Pathological Tumor Research Articles

The surgical management of third ventricle region tumors

ObjectivesThe goal of this study was to characterize the largest known cohort of patients presenting with different tumor pathologies in the third ventricle region to better understand outcomes of surgical management. MethodsAll patients undergoing surgical intervention on tumors in or encroaching upon the third ventricle at Loyola University Medical Center between the years 1986–2021 were reviewed. Information recorded included presenting symptoms, pre- and post-operative interventions, tumor pathology, operative technique, extent of resection (EOR), and approach of operation. The primary clinical outcome was Karnofsky Performance Status (KPS) score. ResultsNinety-seven patients underwent 123 operations. Forty-six (47.4 %) patients were female, and the median age at operation was 39 years. Eighty-seven (70.7 %) operations were open, and 36 (29.3 %) were endoscopic. Gross total resection (GTR) was achieved in 34.4 % of operations, near-total resection (NTR) in 31.5 %, subtotal resection in 25.0 %, and biopsy alone in 9.3 %. Median KPS increased pre- to postoperatively, regardless of surgical technique. Adjusting for preoperative KPS, age, and operation number, regression analysis demonstrated a trend that lesser EOR is associated with lower KPS at most recent follow-up (p=0.031 for NTR vs GTR, p=0.022 for biopsy vs GTR). There was no statistically significant association between the most recent KPS and either open or endoscopic surgical technique, with or without adjusting for the previously stated factors (p=0.26). There was no association between postoperative complication rates or age with either surgical technique. ConclusionsHere, we characterize a large cohort of patients presenting for neurosurgical evaluation of tumors in the region of the third ventricle. Our results demonstrate a trend that a more aggressive resection may yield better KPS outcomes. Additionally, both open and endoscopic techniques lead to a similar improvement in clinical outcome and rates of complication. While ultimate surgical approach and technique is determined by individual tumor characteristics, patient health status, and surgeon expertise, ability to resect the tumor in its entirety should be taken into consideration.

Frequency of KRAS and BRAF mutations in colorectal carcinoma and their association with clinical-pathological characteristics in a tertiary hospital in Kenya.

Colorectal carcinoma is a leading cause of cancer morbidity and mortality globally. Its management includes the use of targeted therapy which require assessment for biomarkers to choose eligible patients. KRAS and BRAF mutations are biomarkers predictive of response to anti-EGFR therapy. This study aimed at determining the frequency of BRAF V600E and KRAS exon 2,3,4 mutations in colorectal carcinoma patients at the Aga Khan University Hospital Nairobi, Kenya. Study participants were patients who had colectomy for colorectal carcinoma. They were identified from the laboratory information system. The patients age, gender and tumor location were determined from the medical records. The histological diagnosis, pathological tumor and nodal stage were confirmed by examining hematoxylin and eosin-stained slides prepared from the colectomy specimen. DNA was extracted from the specimens using Qiagen QIAamp DNA FFPE Tissue Kit and PCR performed using EntroGen KRAS/BRAF mutation analysis kit following manufacturer's protocol. One hundred fourteen patients were enrolled. Colorectal carcinoma was significantly more common in males than females. The mean age at diagnosis was 58 years. Majority of the tumors were in the right colon, were of pathological tumor stage T3 and had nodal involvement. Forty six percent (46%) of the cases had KRAS mutations while 5.3% had BRAF V600E mutation. KRAS mutation was associated with a high pathological tumor stage and nodal involvement. Colorectal carcinoma in our patients is more common in males and tend to occur at a younger age. The patients tend to have a high tumor pathological stage and nodal involvement at diagnosis. The high frequency of KRAS exon 2,3,4 mutation and low frequency of BRAF V600E mutations is similar to what has been reported in literature.

Diet Impacts on Gene Expression in Healthy Colon Tissue: Insights from the BarcUVa-Seq Study.

