Prediction of the number of positive axillary lymph nodes according to sentinel lymph node involvement and biological subtypes in patients receiving neoadjuvant chemotherapy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for assessing axillary lymph node status in clinically node-negative breast cancer patients. However, the approach to axillary surgery after neoadjuvant treatment is still controversial. In the present study, our objective was to predict the pathological nodal stage based on SLNB results and the clinicopathological characteristics of patients who initially presented with clinical N1 positivity but whose disease status was converted to clinical N0 after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: After NAC, 150 clinically node-negative patients were included. The relationships between clinicopathologic parameters and the number of positive lymph nodes in SLNBs and ALNDs were assessed through binary/multivariate logistic regression analysis. RESULTS: Among 150 patients, 78 patients had negative SLNBs, and 72 patients had positive SLNBs. According to the ALND data of 21 patients with SLNB1+, there was no additional node involvement (80.8%), 1-2 lymph nodes were positive in 5 patients (19.2%), and no patient had ≥ 3 lymph nodes involved. Following the detection of SLNB1 + positivity, the rate of negative non-sentinel nodes were 75% in the luminal A/B subgroup, 100% in the HER-2-positive subgroup, and 100% in the triple-negative subgroup. Patients with a lower T stage (T1-3 vs. T4), fewer than 4 clinical nodes before NAC (< 4 vs. ≥4), and a decreased postoperative Ki-67 index (< 10% vs. stable/increase) were included. According to both univariate and multivariate analyses, being in the triple-negative or HER2-positive subgroup, compared to the luminal A/B subgroup (luminal A/B vs. HER2-positive/triple-negative), was found to be predictive of complete lymph node response. CONCLUSION: The number of SLNB-positive nodes, tumor-related parameters, and response to treatment may predict no additional nodes to be positive at ALND.

Should We Completely Exclude Locoregional Therapy for the Primary Tumor from Our Clinical Practice in De Novo Metastatic Breast Cancer?

Locoregional therapy (LRT) for the primary site of breast cancer (BC) is one of the most debated topics in de novo metastatic disease. We have four main randomized controlled trials, three negative and one positive, together with one positive prospectively designed non-randomized study investigating the contribution of LRT to the literature. We aimed to discuss the possible reasons for the positive or negative results of the studies and to identify specific subgroups that may benefit from primary breast surgery.

Dramatic response to crizotinib in a breast cancer patient with ALK gene rearrangement.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3-5% of non-small-cell lung cancer (NSCLC), while it was 0.2% in NSCLC tumors. Due to its low frequency, it is extremely challenging to conduct randomized clinical trials of ALK-targeted therapies in NSCLC tumors. In the present case, we describe the first reported case of triple-negative breast cancer (TNBC) harboring the ALK fusion mutation that responded to ALK-targeted therapy after progression with two lines of chemotherapy. Searching for ALK gene rearrangement or other fusion, especially in patients with chemotherapy-resistant TNBC, opens the door to new treatment strategies.

The predictive value of vitamin D follow-up and supplementation on recurrence in patients with colorectal cancer.

Aim: Vitamin D has a role in carcinogenesis and may have effect on recurrence. Thus, we aim to analyze the prognostic effect of vitamin D levels at beginning and follow-up together with the contribution of vitamin D supplementation on patients with colorectal cancer (CRC). Materials & methods: CRC patients who underwent curative surgery were included. Patients' vitamin D values were assessed under four groups according to baseline and follow-up vitamin D values, and whether vitamin D supplementation was used. Survival distributions were compared for vitamin D groups. Results: Patients with a high follow-up vitamin D level and a high vitamin D level after supplementation presented with better disease-free survival and overall survival than patients with low vitamin D and low vitamin D levels after supplementation. Conclusion: Follow-up vitamin D values seems to be a good predictive biomarker and vitamin D supplementation may have a positive effect on survival.

