Autologously transplanted dermis-derived cells alleviated monobenzone-induced vitiligo in mouse.

Vitiligo is a depigmentation disease which affects skin and hair follicles with a prevalence of 0.5%-1% worldwide. In this study, we aimed to investigate treatmental potential of dermis-derived cells in monobenzone (MBEH)-induced mouse vitiligo model with light and electron microscopy. MBEH (40%) cream was topically applied to C57BL/6 mice until depigmentation occured in vitiligo and experimental groups. In experimental groups, dermis-derived cells obtained from back skin biopsy samples before induction of vitiligo, were injected intradermally to vitiligo mice. On Days 3 and 15 after cell transplantation to experimental groups, skin biopsies were compared with biopsies of control and vitiligo groups. Dermis-derived cells obtained from back skin biopsy samples of experimental groups showed nestin and versican immunoreactivity. Melanin in hair follicles of control group was detected by histochemical stainings (Haematoxylin and eosin and Fontana-Masson) whereas sparse melanin granules were observed in hair follicles of vitiligo group. In experimental groups, there was an increase in the number of hair follicles with melanin compared with vitiligo group. We observed MART-1 immunoreactive cells mostly around the hair follicles in control group and within dermis in vitiligo group. Electron microscopic investigation showed presence of melanosomes in hair follicles of control group and lacking in vitiligo group. In experimental groups, both type of hair follicles were observed with electron microscope. Our data suggest that autologously transplanted dermis-derived cells may be effective in vitiligo treatment by contrubuting to melanin production.

Prospective external validation of an updated algorithm to quantify risk of febrile neutropenia in cancer patients after a cycle of chemotherapy.

PURPOSE: Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile neutropenia, and this study now extends and modifies the previous model as well as tests its external validity. METHODS: We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm. RESULTS: A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of ≥ 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use. CONCLUSION: Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.

Programmed death-1 or programmed death ligand-1 inhibitors? A meta-analysis of differential efficacy as compared to chemotherapy in advanced non-small cell lung cancer.

BACKGROUND: Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1) inhibitors have improved survival over chemotherapy in advanced Non- Small Cell Lung Cancer (NSCLC). However, it is unclear if there are class specific differences in the efficacy of Checkpoint Inhibitors (CPIs) in NSCLC, and this paper is designed to answer these clinical questions. METHODS: For this Meta-analysis, we searched PubMed, Science of Web, "Clinicaltrials.gov" and online sources for trials comparing PD-1 and PDL-1 CPIs in advanced NSCLC. The data for Hazard Ratio (HR) and their Confidence Intervals (CI) for Overall Survival (OS) was extracted. RESULTS: A sum of 9739 patients from 16 trials were included in the efficacy evaluation. For the OS endpoint, both PD-1 inhibitors (HR = 0.76, 95%CI = 0.69-0.83, P < 0.001) and PDL-1 inhibitors (HR = 0.84, 95%CI = 0.74-0.95, P < 0.001) were superior to chemotherapy in treatment naïve (upfront) patients, the results were similar in treatment refractory patients (PD-1 inhibitors (HR = 0.67, 95%CI = 0.60-0.75, P < 0.001) and PDL-1 inhibitors (HR = 0.78, 95%CI = 0.69-0.88, P < 0.001) were superior to chemotherapy). There was no difference in the effect of PD-1 and PDL-1 classes of CPIs over chemotherapy in treatment naïve and treatment refractory settings (Q = 1.88, df = 1, P = 0.017, and, Q = 3.27, df = 1, P = 0.070, respectively). CONCLUSION: Efficacy of PD-1 and PDL-1 class of CPIs was not different, although differences among individual CPIs or their combinations cannot be excluded. We were also able to compute pooled efficacy data, as compared to chemotherapy alone, for trials where these groups of CPIs were utilized.

Effects of Monobenzyl ether of hydroquinone on 3T3 mouse fibroblast viability and ultrastructure.

