Atezolizumab-induced cerebellar ataxia in a patient with metastatic small cell lung cancer: A case report and literature review.

INTRODUCTION: The use of immune checkpoint inhibitors, which have an important role in the treatment of malignant tumors, is increasing. Although rarely observed, neurological immune-related adverse events associated with immune checkpoint inhibitors result in high morbidity and mortality. Small cell lung cancer is a common cause of neurological paraneoplastic syndromes. The differentiation between paraneoplastic syndromes and neurological immune-related adverse events is important in patients using immune checkpoint inhibitors. Cerebellar ataxia caused by atezolizumab is a rare immune-related adverse event. CASE REPORT: In this context, we present a 66-year-old man with small cell lung cancer who developed immune-mediated cerebellar ataxia after three cycles of atezolizumab, a programmed cell death ligand-1 inhibitor. The admission of brain and spinal gadolinium-based contrast-enhanced magnetic resonance imaging supported the preliminary diagnosis and indicated leptomeningeal involvement. However, the blood tests and a lumbar puncture did not reveal any structural, biochemical, paraneoplastic, or infectious cause. MANAGEMENT AND OUTCOME: High-dose steroid treatment resulted in an improvement in the radiological involvement, as evidenced both clinically and on follow-up whole spine magnetic resonance imaging. Therefore, the immunotherapy was discontinued. The patient was discharged on day 20 without neurological sequelae. DISCUSSION: In light of this, we present this case to emphasize the differential diagnosis of neurological immune-related adverse events originating from immune checkpoint inhibitors, which require rapid diagnosis and treatment, and clinically similar paraneoplastic syndromes and radiologically similar leptomeningeal involvement, in a case of small cell lung cancer.

Polypharmacy and drug-drug interactions in metastatic breast cancer patients receiving cyclin-dependent kinase (CDK) 4/6 inhibitors.

INTRODUCTION: Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly changed the treatment strategy for patients with locally advanced or metastatic hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2) breast cancer. The purpose of the study was to determine the prevalence of drug-drug interactions (DDI) in breast cancer patients using CDK 4/6 inhibitors and the extent of DDI reflected in the clinic and to increase clinical awareness among physicians. METHOD: The data of 115 metastatic breast cancer patients using CDK 4/6 inhibitors who were admitted to the Medical Oncology outpatient clinic between July 2021 and July 2023 were retrospectively reviewed. The Drugs.com® Drug Interaction Checker application was used for the interaction between the CDK 4/6 inhibitor and other drugs. RESULTS: Among patients included in the study, 97.3% had at least one additional drug use. We have identified a total of 170 potential DDI risks in 63.5 % of patients. Among these, 50.5% had a major potential DDI. In our study, there was a potential risk of QT prolongation in 45.2% of 170 DDI, an increase in the potential toxicity of the additional drug in 44.1%, an increase in the potential toxicity of the CDK 4/6 inhibitor in 5.3%, a decrease in the potential efficacy of the CDK 4/6 inhibitor in 2.9%, a decrease in the potential efficacy of the additional drug in 1.1%, and a serious potential infection risk in 1.1%. Most of the drug interactions were QT prolongation and increased toxicity of the additional drug. In terms of cardiovascular events, grade-2 and grade-3 QTc prolongation was found in 4.3% and 1.7% of these interactions, respectively. When evaluated in terms of CDK 4/6 inhibitor subtype, there was a potential risk of DDI at major level with Ribocilib and at moderate level with Palbociclib. CONCLUSION: If CDK 4/6 inhibitors interact with concomitant drugs, they may cause an increase in the incidence of cardiac side effects and a decrease in the effect of the CDK 4/6 inhibitor or additional drug or an increase in toxicity. Increasing awareness of this issue will help to reduce the rates of side effects or toxicity and provide effective antitumour therapy.

Ribociclib-induced visual hallucination in a patient with metastatic breast cancer.