Association of illness perception with chemotherapy-induced nausea and vomiting: a Turkish Oncology Group (TOG) study.

Chemotherapy-induced nausea and vomiting (CINV) may be linked to the psychological status of cancer patients. Therefore, the authors aimed to better understand the underlying risk factors for CINV using the Brief Illness Perception Questionnaire. A total of 238 patients were recruited during three cycles of chemotherapy. Patient, disease and treatment characteristics were noted at the onset of chemotherapy. The Brief Illness Perception Questionnaire was administered face-to-face prior to chemotherapy. The relationship between illness perceptions and CINV was analyzed using Spearman's rank correlation. Positive illness perception parameters, including personal and treatment control, were negatively correlated, whereas negative illness perception parameters, including consequences, timeline, identity, concern and emotions, were positively correlated with CINV after adjusting for age, sex and emetogenic potential of chemotherapy (p < 0.001). Illness perception may be an underlying risk factor for CINV.

Recurrence pattern in the presence of hepatosteatosis in breast cancer: does it facilitate liver metastasis?

Aim: We aimed to investigate the impact of hepatosteatosis (HS) severity on the recurrence pattern of breast cancer and to clarify whether HS causes affinity to recurrence with liver metastasis. Materials & methods: The median follow-up was 80.0 (4-217) months and the mean age was 47.9 ± 11.3 years. Among all, 181 (39.9%) patients were diagnosed with grades 2 and 3 HS. Of total, 158 (34.8%) patients have experienced recurrence. Results: While higher degree of HS was more common in patients presented with liver recurrence (odds ratio; 95% CI: 2.50; 1.27-4.92; p = 0.007), it was lesser in those with other metastatic sites (all were >0.05). Liver-recurrence-free survival was significantly worse in the group with higher degree of HS (hazard ratio; 95% CI: 2.46; 1.4-4.3; p = 0.002) together with younger age (hazard ratio; 95% CI: 2.44; 1.4-4.3; p = 0.002) in multivariate analysis. Conclusion: HS might have produced an affinity for liver metastasis in common types of breast cancer patients in remission independent from metabolic disorders or clinicopathologic features.

Durable response after interruption of nivolumab in patients with metastatic renal cell carcinoma: Is renal toxicity a marker to predict the benefit of nivolumab?

INTRODUCTION: Nivolumab is a human IgG4 programmed death-1 immune checkpoint inhibitor antibody. Immune-related toxicity may be associated with higher response even after interruption of nivolumab. CASE REPORT: We reported a case diagnosed with metastatic clear cell renal cell carcinoma and treated with nivolumab as fourth-line therapy. Although nivolumab treatment was stopped after two cycles due to grade 3 renal toxicity, progression-free survival rates of 11 months, that is quite a long time for fourth-line treatment of renal cell carcinoma was observed. MANAGEMENT AND OUTCOME: Therefore, we speculate that when renal toxicity develops, response may continue even after interruption of nivolumab in renal cell carcinoma. DISCUSSION: Nivolumab was approved to be used for second-line treatment of renal cell carcinoma with 4.6 months of median progression-free survival benefit. Higher immune-related toxicity can produce higher efficacy for some instances such as malignant melanoma, lung cancer, and renal cell carcinoma. Renal disturbance during nivolumab treatment is extremely rare, and there are no data on survival after interruption due to renal toxicity of nivolumab without further treatment in renal cell carcinoma. In the present case, we obtained long duration of stable disease, with two cycles of nivolumab after the development of nephrotoxicity. Close follow-up without any treatment until progression may be a treatment choice, because nephrotoxicity can be a sign of benefit and durable response to nivolumab.

Illness perception is a strong parameter on anxiety and depression scores in early-stage breast cancer survivors: a single-center cross-sectional study of Turkish patients.