(1) Introduction: The global rise of gastrointestinal diseases, including colorectal cancer and inflammatory bowel diseases, highlights the need to understand their causes. Diet is a common risk factor and a crucial regulator of gene expression, with alterations observed in both conditions. This study aims to elucidate the specific biological mechanisms through which diet influences the risk of bowel diseases. (2) Methods: We analyzed data from 436 participants from the BarcUVa-Seq population-based cross-sectional study utilizing gene expression profiles (RNA-Seq) from frozen colonic mucosal biopsies and dietary information from a semi-quantitative food frequency questionnaire. Dietary variables were evaluated based on two dietary patterns and as individual variables. Differential expression gene (DEG) analysis was performed for each dietary factor using edgeR. Protein-protein interaction (PPI) analysis was conducted with STRINGdb v11 for food groups with more than 10 statistically significant DEGs, followed by Reactome-based enrichment analysis for the resulting networks. (3) Results: Our findings reveal that food intake, specifically the consumption of blue fish, alcohol, and potatoes, significantly influences gene expression in the colon of individuals without tumor pathology, particularly in pathways related to DNA repair, immune system function, and protein glycosylation. (4) Discussion: These results demonstrate how these dietary components may influence human metabolic processes and affect the risk of bowel diseases.

Potential predictor of prognosis in breast carcinoma: Tumor budding

ABSTRACT Background: Breast cancer is the most common cancer in women, with invasive breast carcinoma of no special type (IBC-NST) accounting for the majority of cases. Aim: This study aimed to evaluate the relationship between tumor budding (TB), which is the earliest histological indicator of tumor spread and represents epithelial–mesenchymal transition, and prognostic factors as well as the effect of TB on survival in patients with IBC-NST, thereby demonstrating its potential prognostic value. Materials and Methods: This study included 278 cases of breast resection diagnosed with IBC-NST from 2014 to 2019. Total tumor buds were counted in 10 high-power fields of a hematoxylin and eosin–stained section with the most infiltrative area at 400× magnification. The cutoff value for TB was obtained using receiver operating characteristic analysis for mortality and recurrence risk; this cutoff value was used to classify TB into two categories: low and high grades. The relationship between TB and prognostic factors and the effect of TB on the survival of patients were investigated. Results: This study revealed a statistically significant relationship between high-grade TB and increased tumor size, advanced pathological primary tumor (pT) category, lymph node metastasis, lymphatic invasion, blood vessel invasion, increased recurrence, and mortality as well as reduced overall and disease-free survival. Conclusion: TB in breast carcinomas may have significant predictive value for prognosis. It emerges as a simple, reproducible, and cost-effective histological marker. With the standardization of evaluation criteria, TB may be readily integrated into routine pathological examination, thereby increasing its value in clinical patient management.

Predictive value of mono-exponential and multiple mathematical models in locally advanced rectal cancer response to neoadjuvant chemoradiotherapy.

This prospective study aimed to assess the predictive value of mono-exponential and multiple mathematical diffusion-weighted imaging (DWI) models in determining the response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). The study included 103 LARC patients scheduled for preoperative chemoradiotherapy between December 2021 and June 2023 Magnetic resonance imaging (MRI) scans were performed using a 3.0-T MR scanner, encompassing sagittal, axial, and oblique coronal T2-weighted images without fat saturation, along with DWI perpendicular to the rectum's long axis. Various DWI parameters, including apparent diffusion coefficient (ADC), stretched exponential model (SEM), continuous-time random-walk model (CTRW), and fractional-order calculus model (FROC), were measured. The pathologic complete response (pCR) rate and tumor downstaging (T-downstage) rate were determined. After nCRT, SEM-α, SEM-DDC, CTRW-α, CTRW-β, CTRW-D, FROC-β, and ADC values were significantly higher in the pCR group compared to the non-pCR group (all P < 0.05). SEM-DDC, CTRW-α, CTRW-D, FROC-β, FROC-µ, and ADC values were significantly higher in the T-downstage group (ypT0-1) than in the non-T-downstage group (ypT2-4) (P < 0.05). The combination of CTRW (α + β + D) exhibited the best diagnostic performance for assessing pCR after nCRT (AUC = 0.840, P < 0.001). Pre-nCRT CTRW (α + β) demonstrated a predictive AUC of 0.652 (95%CI: 0.552-0.743), 90.3% sensitivity, and 43.1% specificity for pCR. Regarding T-downstage assessment after nCRT, the combination of CTRW (α + D) yielded the best diagnostic performance (AUC = 0.877, P = 0.048). In LARC patients, imaging markers derived from CTRW show promise in predicting tumor response before nCRT and assessing pCR after nCRT.

