Predominant Histological Type Research Articles

Epidemiological and Histological Profile of Breast Cancer in the Ghrab Chrarda Bni Hsein Region, Morocco

Introduction Breast cancer is the most common cancer, accounting for 38.9% of all cancers diagnosed, it is also the most fatal among Moroccan women. The aims of this study were to draw up an epidemiological profile of breast cancer and to establish the link between patient characteristics and the histological types of cancer observed. Methods This was a retrospective study including 877 patients with histologically confirmed breast cancer. The study was conducted at the Reproductive Health Reference Center in the province of Kénitra (Morocco). It covered the period 2013 - 2018. Results The median age of patients at diagnosis was 50 years (Q1-Q3: 42 - 58 years). Most patients were aged 40 years or older (84.04%) and married (67.32%). They were nulliparous in 18.61% of cases. The average number of live children (LVC) was 3.5 LVC (Q1- Q3: 2 - 5 LVC). Approximately 10.22% of patients had a family history of invasive carcinoma (96.58%). The median tumour size was 25 mm (Q1 - Q3: 20 - 36 mm). The predominant histological type was invasive ductal carcinoma. The most common Scarff- Bloom-Richardson (SBR) grade was SBR II (63.64%). High histological grade correlated with large tumour size. Histological type showed a significant association with time to consultation (p<0.05) and age at first pregnancy (p<0.05). Conclusion All the contextual factors need to be taken into account to improve the assessment of the risk of developing breast cancer, and even of dying from it. Research, awareness-raising and ongoing education are essential if we are to develop more effective prevention strategies and treatments. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1129-1136

Epidemiological distribution of high-risk human papillomavirus genotypes and associated factors among patients with esophageal carcinoma at Bugando medical center in Mwanza, Tanzania

BackgroundEsophageal carcinoma is a growing concern in regions that have a high incidence of human papillomavirus (HPV) infection such as East Africa. HPV, particularly the high-risk genotypes, is increasingly recognized as a risk factor for esophageal carcinoma. We set out to investigate the prevalence and associated factors of high-risk HPV in formalin-fixed paraffin-embedded (FFPE) tissue blocks with esophageal carcinoma at Bugando Medical Center, a tertiary referral hospital in Mwanza, Tanzania, East Africa.MethodsA total of 118 esophageal carcinoma FFPE tissue blocks, collected from January 2021 to December 2022, were analyzed. Genomic DNA was extracted from these tissues, and multiplex polymerase chain reaction (PCR) was performed to detect HPV using degenerate primers for the L1 region and type-specific primers for detecting HPV16, HPV18, and other high-risk HPV genotypes. Data were collected using questionnaires and factors associated with high-risk HPV genotypes were analyzed using STATA version 15 software.ResultsOf the 118 patients’ samples investigated, the mean age was 58.3 ± 13.4 years with a range of 29–88 years. The majority of the tissue blocks were from male patients 81/118 (68.7%), and most of them were from patients residing in Mwanza region 44/118 (37.3%). Esophageal Squamous Cell Carcinoma (ESCC) was the predominant histological type 107/118 (91.0%). Almost half of the tissue blocks 63/118 (53.3%) tested positive for high-risk HPV. Among these, HPV genotype 16 (HPV16) was the most common 41/63 (65.1%), followed by HPV genotype 18 (HPV18) 15/63 (23.8%), and the rest were other high-risk HPV genotypes detected by the degenerate primers 7/63 (11.1%). The factors associated with high-risk HPV genotypes were cigarette smoking (p-value < 0.001) and alcohol consumption (p-value < 0.001).ConclusionA substantial number of esophageal carcinomas from Bugando Medical Center in Tanzania tested positive for HPV, with HPV genotype 16 being the most prevalent. This study also revealed a significant association between HPV status and cigarette smoking and alcohol consumption. These findings provide important insights into the role of high-risk HPV in esophageal carcinoma in this region.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

Prognostic Factors of Survival in Patients With Gastric Cancer Under 45 Years Old Treated With Surgery in a Single Center in Mexico City.

