Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer.

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25-30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

Prognostic implications of response to neoadjuvant chemotherapy in breast cancer subtypes.

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice.

Background: Group 2 innate lymphoid cells (ILC2) can be activated by interleukin (IL)-33 or IL-25. IL-25-activated ILC2 cells help protect the host against helminth infection while exacerbating allergic-like inflammation and tissue damage in the lung. In the context of cancer, IL-33-activated ILC2 cells were found to bear anti-tumoral functions in lung cancer while IL-25-activated ILC2 cells promoted tumorigenesis in colorectal cancer. The role of IL-25-activated ILC2 cells in lung cancer remains to be addressed. Methods: We examined the overall survival of human non-small cell lung cancer (NSCLC) patients according to IL25 expression as well as the distribution of ILC2 cells and regulatory T cells (Tregs) in various NSCLC patient tissues and peripheral blood (PB) of healthy donors (HDs). We analyzed the effect of adoptive transfer of IL-25-activated ILC2 cells on tumor growth, metastasis and survival in a heterotopic murine model of lung cancer. Results: We report that human NSCLC patients with high IL-25 expression have reduced overall survival. Moreover, NSCLC patients bear increased frequencies of ILC2s compared to HDs. Frequencies of Tregs were also increased in NSCLC patients, concomitantly with ILC2s. In mice bearing heterotopic lung cancer, adoptive transfer of IL-25-activated ILC2s led to increased tumor growth, increased metastasis and reduced survival. The frequencies of monocytic myeloid-derived suppressor cells (M-MDSCs) were found to be increased in the tumors of mice that received ILC2s as compared to controls. Conclusion: Overall, our results indicate that the IL-25/ILC2 axis promotes lung cancer potentially by recruiting immune-suppressive cells to the tumors both in humans and in mice, and that it may therefore represent a suitable novel target for NSCLC immunotherapeutic development.

Spinal Melorheostosis: A Rare Presentation.

CASE: A 22-year-old female patient was referred to the orthopaedic department for further examination after a radiopaque area was observed in the T6 vertebra in her chest radiograph. Computed Tomography (CT) showed a sclerotic mass with smooth borders, involving the entire body of the T6 vertebra, left posterior elements, posterior of the rib past the left zygapophyseal joint, and a "flowing candle wax" image toward the T7 vertebra. Spinal melorheostosis was considered radiologically in the patient, but malignancy could not be completely excluded. Thereupon, open biopsy was performed under general anesthesia. CONCLUSION: Spinal melorheostosis is a rare condition. Histological examination should be considered in cases where the diagnosis remains suspicious after clinical and radiological evaluations.

Relationship between the change in tumour-infiltrating lymphocyte level and residual tumour after neoadjuvant chemotherapy in patients with locally advanced breast cancer.

To evaluate the tumour-infiltrating lymphocyte (TIL) rates in breast tissue before and after neoadjuvant chemotherapy (NAC) and their impact on survival, eighty-four patients with locally advanced breast cancer (LABC) were assessed. Pre- and post-NAC TIL levels were determined using biopsy and surgical specimens, respectively. The median TIL rate was significantly different before (17.5%) and after (5%) NAC. Pre- and postoperative Ki-67 index, molecular subtype, pre- and post-NAC TIL concentration, and preoperative residual-cancer-burden TIL were significantly associated with pathological complete response (pCR). Specifically, higher pre-NAC TIL levels were associated with higher pCR rates. Postoperative Ki-67 index and pCR, and postoperative Ki-67 index were significant predictors of disease-free (DFS) and overall survival, respectively. The independent prognostic factors for DFS were postoperative Ki-67 score (hazard ratio [HR]: 6.16; p = 0.012), post-NAC TIL score (HR: 0.42; P = 0.041), and pCR (HR: 0.10; P = 0.038). Our study confirms that higher pre-NAC and lower postoperative TIL levels may be surrogate factors for longer DFS, and postoperative TIL rate may predict post-NAC pCR in patients with LABC.

Should Core Needle Lymph Node Biopsy be a Relevant Alternative to Surgical Excisional Biopsy in Diagnostic Work Up of Lymphomas?

