because of increasing risk of spontaneous abortion, fetal malformation, and mortality. We evaluated mostly seen tumors during pregnancy and assessed treatment type and outcome of pregnancy after chemotherapy in our population. METHODS: We retrospectively analyzed 27 patients who have been treated during pregnancy or after the delivery because of several malignancies. RESULTS: The tumors associated with pregnancy were breast cancer, hematologic malignancies,gynecologic malignancies, sarcomas, and others. The chemotherapy regimens were given in 17 of 27 patients in the second or third trimester of pregnancy. Four of the patients were diagnosed with cervical cancer, hemangiopericytoma, chronic myeloid leukemia,and breast cancer during the first trimester, so their pregnancies were ended by therapeutic abortion. Although 1 of the 3 fetuses who were exposed to chemotherapy in utero at the second or third trimester was born prematurely and low birth weight was diagnosed in the other 2 fetuses, fetal malformation was not seen in any of them. There were 7 normal and 9 cesarean deliveries. Twenty-three healthy babies survived from 27 pregnancies, of whom 17 babies were exposed to chemotherapeutic agents. CONCLUSIONS: We reported herein 27 patients with malignancies diagnosed during pregnancy; 17 patients received chemotherapy during the gestational period without any fetal or maternal abnormalities. Because of the low incidence of malignancy during pregnancy, our report is noteworthy.

Human telomerase reverse transcriptase expression in colorectal tumors: correlations with immunohistochemical expression and clinicopathologic features.

Human telomerase reverse transcriptase (hTERT) proteins in colorectal cancer investigated in several studies, but to our knowledge, hTERT expression has not been evaluated in all of colorectal tumors, including hyperplastic polyps (HPs), adenomas, and carcinomas, on paraffin-embedded tissue sections. The aim of the present study is to investigate immunohistochemical hTERT expression and its relationship with the clinicopathologic features in a spectrum of colorectal tumors. In this study, hTERT expression was determined in HP (n = 20), adenomatous polyp (AP) (n = 20), colorectal adenocarcinomas (n = 20), and normal mucosa (n = 20) by immunohistochemical method. The findings were correlated with the clinicopathologic features. The staining level of hTERT in adenomas and carcinomas was significantly higher than in normal tissues (P < .05). There was also significant difference between HP and AP (P < .05). Level of hTERT in carcinomas was higher than in adenomas, but the difference was of no statistical significance (P > .05). There was no significant association of hTERT expression in cancerous, precancerous, or normal mucosa related to clinicopathologic parameters including age, sex, and size of lesion, (P > .05), but only association with histologic grade for carcinoma was found (P < .05). Levels of hTERT by immunohistochemistry demonstrated that the expression of hTERT was very little in normal mucosa and HP, moderate in AP, and highest in carcinoma. Thereby, hTERT expression may use the aggressiveness of the colorectal tumors as a marker, but it is not related to clinicopathologic data.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

Expression of obestatin and ghrelin in papillary thyroid carcinoma.

Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto's thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto's disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies.

Ghrelin expression in normal kidney tissue and renal carcinomas.

Ghrelin expression in cancers is either reduced/absent or increased depending on the organs involved. The aims of this study were to investigate: (i) whether there are differences in ghrelin peptide expression between kidney tissues from a series of renal cell carcinoma cases, oncocytomas, and normal controls; (ii) whether there are correlations between tissue ghrelin levels in a series of renal carcinoma cases and normal controls; and (iii) how normal is kidney ghrelin expression per mg tissue as compared with the normal stomach tissue ghrelin level. We studied 7 normal stomach and 7 normal kidney samples, 21 clear cell renal carcinomas, 7 chromophobe type renal cell carcinomas (RCC), 7 papillary type RCC, and 7 oncocytoma samples. Tissue ghrelin expression was measured by RIA and immunohistochemistry. Grades 1-3 clear renal cell carcinomas, chromophobe type RCC, papillary type RCC, and oncocytomas expressed 88%, 94%, 95%, 51%, 75%, and 48% less ghrelin than the normal kidney, respectively. Overall, we concluded that ghrelin expression in renal cell carcinoma tissues is always lower than that in normal kidney or is absent. This low level or lack of ghrelin may play a role in the etiopathogenesis and progression of cancer.

Uterine primitive neuroectodermal tumor: a case report.

BACKGROUND: Primitive neuroectodermal tumors of uterus (PNET) are extremely rare in tumors of the female genital system and therefore there is no sufficient information about their diagnosis, treatment, and follow-up. CASE: The case is a 32-year-old, operated in emergency conditions due to intra-abdominal hemorrhage, and discusses our diagnosis and treatment approaches in the light of literature data. CONCLUSION: To the best of our knowledge, this is first report of uterine PNET that presented with intraabdominal hemorrhage due to uterine rupture. Despite advances in therapy, the prognosis is poor. The low number of these cases precludes accurate standardization of therapy.

Epidemiology and survival of hepatocellular carcinoma in Turkey: outcome of multicenter study.