Introduction Gastric cancer is a significant major global health concern, particularly prevalent in Asia. In recent years, a large number of new cases have been diagnosed worldwide, leading to a substantial number of deaths. The disease tends to present more aggressively in these cases, leading to debates about the prognosis and survival outcomes. Nonetheless, research has shown that survival rates improve significantly when the tumor is completely surgically resected. Materials and methods This retrospective study included patients between 16 and 45 years old, diagnosed with gastric cancer, with the support of the pathology department, who underwent surgery in the upper GI service, in the period from January 2006 to December 2012.Data collected encompassed variables such as gender, age, tumor size, type of surgery, overall survival, disease-free period, type and histological degree of the tumor, clinical stage of the cancer, and R0 resection (curative resection). All patients with a confirmed diagnosis of gastric cancer were included and treated with surgery and D1 limited dissection or extended D2 dissection. Patients who have received chemotherapy prior to surgical treatment and those who have been surgically treated outside the XXI Century National Medical Center were excluded. Results A total of 104 patients were included; the predominant histological type was diffuse adenocarcinoma accounting for 79.8% and 81.7% of the cases were histologicalgrade 3. The most common clinical stage was IIIA in 41.3% of the cases. In 53.8% of the cases, we obtained an R0 resection. D2 lymphadenectomy was performed in 53.8% of the cases, with an overall survival rate of 82.69%. Significant prognostic factors for survival included T4 depth with an increase in risk for mortality (OR: 25.93; 95% CI: 6.41-53.54; p=0.001), lymph node status (OR: 14.76; 95% CI: 4.6-46.83; p<0.001), and size greater than 5 cm (OR: 1.8; 95% CI: 0.61-6.35; p<0.001). Conclusions Gastric cancer is more common in adults aged above 60 years old, but the incidence in young adults under 45 years old has been increasing. Although young gastric cancer patients present with more aggressive tumor behavior, these patients can have similar or even better overall survival compared to older patients, being 35% in some cases, especially in the resectable setting. Further research is still needed to fully characterize the unique biology and optimal management of gastric cancer in young adults.

Glioma of the anterior visual pathway in children. Part II. Current treatment trends

The literature review presents modern treatment aspects for anterior optic pathway gliomas (OPGs), which are low-grade brain tumors accounting for 20%–30% of childhood gliomas, can occur anywhere along the visual pathways and in the development of the surrounding structure, and are predominantly benign. The predominant histological type of tumor in this localization is piloid astrocytoma (PA), less commonly pilomyxoid astrocytoma (PMA). However, the course of anterior OPGs is unpredictable and varies from spontaneous regression to progression with severe visual, neurological, and endocrine disorders, affecting treatment and disease prognosis. Although there have been advances in clinical studies based on histological and molecular genetic analyses, no fundamental changes in survival rates and recurrence-free periods and improvements in functional outcomes have been achieved. Furthermore, no studies have comprehensively analyzed the functional results depending on the management tactics of pediatric patients with anterior visual pathway gliomas. Anterior optic pathway glioma treatment is challenging and complex problem, which depends on the patient’s age, clinical picture, localization, surgical resectability, and histological and molecular genetic study results. It includes surgical treatment, chemotherapy, radiation therapy, the use of targeted therapy drugs, and additional advanced techniques that are still under development and research. Optimal treatment of anterior optic pathway gliomas in children remains a topic of discussion in the current literature.

Unraveling Differences in Molecular Mechanisms and Immunological Contrasts between Squamous Cell Carcinoma and Adenocarcinoma of the Cervix.

This study aims to refine our understanding of the inherent heterogeneity in cervical cancer by exploring differential gene expression profiles, immune cell infiltration dynamics, and implicated signaling pathways in the two predominant histological types of cervix carcinoma, Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC). Targeted gene expression data that were previously generated from samples of primary cervical cancer were re-analyzed. The samples were grouped based on their histopathology, comparing SCC to ADC. Each tumor in the study was confirmed to be high risk human papilloma virus (hrHPV) positive. A total of 21 cervical cancer samples were included, with 11 cases of SCC and 10 of ADC. Data analysis revealed a total of 26 differentially expressed genes, with 19 genes being overexpressed in SCC compared to ADC (Benjamini-Hochberg (BH)-adjusted p-value < 0.05). Importantly, the immune checkpoint markers CD274 and CTLA4 demonstrated significantly higher expression in SCC compared to ADC. In addition, SCC showed a higher infiltration of immune cells, including B and T cells, and cytotoxic cells. Higher activation of a variety of pathways was found in SCC samples including cytotoxicity, interferon signaling, metabolic stress, lymphoid compartment, hypoxia, PI3k-AKT, hedgehog signaling and Notch signaling pathways. Our findings show distinctive gene expression patterns, signaling pathway activations, and trends in immune cell infiltration between SCC and ADC in cervical cancer. This study underscores the heterogeneity within primary cervical cancer, emphasizing the potential benefits of subdividing these tumours based on histological and molecular differences.

The Coexistence of Occult (Latent) Thyroid Cancer and Multinodular Goiter After Total Thyroidectomy: A Retrospective Study.