BACKGROUND: Illness perception has been suggested to have a significant effect on anxiety and depression in cancer patients. In this cross-sectional study, we aimed to evaluate this on Turkish breast cancer patients with follow-up periods up to 12 years. PATIENTS AND METHODS: A total of 225 patients (with 6 months to 12 years follow-up) were recruited in this cross-sectional study. The patients were divided into three groups of follow-up: 6 months-2 years, 2-5 years, and >5 years. Beck Depression Inventory, Beck Anxiety Inventory, Duke-University of North Carolina Functional Social Support Questionnaire, and Brief Illness Perception Questionnaire were used to assess the depression, anxiety, functional social support (FSS), and illness perception, respectively. Statistical significance of the associations was analyzed using Spearman correlation, Student's t, Mann-Whitney U, and ANOVA tests. RESULTS: Rates of moderate-severe anxiety and depression scores were not correlated with follow-up period and disease stage, whereas all these parameters were associated significantly with FSS and age. Parameters of illness perception were also not correlated with follow-up period and stage of disease. However, illness perception scores were noticeably better with increments in FSS. Also, the parameters of illness perception were strongly associated with the depression/anxiety score. CONCLUSION: Illness perception is an important determinant of the depression/anxiety score in Turkish breast cancer patients.

Sorafenib with TACE improves the survival of hepatocellular carcinoma patients with more than 10 cm tumor: a single-center retrospective study.

PURPOSE: Sorafenib, a multikinase inhibitor, is effective in patients with advanced hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is an important palliative treatment for unresectable HCC, but TACE-induced ischemic injury can upregulate angiogenic factors and it might be associated with poor prognosis. The purpose of this study was to evaluate the efficacy of conventional TACE with or without sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage A-B HCC. METHODS: Thirty patients with BCLC stage A or B HCC who had undergone TACE were enrolled in this retrospective study. Child-Pugh score, BCLC staging classification, size and number of lesions were recorded. Sorafenib was given 1 month after TACE to some patients who responded to TACE. Repeated TACE was performed on demand. Tumor response was assessed every 12 weeks. The primary objective of this trial was the progression free survival (PFS). Secondary objectives were overall survival (OS), disease control rate (DCR) and total number of TACE interventions. Kaplan-Meier method was used for the estimation of survival and survival curves were compared with Log-rank test. RESULTS: Twenty-five (83.3%) patients had Child-Pugh A and 5 (16.7%) Child-Pugh B, and 24 (80%) patients had BCLC stage B disease and remanining had stage A disease. Lesion size >10 cm was found in 6 patients and 16/7/7 patients had single/two/multiple lesions, respectively. Mean number of TACE was 2.10±1.369. Seventeen (56.7%) patients used sorafenib after TACE whereas 13 (43.3%) patients were followed without any treatment but received consequent TACEs if needed. PFS of all patients was 10 months (range 3-48); it was 13 months for TACE plus sorafenib group and 9 months for TACE group (p=0.081). In subgroup analysis, TACE plus sorafenib group had better PFS (36 vs 12 months) in patients with tumor size > 10 cm (p=0.025). In the analysis of Child- Pugh A cases, PFS of TACE plus sorafenib group was 23 months while it was 10 months in TACE group (p=0.007). CONCLUSION: Concurrent treatment in Child-Pugh A group HCC with conventional TACE and sorafenib demonstrates a significant efficacy in patients having tumor size >10 cm. In Child-Pugh A group, PFS was superior in the sorafenib plus TACE group than in TACE alone group.

Taxane-induced peripheral sensorial neuropathy in cancer patients is associated with duration of diabetes mellitus: a single-center retrospective study.

