Tumor Side Research Articles

Epoxymicheliolide Reduces Radiation-Induced Senescence and Extracellular Matrix Formation by Disrupting NF-κB and TGF-β/SMAD Pathways in Lung Cancer.

Lung cancer is a major cause of cancer-related mortality, and radiotherapy is often limited by tumor resistance and side effects. This study explores whether epoxymicheliolide (ECL), a compound from feverfew, can enhance radiotherapy efficacy in lung cancer. We tested ECL on A549 and PC-9 lung cancer cell lines to evaluate its effect on x-ray irradiation. We measured apoptosis, NF-κB pathway inhibition, TGF-β secretion reduction, and epithelial-mesenchymal transition suppression. Invivo, C57BL/6 mice with lung tumors received ECL and radiotherapy. ECL enhanced the antiproliferative effects of x-ray irradiation, induced apoptosis in senescent cells, inhibited the NF-κB pathway, reduced TGF-β levels, and suppressed epithelial-mesenchymal transition. ECL also inhibited tumor growth and improved survival in mice. ECL is a promising adjunct to radiotherapy for lung cancer, improving treatment outcomes by targeting multiple tumor progression mechanisms. It offers potential for enhanced management of lung cancer.

Asymmetry of the Frontal Aslant Tract and Development of Supplementary Motor Area Syndrome

Background/Objectives: The purpose of this study was to investigate preoperative interhemispheric differences of the FAT in relation to the onset of postoperative SMA syndrome. Methods: This was a single-center retrospective analysis of patients who underwent surgical resection of diffuse gliomas involving the SMA between 2018 and 2022. Inclusion criteria were availability of preoperative and postoperative Magnetic Resonance Imaging, no previous surgery, and no neurological deficits at presentation. Diffusion-weighted data were processed by spherical deconvolution (SD) and diffusion tensor imaging tractography algorithms, and TrackVis was used to dissect the FAT of both hemispheres. The FAT data were analyzed for correlation with postoperative SMA syndrome onset. Results: N = 25 cases were included in the study, among which n = 23 had preoperative bilaterally identifiable FAT by SD. N = 12 developed an SMA syndrome, 6 demonstrated a motor-only syndrome, 4 had a verbal-only syndrome, and 2 had mixed verbal and motor features. The SMA syndrome incidence was significantly more frequent in lower-grade gliomas (p = 0.005). On the tumor side, the FAT identified by SD was smaller than the contralateral (mean volume 6.53 cm3 and 13.33 cm3, respectively, p < 0.001). In the 6 cases that developed a verbal SMA syndrome, a normalized FAT volume asymmetry (FAT-VA) demonstrated an asymmetry shifted towards the non-dominant side (mean FAT-VA = −0.68), while the cases with no postoperative verbal impairment had opposite asymmetry towards the dominant side (mean FAT-VA = 0.42, p = 0.010). Conclusions: Preoperative interhemispheric FAT volume asymmetry estimated according to functional dominance can predict postoperative onset of verbal SMA syndrome, with proportionally smaller FAT on the affected dominant hemisphere.

The Inter-Laennec Approach for Liver Tumors in Contact with Hepatic Veins in Laparoscopic Liver Resection.

Patients with liver tumors that are in contact with the major hepatic veins may require hepatic vein resection to achieve an adequate surgical margin; however, the potential for venous congestion and impaired remnant liver function must be considered. We introduce the anatomy of the hepatic vein related to Laennec's capsule as well as the surgical techniques to overcome these limitations in the laparoscopic approach.1,2 PATIENTS AND METHODS: A patient with hepatocellular carcinoma underwent resection of the paracaval portion of the caudate lobe. A 4.5-cm tumor was located on the hepatic hilum, compressing the middle and right hepatic veins (MHV and RHV). The Laennec's capsule around the hepatic veins consists of cardiac and hepatic layers. In the inter-Laennec approach, the hepatic veins and inferior vena cava were continuously exposed from the root side, during entry into the space between the hepatic and cardiac Laennec's capsules.3,4 Hence, the cardiac Laennec's capsule was preserved on the venous side, and the strength of the hepatic vein walls was maintained without exposing the tumor. Parenchymal transection was performed while preserving the MHV and RHV. The operative time was 331 min, with minimal estimated blood loss. The patient was discharged on postoperative day 6 without complications. A pathological examination revealed the presence of focal capsular invasion; however, the surgical margin was maintained by leaving the hepatic Laennec's capsule on the tumor side. Understanding the structure of the Laennec's capsule can contribute to the establishment of safe and feasible liver resection techniques.