Introduction Multinodular goiter (MNG) is a common thyroid disorder characterized by the presence of multiple nodules within the thyroid gland. While most cases of MNG are benign, there is a risk of malignancy, particularly in nodules with certain features. The coexistence of occult (latent) thyroid cancer within MNG presents diagnostic and management challenges, underscoring the need for comprehensive investigation and treatment strategies. Objective The objective of this retrospective study is to investigate the prevalence of occult thyroid carcinoma in non-toxic MNG following total thyroidectomy. Materials and methods The study population consisted of 412 patients who underwent total thyroidectomy between 2004 and 2022 at the Second Surgical Department of the 424 General Military Hospital of Education in Thessaloniki. Data collection included patients' demographic characteristics, surgical indications for thyroidectomy, and histopathological examination findings. Initial data were available for all 412 patients, while sufficient information was present for 319 individuals, with a subset of 271 undergoing total thyroidectomy due to non-toxic MNG. Out of the aforementioned group, 253 cases were histologically confirmed as MNG. Subsequently, a statistical analysis was conducted concerning age, gender, the association of MNG with malignancy, and other thyroid disorders. Results Out of the total 412 thyroidectomies performed, 271 patients remained for statistical analysis and study. Among them, 253 patients had histologically confirmed MNG. Among the histological findings, 38 cases (14.02%) were identified with occult carcinoma within MNG. The predominant histological type was papillary thyroid carcinoma (PTC), comprising 93.3% of cases. Additionally, 18 patients (6.64%) were diagnosed with MNG, Hashimoto's thyroiditis (HT), and malignancy concurrently. Conclusions The coexistence of occult thyroid carcinoma within MNG underscores the importance of vigilant evaluation and management strategies in patients undergoing total thyroidectomy. These findings emphasize the need for comprehensive preoperative assessment and postoperative surveillance to detect and address occult thyroid cancer, thereby optimizing patient care and outcomes.

Metastatic breast cancer in elderly women: A retrospective cohort study in Morocco.

e13073 Background: Breast cancer (BC) stands as the predominant malignancy among women worldwide, presenting a significant global public health problem. In Morocco, it is the leading cause of cancer-related mortality in females. However, there exists a limited understanding of outcomes and treatment patterns for elderly patients with metastatic breast cancer (MBC) in our context. Methods: We conducted a retrospective cohort study at the Department of Medical Oncology, Hassan II University Hospital of Fez, focusing on 92 female patients aged 65 years or older diagnosed with MBC, between January 2012 and December 2016. The primary objectives were to estimate overall survival (OS) and progression-free survival (PFS), describe treatment patterns, and characterize the clinicopathological, and prognostic aspects of MBC in elderly women in Morocco. Results: The cohort’s median age was 70.88 (range, 65-88years) with 45.6% of patients aged of 65 to 69 years, 34.8% between 70 to 74 years old, and 19.6% over 75. Most patients (77.2%) had an Eastern Cooperative Oncology Group (ECOG) score of 0 to 1, and only 33.7% had comorbidities. De novo stage IV constituted 59.8% of all cases. Metastatic recurrences represent 40.2% with 16.2% having recurrence within 12 months, and 83.8% having a recurrence interval exceeding 12 months. The median time to recurrence was 45.5 months. Invasive ductal carcinoma (IDC) was the predominant histological type (81.1%), with SBR grade II (51%) and grade III (21.7%). Metastases were observed in pleuropulmonary (78.3%), bone (56.5%), lymph nodes (33.7%) and liver (30.4%). With 71.7% having metastases in fewer than three sites, while 28.3% had metastases in three or more sites. Molecular profiling showed Luminal A (38%) and Luminal B (26.1%) subtypes as the most prevalent, followed by triple-negative (17.4%) and HER2+ (15.2%). Treatment modalities included chemotherapy (50%), hormone therapy (15.2%) or a combination of the two (17.4%), and anti-HER2 targeted (14.1%). Median OS was 37 months (95% CI: 16.86 - 57.13 months), and median PFS was 33.16 ± 4.1 months. Anti-HER2 therapy showed a significant association with survival (p = 0,05). Conclusions: This study highlights the characteristics, survival, and treatment modalities of elderly patients with MBC in Morocco. Despite the predominance of luminal BC an intriguing observation was the frequent use of chemotherapy as first line modality.