OBJECTIVE: Surgical excisional biopsy is accepted as the standard of care approach in the diagnosis of lympho- mas. Financial issues related to the increased cost and the invasive nature of the procedure forced physicians to use some alternative diagnostic methods. Percutaneous core needle biopsy, which gained a reputation for the diagnosis of lymphomas with the advent of improved pathological, immunohistochemical, and molecular analysis, made it possible to have an accurate diagnosis with limited tissue samples. In this retrospective study, we aimed to compare the diagnostic yield of surgical excisional biopsy and core needle biopsy. MATERIALS AND METHODS: This study included 131 patients who were diagnosed with lymphoma with a nodal biopsy which was acquired via surgical excisional biopsy or core needle biopsy between 2014 and 2020 in our center. Around 68 patients underwent surgical excisional biopsy and the remaining 63 underwent core needle biopsy. Samples that allowed to the identification of the exact tumor type and/or subtype were accepted as fully diagnostic. Sufficient amount of tissue that the pathologist could have any suspicious findings considering malignant lymphoma was classified as partial diagnostic group. Inadequate samples were the ones who were not enough to report any final diagnosis. RESULTS: The patients who underwent a core needle biopsy were significantly older than the patients who underwent to surgical excisional biopsy (56.8 vs. 47.6, P = .003). Despite the full diagnostic ability of surgical excisional biopsy outperformed core needle biopsy (95.2 % vs. 83.8 %, P=.035), in 92.6% of the patients whose tissue samples were obtained via core needle biopsy were accepted to have a sufficient diagnosis to initiate the treatment and not required a second biopsy, which was comparable with the ones achieved by surgical excisional biopsy (92.6% vs. 95.2%, P = .720). CONCLUSION: According to the results obtained in our study, we may conclude that core needle biopsy is a viable and comparable alternative to surgical excisional biopsy, offering a less invasive and less-expansive approach.

Formation of precipitates in off-stoichiometric Ni-Mn-Sn Heusler alloys probed through the induced Sn-moment.

The shell-ferromagnetic effect originates from the segregation process in off-stoichiometric Ni-Mn-based Heusler alloys. In this work, we investigate the precipitation process of L21-ordered Ni2MnSn and L10-ordered NiMn in off-stoichiometric Ni50Mn45Sn5 during temper annealing, by X-ray diffraction (XRD) and 119Sn Mössbauer spectroscopy. While XRD probes long-range ordering of the lattice structure, Mössbauer spectroscopy probes nearest-neighbour interactions, reflected in the induced Sn magnetic moment. As shown in this work, the induced magnetic Sn moment can be used as a detector for microscopic structural changes and is, therefore, a powerful tool for investigating the formation of nano-precipitates. Similar research can be performed in the future, for example, on different pinning type magnets like Sm-Co or Nd-Fe-B.

Newly onset cytopenias not always indicate a relapsing AML after allogeneic HSCT, a case of non-destructive post transplant lymphoproliferative disorder.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an effective option for the treatment of intermediate and high-risk Acute myeloid leukemia (AML). Post-transplant lymphoproliferative disorder (PTLD) is related to the intensity of post-transplant immunosuppression. Although Epstein-Barr virus (EBV) seropositivity and reactivation can be a major risk factor for PTLD. A few PTLDs could be EBV negative. There are a very limited number of PTLD cases following HSCT in patients with AML. We present a differential diagnosis of cytopenias after allo-HSCT. This is the first report of an AML patient developing bone marrow EBV-negative PTLD relatively late in their post-transplant course.

Chordoid meningioma: report of 5 cases and review of the literature.

Chordoid meningioma is a rare, more aggressive subtype of meningioma. This study documents the histological, radiological and clinical features of seven tumours in five patients among 131 meningioma patients who were treated in the Department of Neurosurgery at Istanbul Medipol University between 2014 and 2019. There were two males and three females. All tumours were supratentorial. Surgical Simpson grade II resection was achieved in two cases, grade I in one and grade IV in two. One case relapsed and underwent further surgeries and adjuvant treatment. The chances of survival without recurrence after the Simpson grade I-II resection are high but close follow-up is recommended particularly if grade I cannot be achieved.

Pretreatment platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as a predictor of pathological complete response to neoadjuvant chemotherapy in patients with breast cancer: single center experience from Turkey.

The aim of this study was to investigate the predictive value of PLR and NLR as an indicator of pathological complete response (pCR) in patients with breast cancer after NACT. One hundred thirty-nine patients with early or LABC and candidates to NACT were retrospectively analyzed. The prognostic significance of PLR and NLR was analyzed. In addition, predictive indicators of pCR to NACT were also evaluated. pCR was obtained in 48.9% of patients. Significant difference was detected between pCR and PLR, tumor grade, clinical lymph node status and molecular subgroup. The higher rate of pCR was significantly achieved for patients with PLR low ( < 181.7) compared with those with PLR high (>181.7) (68.6% vs. 33.4%; P < 0.001). PLR, tumor grade and pCR to NACT for disease-free survival (DFS), and PLR, NLR, tumor grade and pCR to NACT for overall survival were detected to be prognostic factors by univariate analysis. On the other hand, a logistic regression analysis indicated that PLR and NLR were found to be an independent factors for predicting pCR to NACT ( P < 0.001; OR, 0.07; 95% CI, 0.02-0.25 and P = 0.016; OR, 4.66; 95% CI, 1.33-16.2, respectively), as were molecular subtypes ( P = 0.001; OR, 0.23; 95% CI, 0.09-0.56). Our results showed that PLR low and NLR low before NACT are readily feasible and simple and also inexpensive biomarkers predicting pCR to NACT for patients with LABC.