Endoscopic Endonasal Skull Base Surgery: Analysis of the Results in the Author’s Initial 200 Cases

Background Endoscopic endonasal approaches represent currently an important tool for approaching the skull base. The evolution of new techniques is based in the continuous acquisition of skills and abilities and it is paramount to determine the safety and effectiveness of new approaches. Based on that, the aim of this study is to analyze our results after the first 200 cases. Material and methods We performed a retrospective review of all cases operated on through an endoscopic endonasal approach in our Skull Base Unit, between January 2007 and May 2018. We analyze the results and all the per-operative complications associated. Results In this study we included 200 cases, comprising 105 female (52,2 %) and 95 male (47,5 %), with a mean age of 45,6 (range 21-85 years-old). The most commonly reported pathology was the pituitary adenoma, comprising 121 cases (60,5 %), followed by 13 meningocele (6,5 %), 9 chordoma (4,5 %), 6 skull base meningioma (3 %) and 7 cranyopharingioma (3,5 %). 161 cases (81 %) represented first surgery. The most frequently reported complication was diabetes insipidous in 17 % of all cases, followed by CSF leak, represented by 15 cases (7,5 %). 12 CSF leak cases were successfully treated by external lumbar draining and 3 patients required second surgery to skull base repair. In the last 50 cases, only one CSF leak has been reported, representing an incidence of 2 %, successfully treated by endoscopic repair. This decrease in CSF leak represents the impact of the learning curve in skull base reconstruction. 5 % of patients suffered meningitis and 5 % presented permanent anosmia. In our serie we reported 1,6 % of transient neurologic deficit represented by oculomotor palsy and 1,6 % of permanent neurologic deficit due to infarction. 3 patients in this serie has died, two due to malignant ICA occlusion and 1 due to infection (overall mortality 1,5 %). The most commonly used approach was the transsphenoidal transsellar approach (58 %), followed by transplanum-transtubercullum approach (8 %). Gross total resection was achieved in 76 % of tumoral pathology, 71 % in cases of pituitary adenomas. Conclusion From this review we can conclude that, in our serie, endoscopic endonasal surgeries represent safe approaches to the skull base to a huge variety of pathologies. Progressive acquisition of skills and experience is paramount to improve the results, avoiding and reducing complications. Appropriate patient and pathology selection is also mandatory.

Development of microsurgical forceps equipped with haptic technology for in situ differentiation of brain tumors during microsurgery

The stiffness of human cancers may be correlated with their pathology, and can be used as a biomarker for diagnosis, malignancy prediction, molecular expression, and postoperative complications. Neurosurgeons perform tumor resection based on tactile sensations. However, it takes years of surgical experience to appropriately distinguish brain tumors from surrounding parenchymal tissue. Haptics is a technology related to the touch sensation. Haptic technology can amplify, transmit, record, and reproduce real sensations, and the physical properties (e.g., stiffness) of an object can be quantified. In the present study, glioblastoma (SF126-firefly luciferase-mCherry [FmC], U87-FmC, U251-FmC) and malignant meningioma (IOMM-Lee-FmC, HKBMM-FmC) cell lines were transplanted into nude mice, and the stiffness of tumors and normal brain tissues were measured using our newly developed surgical forceps equipped with haptic technology. We found that all five brain tumor tissues were stiffer than normal brain tissue (p < 0.001), and that brain tumor pathology (three types of glioblastomas, two types of malignant meningioma) was significantly stiffer than normal brain tissue (p < 0.001 for all). Our findings suggest that tissue stiffness may be a useful marker to distinguish brain tumors from surrounding parenchymal tissue during microsurgery, and that haptic forceps may help neurosurgeons to sense minute changes in tissue stiffness.