Assessing response and adherence to neoadjuvant treatment in soft tissue sarcomas of the extremities.

e23559 Background: The standard treatment for large, intermediate, and high-grade extremity soft tissue sarcoma (ESTS) involves surgery and radiotherapy. The addition of chemotherapy has improved oncological outcomes, such as reduced recurrence and prolonged survival. However, the relationship between neoadjuvant treatment and tumor response in ESTS is not well understood. Pathological evaluation of viable tumor cells after treatment is an indicator of tumor response, yet the proportion of viable tumor cells remains high, particularly in high-risk sarcomas. Combining radiotherapy with chemotherapy may enhance the response of tumor cells. Objective: This study aims to evaluate the effects of neoadjuvant chemotherapy (NCT) and chemoradiotherapy (CRT) on patients with high-risk ESTS and to determine its impact on the pathological response. Methods: We enrolled adult patients with high-risk ESTS (SARCULATOR OS &lt; 60%) at a single center in Latin America. The study was designed to analyze the pathological response in patients with high-risk sarcomas who underwent neoadjuvant CRT and resection and to correlate these responses with various variables. The treatment response was evaluated using the EORTC–STBSG criteria. Results: Thirty-four patients were recruited, with a median age of 44 years (IQR 23-74). Fifty-two percent had T3 tumors (mean size 18 cm), and 79.4% were diagnosed at stage III. The predominant histological subtypes were synovial sarcoma (35.3%) and dedifferentiated liposarcoma (29.4%). The most used NCT regimen was doxorubicin/ifosfamide (84.4%), with 62.5% receiving a dosage intensity of Q4W, affected by overcapacity, and 25% received Q3W. Concurrent CRT was administered to 64.7% of patients, with a median delay to onset of 36 days due to overcapacity (43.5%). Only 79.4% completed three preoperative cycles of treatment. As for the response, 41.2% had an EORTC-E response, and 17.6% had an EORTC-D response. Grade 3 neutropenia and anemia occurred in 17.2% and 8.8% of patients, respectively. Disease progression during NCT was observed in six patients. No significant difference was found in the pathological response between the Q4W and Q3W dosage intensities (p = 0.62). Conclusions: The impact of NCT on pathological responses was not significantly high, which may be due to the predominant histological type in our series. The main cause of treatment delay at our center was due to overcapacity; however, this did not influence the pathological response relative to dose intensity. Additional follow-up assessments are required to determine the influence on relapse-free and overall survival based on the response after preoperative CRT.

Clinical and Pathological Features of Osteosarcomas of the Jaws: A Retrospective Study.

Osteosarcomas of the jaw (OSJs) are rare tumors with distinct characteristics from osteosarcomas affecting other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of OSJs. A retrospective, descriptive cross-sectional study including patients diagnosed with OSJ registered at the "La Paz" University Hospital, Madrid, was performed. Data of eight patients with a diagnosis of OSJ were obtained during the study period of 22 years (2002-2024). The mean age of the patients was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most predominant histological type. Survival rate at 5 years was 50%, which decreased to 25% at 10 years. OSJs differ from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment. However, more studies are needed through which more standardized protocols can be proposed for adjuvant therapeutic management.

The Prevalence of BRCA1 and BRCA2 Mutations in Breast Cancer Patients

Aim: Genetic mutations in BRCA1 and BRCA2 are crucial for breast cancer risk assessment and treatment planning. Methods: This prospective observational study at Jinnah Postgraduate Medical Centre, Pakistan, involved female breast cancer patients aged 18 or older. The sample size calculation was based on a 3.4% prevalence rate of BRCA mutations, aiming for a 95% confidence level. Data on demographic, clinical characteristics, and genetic testing for BRCA mutations were collected and analyzed using SPSS version 23. Results: Among the study participants, 10% exhibited BRCA1 or BRCA2 mutations. The majority were diagnosed at stage 3 tumor development, with invasive ductal carcinoma being the predominant histological type. No significant familial predisposition to breast cancer was noted among the majority. Educational status and ethnicity showed varying associations with BRCA mutation presence. Conclusion: The study highlights a modest incidence of BRCA mutations among Pakistani breast cancer patients, underscoring the importance of genetic testing for risk assessment and targeted treatment. The findings support the need for comprehensive genetic screening programs in Pakistan, considering the diverse demographic and clinical characteristics of the population. Keywords: BRCA mutations, breast cancer, genetic testing, Pakistan, risk assessment, targeted treatment.