ABNORMAL CORTICAL EXCITABILITY IS ASSOCIATED WITH DECREASED OVERALL SURVIVAL IN PATIENTS WITH GLIOBLASTOMA

Abstract AIMS Navigated transcranial magnetic stimulation (nTMS) is a well-established technique for motor cortex mapping and assessing motor tract integrity in patients with brain tumours. Pre-surgical nTMS mapping in patients with glioma has shown an altered interhemispheric excitability that correlates well with WHO grade. The aim of this study is to correlate the preoperative nTMS findings with overall survival (OS) in patients with motor-eloquent brain tumours operated at our institution. METHOD We conducted a retrospective cohort study using electronic patient records to search for all patients with a motor-eloquent brain tumour resected between 2017 and 2023. We included all adult patients (>18 years) with pre-operative nTMS mapping and a tissue diagnosis. Two nTMS measures of cortical excitability were assessed; cortical excitability score (CES) and the intraM1 excitability score (IMES). Our outcome measure was OS. RESULTS 160 patients fulfilled the inclusion criteria (mean age 48.34 years). The commonest tumour histology was glioblastoma (n=51; 32%). Among patients with diffuse gliomas, IDH was mutated in 59% patients and MGMT was methylated in 61%. Majority of patients (62.5%) underwent gross total resection. Resting motor thresholds (RMTs) for both upper and lower limbs between the tumour and healthy side were not significantly different. Interhemispheric RMT ratio in the upper limbs was abnormal in 60.93% patients and in the LLs was abnormal in 57.14%. A higher CES was related to lower overall survival (p=0.04). A subgroup analysis showed this was particularly the case among patients with a diagnosis of Glioblastoma (p=0.015). When adjusted for cofounding factors EOR, MGMT methylation and age, both CES and IMES were inversely related to OS (p=0.002). CONCLUSION A higher CES and IMES is related with poor overall survival in patients with Glioblastoma even when other cofounding factors affecting OS are considered. This information can be used when counselling patients and planning surgical approach to motor-eloquent tumours.

Single-Atom Iridium Nanozyme-Based Persistent Luminescence Nanoparticles for Multimodal Imaging-Guided Combination Tumor Therapy.

Persistent luminescence nanoparticles (PLNPs) can achieve autofluorescence-free afterglow imaging, while near-infrared (NIR) emission realizes deep tissue imaging. Nanozymes integrate the merits of nanomaterials and enzyme-mimicking activities with simple preparation. Here PLNPs are prepared of Zn1.2Ga1.6Ge0.2O4:Cr0.0075 with NIR emission at 700 nm. The PLNPs are then incubated with IrCl3 solution, and the nanoparticles are collected and annealed at 750 °C to obtain iridium@PLNPs. Iridium is observed on the PLNPs at the atomic level as a single-atom nanozyme with peroxidase-like catalytic activity, photothermal conversion, and computed tomography (CT) contrast capability. After coating with exosome membrane (EM), the Ir@PLNPs@EM composite exhibits long-lasting NIR luminescence, peroxidase-like catalytic activity, photothermal conversion, and CT contrast capability, with the targeting capability and biocompatibility from EM. Thus, NIR afterglow/photothermal/CT trimodal imaging-guided photothermal-chemodynamic combination therapy is realized as validated with the in vitro and in vivo inhibition of tumor growth, while toxicity and side effects are avoided as drug-free treatment. This work offers a promising avenue for advanced single-atom nanozyme@PLNPs to promote the development of nanozymes and PLNPs for clinical applications.