A case of postpartum dermatomyositis with onset at three months: expanding the clinical spectrum

Introduction and importance: Dermatomyositis (DM) is an autoimmune disorder affecting all age groups, with a higher prevalence in women. Diagnosis typically occurs around age 40. Manifestation can be acute or chronic. Diagnosis relies on clinical, laboratory, EMG, and histopathological tests. Limited information exists regarding DM’s occurrence during pregnancy and its connection to pregnancy. Case presentation: A 31-year-old, 3-month postpartum female presented with features of proximal muscle weakness and generalized erythematous itchy rash. The weakness was associated with muscle tenderness. Laboratory evaluation and skin biopsy revealed features consistent with Dermatomyositis. Pulmonary pathology and occult tumors were investigated. Symptoms gradually improved on steroids and azathioprine. Clinical discussion: The relationship between dermatomyositis and pregnancy remains poorly understood, with only a few documented cases highlighting the impact of pregnancy on the development and progression of the disease. From the available literature, it is evident that postpartum dermatomyositis is uncommon yet significant, necessitating careful attention during pregnancy to enhance outcomes for both the mother and the unborn child. Conclusion: Our experience highlights a rare case of postpartum dermatomyositis, with symptoms emerging three months after childbirth, differing from documented cases. More research is needed to understand pregnancy’s role in dermatomyositis development and improve treatment for pregnant women with autoimmune skin diseases.

Predicting cerebellar mutism syndrome in children using lesion map combined with clinical features.

This study aimed to develop a predictive model for cerebellar mutism syndrome (CMS) in pediatric patients with posterior fossa tumors, integrating lesion-symptom mapping (LSM) data with clinical factors, and to assess the model's performance. A cohort of pediatric patients diagnosed with posterior fossa tumors and undergoing surgery at Beijing Children's Hospital from July 2013 to December 2023 was analyzed. Clinical variables gender, age at surgery, tumor characteristics, hydrocephalus, surgical route and pathology were collected. LSM was used to link tumor locations with CMS outcomes. Lasso regression and logistic regression were employed for feature selection and model construction, respectively. Model performance was assessed using area under the curve (AUC) and accuracy metrics. The study included 197 patients in total, with CMS rates consistent across training, validation, and prospective groups. Significant associations were found between CMS and gender, tumor type, hydrocephalus, paraventricular edema, surgical route, and pathology. A predictive model combining voxel location data from LSM with clinical factors achieved high predictive performance (C-index: training 0.956, validation 0.933, prospective 0.892). Gender, pathology, and voxel location were identified as key predictors for CMS. The study established an effective predictive model for CMS in pediatric posterior fossa tumor patients, leveraging LSM data and clinical factors. The model's accuracy and robustness suggest its potential utility in clinical practice for early CMS risk assessment and intervention planning.

Phase III randomized trial comparing neoadjuvant paclitaxel+platinum to 5-fluorouracil+platinum in esophageal/GEJ squamous cell carcinoma.

Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed. Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 1000 mg/m2 continuous infusion (days 1-4), followed by surgery. Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+platinum (170 [85.9%]), P = .009. 5FU + platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel + platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU + platinum vs 139 (66.2%) on paclitaxel + platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU + platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346. Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel + platinum should replace 5FU + platinum as NACT for resectable LAEGSC. CTRI/2014/04/004516.

The Relationship between Treatment Response and Overall Survival in Borderline, Non-Resectable and Resectable Pancreatic Cancer Patients Treated with Neoadjuvant FOLFIRINOX.