OBJECTIVE: Hepatocellular cancer (HCC) is one of the important health problems in Turkey. We aimed to determine the clinical and demographic features of HCC in the Turkish population and to evaluate the prognostic and survival features. METHOD: Two hundred and twenty-one patients with HCC from five hospitals in Turkey are included in this study. RESULTS: In 44.4% of the 221 patients with hepatitis B virus and in 21.3% of the 221 patients with hepatitis C virus were found to be responsible for HCC etiology. It has been shown that HCC developed on cirrhosis basis in 74.2% of the patients. HCC was presented with single solitary nodule in 69.2% of the patients. Non-liver metastasis was present in 12.5% of the patients. In 21.7% of the patients, alpha-fetoprotein (AFP) levels were above the diagnostics level of 400 ng/ml. The median overall survival (OS) of 221 patients was 14 months. The median OS of the patients with Child-Pugh A class was significantly longer than that with Child-Pugh B and C classes. The OS of the individuals with normal AFP levels was also longer than that with high AFP levels. The OS of the patients with Stage I HCC according to tumor node metastasis (TNM) classification, the female patients and the treated patients group was found to be significantly good. CONCLUSIONS: In conclusion, the viral etiology (hepatitis B and C infections) in Turkish population is found to be an important factor in HCC development. The Child-Pugh classification, AFP levels, TNM classification, being female and treatment were determined to be important prognostic factors in HCC patients.

Primary mucinous adenocarcinoma of appendix treated with chemotherapy and radiotherapy: a case report.

A rare case of primary appendiceal mucinous adenocarcinoma is reported. The presenting signs and symptoms were suggestive of acute appendicitis. An appendectomy was performed resulting in a histological diagnosis of grade 2 mucinous adenocarcinoma of the appendix. The patient was referred to our clinic where he underwent a complementary right hemicolectomy with lymph node dissection. Two of the 17 resected lymph nodes were tumor positive but there was no residual tumor in the hemicolectomy specimen. The patient was staged as T4N1M0 and adjuvant multimodality treatment was planned because he was considered at high risk for local-regional recurrence and distant metastasis. Three cycles of capecitabine 1250 mg/m2 on days 1-14 and oxaliplatin 130 mg/m2 on day 1, every 21 days (CAPOX) were administered, then a total dose of 50.4 Gy external-beam radiation therapy was delivered to the primary tumor region and 45 Gy to the lymphatics, and finally 3 further cycles of the CAPOX regimen were administered. Multimodality treatment was well tolerated by the patient, who is still alive 25 months after the hemicolectomy procedure with no evidence of disease progression.

Localized palmar-plantar epidermal hyperplasia associated with use of sorafenib.

A 45-year-old man receiving oral sorafenib 400 mg twice daily for metastatic renal cell carcinoma developed pain and rash on his hands and feet 3 weeks after commencement of treatment. Dermatological examination revealed hyperkeratotic plaques surrounded by erythema and with a callus-like brownish-yellow appearance centrally, together with bullae with purulent content under the plaques. Histopathological examination revealed intense hyperkeratosis in the upper part of the epidermis and parakeratosis beneath the epidermis. The integrity of the epidermis was therefore compromised and intense neutrophilic infiltration was seen. The patient was diagnosed on clinical and histopathological grounds as having localized palmar-plantar hyperplasia associated with use of sorafenib, representing the second case reported in the literature. The patient's skin lesions improved markedly after the sorafenib dose was decreased to 200 mg twice daily, a regimen that he continues to take. In the authors' opinion, use of the term localized palmar-plantar hyperplasia, as diagnosed in this patient, is more appropriate in this clinical setting than related terms such as palmoplantar erythro-dysaesthesia or hand-foot syndrome.

A national, multicenter, non-interventional, observational study on treatment patterns in patients with metastatic renal cell carcinoma in Turkey - NOTES study.

INTRODUCTION: The introduction of targeted therapies in renal cell carcinoma has significantly improved its prognosis and treatment outcomes in recent years. Such treatment options are targeted therapies of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of the rapamycin pathway. With the use of tyrosine kinase inhibitors (TKIs) and mammalian target of the rapamycin inhibitors, overall survival has increased up to 2 years. In Turkey, due to applicable reimbursement conditions for patients with metastatic renal cell carcinoma (mRCC), interferon use is mandated as a first-line treatment, thus providing information on the use of everolimus only after initial interferon and second-line VEGF-targeted treatments such as VEGF-TKI. PATIENTS AND METHODS: To provide a first real-life data set in Turkey, we conducted a prospective, non-interventional, observational study and assessed the efficacy and safety of everolimus after two lines of treatment including interferon. A total of 100 patients with histologically confirmed mRCC were enrolled in the study from 11 centers between June 2012 and March 2014 (70 males and 30 females). Efficacy was assessed on the basis of progression-free survival and overall survival; safety of everolimus was assessed on the basis of adverse event occurrence. RESULTS: The study results showed that the median progression-free survival with everolimus treatment was 8.1 months (95% CI: 5.1-11.1) and the median overall survival was 17.6 months (95% CI: 10.1-25.1), thus indicating a better overall response based on survival durations than those from the randomized Phase III REnal Cell cancer treatment with Oral RAD001 given Daily study results (4.9 and 14.8 months, respectively). CONCLUSION: The study showed that everolimus treatment is a safe and effective treatment option in the treatment of mRCC after VEGF-TKI, with an acceptable safety and tolerability profile in real-life settings.