Monobenzyl ether of hydroquinone (MBEH) is a topical depigmentation agent used by vitiligo patients to even the skin tone. We aimed to investigate the effects of MBEH on 3T3 mouse fibroblasts. Fibroblasts were treated with 250 µM, 500 µM, and 750 µM MBEH and vehicle (EtOH:DMSO) for 24 hours. Cell numbers of 250 µM, 500 µM, and 750 µM MBEH treated and vehicle groups decreased significantly compared to control group. TUNEL positive cell rate increased with MBEH concentration. In electron microscopic examination, control and vehicle groups showed active cells features, while mitochondrial swelling and cristae loss were seen in 250 µM MBEH-treated group. In cytoplasm of 500 µM MBEH-treated group, there were many multivesicular bodies and autophagic vacuoles. As an indication of apoptosis, cell membrane blebs and reduction in cell size were observed. In 750 µM MBEH-treated group, cells were completely degenerated. Our findings show that MBEH, which is used as a depigmentation agent to lighten the skin by destroying melanocytes, may also have dose-dependent negative effects on the viability of 3T3 mouse fibroblasts, and these may be mediated through autophagic and apoptotic cell death mechanisms.

A comparison of metacognitive factors among patients with cancer and the control group.

OBJECTIVE: Research examining the relationship between metacognitions and cancer has only recently begun to emerge. This study attempted to compare the metacognitions of the patients with and without cancer. The effects of stage of cancer, type of cancer, and treatment modality (chemotherapy, radiotherapy, operation) on metacognitions were investigated. Patients with cancer were hypothesized to have higher levels of negative metacognitions. METHODS: Participants were patients with cancer (N = 279) and patients without cancer (control group, N = 212). The Metacognition Questionnaire-30 was administered to all participants. Results were analyzed according to demographic and histopathological characteristics of the patients. RESULTS: The results showed that patients with different cancer diagnoses scored higher than the controls on all subscales of the MCQ-30. Those who received chemotherapy scored the highest on the MCQ-30. The patients who were in early stages of cancer had higher levels of negative metacognitions. Patients who did not have operation but had chemotherapy had the highest levels of negative metacognitions. Patients who were in locally advanced stage, did not have operation but had received or was receiving chemotherapy had the highest levels of negative metacognitions. CONCLUSIONS: Patients who were in early stages of cancer appeared to be in greater need for psychological help and access to services. Findings indicated a need for psychological support for patients who undergo chemotherapy.

Severe periocular bleeding induced by bevacizumab in a patient with recurrent glioblastoma multiforme.

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor, and it has been shown to improve progression-free survival in patients with recurrent glioblastome multiforme when administered as second-line therapy. However, it has been associated with serious and fatal hemorrhagic events. Here, we present a 68-year-old male who developed severe periocular bleeding while on bevacizumab for recurrent temozolamide-resistant glioblastome multiforme.

An unexpected image on a chest radiograph.

Introduction Central venous catheterisation is an essential component of patient care in hospital. A forgotten complete guide-wire is a rare complication, although the reported incidence has increased rapidly over the last decade. Case report We report a 72-year-old man with a complete guide-wire inadvertently overlooked during catheter insertion. A central venous catheter had been inserted for total parental nutrition during treatment for pancreatitis. Five years later, the patient was readmitted with a painful lesion on his neck and the sensation of a sharp object under his skin. He was discharged without complication following removal of the free part of the guide-wire that had not become attached to the endothelial layer. Conclusion Inattention, inexperience and lack of supervision by a more experienced clinician are considered the most important contributing factors to this complication. Ultrasonography assistance during the procedure, senior supervision, a set count and a chest X-ray after the procedure are recommended in order to prevent forgotten guide-wires.

Can fentanyl transdermal patches prevent the cutaneous hyperpigmentation related to radiotherapy in patients with cancer?

Dermatologic adverse effects related to radiotherapy are one of the most important cosmetic problems and affect the quality of life in patients with cancer. In a male patient with non-small cell lung cancer who received palliative radiotherapy, the hyperpigmentation related to radiotherapy was examined two months later except for fentanyl transdermal patch area. The inhibitory effect of fentanyl on cell cycle may prevent hyperpigmentation related to radiotherapy.

Fatal posterior revesible leukoencephalopathy syndrome associated coma induced by bevacizumab in metastatic colorectal cancer and review of literature.