Background: The National Comprehensive Cancer Network (NCCN)-recommended treatment for patients with borderline-resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) involves a combination of neoadjuvant FOLFIRINOX chemotherapy and the curative surgical resection of the tumor. This study seeks to identify the clinical, radiological, laboratory, and pathologic predictors that can anticipate the oncological outcomes of patients. Methods: In this study, we conducted a retrospective analysis of patients who had undergone curative surgical resection for BRPC, LAPC, or resectable disease with high-risk features after receiving neoadjuvant FOLFIRINOX at two institutions. We evaluated by means of multivariate analysis whether clinical and laboratory response, tumor markers, radiological response, and pathologic tumor response grade correlated with overall survival (OS) and disease-free survival (DFS). Results: The study enrolled a total of 70 patients with BRPC, LAPC, and resectable disease with high-risk features who underwent resection after neoadjuvant FOLFIRINOX. Age above 65 years and fewer than nine cycles of chemotherapy (OR 4.2; 95% CI 1.4-12.0; p-value 0.007); locally advanced tumors after neoadjuvant treatment (NAT) (OR 7.0; 95% CI 1.9-25.7; p-value 0.003); and lymph node disease and histological tumor regression grade 2 and 3 (OR 4.3; 95% CI 0.9-19.2; p-value 0.05) were risk factors linked to adverse OS and DFS. The median OS and DFS were 33 (22-43.9) months and 16.5 (11.3-21.6) months, respectively. Conclusions: Classification as a LA tumor after NAT was the only preoperative radiological factor that predicted adverse survival in patients undergoing curative surgery after NAT. Other clinical, biochemical, and radiological measures of response were not found to predict OS. Patient age, the cumulative administration of more than eight cycles of chemotherapy, and a significant pathological response were associated with better OS. The results of this study are important for treatment decision-making and prognostication in patients with BRPC and LAPC.

374. INCIDENCE AND PREDICTORS OF STRICTURE DEVELOPMENT FOLLOWING ESOPHAGECTOMY: A RETROSPECTIVE ANALYSIS

Abstract Objective Anastomotic stricture (AS) is a well described complication after esophagectomy and not only affects nutritional status but also has a detrimental impact on long-term quality of life. This retrospective study explores the incidence of clinically relevant AS in patients undergoing esophagectomy for cancer and investigates the potentially reversible factors associated with AS. Methods A prospectively entered clinical database of consecutive patients undergoing esophagectomy at a high-volume referral center over a decade (1/2013-12/2022) was queried for the presence of post-operative clinically significant AS, defined as stricture requiring endoscopic dilation. Multiple variables encompassing patient-related risk factors, tumor pathology, prior treatment, operative factors, and post-op complications were included in logistic regression analyses to delineate predictors of stricture formation. Results Of 1015 patients in the database, 115 (11.3%) developed AS requiring at least 1 post-op dilation. Although higher American Society of Anesthesiologists (ASA) grading was associated with elevated AS rate impact with most patients being ASA 2 and 3; 24% and 49% respectfully (p &amp;lt; 0.05). Specific patient factors/comorbidities such as age, peripheral or coronary vascular disease, and diabetes mellitus did not emerge as significant predictors. Surprisingly, neither histology, nor neoadjuvant therapy (chemo or chemoradiation) were associated with AS. Both a cervical anastomosis and a intra-operative pyloromyotomy had a higher AS rate than an intra-thoracic anastomosis (OR 13.3, p=0.006) and patients without a myotomy (p=&amp;lt;0.006). Other operative factors including approach (open vs MIE) conduit type (stomach/jejunum/colon) or width (3/4/5/6 cm) did not impact AS rate. All patients had a hand-sewn anastomosis. No post-operative outcome measures (e.g. leak, epidural use, hypotension) was associated with the development of AS. Conclusion Our results highlight the interplay of patient-related risk factors, tumor pathology, prior treatment, and operative factors in the development of post esophagectomy strictures. Understanding these predictors could potentially influence risk stratification and may facilitate tailored postoperative care strategies for improved patient outcomes.