Route patterns of the collateral venous pathway in patients with tumors invading the superior sagittal sinus: an angiographic study and clinical applications

Chronic occlusion of the superior sagittal sinus (SSS) by tumors in the midsagittal region causes the collateral venous pathway (CVP). Understanding common patterns of CVP is helpful in reducing surgical complications. This study aimed to investigate the CVP found in patients with SSS-invading tumors, and to provide information on the prevention of operative venous complications. From January 2015 to December 2022, this retrospective study collected patients with tumors that invaded the SSS and underwent digital subtraction angiography of intracranial vessels. Data collected included sex, age, tumor pathology, tumor location along the SSS, tumor side, degree of obstruction of the SSS, types and route patterns of the CVP, and the distance between the tumor and the diploic vein (DV). Twenty patients (6 males, 14 females) were recruited. The prevalence of CVP types was 90% for DV, 35% for end-to-end anastomosis of superficial cortical vein, 15% for meningeal vein, and 20% for other types of CVP. The pteriofrontoparietal and occipitoparietal diploic routes were found on the cerebral hemisphere contralateral to the tumor significantly more than in the cerebral hemisphere ipsilateral to the tumor. Of all patients with presence of collateral DV, 61% had a very close (less than 1 cm) distance between the nearest DV and tumor attachment in the SSS. DV in the cerebral hemisphere contralateral to the tumor was the most common type of CVP found in patients with tumor-induced SSS obstruction. Most of the collateral DV was located very close to the SSS tumor attachment. Neurosurgeons should realize these findings when planning a craniotomy.

Immunohistochemical expression of CD44 in invasive breast carcinoma

Background: In India, breast cancer forms the most common malignancy, accounting for 28.2% of all female cancers. Breast cancer consists of phenotypically diverse group of diseases. Due to different relapse abilities, doubling times, and different infiltrative capacities, it is important to identify potential biomarkers that could be used to screen high-risk patient and predict breast cancer prognosis in conjunction with classical pathological parameters. Aims and Objectives: The present study was conducted to evaluate immunohistochemical expression of CD44 in breast carcinoma and to correlate CD44 expression with other clinicopathological parameters and molecular classification of carcinoma breast. Materials and Methods: The present study was a prospective descriptive study conducted on 100 cases of carcinoma breast diagnosed on modified radical mastectomy specimens that were submitted to the Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, over the period of 2 years. Results: Out of 100, 64 cases (64%) were CD44 positive. Out of these 64 cases, 9 (9%) cases were 1+, 34 (34%) cases were 2+, and 21 (21%) cases showed 3+ positive expression of CD44 in tumor cells. Loss of CD44 expression was seen in 36 (36%) cases. A statistically significant association of CD44 was seen with multifocality of the tumor, negative estrogen receptor/progesterone receptor (ER/PR) expression, and molecular subtypes. No statistically significant association of CD44 was seen with age, side of tumor, lymph node metastasis, lymphovascular invasion, ductal carcinoma in situ and Ki67, and HER2neu expression. Conclusion: A high CD44 expression in breast carcinoma correlates with aggressive tumor characteristics such as multifocality, negative ER/PR expression, and belonging to the basal subtype which is associated with poor prognosis. Conversely, low CD44 expression is linked to Luminal A and Luminal B subtypes which have good prognosis. These indicate the role of CD44 as a prognostic biomarker in the carcinoma breast.

The effect of obesity on the outcomes of laparoscopic adrenal surgery in patients with Cushing syndrome.