Histopathological and Molecular Characteristics of Malignant Breast Tumors in the Kurdish Population During 2019 - 2021

Background: Breast cancer, the most prevalent cancer in women and the second leading cause of cancer-related deaths worldwide, is a complex and heterogeneous disease characterized by multiple tumor types with distinct tissue patterns, biological characteristics, and clinical behaviors. Given the critical role of histopathological and molecular characteristics in the treatment and management of breast cancer. Objectives: This study was undertaken to investigate the histopathological characteristics of malignant breast masses in the city of Sanandaj from 2019 to 2021. Methods: In this descriptive-analytical study, out of 1,631 pathology reports from breast tissue samples collected in Sanandaj, a city in northwest Iran, between 2019 and 2021, 597 (36%) malignant cases were examined for their pathological type and molecular characteristics. Data analysis was performed using SPSS 26 software, employing chi-square and Fisher's exact tests. Results: The mean age of the patients at diagnosis was 49.7 ± 11.9 years. The most prevalent molecular subtype was luminal A (56.4%), followed by triple-negative (16.7%), human epidermal growth factor receptor 2 (HER2)-positive/enriched (14.1%), and luminal B (14%). Invasive ductal carcinoma was the predominant histological type, accounting for 82.7% of cases, followed by lobular invasive carcinoma (8.2%). Papillary carcinoma accounted for 5.9% of cases, metaplastic carcinoma for 1.8%, and mucinous carcinoma for 1.3%. Higher grades at the time of diagnosis were associated with the metaplastic subtype (P &lt; 0.001). The only biomarker that showed a significant association with pathological types of breast cancer was Ki-67. The percentage of cases positive for Ki-67 was higher in three types of breast cancer: Infiltrating ductal carcinoma, metaplastic, and papillary (intraductal) carcinoma, compared to the other types (P &lt; 0.001). Conclusions: According to our data, infiltrating ductal and lobular carcinoma are the most prevalent pathological types, and luminal A is the most common molecular subtype among Kurdish women in Iran. It is recommended that future studies examine patient survival based on the pathological and molecular types of tumors, including the evaluation of additional biomarkers. Furthermore, comparing these results with those from other ethnic groups could provide valuable insights into the impact of ethnicity on breast cancer characteristics and outcomes.

Long-term exposure to ambient fine particulate matter and risk of liver cancer in the NIH-AARP Diet and Health Study

BackgroundFine particulate matter (PM2.5) exposure has been associated with liver cancer incidence and mortality in a limited number of studies. We sought to evaluate this relationship for the first time in a U.S. cohort with historical exposure assessment. MethodsWe used spatiotemporal prediction models to estimate annual average historical PM2.5 concentrations (1980–2015) at residential addresses of 499,729 participants in the NIH-AARP Diet and Health Study, a cohort in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, Georgia, and Detroit, Michigan) enrolled in 1995–1996 and followed up through 2017. We used a time-varying Cox model to estimate the association for liver cancer and the predominant histologic type, hepatocellular carcinoma (HCC), per 5 µg/m3 increase in estimated outdoor PM2.5 levels, incorporating a 5-year average, lagged 10 years prior to cancer diagnosis and adjusting for age, sex, race/ethnicity, education level and catchment state. We also evaluated PM2.5 interactions with hypothesized effect modifiers. ResultsWe observed a non-significantly increased risk of liver cancer associated with estimated PM2.5 exposure (Hazard ratio [HR] = 1.05 [0.96–1.14], N = 1,625); associations were slightly stronger for HCC, (84 % of cases; HR = 1.08 [0.98–1.18]). Participants aged 70 or older at enrollment had an increased risk of liver cancer versus other age groups (HR = 1.50 [1.01–2.23]); p-interaction = 0.01) and risk was elevated among participants who did not exercise (HR = 1.81 [1.22–2.70]; p-interaction = 0.01). We found no evidence of effect modification by sex, smoking status, body mass index, diabetes status, or alcohol consumption (p-interaction > 0.05). ConclusionsOur findings in this large cohort suggest that residential ambient PM2.5 levels may be associated with liver cancer risk. Further exploration of the variation in associations by age and physical activity are important areas for future research.

Abstract 4085: The anti-VISTA x MSLN bispecific antibody-interferon beta mutein fusion protein: A trispecific immunocytokine with potent therapeutic efficacy against malignant pleural mesothelioma