Same Or Different? Resolution of Diagnostic Difficulty of Two Mixed Cell-Type Tumors in Ovarian Pathology

Same Or Different? Resolution of Diagnostic Difficulty of Two Mixed Cell-Type Tumors in Ovarian Pathology

Advance in HIF expression and immune microenvironment in pseudohypoxic HNPGL

This article systematically reviewed the pathological features, molecular mechanisms, and tumor microenvironment of head and neck paraganglioma（HNPGL）, with a focus on pseudohypoxic HNPGL. It was demonstrated that pseudohypoxic HNPGL mainly involves multiple gene mutations, such as SDHx and VHL/EPAS1, which affect the stability and activity of HIF protein and exacerbate the development of the tumor. Meanwhile, the paper also analyzed the expression patterns of HIF-1α and HIF-2α in HNPGL, and found that differences in HIF activation may have an impact on the therapeutic response of specific subtypes. In addition, the paper explored the tumor microenvironment of HNPGL and found that immune cells such as macrophages, CD4⁺T cells, and CD8⁺T cells play an important role in the tumor, and the heterogeneity of the immune microenvironment also affects the choice of therapeutic approaches and responsiveness. Through comprehensive analysis, these findings not only contribute to a deeper understanding of the pathogenesis and developmental process of HNPGL, but also provide clues for future personalized treatments for specific subtypes.

754. PATHOLOGICAL RESPONSE PREDICTS EFFICACY OF ADJUVANT FLOT CHEMOTHERAPY IN GASTROESOPHAGEAL CANCER: AN INTERNATIONAL COHORT STUDY

Abstract Background Perioperative FLOT-based chemotherapy is the current standard of care for all patients with locally-advanced gastroesophageal cancer. However, many patients are unable to complete all planned adjuvant FLOT cycles due to treatment related toxicity and diminished performance status after radical surgery. Within this context, it is unclear whether adjuvant FLOT will improve oncological outcomes for patients with cancers that either don’t respond or respond exceptionally well to neoadjuvant FLOT. To facilitate clinical decision-making, we examined whether pathological response to neoadjuvant FLOT can guide its adjuvant use. Methods Prospectively collected data from 43 centres across 12 countries was analysed. Patients with non-metastatic gastroesophageal adenocarcinoma who received neoadjuvant FLOT followed by radical surgery between 2017-2022 were included. Pathological response was assessed using validated tumour regression grading (TRG) systems. All TRG were trichotomized into minimal responders (MR=worse TRG category), complete responders (CR=pathological complete response), and partial responders (PR=all TRG categories between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT within these cohorts were compared using Kaplan Meier and Cox regression analysis. These findings were validated using propensity score matched analysis. Results 1887 patients (MR n=459, CR n=221, PR n=1207) were evaluated. The median follow-up was 25.5 months. In the MR group, there was no DFS (HR=1.03, 95%CI 0.78-1.36) or adjusted-OS (HR=0.96, 95%CI 0.70-1.30) difference between those who did (n=272) and did not (n=187) receive adjuvant FLOT. In the CR group, there was no DFS (HR=0.88, 95%CI 0.41-1.85) or OS (HR=0.69, 95%CI 0.31-1.54) difference between those who did (n=136) and did not (n=85) receive adjuvant FLOT. In the PR group (adjuvant FLOT n=847, no adjuvant FLOT n=360), adjuvant FLOT conferred a significant DFS (HR=0.68, 95%CI 0.55-0.86) and OS (HR=0.55, 95%CI 0.44-0.69) benefit. Conclusions Pathological response to neoadjuvant FLOT predicts therapeutic efficacy to adjuvant FLOT. Only partial responders benefit from adjuvant treatment. Our findings challenge the current doctrine that perioperative FLOT should be applied to all patients regardless of pathological tumour response.

Preoperative breast MR imaging influences surgical management in patients with invasive lobular carcinoma.