INTRODUCTION: Cyclin-dependent kinase (CDK) 4/6 inhibitors are widely used in combination with aromatase inhibitors or fulvestrant for the treatment of locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Hematological toxicities (e.g. neutropenia, thrombocytopenia, anemia, lymphopenia, or febrile neutropenia), infections, decreased appetite, exhaustion, headache, dizziness, cough, nausea, vomiting, diarrhea, alopecia, rash, increased alanine aminotransferase and aspartate aminotransferase levels, and QT interval prolongation are frequent side effects associated with the use of CDK 4/6 inhibitors. However, to our knowledge, no case of hallucination associated with CDK 4/6 inhibitor use has been described in the English-language literature. CASE REPORT: We report a case of a 72-year-old woman with metastatic breast cancer who developed visual hallucinations after receiving ribociclib, a CDK 4/6 inhibitor, and letrozole for 3 days. Cranial imaging and blood tests did not reveal the cause of the hallucinations. MANAGEMENT AND OUTCOME: The visual hallucinations completely resolved within 4 days after the ribociclib treatment was terminated. The patient received only letrozole for 2 weeks, and ribociclib treatment was restarted 2 weeks later. Visual hallucinations recurred on the third day of treatment, and ribociclib treatment was discontinued again. The patient recovered completely from visual hallucinations 4 days after discontinuation. Subsequently, treatment was continued with letrozole and palbociclib, another CDK 4/6 inhibitor. Hallucinations did not recur during follow-up. DISCUSSION: To our knowledge, this is the first reported case of hallucinations caused by ribociclib; notably, it shows that symptoms may develop in the early stage of treatment.

The extent of agreement between frozen and paraffin block data from axillary samples in patients with early-stage breast cancer.

INTRODUCTION: Patients with early-stage breast cancer currently undergo sentinel lymph node dissection to evaluate the axillary region. Frozen tissue blocks are evaluated intra operatively and paraffin-embedded samples are studied postoperatively. We explored whether sentinel lymph node dissection adequately reflected axillary involvement (as revealed by the paraffin blocks) in patients with early-stage breast cancer; we sought to avoid axillary dissection. METHODS: The agreement/non-agreement rates between the results of axillary ultrasonography and biopsy, sentinel lymph node and axillary dissections, and frozen and paraffin block results, were retrospectively analyzed for 200 patients with early-stage breast cancer. The positive predictive values and accuracies were recorded in those who were positive on both ultrasonography and biopsy. The negative predictive values were calculated for doubly negative cases. RESULTS: The frozen and paraffin block results disagreed in 19 (9.5 %) cases and agreed in 181 (90.5 %). The frozen block and dissection results differed in five of 38 patients who underwent axillary dissection (AD) (one patient did not undergo AD); the results were in agreement in 32. Of the 19 block-disagreement cases, 16 were in the non-neoadjuvant chemotherapy (NAC) group and three in the NAC treatment group. Clinically, the negative predictive values of the frozen and paraffin block data were 80 % in patients lacking axillary involvement. CONCLUSION: Paraffin block evaluations only (thus, without frozen block examinations) of early-stage breast cancer lymph nodes seem to be sufficient to guide treatment. Also, a thorough clinical examination (with ultrasonography and axillary biopsy) reduces the dissection rate and the associated functional impairments.

Diagnostic value of the preoperative platelet/lymphocyte ratio and red cell distribution volume in patients with renal masses.

OBJECTIVES: Inflammatory markers indicate immune system responses. BACKGROUND: We retrospectively explored whether the platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), and red blood cell distribution width (RDW) were predictive of malignant disease. MATERIAL AND METHODS: Between 2019 and 2023, 148 patients diagnosed with malignant and benign renal tumors via imaging or biopsy were included. Of these tumors, 117 were malignant and 31 were benign. Blood samples were taken for calculation of the NLR, PLR, and RDW prior to renal biopsy or operation. RESULTS: The NLR, PLR, and RDW did not differ significantly between patients with malignant and benign renal masses (all p > 0.05). The PLR significantly increased with the T stage of malignant masses (p = 0.011). According to the T stage, the RDW cutoff was 45.7, the sensitivity was 40 %, and the specificity 82.4 %; the respective values for PLR were 134.9, 70 %, and 70.5 % (p = 0.026 and p = 0.003, respectively). CONCLUSION: The NLR, PLR, and RDW were not predictive in this study because we only included early- stage patients lacking lymph node involvement and the follow-up was short. In patients with renal cell carcinomas, the RDW and PLR increase with the tumor burden and predict poor prognosis (Tab. 5, Fig. 1, Ref. 23). Text in PDF www.elis.sk Keywords: neutrophil/lymphocyte ratio, platelet/ lymphocyte ratio, renal mass.