PURPOSE: The purpose of this study was to determine whether the presence of diabetes mellitus (DM) influences the incidence and severity of peripheral sensory neuropathy (PSN) in patients using taxane therapy. METHODS: A retrospective single-center analysis was conducted: Patients with PSN at baseline were excluded. The incidence of PSN was evaluated retrospectively in patient subgroups who received taxane arm and taxane-plus-platinum-agents combination arm with or without known DM at baseline. RESULTS: Three hundred seventy-four patients were enrolled in this study, 81 (21.6%) of patients had DM at baseline. The incidence of grade 1 PSN (non-DM/DM) in patients receiving taxane-based chemotherapy was 33.4/25.9% and more than grade 2 PSN (non-DM/DM) was 15/34.6%. The rate of neuropathy of non-diabetic patients was 48.8%, while the rate of diabetic patients was 52.8 and 75% in DM duration below 5 years and above 5 years group, respectively. CONCLUSIONS: This retrospective analysis indicates that taxane-based therapy in DM patients whose disease duration is above 5 years appears to affect the incidence and severity of PSN without known baseline neuropathy. The probability of PSN with taxane-based therapy was similar in DM duration below 5 years and non-DM patients.

Efficacy of venlafaxine for the relief of taxane and oxaliplatin-induced acute neurotoxicity: a single-center retrospective case-control study.

BACKGROUND: Oxaliplatin and taxane-induced neurosensory toxicity is dose-limiting and mostly presents with acute symptoms that affect the activities of daily living and overall quality of life. The objective of the present study is to assess the relief of acute neuropathy with venlafaxine treatment during the chemotherapy period. PATIENTS AND METHODS: In this retrospective case-control study, from January 2010 to February 2015, patients who experienced treatment with oxaliplatin and taxane-induced acute neurotoxicity were evaluated according to the NCI-CTCAE v. 4.03 grading scale. Neurotoxicity was evaluated using a numeric rating scale (NRS) for pain intensity and experienced relief under the treatment of venlafaxine and using a neuropathic pain symptom inventory scale (NPSI) for the style of complaints. Patients who were diagnosed as mildly depressed according to the HOST anxiety and depression scale and who had grade 1 to 3 sensory neurotoxicity based on the NCI-CTCAE v. 4.03 grading scale, and who also reported ≥ 4/10 on a NRS were eligible. The primary end point was the rate of more than 75 % symptomatic relief under venlafaxine treatment. RESULTS: Two hundred six patients were included (82 % female, median age: 52.7 years). Most patients had breast, gynecologic, and colon cancer (93.4 %). Ninety-one patients who received venlafaxine and 115 patients as the control group were assessed for neurotoxicity every 3 weeks. Based on the NRS, a rate of more than 75 % symptomatic relief was 53.5, 58.3, and 45.2 % in venlafaxine arm versus 0, 0, and 0 % in the control arm in the first, second, and third visits, respectively. Side-effects of venlafaxine (n = 7) were grade 1-2 nausea/vomiting (3.2 %) and asthenia/somnolence (3.2 %) without grade 3-4 events. CONCLUSION: Venlafaxine has a significant clinical activity against taxane-oxaliplatin-induced acute neurosensory toxicity.

Atypical presentation of disseminated intravascular coagulation with synchronous peripheral venous thromboembolism and arterial gangrene in a pancreatic cancer patient: a case report.

CONTEXT: Cancer is a prothrombotic state and anticancer therapies are often complicated by vascular events. The risk of developing thromboembolic events is substantially increased in patients with pancreatic cancer. One possible presentation of vascular events in pancreatic cancer is disseminated intravascular coagulation (DIC). CASE REPORT: In our case a patient with a diagnosis of pancreatic cancer initially presented with thrombosis and received low molecular weight heparin (LMWH) in addition to standard chemotherapy regimen. He was thought to have DIC by assessment of clinical and laboratory findings. CONCLUSION: Clinically, thrombosis was first located in the left femoral vein and encountered at right femoral artery after three weeks. This pattern was an unusual presentation of DIC. Subclinical DIC is common in patients presenting with pancreatic cancer and is considered a 'poor' prognostic factor. Acute DIC, on the other hand is a potentially mortal condition.

Lessons learned from biomechanical studies on cephalomedullary nails for the management of intertrochanteric fractures. A scoping review.