The purpose of the study is to assess the role of preoperative magnetic resonance (MR) imaging on the surgical management of invasive lobular carcinoma (ILC) and to evaluate whether breast density and background parenchymal enhancement (BPE) influence surgical treatment. This retrospective study was conducted on 56 patients who were diagnosed with ILC between 2014 and 2020. All patients had mammogram and ultrasound. Preoperative MRI was available in 34 patients. Age, menopausal status, breast density, BPE, multifocality/multicentricity and surgical treatment were collected. Mean pathological tumour size was 36.4 mm (range 5-140 mm). Dense breasts had larger tumours compared to non-dense breasts (P = 0.072). Of the 34 patients with MRI, 6 opted for mastectomy. Of the remaining 28 cases, MRI findings upgraded surgery to mastectomy in 54% (15/28) because mammogram/ultrasound underestimated tumour extent in 25% (7/28), or multifocal/multicentric disease was identified in 29% (8/28). Tumour size was underestimated by MRI in 7% (2/28). In the non-MRI subgroup, 64% (14/22) of patients underwent breast-conserving surgery, but 29% of them (4/14) required a second-stage mastectomy due to extensive margin involvement. There was no difference in mastectomy rate between patients with MRI (62%) and without MRI (55%) (P = 0.061). Tumour size correlation between MRI and histopathology demonstrated an excellent intraclass correlation coefficient (P < 0.001). Surgical treatment recommendation was not significantly impacted by breast density or BPE. Breast MRI improves surgical management of patients with ILC in providing additional diagnostic information often missed with standard imaging modalities, and without increasing mastectomy rate. Surgical treatment is not impacted by breast density or BPE.

Factors associated with favourable pathological tumour response after neoadjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma

IntroductionPathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemotherapy (NAT) has been associated with oncological outcome. The aim of the study was to investigate factors associated with favourable tumour regression in patients undergoing pancreatic resection for PDAC. MethodsPatients who received NAT before undergoing PDAC resection at two institutions were reviewed. Tumour regression grading (TRG) was scored according to the College of American Pathologists (CAP) system. Interactions between chemotherapy, tumour and surgical factors with TRG were explored. Results54 patients were identified, with 12 (22%) displaying a favourable response to NAT. The type of chemotherapy agent received, the number of cycles or a dose reduction during NAT course was not significantly different between the groups. The time from diagnosis to chemotherapy and time from end of chemotherapy to surgery were also similar between the groups. A favourable TRG was associated with greater disease-free survival median 33.2 months vs. 10.3 months; p = 0.0) but not overall survival (median 43.8 months vs. 32.3 months; p = 0.200), which may be due to small sample size. ConclusionsChemotherapy factors were not significantly related to a favourable response to NAT. Future studies should seek to identify modifiable factors associated with a favourable TRG.

Pheochromocytoma - diagnosis and treatment, review of literature

Introduction: Pheochromocytomas are rare tumors originating from the adrenal medulla, which can occur sporadically or as part of hereditary syndromes. Many patients with chromaffin tumors harbor genetic mutations, typically inherited in an autosomal dominant manner, hence genetic testing is recommended for all patients. Symptoms can result from both excessive catecholamine production and the mass effect of the tumor. Diagnosis is confirmed by elevated levels of metanephrines or normetanephrines in the plasma or urine. Radiological imaging aids in tumor localization and assessment of potential local invasion or metastasis. Preoperative preparation of all patients involves the use of α-receptor blockers and/or other medications to control arterial hypertension, arrhythmias, and fluid volume. Surgery remains the treatment of choice, with lifelong follow-up recommended.Objective:The review article aims to provide an overview of chromaffin tumor pathology, their etiology, discuss diagnostic possibilities, and indicate therapeutic options for patients.Materials and Methods:A summary of reports available in medical publications and scientific studies found in databases such as PubMed, CrossRef, Google Scholar, as well as relevant textbooks.Results:Chromaffin tumors are rare but dangerous for patients; adequate pharmacological preparation for surgery, which is usually necessary, is extremely important.Conclusions:The main role is to establish the correct diagnosis, or even suggest and conduct diagnostic tests towards a chromaffin tumor. Patient management involves controlling blood pressure, appropriate premedication, and surgical intervention. After such treatment, patients require continuous monitoring to detect any potential disease recurrence.