Posterior reversible leukoencephalopathy syndrome (PRES) is a syndrome characterized by headache, hypertension, confusion, visual disturbance, and seizures accompanied by subcortical vasogenic edema, predominantly involving the parietal and occipital lobes. The syndrome is usually described in malignant hypertension, eclampsia, renal failure, immunosuppressive, and cytotoxic chemotherapies. Bevacizumab, a monoclonal antibody that binds to the vascular endothelial growth factor (VEGF) has been linked to PRES. We carried out review of reports documenting the occurrence of PRES in patients receiving bevacizumab. This literature review was conducted by utilizing PubMed Database. If early diagnosed, PRES is reversible. We present a case of fatal PRES-associated coma induced by bevacizumab in metastatic colorectal cancer.

Ipilimumab may increase the severity of cutenaous toxicity related to radiotherapy.

Ipilimumab, monoclonal antibody against cytotoxic T-lymphocyte antigen-4 and, radiotherapy are commonly used to treat unresectable and metastatic melanoma. As a result of upregulation of immune system with ipilimumab, many immune-related adverse effects, such as dermatitis, colitis, hepatitis, and hypophysitis, have been previously reported in literature. Typically, these effects are treated with high-dose steroids and mostly heal up. Here, we report a case who was receiving radiotherapy due to metastatic malignant melanoma with atypical generalized rash, which was enlarged with concurrent ipilimumab treatment.

Sorafenib-induced severe urticaria in a patient with hepatocellular cancer.

Sorafenib which is used in the treatment of renal, thyroid and hepatocellular cancers is a multi-targeted tyrosine kinase inhibitor. Though sorafenib is associated with some side effects, it is known that sorafenib is generally well tolerated compared to other tyrosine kinase inhibitors. In the present case, hepatocellular cancer was diagnosed seven months ago. The disease was in stage IIIB at the time of diagnosis. Sorafenib was initiated with a dose of 400 mg twice daily because of disease progression after two cycles of doxorubicin. The reactions on the skin of the arms and the body of the patient occurred in the eighth week of treatment. Skin biopsy was performed and urticaria was diagnosed after pathologic examination. No other disorders or drugs which may cause urticaria were detected in the patient. Skin reactions disappeared one week after sorafenib discontinuation without any further intervention.

Metronomic maintenance chemotherapy in patients presenting with paraneoplastic autoimmune hepatitis with recurrent thymic carcinoma.

Autoimmune hepatitis is a rarely seen autoimmune paraneoplastic syndrome of thymic carcinoma. Chemotherapy may be an effective choice in the treatment of primary tumor and paraneoplastic disorder. In this case, we report a 32-year-old man presented with increased liver enzymes and cholestasis with a history of thymoma surgically removed four years ago. Liver biopsy showed chronic active autoimmune hepatitis. Computed tomography scan showed pulmonary metastases and pleural mass as a recurrence of thymic carcinoma, proven by biopsy. After four cycles of cisplatin plus adriamycin plus cyclophosphamide plus vincristine and six cycles of paclitaxel plus gemcitabine, maintenance metronomic cyclophosphamide plus etoposide regimen was offered to the patient. Complete biological signs of hepatitis without need for steroids or immune suppressors and complete radiologic response in primary tumor were achieved. Maintenance metronomic chemotherapy regimens may be an alternative to the current treatment options in patients with thymic carcinomas.

The combination of weekly trastuzumab plus vinorelbine may be preferable regimen in HER-2 positive breast cancer patients with brain metastasis.

Brain metastasis is one of the most important life-threatening conditions in patients with metastatic HER-2 positive breast cancer. A lot of conventional chemotherapeutic and antibody-based regimens used routinely in treatment of the patients with breast cancer are not effective due to blood-brain barrier. In our cases, we reported on three HER-2 positive breast cancer patients with brain metastasis who were offered a combination of weekly trastuzumab plus vinorelbine after brain metastasis. In our cases, the progression-free survival were 12, 16 and 9 months for Case 1, Case 2 and Case 3, respectively. In Case 1, there was no progression in the brain. In Case 3, we did not detect any progress but the patient died due to cerebrovascular embolic events. After local treatment, the combination of weekly trastuzumab plus vinorelbine may be an effective alternative regimen in HER-2 positive breast cancer patients with brain metastases.