Abstract Background Malignant pleural mesothelioma (MPM) is a rare and highly fatal cancer primarily induced by asbestos exposure. The 5-year overall survival rate for MPM patients is less than 20%. Before the FDA approval of the combination of immune checkpoint inhibitors (Nivolumab + Ipilimumab, CHECKMATE-743), chemotherapy was the only systemic therapy for MPM. However, the predominant histological type of MPM, epithelioid MPM, comprising approximately 70% of cases, showed limited clinical benefits from immune checkpoint inhibitors when compared to non-epithelioid histology. Consequently, there is an unmet medical need to develop a new anti-cancer drug specifically for the treatment of epithelioid MPM. In this study, we discovered that V-domain Ig suppressor of T cell activation (VISTA), an immune checkpoint protein, and Mesothelin (MSLN), a tumor differentiation antigen, are co-expressed in epithelioid MPM. Subsequently, we developed a biomarker-based anti-VISTA x MSLN bispecific antibody (BsAb) and anti-VISTA x MSLN BsAb-IFN-β mutein fusion protein (trispecific immunocytokine) for the treatment of epithelioid MPM. Method We designed and screened various structures of the anti-VISTA x MSLN BsAb. To produce the trispecific immunocytokine, we fused IFN-β mutein (R27T/C17S), which exhibits improved stability, productivity, and pharmacokinetic properties compare to recombinant IFN-β. The in vitro efficacy of the trispecific immunocytokine was tested in human MPM cell lines, and its in vivo efficacy was evaluated in a human MPM xenograft mouse model and a human IFNAR1/2 Knock-in (KI) mouse model. Results We demonstrated a strong positive correlation between the expression levels of VISTA and MSLN in epithelioid MPM. The Anti-VISTA x MSLN BsAb showed improved binding affinity and antibody-dependent cell cytotoxicity (ADCC) activity. The trispecific immunocytokine displays analogous biological activities to both Anti-VISTA x MSLN BsAb and IFN-β mutein. The trispecific immunocytokine exhibited potent in vivo and in vitro anti-cancer activities against epithelioid MPM preclinical models, operating through both direct cytotoxicity and indirect activation of immune cells. Conclusion The trispecific immunocytokine demonstrated robust in vitro and in vivo anti-cancer efficacy in the epithelioid MPM model. Our findings suggest that the trispecific immunocytoine is a promising drug candidate for epithelioid MPM. Citation Format: Hee Geon Park, Hyeon Ju Kim, Myeung Ryun Seo, Ji Eun Park, Tae Won Kim, Jeung Hoo Choi, Jay Park, Kyoung Song, Chan Gyu Lee, Hae Min Jeong, Jun Young Choi, Yeong Jeong Jeon, Yoon La Choi, Sung Youl Hong, Young Kee Shin. The anti-VISTA x MSLN bispecific antibody-interferon beta mutein fusion protein: A trispecific immunocytokine with potent therapeutic efficacy against malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4085.

Utility of CT Scan in Detecting Bladder Involvement Among Patients With Cervical Carcinoma.

Background Cervical cancer is a widespread health issue in India, particularly affecting women as the second most common cancer. The burden of cervical cancer in the country necessitates accurate staging for treatment optimization. The revised International Federation of Gynecology and Obstetrics (FIGO) staging system is vital for this purpose, emphasizing the extent of parametrial and pelvic sidewall involvement. Cervical cancer's propensity to infiltrate neighboring pelvic organs, including the bladder, necessitates precise staging. In India, traditional methods like cystoscopy have been relied upon, but they have limitations. Recent advancements in medical imaging, notably the increased use of computed tomography (CT) scans, provide a non-invasive alternative for staging and evaluating bladder involvement. This study aimed to evaluate the utility and accuracy of CT scans in assessing bladder involvement. Methods This cross-sectional study examined 127 newly diagnosed cervical carcinoma cases in women over a two-year period from August 2021 to July 2023. Patients underwent CT scans (plain) and cystoscopy, and bladder involvement was determined following the revised FIGO staging. Data collected comprised patient demographics, medical history, clinical symptoms, and FIGO staging. Cystoscopy was performed using an Olympus CYF-5 flexible cystoscope, and CT scans utilized a 64-slice multidetector CT scanner. Radiological reports detailed primary tumor characteristics and proximity to the bladder. Statistical analysis encompassed descriptive statistics, and calculation of sensitivity, specificity, positive predictive value, and negative predictive value for CT scans in comparison to cystoscopy. Statistical significance was considered at p < 0.05. Results In our study, the mean participant age was 45.3 years, with 61.4% falling in the 40-60 years age group. Socioeconomic status (SES) varied, with 37.8% classified as low SES, 48.8% as middle SES, and 13.4% as high SES. Parity data showed that 76.4% had three or more pregnancies. Among presenting symptoms, abnormal vaginal bleeding (65.4%) was the most prevalent, and squamous cell carcinoma (78.7%) was the predominant histological type. The prevalence of bladder involvement was 9.4% by cystoscopy and 30.7% by CT scans. CT scan demonstrated a high sensitivity (100%) but lower specificity (76.52%), with 78.80% overall accuracy. Conclusion A combined approach, using CT scans as a screening tool and cystoscopy as a confirmatory method, could provide the most comprehensive and reliable assessment of bladder involvement in cervical carcinoma patients, ultimately contributing to improved patient care and management.