The aim of this study is to investigate the effect of obesity on the results of laparoscopic adrenal surgery in patients with Cushing syndrome. This retrospective study was performed in Department of General Surgery at Erciyes University School of Medicine between January 2010 and January 2023. Our analysis included Cushing syndrome patients who underwent unilateral laparoscopic adrenalectomy (LA) with the transabdominal lateral approach. All patients were evaluated in terms of age, sex, tumor diameter, body mass index (BMI), American Society of Anesthesiologists physical status classification, morbidities, surgery history, tumor side, operative time, conversion to open surgery, complications, and length of hospital stay. A total of 90 patients (75 females and 15 males) underwent a transperitoneal LA. Patients were divided into 2 groups according to their BMI: obese group (≥30 kg/m2; n = 53, 58.8%) and nonobese group (<30 kg/m2; n = 37, 41.2%). All patients were classified into 3 subgroups: obese patient group, BMI ≥30-39 kg/m2 (n = 23); morbidly obese patient group, BMI ≥40 kg/m2 (n = 14); and nonobese patient group, BMI <30 kg/m2 (n = 53). There was no significant difference in intraoperative complications, conversion to open surgery, operative time, or length of hospital stay between the groups. Only conversion to open surgery was a risk factor for postoperative complications in univariate and multivariate analyses (odds ratio, 15.4; 95% confidence interval, 1.277-185.599; P = 0.031). Our results showed that LA is safe and effective in patients with Cushing syndrome with morbid obesity, allowing acceptable morbidity and length of hospital stay.

Minimally invasive pancreaticoduodenectomy for circumportal pancreas: literature review and report of two type IIIA cases

BackgroundCircumportal pancreas is a rare morphological variant with clinical significance due to the high risk of postoperative pancreatic fistula in patients undergoing pancreaticoduodenectomy. Type IIIA (suprasplenic anteportal) is the most common type of circumportal pancreas. We present two cases of type IIIA treated with minimally invasive pancreaticoduodenectomy, and review the literature on patients with circumportal pancreas who underwent pancreatic surgery.Case presentationCase 1: Laparoscopic Pancreaticoduodenectomy for Non-functioning Pancreatic Neuroendocrine Neoplasm with Circumportal Pancreas. A 69-year-old female with no prior medical history presented with a pancreatic head mass detected during routine ultrasound. CT revealed a 20 mm hypervascular tumor in pancreas head and a suprasplenic circumportal pancreas with an anteportal duct. The main pancreatic duct (MPD) was not in the parenchyma on the dorsal side of the portal vein (PV). Laparoscopic pancreaticoduodenectomy was performed. The anteportal side was resected with an ultrasonic device, and the retroportal side with a mesh-reinforced stapler. Pancreaticojejunostomy was performed without complications. Case 2: Robot-assisted Pancreaticoduodenectomy for Pancreatic Head Cancer and Non-functioning Pancreatic Neuroendocrine Neoplasm in the pancreatic tail with Circumportal Pancreas. A 72-year-old male with no prior medical history presented with a dilated main pancreatic duct on ultrasound. Diagnosed with pancreatic head cancer (Stage IIA), he underwent neoadjuvant chemotherapy. Contrast-enhanced CT revealed pancreatic cancer in the head and a tumor in the tail with unknown pathology. Robot-assisted pancreaticoduodenectomy was performed, and pancreatectomy on the left side of the tail tumor was planned. Intraoperative findings revealed a circumportal pancreas with the MPD not running through the dorsal parenchyma. After resected the parenchyma on the left side of the tail tumor, parenchyma on the dorsal side of the PV was dissected using SynchroSeal®. Pancreaticojejunostomy was performed without complications. The postoperative course was uneventful.ConclusionsThe optimal location and method of pancreatic resection should be selected according to the type of circumportal pancreas and the location of the lesion to be resected to minimize the risk of pancreatic fistula. Minimally invasive surgery for circumportal pancreas remains challenging even for surgical teams with sufficient experience and skills, and careful consideration are necessary for its application.

Implications of TP-positive CAFs in the Bone Invasion of Oral Squamous Cell Carcinoma.

Cancer-associated fibroblasts (CAFs) have recently been suggested as critical cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms and subtypes related to their bone-invasive function are unclear. This study investigated the implications of thymidine phosphorylase (TP)-positive CAFs (TP+CAFs) in OSCC bone invasion. TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TP+CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models. In bone-invasive OSCC tissues, TP+CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TP+CAFs were significantly associated with higher T-stage, bone invasion, and worse overall survival and recurrence-free survival in our study cohort. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, related to bone resorption. In the PDX mouse models, TP+CAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TP+CAFs than in those without. TP+CAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides insights into cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.

Does bilateral Wilms’ tumor involving the collecting system in children have a worse prognosis?