Activation of Wnt/β-catenin signaling is critical for the tumorigenesis of choroid plexus.

Choroid plexus (ChP) is the secretory epithelial structure located in brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of the tumor pathology and limited availability of valid models. Genomic and transcriptomic data from CPT patients were analyzed to identify the putative pathological pathway. Cellular and molecular techniques were employed to validate bioinformatic results in CPT patient samples. Pharmacologic inhibition of Wnt/β-catenin signaling was assessed in CPT cells. Cell-based assays of ChP cell lines were performed following CRISPR-Cas9-derived knockout and over-expression of Wnt/β-catenin pathway genes. 3D CPT model was generated through CRISPR-Cas9-derived knockout of APC. We discovered that Wnt/β-catenin signaling is activated in human CPTs, likely as a consequence of large-scale chromosomal instability events of the CPT genomes. We demonstrated that CPT-derived cells depend on autocrine Wnt/β-catenin signaling for survival. Constitutive Wnt/β-catenin pathway activation, either through knock-out of the negative regulator APC or overexpression of the ligand WNT3A, induced tumorigenic properties in ChP 2D in vitro models. Increased activation of Wnt/β-catenin pathway in ChP organoids, through treatment with a potent GSK3β inhibitor, reduced the differentiation of mature ChP epithelia cells. Remarkably, the depletion of APC was sufficient to induce the oncogenic transformation of ChP organoids. Our research identifies Wnt/β-catenin signaling as a critical driver of CPT tumorigenesis and provides the first 3D in vitro model for future pathological and therapeutic studies of CPT.

Prognostic impact of lymph node invasion levels in patients with bladder cancer undergoing radical cystectomy and pelvic lymphadenectomy.

Extranodal extension in metastatic lymph nodes (LNs) is a poor prognostic factor in bladder cancer (BC). Furthermore, cancer invasion levels in sentinel LNs are associated with prognosis in melanoma. The present study aimed to evaluate the LN invasion level, defined as the extent of cancer invasion in anatomical and immunological LN substructures, and compare it with the pathological node (pN) stage of the tumor-node-metastasis staging system in BC. A total of 98 patients with BC who underwent radical cystectomy and pelvic lymphadenectomy were retrospectively assessed. The LN invasion level was classified as follows: Level 0, no cancer cell within the resected LNs; Level 1, cancer cells confined to intracapsular lymph vessels and subcapsular or transverse sinuses; Level 2, cancer cells infiltrating the cortex, paracortex or medulla; and Level 3, cancer cells infiltrating or beyond the LN capsule. The proportion of patients with Levels 0, 1, 2 and 3 was 70.4% (69/98), 8.2% (8/98), 14.3% (14/98) and 7.1% (7/98), respectively. Kaplan-Meier survival curves of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) with LN invasion levels better stratified outcome patient when using Levels 1-3 compared with pN1-3. In addition, LN invasion levels better predicted RFS, CSS and OS, in comparison with the pN stage (c-index of 0.672 vs. 0.646, 0.688 vs. 0.665, and 0.702 vs. 0.661, respectively). Finally, multivariate analysis revealed that the predictive accuracy of the model integrating pathological tumor (pT) stage and LN invasion levels in RFS, CSS and OS was greater than that of the conventional model that included pT and pN stage (c-index of 0.723 vs. 0.703, 0.710 vs. 0.694, and 0.725 vs. 0.692, respectively). In conclusion, the model with LN invasion levels accurately predicted the prognosis of patients with BC after radical cystectomy and pelvic lymphadenectomy.