Insights from a retrospective study: an understanding of pediatric colorectal carcinoma

Pediatric colorectal cancer, comprising just 1% of childhood cancers, has surged among young individuals, underscoring its significant health impact. Diagnostic challenges arise from atypical presentation and nonspecific symptoms in 90% of cases, leading to delayed detection in 19%.Methods A 2-year retrospective study of pediatric colorectal carcinoma cases was conducted across a specialized surgical pediatric center. Data were gathered, including age, symptoms, diagnostics, treatments, and outcomes.Results Six colorectal carcinoma cases (median age, 16) were documented, mainly in males (66%). Predominant histological types included mucinous adenocarcinoma and signet ring cell carcinoma. Metastasis was present in all cases, with symptoms including hematochezia (83%), abdominal pain (100%), weight loss (66%), and anemia (100%). Diagnosis often faced misidentification, fostering disease progression and metastasis. Various diagnostic and treatment modalities were employed, including surgery and neo-adjuvant or adjuvant chemotherapy.Conclusion Swift detection and intervention for pediatric colorectal carcinoma are pivotal. Efficient diagnostics and heightened awareness among medical professionals and the public are imperative. Early surgical intervention remains a cornerstone, especially for patients with pertinent family histories and characteristic symptoms. Tailored guidelines for pediatric patients are needed to enhance outcomes and survival.

The Chaperone System in Tumors of the Vocal Cords: Quantity and Distribution Changes of Hsp10, Hsp27, Hsp60, and Hsp90 during Carcinogenesis

Laryngeal squamous cell carcinoma (LSCC) constitutes a noteworthy subset of head and neck cancers, contributing to about 4.5% of all malignancies. Its clinical behavior and characteristics exhibit variations contingent upon the specific anatomical site affected, with the glottis, supraglottis, and subglottis emerging as the most prevalent locations. Notably, squamous cell carcinoma represents a predominant histological type, accounting for 85% to 95% of all laryngeal cancers. The gender disparity is evident, with a higher incidence among males, exhibiting a ratio of 3.9:1. Moreover, disparities among racial groups are observed, as African American patients tend to manifest the condition at a younger age, coupled with lower overall survival rates compared to their Caucasian, Hispanic, and Asian counterparts. The primary etiological factors implicated in the onset of laryngeal cancer are tobacco and alcohol consumption, with a direct correlation to the intensity and duration of usage. Importantly, the risk diminishes gradually following cessation, necessitating a substantial period of at least 15 years for a return to baseline rates. Given the diverse nature of laryngeal SCC, treatment modalities are tailored based on the specific site and stage of the disease. Therapeutic interventions, such as radiotherapy, transoral laser microsurgery, open horizontal partial laryngectomy, or total laryngectomy, are employed with the overarching goal of preserving organ function. This study delves into the intricate realm of laryngeal SCC, specifically exploring the involvement of heat shock proteins (HSPs) in disease progression. This research meticulously examines the expression levels of Hsp10, Hsp27, Hsp60, and Hsp90 in dysplastic and benign tissue samples extracted from the right vocal cord, utilizing immunohistochemistry analysis. The focal point of the investigation revolves around unraveling the intricate role of these molecular chaperones in tissue differentiation mechanisms and cellular homeostasis, particularly within the inflammatory milieu characteristic of the tumor phenotype. The findings from this study serve as a robust histopathological foundation, paving the way for more in-depth analyses of the underlying mechanisms governing the contribution of the four chaperones to the development of squamous cell carcinoma in the larynx. Additionally, the data gleaned from this research hint at the potential of these four chaperones as valuable biomarkers, not only for diagnostic purposes but also for prognostication and ongoing patient monitoring. As our understanding of the molecular intricacies deepens, the prospect of targeted therapeutic interventions and personalized treatment strategies for laryngeal SCC becomes increasingly promising.

Evaluation of Histomorphological Changes in Breast Cancer Post-Neoadjuvant Chemotherapy.