Is there any cumulative dose for trastuzumab?

Trastuzumab is one of the most important agents that target human epidermal growth factor receptor 2, but its cardiotoxic effect limits to use it. The mechanism of cardiac dysfunction-related trastuzumab is still unclear. In literature, there is no definite information about the cumulative dose of trastuzumab for cardiotoxicity. In presented case, we reported a breast cancer patient who has been receiving long-term trastuzumab. We have not found any cardiac problems for duration of over four years. According to our case and literature review, we may say that trastuzumab is safely used with periodically echocardiographic control in patients with breast cancer.

Reversible slurred speech related to capecitabine and lapatinib combination in patients with breast cancer.

Capecitabine plus lapatinib combination is an effective chemotherapy regimen in patients with advanced breast cancer. Neurological adverse effects secondary to this regimen were reported rarely in literature. A woman with breast cancer presented with complaints of slurred speech while using the capecitabine and lapatinib combination. Her major complaint was slurred speech. No other radiologic or laboratory disorders were detected in the patient. Slurred speech improved one week after the capecitabine and lapatinib combination was discontinued without any further intervention.

Is there any relation between PET-CT SUVmax value and prognostic factors in locally advanced breast cancer?

PURPOSE: To investigate the relation between PET-CT SUVmax value and prognostic factors in locally advanced breast cancer. METHODS: Data of 73 patients were retrospectively analyzed. Relations between SUVmax value, clinical stage, tumor grade and breast cancer molecular subtypes were analyzed by using one-way ANOVA and x(2) tests. Correlations between age, ki-67 scores and SUVmax were evaluated by using Pearson's correlation test. A p value <0.05 was considered statistically significant. RESULTS: Median SUVmax values for clinical stages 1, 2 and 3 were 5 (range 2.1-4.1), 10.6 (range 2.9-19.6), and 12.2 (range 3.2-23.3), respectively. Statistically significant difference was noticed between stage 1 and 2 (p=0.014) and stage 1 and 3 (p=0.001). Median SUVmax values of triple negative, luminal A, luminal B and non-luminal HER2 positive groups were 14.4 (range 6.6-23.3), 8.2 (range 2.1-18.2), 10.1 (range 3.5-19.6), and 14 (range 4.1-22.9), respectively. Statistically significant differences were noticed in SUVmax values between triple-negative and luminal A groups (p=0.005) and between non-luminal HER2 positive and luminal A groups (p=0.02). Median SUVmax values of grade 1, 2 and 3 were 5.7 (range 2.1-18.2), 9.5 (range 2.2-21.3), and 11.6 (range 3.5-23), respectively. Statistically significant difference was noticed only between SUVmax values of grade 1 and 3 (p=0.035). There was negative correlation between age and SUVmax value (r=-0.23, p=0.047) and positive correlation between ki-67 and SUVmax value (r=0.43, p=0.016). CONCLUSION: There were significant positive relations between PET-CT SUVmax value and clinical stage, tumor grade, and certain breast cancer molecular subtypes (triple-negative and non-luminal HER2 positive groups. Moreover, positive correlation was found between SUVmax value and ki-67 and negative correlation between SUVmax value and age.

Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer.

PURPOSE: Relatively few studies have focused on T4N2 (stage IIIB) locally advanced non-small cell lung cancer (NSCLC). In this study, we tried to identify prognostic factors for patients with clinical stage T4N2 NSCLC. METHODS: We retrospectively identified 223 patients, of which 168 met the inclusion criteria. Patients treated with curative intent using concurrent chemoradiotherapy (CRT) with or without adjuvant chemotherapy, or concurrent CRT after induction chemotherapy, were included in this study. Relevant patient, treatment, and disease factors were evaluated for their prognostic significance in both univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: The median progression-free survival (PFS) was 13 months (95% confidence interval [CI], 10.6-15.4). The median overall survival (OS) was 20 months (95% CI, 16.8-23.1), and 71, 40.3 and 28.2% of the patients survived for 1, 2 and 3 years after diagnosis, respectively. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance status (PS) was independent predictor of PFS (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; p=0.001), and OS [HR, 0.48; 95% CI, 0.26-0.87; p=0.015). Absence of multifocal T4 tumors was also associated with a significantly longer OS (HR, 046; 95% CI, 0.31-0.7; p=0.001). There was no statistically significant difference in OS and PFS between treatment modalities. CONCLUSION: PFS and OS were significantly shorter in patients with poor ECOG PS. OS was also significantly shorter in patients with multifocal T4 tumors. There were no differences between the two therapeutic approaches with respect to outcome.