New generation oral anticoagulant apixaban enhances embryo implantation by increasing integrin ß3 expression in rats: A pilot study.

OBJECTIVE: The first aim of this study was to investigate the effect of apixaban on endometrial receptivity via immunohistochemical investigation of integrin ß3 expression in pregnant rats. The second aim was to compare the endometrial effects of both subcutaneous and oral anticoagulant drugs in terms of integrin ß3 expressions. METHODS: A total of 24 rats were selected for this study and divided into three equal groups as control, enoxaparin and apixaban groups. Subcutaneous enoxaparin and oral apixaban were applied for 15 days starting on the first day of pregnancy. On the 15th day of pregnancy, all rats were killed by cervical dislocation, and uterine horns, including pregnancy materials, were investigated for pregnancy success and endometrial receptivity by using immunohistochemical integrin ß3 staining. RESULTS: Living, viable fetuses were higher in the apixaban group compared to the control group (p=0.037). Intensity and universality of immunohistochemical staining of integrin ß3 for endometrial stroma were detected statistically higher in the apixaban group than the other groups. (p=0.009 for intensity, p=0.014 for universality). Endometrial epithelial and myometrial integrin ß3 expression were detected to be identical between the groups (p=0.3). CONCLUSIONS: Apixaban enhances endometrial receptivity via increasing integrin ß3 expression in rats. This result can lead to further studies to be done in the future.

The Role of 18F-FDG PET/CT in Predicting the Neoadjuvant Treatment Response in Patients with Locally Advanced Breast Cancer.

Purpose: Patients with locally advanced breast cancer (LABC) should be treated with neoadjuvant chemotherapy (NAC). Pathological complete response (pCR) is related to better disease-free survival (DFS). The best strategy for assessing the efficacy of NAC has not been established yet, but several studies have shown that 18F-FDG PET/CT is a potential imaging tool for assessing pCR. The aim of this study is to investigate the merits of 18F-FDG PET/CT imaging in predicting pCR in both axillary and breast tissue and to establish a threshold maximum standard uptake value (SUVmax) for predicting the response after completion of NAC. Methods: A total of 186 LABC patients, treated with an NAC regimen according to tumor subtype, were retrospectively analyzed in this study. All patients underwent 18F-FDG PET/CT imaging before and after completion of NAC. PET parameters were measured in the most FDG avid breast tissue and axillary lymph nodes. We analyzed the correlation between the tumor SUVmax of the PET/CT response and the pCR after surgery. DFS was also evaluated with respect to pCR. Results: Higher pCR rates were significantly associated with a higher tumor grade, an initial Ki-67 ≥20% (p = 0.03 and p = 0.003, respectively), a triple-negative subtype (32.9%), and a human epidermal growth factor receptor 2 (HER-2)-positive subtype (24.7%) (p < 0.001). There was a significant correlation between the pCR and a complete response in 18F-FDG PET/CT (p < 0.001). The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT to determine the pCR after NAC were 100%, 72.2%, 85%, 75.2%, and 100%, respectively. We demonstrated a 1.1 cutoff SUVmax for breast tumors after NAC (OR: 3.94, 95% CI: 1.14-5.05, p = 0.004), the 18F-FDG PET/CT response to NAC (OR: 0.50, 95% CI: 0.25-0.99, p = 0.003), and the molecular subtype of breast tumors (OR: 0.58, 95% CI: 0.38-0.88, p = 0.011). Conclusion: Our results confirm that 18F-FDG PET/CT is a useful method for predicting the NAC response in LABC.

Large Schwannoma of the Deep Peroneal Nerve: A Case Report.

This article presents the case of a 32-year-old female patient with schwannoma. The patient had swelling on the anterior aspect of her right foot for 1 year with increasing pain over the past 2 months. Moreover, a positive Tinel sign was present over the swelling. Magnetic resonance imaging revealed a large schwannoma mass in the deep peroneal nerve. Consequently, the patient?s large schwannoma was completely excised along with its capsule. Schwannomas are benign tumors of the peripheral nerves that rarely exhibit malignant transformation. Treatment is considered to be curative if complete resection is achieved.

Does Gabapentin Affect Neural Tube Development? Experimental Study Using an Early Stage Chick Embryo Model.