Breast cancer, a leading cause of global female mortality, demands comprehensive diagnostic and therapeutic strategies. This study delves into the nuanced realm of post-neoadjuvant chemotherapy breast cancer specimens, emphasizing the imperative need for pathologists to discern stromal and nuclear alterations adeptly. The investigation, encompassing 100 female patients with a mean age of 47.5years, elucidates the demographic and clinicopathological parameters. Predominantly presenting as palpable lumps (85%), invasive ductal carcinoma emerged as the predominant histological type (98%). The primary focus of the study revolves around the morphological changes post-neoadjuvant chemotherapy, with a meticulous qualitative analysis encompassing stromal elements (fibrosis, elastosis, calcification) and nuclear features (pyknosis, hyperchromasia). Notably, the response to chemotherapy, classified by the International Union against Cancer criteria, delineates a substantial pathological complete response (55%), partial response (35%), and limited non-response (10%). The therapeutic landscape includes a majority of cases undergoing extensive chemotherapy cycles, primarily featuring the cyclophosphamide, doxorubicin, and paclitaxel regimen. Remarkably, this investigation unveils fibrosis (63%) and elastosis/collagenization (51%) as prevalent stromal changes, while pyknosis (58%) and hyperchromasia (48%) dominate nuclear alterations. In conclusion, this retrospective study provides a comprehensive overview of post-neoadjuvant chemotherapy breast cancer specimens, shedding light on the intricate interplay of clinical parameters, treatment responses, and histopathological changes. The findings underscore the pivotal role of pathologists in accurately diagnosing and grading tumors in the evolving landscape of breast cancer management.

Gastroesophageal junction cancer - current topic and treatment dilemmas

Treatment of gastroesophageal junction carcinomas have been debated for many years. This type of carcinomas has been classified as either gastric or esophageal carcinomas until Siewert's classification was established and they were defined as a distinct entity. Risk factors for development of these cancers are gastroesophageal reflux and Barrett's esophagus, obesity, Helycobacter pylori infection, smoking, and alcohol. Symptoms of this disease include retrosternal pain, dysphagia to aphagia and weight loss. Esophagogastroduodenoscopy with biopsy and pathohistological verification as well as CT of the chest and abdomen are crucial in establishing the diagnosis. Adenocarcinoma is predominant histological type of these tumors. The stage of the disease is defined by the TNM classification. Treatment of gastroesophageal junction cancer is complex, multidisciplinary and multi-modal, and involves the use of surgery, chemotherapy and radiotherapy, alone or in different combinations. Surgery is the major treatment modality for these tumors, especially in local stages. Radiotherapy is used in the treatment of these tumors in all stages of the disease, and especially in the multimodal treatment of locally advanced gastroesophageal junction cancer, both preoperatively and postoperatively, usually in combination with chemotherapy. Chemotherapy is used in the treatment of these cancers as preoperative, postoperative and systemic. Immunotherapy and target therapy, as new promising therapy is usually applied in a systemic and postoperative approach. Future directions in the treatment of these cancers are directed towards new surgical procedures, new types of immunotherapy, as well as new radiotherapy techniques.

Management of Adverse Reactions Related to Lenvatinib Plus Pembrolizumab Treatment Among Patients With Renal Cell Carcinoma

Renal cell carcinoma is the predominant histological type of kidney cancer with historically poor patient outcomes. Lenvatinib in combination with pembrolizumab is an approved first-line regimen for people with advanced renal cell carcinoma that showed clinically meaningful improvements in efficacy over sunitinib in the CLEAR trial; however, reduced patient exposure to treatment (often stemming from adverse reactions) is a potential therapeutic barrier that must be addressed. Here, we present management strategies for adverse reactions associated with this treatment combination: fatigue, diarrhea, musculoskeletal pain, hypertension, stomatitis, decreased appetite, rash, nausea, and proteinuria.Dosing modification of lenvatinib and pembrolizumab should be made according to the prescribing information for each medication. Clinicians should consider that some adverse reactions, such as diarrhea, may be attributable to lenvatinib, or may be a symptom of immune-related adverse reactions to pembrolizumab (such as colitis). Adverse reactions can generally be managed by: (1) advising the patient on precautionary measures (eg, for stomatitis, practice dental hygiene, avoid irritating foods, and maintain adequate hydration), (2) monitoring for changes in symptoms from baseline (eg, changes in bowel movements, blood pressure or level of fatigue), (3) interrupting/dose reducing lenvatinib or interrupting pembrolizumab, if warranted, and advising the patient to manage their current symptoms via self-care (managing diarrhea with antidiarrheal agents and hydration), and (4) implementing medical interventions (eg, thyroid replacement or antihypertensive therapy) when needed.Through successful management of adverse reactions, oncology clinicians can improve the well-being of their patients and likely enhance adherence rates to treatment with lenvatinib and pembrolizumab.