INTRODUCTION: The increasing socioeconomic need for optimal treatment of hip fractures in combination with the high diversity of available implants has raised numerous biomechanical questions. This study aims to provide a comprehensive overview of biomechanical research on the treatment of intertrochanteric fractures using cephalomedullary devices. METHODS: Following the PRISMA-P guidelines, a systematic literature search was performed on 31.12.2022. The databases PubMed/MEDLINE and Web of Science were searched. Scientific papers published between 01.01.2000 - 31.12.2022 were included when they reported data on implant properties related to the biomechanical stability for intertrochanteric fractures. Data extraction was undertaken using a synthesis approach, gathering data on criteria of implants, sample size, fracture type, bone material, and study results. RESULTS: The initial search identified a total of 1459 research papers, out of which forty-three papers were considered for final analysis. Due to the heterogeneous methods and parameters used in the included studies, meta-analysis was not feasible. A comprehensive assessment of implant characteristics and outcome parameters was conducted through biomechanical analysis. Various factors such as proximal and distal locking, nail diameter and length, fracture model, and bone material were thoroughly evaluated. CONCLUSION: This scoping review highlights the need for standardization in biomechanical studies on intertrochanteric fractures to ensure reliable and comparable results. Strategies such as avoiding varus, maintaining a sufficient tip-apex-distance, cement augmentation, and optimizing lesser trochanteric osteosynthesis enhance construct stability. Synthetic alternatives may offer advantages over cadaveric bone. Further research and meta-analyses are required to establish standardized protocols and enhance reliability.

Do admission glucose levels independently predict coagulopathy in multiple trauma patients? A retrospective cohort analysis.

BACKGROUND: Coagulopathy is prevalent in multiple trauma patients and worsens bleeding complications, leading to higher morbidity and mortality rates. Hyperglycemia upon admission predicts hemorrhagic shock and mortality in severely injured patients. This study aimed to assess admission glucose levels as an independent prognostic factor for coagulopathy in multiply injured patients. METHODS: This retrospective cohort study observed multiple trauma patients treated at a level I trauma center between January 1, 2005, and December 31, 2020. Coagulopathy was defined as an international normalized ratio (INR) > 1.4 and/or activated thromboplastin time (APTT) > 40 s. Analysis of variance compared clinical and laboratory parameters of patients with and without coagulopathy. Receiver-operating-characteristic (ROC) and multivariate logistic regression analyses identified risk factors associated with coagulopathy. RESULTS: The study included 913 patients, of whom 188 (20%) had coagulopathy at admission. Coagulopathy patients had higher mortality than those without (26% vs. 5.0%, p < 0.001). Mean glucose level in coagulopathy patients was 10.09 mmol/L, significantly higher than 7.97 mmol/L in non-coagulopathy patients (p < 0.001). Admission glucose showed an area under the curve (AUC) of 0.64 (95% CI [0.59-0.69], p < 0.001) with an optimal cut-off point of 12.35 mmol/L. After adjusting for other factors, patients with high admission glucose had a 1.99-fold risk of developing coagulopathy (95% CI 1.07-3.60). Other laboratory parameters associated with coagulopathy included haemoglobin, bicarbonate (HCO3), and lactate levels. CONCLUSION: This study emphasizes the significance of admission blood glucose as an independent predictor of coagulopathy. Monitoring hyperglycemia can aid in identifying high-risk patients.

Reconstruction of an Extensive Segmental Radial Shaft Bone Defect by Vascularized 3D-Printed Graft Cage.

We report here a 46-year-old male patient with a 14 cm segmental bone defect of the radial shaft after third degree open infected fracture caused by a shrapnel injury. The patient underwent fixed-angle plate osteosynthesis and bone reconstruction of the radial shaft by a vascularized 3D-printed graft cage, including plastic coverage with a latissimus dorsi flap and an additional central vascular pedicle. Bony reconstruction of segmental defects still represents a major challenge in musculo-skeletal surgery. Thereby, 3D-printed scaffolds or graft cages display a new treatment option for bone restoration. As missing vascularization sets the limits for the treatment of large-volume bone defects by 3D-printed scaffolds, in the present case, we firstly describe the reconstruction of an extensive radial shaft bone defect by using a graft cage with additional vascularization.