BackgroundThe literature on nephron-sparing surgery (NSS) in children with bilateral Wilms’ tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence.MethodsPatients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed.ResultsSeventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902).ConclusionsTo preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.

Retrospective Study of Clinicopathologic Features and Outcome of Colonic Cancer in Relation to Primary Tumor Location

Abstract Background Colon cancer is one of the most common cancers worldwide and outcomes of colon cancer are different according to the primary tumor location and could be considered as distinct disease entities of the same organ. Objectives Analyzing and comparing clinical, epidemiological, pathologic features and outcome of colon cancer according to primary location whether the patients are right sided colon cancer (RSCC) and left sided colon cancer (LSCC) patients in different situations. Patients and Methods This is a retrospective, descriptive and analytical study conducted between January 1st, 2013 and January 1st 2019. One hundred and fifty patients diagnosed with colon cancer were enrolled in GIT unit, Department of Clinical Oncology, Ain Shams University Hospital. Results In our study right sided colon cancer patients were more females and clinically presented with higher frequency of anaemia (P value = 0.001) and perforation (P value = 0.02). Left sided colon cancer on the other side were more males (P value = 0.032) and was associated with more constipation (P value &amp;lt;0.001) and intestinal obstruction (P value = 0.085). RSCC was more associated mucinous adenocarcinoma, more advanced T stage (T4), lymphovascular invasion, larger tumor sizes and more poorly differentiated tumor. LSCC was associated with more advanced stage and lymph node positivity. Right side tumor has highest disease-free survival period which is 34.63 months (95% confidence interval [CI] 28.39-40.86) comparing with the left side tumor which was 24.94 months (95% confidence interval [CI] 19.61-30.27). left side tumor has highest progressive free survival period which is 4.77 months (95% confidence interval [CI] 3.33-8.22) comparing with the right-side tumor which was 2.21 months (95% confidence interval [CI] 0.63-3.79). Conclusion RSCCs and LSCCs show different characteristics in clinical presentation and prognostic features, so we can consider the side of tumor is helpful in determining the behavior and the outcome of the disease. We can consider RSCC and LSCC as two separate disease entities.

The role of intraoperative central lymph node biopsy in the treatment of clinically low-risk PTMC.

To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative nodes (cN0) papillary thyroid microcarcinoma (PTMC) without extra-glandular invasion. The clinical data of 465 patients were collected retrospectively. Part of prelaryngeal, pretracheal and ipsilateral paratracheal lymph nodes were taken for frozen pathological examination during the operation. Then the thyroid lobe on the tumor side and isthmus were excised, and central neck dissection of the affected side was performed in all patients. The number of metastases in entire central lymph nodes of the affected side can be obtained by postoperative paraffin pathology. If the number of positive lymph nodes during surgery is ≥3, contralateral gland resection was performed. In this group of 465 patients, there were 186 cases with central lymph node metastasis. The Kappa coefficient of consistency between frozen pathology and paraffin pathology in central lymph nodes was 0.605. The ROC curve for the number of intraoperative frozen metastases-postoperative pathological metastases over 5 showed that the AUC of the curve was 0.793, while the maximum Youden index was 0.5259, whose corresponding number of positive lymph nodes was 3. Intraoperative central lymph nodes biopsy can be used as an important indicator for the status of central lymph node metastasis in unilateral cN0 PTMC patients without extra-glandular invasion and a determinant for central lymph node dissection. While the number of positive lymph nodes intraoperatively is ≥3, total thyroidectomy should be considered.

A Comparative Study Between Pemetrexed and Taxanes as First Line Treatment of Metastatic Lung Adenocarcinoma