Synthesis of some novel pyridine compounds containing bis-1,2,4-triazole/thiosemicarbazide moiety and investigation of their antioxidant properties, carbonic anhydrase, and acetylcholinesterase enzymes inhibition profiles.

Some novel derivatives of thiosemicarbazide and 1,2,4-triazole-3-thiol were synthesized and evaluated for their biological activities. The title compounds were prepared starting from readily available pyridine-2,5-dicarboxylic acid. The reaction carboxylic acid with absolute ethanol afforded the corresponding dimethyl pyridine-2,5-dicarboxylate (1). The reaction of dimethyl-2,5-pyridinedicarboxylate (1) with hydrazine hydrate good yielded pyridine-2,5-dicarbohydrazide (2). Refluxing compound 2 with alkyl/aryl isothiocyanate derivatives for 3-8 h afforded 1,4-disubstituted thiosemicarbazides (3a-e). Base-catalyzed intra-molecular dehydrative cyclization of these intermediates furnished the 4,5-disubstituted bis-mercaptotriazoles (4a-e) in good yield (85%-95%). Among the target compounds, 2,2'-(pyridine-2,5-diyldicarbonyl)bis[N-(p-methoxyphenyl)hydrazinecarbothioamide] (3c) showed very high activity with value of 72.93% against 1,1-diphenyl-2-picrylhydrazyl free radical at the concentration of 25 µg/mL. The inhibitory effects of the target compounds against acetylcholinesterase (AChE), hCA I, and II were studied. AChE, cytosolic hCA I and II isoforms were potently inhibited by synthesized these derivatives with Ki s in the range of 3.07 ± 0.76-87.26 ± 29.25 nM against AChE, in the range of 1.47 ± 0.37-10.06 ± 2.96 nM against hCA I, and in the range of 3.55 ± 0.57-7.66 ± 2.06 nM against hCA II, respectively.

Excellent clinical outcome of triple-negative breast cancer in younger and older women.

PURPOSE: To compare the histopathological features and survival of triple-negative breast carcinomas (TBNC) in younger and older women. METHODS: We documented 312 patients with TBNC between 2008 and 2013. The histopathological and clinical features of women who were 35 years old or younger (N=53) were compared to those of women who were 60 years old and older (N=58). Patients were administered adjuvant or neoadjuvant chemotherapy, and adjuvant radiotherapy. RESULTS: We diagnosed and treated a total of 312 patients with TNBC. The median follow-up was 38 months (mean ±SD:37.36; range: 0.2-383.4). The median age of the younger patients was 32 years (mean ±SD:31.6 ± 3.72; range:19-36) and of older patients 67 years (mean ±SD: 68.21 ± 6.78; range:60-84). The tumor size in young patients was larger than in older patients (p=0.001). More comorbid diseases were observed in older patients than in younger ones (p=0.001). There was no difference in the histological grades, lymphovascular invasion, stage and nodal involvement between the two groups. Local / distant metastases were found in 11 (40.7%) patients in the young patient group and in 16 (59.3%) in old patient group (p=0.704). Three (5.4%) patients died from each group. No significant difference in terms of disease-free survival (DFS) and overall survival (OS) (p=0.914, p=0.939, respectively) was noticed. CONCLUSION: This study showed that older and younger patients with TNBC had similar survival with neoadjuvant and adjuvant chemotherapy and adjuvant radiotherapy, which may be due to similar histopathologic features and intrinsic tumors' activity.

Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio associated with prognosis in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab?

PURPOSE: To investigate whether the pretreatment neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) have any prognostic significance in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab. METHODS: 187 patients were retrospectively analyzed. The patients were separated into two groups according to the mean value of NLR and PLR (low NLR≤2.38, high NLR>2.38; and low PLR≤161.28, high PLR>161.28, respectively). The relationship between pretreatment NLR, PLR and clinicopathological factors was investigated. Univariate and multivariate Cox regression analyses were performed. To evaluate survival rates, the Kaplan-Meier method with log rank test were used. RESULTS: The median duration of follow up was 26.0 months (range 6.0-84.0). In high NLR and PLR groups, the mean age was lower, tumor size was larger and the number of hormone receptor positive patients was higher. No statistically significant relationship was found between clinicopathological factors and both NLR and PLR groups. During follow up, the rate of relapse was 12.6% in the low NLR group, 16.2 % in the high NLR group, 12.6% in the low PLR group and 15.8% in the high PLR group (p=non significant). Although median disease free survival (DFS) was shorter in the high NLR than in the low NLR group, the difference was not statistically significant (p=0.45). No statistically significant difference was found between high and low PLR groups with regard to median DFS and overall survival (OS) (p=0.76, p=0.29, respectively). CONCLUSION: We conclude that in HER2-positive early breast cancer patients receiving adjuvant trastuzumab with high pretreatment NLR, DFS was shorter. As for PLR, no effect either on DFS or on OS was registered. Prospective studies with larger number of patients are required in order to evaluate the prognostic effect of NLR and PLR in HER2-positive breast cancer patients.

Synchronous Double Primary Angiosarcoma Originating from the Stomach and Rectum: A Case Report and a Literature Review.

Angiosarcomas originating from the gastrointestinal tract are rare but highly aggressive tumors with poor prognosis. These tumors can be misdiagnosed as benign and malignant gastrointestinal tract lesions. The definitive histological diagnosis of angiosarcomasis made by pathologists based on immunohistochemical analysis demonstrating cluster of differentiation 31 (CD31), factor VIII-related antigen (FVIIIRAg), erythroblast transformation specific related gene (ERG), and cluster of differentiation 34 (CD34). Angiosarcomas are treated with a single or multimodality approach that may include resection, radiotherapy, chemotherapy, and palliative care, depending on the stage of disease and the condition of the patient. No matter the treatment option, metastasis and death rates are substantially highin patients with angiosarcoma. In this context, a 59-year-old male with synchronous double primary angiosarcoma arising from the gastric and rectum who presented with the complaint of abdominal pain and distention to the outpatient clinic is presented in this case report, along with a brief literature review.

Evaluation of treatment responses among subgroups of breast cancer patients receiving neoadjuvant chemotherapy.

BACKGROUND: Breast MRIs are helpful for determining treatment plans, responses, and prospective survival analyses. In this retrospective cross-sectional study, we compared the preoperative MRI treatment response to neoadjuvant chemotherapy (NAC) administration with the postoperative pathological response in breast cancer patients. MATERIALS AND METHODS: We analyzed data from 108 hospitalized patients receiving NAC between 2020 and 2022. We used MRI to evaluate the treatment response to NAC in patients with locally advanced breast cancers who had not received any prior treatment. We recorded the longest diameter of the primary tumor and the numbers of secondary tumors and axillary lymph nodes. In addition, we examined the correlation between the MRI response rate and pathological specimen results. RESULTS: In our subgroup analyses, we found the best pathological response in patients with luminal B (Ki-67 index >14%) breast cancer and positivity for both hormone receptor and HER-2 markers. After comparing the pathological and radiological treatment responses in tumors and lymph nodes, the sensitivities were 90.3% for the pathological assessment and 42.8% for the radiological assessment, while the accuracies were 84.2% for the pathological assessment and 61.1% for the radiological assessment. CONCLUSION: Using MRI techniques and sequence intervals and examining the histopathological characteristics of tumors may help increase the accuracy of the pathological complete response.