The Optimal Treatment Modality in Patients with T4N2M0 Non-Small Cell Lung Cancer: The Best Choice May Be Definitive Chemoradiotherapy Followed by Consolidation Chemotherapy.

BACKGROUND: Stage IIIB non-small cell lung cancer (NSCLC) consists of T4N2M0 and TXN3M0 NSCLC. In the present study, we aimed to evaluate the efficacy of different treatment strategies on the survival of patients with radiologically confirmed T4N2M0 NSCLC. METHODS: A total of 145 patients were evaluated in three groups according to the treatment protocol: induction chemotherapy followed by chemoradiotherapy (induction group); chemoradiotherapy (CRT group), and chemoradiotherapy followed by consolidation chemotherapy (consolidation group). The groups were compared regarding survival. RESULTS: The median progression-free survival (PFS) was 10.9, 10.8 and 17.1 months for the induction, CRT and consolidation groups, respectively (p = 0.021). The median overall survival (OS) was 17.6, 13.8 and 25.2 months for the induction, CRT and consolidation groups, respectively (p = 0.001). CONCLUSIONS: The patients with T4N2M0 NSCLC who were treated with chemoradiotherapy followed by consolidation chemotherapy had the best outcome in terms of PFS and OS.

Sunitinib-induced reversible purpuric rash in a patient with gastrointestinal stromal tumor.

Sunitinib which is used in the treatment of kidney cancer, gastrointestinal stromal tumor, and advanced pancreatic neuroendocrine tumor is a multi-targeted tyrosine kinase inhibitor. Although sunitinib is associated with some side effects, it is generally well tolerated. In the present case, the diagnosis of gastrointestinal stromal tumor was four years ago. The patient had multiple liver metastases at the time of diagnosis. Sunitinib was initiated with a dose of 50 mg daily for four weeks and two weeks off, because of resistance of imatinib. The patient was admitted to the hospital with purpuric rash on her arms and body in the eighth week of treatment. No other disorders or drugs which may cause purpuric rash were detected in the patient. Purpuric rash disappeared two weeks after sunitinib discontinuation without any further intervention.

Prolonged progression-free survival with maintenance metronomic oral cyclophosphamide and etoposide treatment in macroscopic residual disease or recurrent/advanced stage ovarian cancer.

PURPOSE: In ovarian cancer permanent remission may be provided with optimal cytoreductive surgery and adjuvant chemotherapy. However survival is short in patients with residual macroscopic disease after surgery or recurrent ovarian cancer. Applicable maintenance therapies with low toxicity are required to prolong progression-free survival (PFS) for patients with no curative treatment options. In this study, we investigated the effect of maintenance metronomic oral cyclophosphamide and etoposide (CE) in ovarian cancer patients with post operative residual or recurrent disease. METHODS: Forty five patients that received metronomic oral CE (cyclophosphamide 50 mg/daily and etoposide 50 mg for 1-5 days, every 21 days) as maintenance therapy for residual disease due to incomplete surgical resection or recurrent advanced-stage ovarian cancer were evaluated. The time between the beginning of oral CE and disease progression was also evaluated. RESULTS: The mean patient age was 58 years, the vast majority had serous adenocarcinoma (78%) and received a mean of 2 (range 1-4) lines of various intravenous regimens for postoperative residual or recurrent disease. Mean duration of oral CE was 11.3 months (range 2.9-29). Median PFS was 10.3 months (range 7.9-12.8). Only 5 patients discontinued treatment due to intolerance and grade 3-4 toxicity was recorded in 3 patients (7%). CONCLUSION: Maintenance metronomic oral CE treatment was found effective, minimally toxic and sustainable in patients with macroscopic residual or recurrent advanced-stage ovarian cancer. However, randomized and placebo-controlled well designed studies are required.