AIM: To determine whether using gabapentin (GBP), especially in the first maternal trimester, would affect the neural tube development of embryos in an early stage chick embryo (ESCE) model. MATERIAL AND METHODS: One hundred fertile specific pathogen-free (SPF) chick eggs were used to investigate neurulation; they were divided into four groups of 25 eggs (Groups A, B, C, and D including control, subtherapeutic, therapeutic, and supratherapeutic dose subjects, respectively). After 30 hours of incubation, all eggs reached the ninth stage of embryonic development, as defined by Hamburger and Hamilton. GBP was administered through the subblastoderm, and the eggs were incubated for 72 hours. The embryos were macroscopically and histopathologically investigated with hematoxylin eosin following incubation and extraction. RESULTS: In the 72nd hour of the study, a total of 6 eggs showed no embryo development. We detected 1 (4.34%), 13 (59.09%), 15 (65.21%), and 18 (81.81%) neural tube defective embryos in groups A, B, C, and D, respectively. Statistically, the differences between the groups were significant, especially in the comparisons of all GBP groups to the control group (p?0.001). However, there was no significant difference between groups B, C, and D. Additionally, we suggest that at all doses, GBP could cause neural tube defects in the ESCE. CONCLUSION: Based on these results, we concluded that GBP use at any dose led to midline closure defects in ESCEs. This is the first report in the literature on GBP using an ESCE model. However, further investigations with a larger sample size are required to assess its effect at lower doses and to determine the mechanisms of embryonic damage.

Unusual Clinical Presentation of Hodgkin Lymphoma in a Child: Both Spinal Cord Compression and Hydronephrosis.

BACKGROUND: Hodgkin lymphoma (HL) is predominantly a nodal disease with extranodal presentation being uncommon. Presentation with neurological symptoms is not uncommon in adult patients with HL. Subdiaphragmatic involvements are less common especially in childhood. In the literature, there has been no case which presented with both spinal cord compression and bilateral hydronephrosis in pediatric patients with HL. OBSERVATION: We report a 9-year-old boy diagnosed with HL who presented with bilateral hydronephrosis and epidural involvement. CONCLUSION: Differential diagnosis of abdominal mass in patients presenting with spinal cord compression and/or hydronephrosis should include HL. Retrograde J ureteral stenting is the treatment of choice for malignant ureteral obstruction.

Artificial intelligence assistance significantly improves Gleason grading of prostate biopsies by pathologists.

The Gleason score is the most important prognostic marker for prostate cancer patients, but it suffers from significant observer variability. Artificial intelligence (AI) systems based on deep learning can achieve pathologist-level performance at Gleason grading. However, the performance of such systems can degrade in the presence of artifacts, foreign tissue, or other anomalies. Pathologists integrating their expertise with feedback from an AI system could result in a synergy that outperforms both the individual pathologist and the system. Despite the hype around AI assistance, existing literature on this topic within the pathology domain is limited. We investigated the value of AI assistance for grading prostate biopsies. A panel of 14 observers graded 160 biopsies with and without AI assistance. Using AI, the agreement of the panel with an expert reference standard increased significantly (quadratically weighted Cohen's kappa, 0.799 vs. 0.872; p = 0.019). On an external validation set of 87 cases, the panel showed a significant increase in agreement with a panel of international experts in prostate pathology (quadratically weighted Cohen's kappa, 0.733 vs. 0.786; p = 0.003). In both experiments, on a group-level, AI-assisted pathologists outperformed the unassisted pathologists and the standalone AI system. Our results show the potential of AI systems for Gleason grading, but more importantly, show the benefits of pathologist-AI synergy.

Giant Sacral Schwannoma Causing Bilateral Hydronephrosis: Case Report and Review of the Literature.

BACKGROUND: Giant sacral schwannomas are very rare, and less than 1%-5% of spinal schwannomas are found in the sacral region. These frequently grow to considerable size because of permissive anatomic location and benign, slow growth of tumor. They can be unnoticed before reaching a huge size. CASE DESCRIPTION: We report a rare case of a giant sacral schwannoma in a 46-year-old man. The patient presented with difficulty in passing urine, episodic constipation, and swelling of the right lower extremity for 6 months. Magnetic resonance imaging revealed 160 x 110 x 110 mm encapsulated heterogenous solid mass originated from left S1 spinal nerve extending into the pelvis and abdomen. Sigmoid colon and rectum were displaced to the right side, and bladder was displaced anteriorly. Left side of the S1 and S2 vertebral bodies, left S1 and S2 neural foramen were also eroded. It also compressed ureters causing bilateral hydronephrosis. The patient underwent a 2-stage procedure in which complete resection was achieved. CONCLUSIONS: We report the second case of a completely resected giant sacral schwannoma with bilateral hydronephrosis in the literature. Performing a 2-stage procedure is important in giant sacral schwannomas. Morbidity can be minimized, and extent of resection can be maximized with the help of combined anterior/posterior approach.

Concordance of PD-L1 expression and CD8+ TIL intensity between NSCLC and synchronous brain metastases.

Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values <1%, 1-49%, and ≥50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3+/CD8+ TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3+/CD8+ TIL proportions and the intensity of CD8+ TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values <1%, 1-49%, and ≥50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3+/CD8+ TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.