Hydrocortisone may act through the angiotensin II receptor-2 level in patients with catecholamine-resistant septic shock.

BACKGROUND: This study aimed to compare the serum angiotensin II and its receptor levels (AT1, AT2) in septic patients with catecholamine-responsive or resistant. The effect of hydrocortisone treatment on angiotensin II levels in the catecholamine-resistant septic patients was evaluated. METHODS: This prospective observational study enrolled 40 patients diagnosed with septic shock based on sepsis-3 criteria. Patients were divided into two groups according to the noradrenalin infusion rate required to keep the mean arterial pressure above 65 mmHg: control group and hydrocortisone group (control group: below 0.5 µg/kg/min, hydrocortisone group: above 0.5 µg/kg/min). Serum angiotensin II, AT1, AT2 levels were measured at the time of diagnosis (A), one hour after hydrocortisone treatment (B), and three days later (C). RESULTS: In the catecholamine-resistant group, angiotensin II and AT1 levels were higher than the catecholamine-responder group in all periods. The sensitivity and specificity of AT-1 was observed to be high in all periods. AT2 levels decreased after hydrocortisone treatment in the catecholamine-resistant group and cut-off value was found 11%. CONCLUSIONS: It was concluded that angiotensin II and AT1 can be used as a biomarker of refractory septic shock and hydrocortisone may provide their blood pressure correcting effect by reducing AT2 level in these patients. AT2 can be a therapeutic target in the catecholamine-resistant septic shock patients.

Angiotensin II and angiotensin II receptor 2 levels can predict shock and mortality in septic patients.

BACKGROUND: The aim of this study was to evaluate the place of angiotensin II and its receptors in the prognosis of septic patients. METHODS: Patients with sepsis and septic shock were included in the study group. The control group consisted of patients who were followed up in the ICU and had no sepsis/septic shock. Plasma angiotensin II, angiotensin receptor-1 and 2 (AT-1, AT-2) levels were evaluated first and third days. RESULTS: Angiotensin II levels were significantly lower in the septic shock and non-survivor. AT-1 levels were lower in all septic patients on the first day compared to the control. While AT-1 levels on the third day decreased in the septic shock group, it increased in the sepsis group. AT-2 levels were significantly higher in sepsis, and lower in septic shock compared to controls on the first day. Angiotensin II (95%, 82%) and AT-2 levels (100%, 87%) were observed to have high sensitivity and specificity in demonstrating the presence of shock in septic patients. Angiotensin II and AT-1/AT-2 ratios were observed to have high sensitivity and low specificity in the development of mortality. CONCLUSIONS: In septic patients, angiotensin II, AT-2 and AT-1/AT-2 levels can predict the probability of shock development and mortality.

The Relationship Between Suicide Attempt and Gonadotropins, Gonadal Hormones, and Cortisol in Females.

Objective: The aim of this study was to examine the relationship between suicidal behavior and gonadotropins, gonadal hormones, and cortisol in females. Methods: The study included 3 groups of 23 females each, aged 18-45 years; one group comprising those who had attempted suicide, another group of females matched for age, menstrual phase, and body mass index, with depression but no suicidal tendencies, and a control group of 23 healthy females. For all participants, a sociodemographic information form was completed, and the Beck Depression Inventory, the Beck Anxiety Inventory, and the Beck Hopelessness Scale were used. Blood samples were taken at 8 am (in the attempted-suicide group, within 24 hours of the attempt), and follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, progesterone, and cortisol levels were measured. Results: No statistically significant differences were observed between the groups with respect to gonadotropin and gonadal hormone levels. There were statistically significant differences in the cortisol levels between the attempted suicide and control groups and between the depression and control groups (P < .05). The cortisol levels negatively correlated with all scale scores. Conclusion: Studies on suicidal patients should pay more attention to the potential role of hypocortisolism. More studies with larger samples are needed to investigate the relationship between gonadotropins, gonadal hormones, and suicidal behavior.

Favorable results of patients with pT1a, b, c, lymph node-negative early breast cancer in the long interval.