Background: Adenocarcinoma of the lung is the most common type of lung cancer. Platinum agents in combination with other chemotherapy are currently the cornerstone for chemotherapy of advanced cases with metastasis. Objective: To compare the response rate of pemetrexed doublets versus taxanes doublets in patients with metastatic lung adenocarcinoma. Patients and Methods: This a prospective study that included 60 patients with pulmonary adenocarcinoma. Those patients received a platinum based doublet chemotherapy with additional treatment protocol; combined with either pemetrexed or taxanes (paclitaxel or docetaxel) with 30 patients in each arm. Tumor size, response rate and side effects of chemotherapy were evaluated in both arms. Results: The median reduction in tumor size in pemetrexed and taxan arms were 4.72 cm2 and 6.53 cm2 respectively. Nausea, fatigue, constipation and anorexia were more common in pemetrexed arm, while leukopenia, arthralgia and peripheral neuropathy were more common in taxan arm. Conclusion: Serious side effects such as leukopenia, and peripheral neuropathy were more common in taxan than pemetrexed arm. Pemetrexed is preferable to use as a fist line treatment for patients with metastatic adenocarcinoma of the lung. Keywords: Adenocarcinoma, Pemetrexed, Taxanes, metastatic lung cancer.

A Comparative Study Between Pemetrexed and Taxanes as First Line Treatment of Metastatic Lung Adenocarcinoma

Background: Adenocarcinoma of the lung is the most common type of lung cancer. Platinum agents in combination with other chemotherapy are currently the cornerstone for chemotherapy of advanced cases with metastasis. Objective: To compare the response rate of pemetrexed doublets versus taxanes doublets in patients with metastatic lung adenocarcinoma. Patients and Methods: This a prospective study that included 60 patients with pulmonary adenocarcinoma. Those patients received a platinum based doublet chemotherapy with additional treatment protocol; combined with either pemetrexed or taxanes (paclitaxel or docetaxel) with 30 patients in each arm. Tumor size, response rate and side effects of chemotherapy were evaluated in both arms. Results: The median reduction in tumor size in pemetrexed and taxan arms were 4.72 cm2 and 6.53 cm2 respectively. Nausea, fatigue, constipation and anorexia were more common in pemetrexed arm, while leukopenia, arthralgia and peripheral neuropathy were more common in taxan arm. Conclusion: Serious side effects such as leukopenia, and peripheral neuropathy were more common in taxan than pemetrexed arm. Pemetrexed is preferable to use as a fist line treatment for patients with metastatic adenocarcinoma of the lung.

Optimal Surgical Approaches for Thyroid Cancer: A Comparative Analysis of Efficacy and Complications.

BACKGROUND Completion thyroidectomy (CTx) is performed following hemithyroidectomy (HTx) when the risk of malignancy persists or is discovered postoperatively. Different surgical approaches, including CTx after HTx (CTx-HTx), total thyroidectomy (TTx), and revision surgery after TTx (RTx-TTx), offer varying risks and benefits, including pathological outcomes and complication rates. Understanding the predictors and rates of malignancy in these procedures is crucial for optimizing surgical management of thyroid disorders. MATERIAL AND METHODS This retrospective study analyzed data from January 2014 to October 2019, including 60 patients each in the CTx-HTx and TTx groups, and 47 in the RTx-TTx group. The CTx-HTx group was subdivided based on benign or malignant findings in CTx specimens. Clinicodemographic data and pathological features such as tumor type, size, side, capsular and vascular invasion, extrathyroidal spread, multifocality, and lymph node metastasis were reviewed. RESULTS Age and sex distributions were similar across groups. In the CTx-HTx group, 76.7% of specimens were benign and 23.3% malignant. No significant predictors of malignancy were found between the benign and malignant subgroups in univariate and multivariable analyses. In the TTx group, 75.0% of initial lobes and 13.3% of contralateral lobes were malignant. TTx was associated with a significant postoperative decrease in calcium and longer hospital stays. Multivariable analysis identified TTx as an independent risk factor for hypocalcemia. CONCLUSIONS Reducing overtreatment in thyroid cancer may involve limiting CTx after HTx and considering more conservative initial surgeries, particularly when indications for TTx are not definitive.