The Effectiveness of Adjuvant PD-1 Inhibitors in Patients With Surgically Resected Stage III/IV Acral Melanoma.

Our aim was to assess the efficacy of adjuvant programmed cell death protein-1 (PD-1) inhibitors and compare the other adjuvant treatments in patients with surgically resected stage III or IV acral melanoma. This study is a multicenter, retrospective analysis. We included 114 patients with stage III or IV acral malignant melanoma who underwent surgery within the past 10 years. We analyzed the effect of adjuvant programmed cell death protein-1 inhibitors on disease-free survival (DFS). The mean follow-up was 40 months, during which 69 (59.5%) patients experienced recurrence. Among the participants, 64 (56.1%) received systemic adjuvant therapy. Specifically, 48.4% received anti-PD-1 therapy, 29.7% received interferon, 14.1% received tezozolomide, and 7.8% received B-Raf proto-oncogene/mitogen-activated protein kinase inhibitors. Patients who received adjuvant therapy had a median DFS of 24 (10.9-37.2) months, whereas those who did not receive adjuvant therapy had a median DFS of 15 (9.8-20.2) months. Multivariate analysis for DFS revealed that the receipt of adjuvant therapy and lymph node metastasis stage were independent significant parameters ( P = 0.021, P = 0.018, respectively). No statistically significant difference was observed for DFS between programmed cell death protein-1 inhibitor treatment and other adjuvant treatments. Regarding overall survival (OS), patients who received adjuvant treatment had a median OS of 71 (30.4-111.7) months, whereas those who did not receive adjuvant treatment had a median OS of 38 (16.7-59.3; P = 0.023) months. In addition, there were no significant differences in OS observed between various adjuvant treatment agents ( P = 0.122). In our study, we have shown that adjuvant therapy had a positive effect on both DFS and OS in patients with stages III-IV acral melanoma who underwent curative intent surgery. Notably, we found no significant differences between anti-PD-1 therapy and other adjuvant therapies.

[Biological reconstruction of large bone defects : Masquelet technique and new procedures]. / Biologische Rekonstruktion von großen Knochendefekten : Masquelet-Technik und neue Verfahren.

Extensive diaphyseal and metaphyseal bone defects continue to pose a major challenge for orthopedic trauma surgeons. Various treatment options have been described for the biological reconstruction of these defects. The most frequently used methods are bone segment transport, the Masquelet technique and 3D printed scaffolds. As far as the Masquelet technique is concerned, in the first stage spacers, such as polymethyl methacrylate (PMMA), calcium sulfate or polypropylene are inserted into the bone defects to induce a foreign body membrane. In the second stage the bone defect surrounded by the induced membrane is filled with autologous cancellous bone. The time interval between the first and second interventions is usually 4-8 weeks whereby the induced membranes do not lose their bioactivity even with a latency period longer than 8 weeks. Three-dimensional printed scaffolds are increasingly used but large clinical studies are lacking in order to show the exact role of this procedure in the reconstruction of bone defects.

Clinical Characteristics and Outcomes of Cancer Cases Among Syrian Refugees From Southern Turkey.

Importance: Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are needed. Objective: To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees. Design, Setting, and Participants: This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022. Main Outcomes and Measures: Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment. Results: A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 [13.8%]), leukemia and multiple myeloma (147 [13.2%]), and lymphoma (141 [12.7%]) were common among adults, and leukemias (180 [42.8%]), lymphomas (66 [15.7%]), and central nervous system neoplasms (40 [9.5%]) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children. Conclusions and Relevance: Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.