BACKGROUND: The clinical characteristics of patients who had lymph node-negative early breast cancer were assessed. PATIENTS AND METHODS: We assessed a total of 576 patients in the study, including 74 patients (12.8%) with T1a, 119 patients (20.7%) T1b, and 367 patients (63.7%) with T1c. Patients with T1 tumors were further classified into three groups according to hormone receptor (HR) and human epidermal growth factor-receptor 2 (HER2) status. RESULTS: In patients with T1a, the disease-free survival (DFS) rate was 98.4% at 2 years (P = 0.001). In subgroup analysis of early breast cancers, 10-year-DFS rates of the patients in HR+/HER2-, HR-/HER2+, and HR-/HER2- subgroups were not significantly different (P = 0.917). CONCLUSION: The T1a group had a worse prognosis than T1b and T1c groups in second years (P = 0.001); however, there was not statistically important difference between HR+, HER2+ and triple negative subgroups (P = 0.917). Although there are differences in patients and tumor features, the prognosis of patients with T1a, b, c N0M0 breast cancer is excellent.

Diffuse Large B-Cell Lymphoma Involvement in Two Different Localizations: A Case Report.

The genital system and skin involvement of diffuse B-cell lymphomas are quite rare. The appearance of these rare types in the same patient and the same period makes the treatment of the disease difficult. But both types respond well to anthracyclines and immunotherapies. A 74-year-old woman was treated with R-CHOP (Rituximab, cyclophosphamide, doxorubicine, vincristine, prednisolone) without surgery and/or radiotherapy, and no recurrence at 2 years follow-up. Despite the poor prognosis of these types of lymphomas, treatment responses are quite good as they are in other subtypes.

Misleading 18FDG-PET/CT finding caused by chronic HIV infection in a patient with gastric carcinoma: a case report.

The aim of this study was to describe the influence of HIV infection on the staging of gastric cancer by using positron emission tomography/computed tomography (PET/CT) imaging. We treated a patient with local advanced gastric cancer. PET/CT showed an unusual hypermetabolic activity of lymph nodes, and the patient was later found to be HIV-positive. PET/CT scans in cancer staging of patients with chronic HIV infection may show advanced stage disease. Spread of primary tumor to unusual sites should be a warning sign for the possible concurrent diseases.

A Case of Ruptured Pulmonary Hydatid Cyst of the Liver and Review of the Literature.

BACKGROUND: Hydatid cyst is an endemic disease frequently localized to the liver. It is frequently observed in Southeast Europe, Middle East, and Turkey. Although the cyst rupture can occur spontaneously, it can also occur upon albendazole treatment. Its surgical treatment includes cystotomy, capitonnage, and wedge resection. MATERIAL-METHOD: A 56-year-old male immigrant was admitted with fever, pain, and cough. Albendazole treatment was initiated and elective surgery was planned. Upon his admission to emergency service, he was diagnosed with pneumonia, and a spontaneous cyst rupture was detected. RESULT: Thoracotomy and cystotomy were performed. Bile leakage aspiration and lung wedge resection were also performed. CONCLUSION: Different surgical methods are used in the treatment of hydatid cysts depending on the localization and complications. Follow-up with antihelminthic drugs such as albendazole and mebendazole is recommended in medical treatment.

Surgical Approach to Anorectal Melanoma with PET-CT Staging: A Case Report.

Rectal hemorrhage should be evaluated within a wide spectrum ranging from benign diseases to a malignant process. Especially, the melanomas of rectum are detected at an advanced stage when diagnosed since the present symptoms of rectal melanomas are similar. The question of what will be the surgical approach with MR, CT, and PET-CT imaging methods performed after histopathological diagnosis still conserves its topicality. PET-CT is a good imaging method for determination of distant metastasis and lymphatic involvement. In the present case, a patient with early-stage rectal melanoma was treated with APR. No relapse/metastasis was detected during the 18-month follow-up. The aggressive course of the disease and its low response rates to medical treatments may cause the surgical approaches to be more extensive.