The clinical significance of PRMT8 expression in esophageal squamous cell carcinoma and the influence on prognosis.

e16066 Background: Protein arginine methyltransferase 8 (PRMT8), a member of protein arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical post-translational modications (PTMs). Esophageal squamous cell carcinoma (ESCC) is the third most common cancer type of the gastrointestinal tract with poor prognosis. Abnormal arginine methylation modifications are closely associated with the development of ESCC and can exert oncogenic effects by regulating a variety of cellular processes. However, the expression of PRMT8 in ESCC and its influence on prognosis is currently unknown. Methods: After passing the application and obtaining the approval of the hospital ethics review committee and obtaining the informed consent of all patients and their families, we collected 46 cases of renal cell carcinoma diagnosed in the Fourth Hospital of Hebei Medical University from 2018 to 2023, and postoperative pathological reports of all patients confirmed to be ESCC. We followed the selected patients and obtained complete data. All the pathological specimens of the selected patients were resectioned and then subjected to immunohistochemical examination to observe the expression differences of PRMT8 in ESCC, and parallel semi-quantitative analysis. Finally, the data of the patients were statistically built. Results: PRMT8 is mainly stained on the plasma membrane of tumor cells. The difference in expression levels between ESCC and normal tissue adjacent to the cancer was statistically significant (P &lt; 0.01). This study found that the patient’s gender, age, tumor side have no correlation with the expression levels of PRMT8 (P &gt; 0.05), while the three indicators of tumor size, TNM stage, and lymph node metastasis are positively correlated with the expression levels of PRMT8 and the difference is statistically significant (P &lt; 0.01). Moreover, the positive staining of PRMT1 in ESCC was significantly correlated with poor prognosis of ESCC patients. Conclusions: The expression of PRMT8 is highly expressed in ESCC and associated with aberrant clinicopathological characteristics and poor prognosis. PRMT8 is a potential target for the stratification and treatment of ESCC.

Phase II randomized study of maintenance therapy with regorafenib (REGO) versus placebo after first-line platinum and fluoropyrimidines-based chemotherapy in HER2 negative locally advanced/metastatic gastric (GC) or gastroesophageal junction (GEJ) cancer: Results of a-MANTRA study (GOIRC-05-2016).

4056 Background: REGO is an oral multi-targeted TKI that showed promising activity in advanced HER2-neg gastric cancer pts. The a-MANTRA study aimed to evaluate the efficacy and safety of REGO as maintenance after first-line (1L) therapy in advanced GC/GEJ tumors. Methods: This is a randomized, double-blind, placebo-controlled, multicenter Phase-II study in which HER2 neg advanced GC/GEJ pts with disease control after 1L platinum and fluoropyrimidines-based therapy, were randomized (1:1 ratio) to receive maintenance placebo (ARM A) or REGO (ARM B) starting at 80 mg with an escalation up to 160 mg (once daily on d1-21 q28 days), until intolerance or PD. The primary endpoint was Progression Free Survival 1 (PFS1). Two-sided 80% CIs were calculated to detect HR of 0.57, using a one-sided α=0.10 to have 90% power, translating to 3 months of improvement in mPFS. 118 subjects were required to observe 88 events. The interim analysis (IA) was planned after 44 events. Results: 67 pts were randomized in 18 Italian Cancer Centers; 64 pts (33 in ARM A and 31 in ARM B) received treatment. Most of the pts were male (64.1%), Caucasian (96.8%), ECOG PS 0 (81.2%), and median age 66 (40-80) yrs; the main primary tumor side was proximal (64.1%) with intestinal subtype (54.7%). Peritoneum metastases were present in 42.2%. IA showed a 98% probability of achieving a positive and statistically significant result for mPFS1. The study was stopped early due to the introduction of ICIs as 1L in PD-L1-positive pts. The objective responses to 1L chemotherapy were RP (50.0%), SD (42.2%), and CR (7.8%). At a median follow-up of 31 months (IQR 19.1-33-8), 28 (84.8%) and 26 (83.8%) events for each arm were reported. The main reason for discontinuation was PD (66.7% and 35.5%). The mPFS was 3.91 (80% CI, 2.27-5.98) and 5.19 months (80% CI, 4.0-7.26) with HR= 0.736 (80%CI, 0.51-1.04; p=0.1318). The mOS was 11.25 and 16.97 months (80%CI, HR=0.596 [0.318-1.103], p=0.1003). The most common G3-4 toxicities in ARM A and B were fatigue (3.0 vs 6.4%), thrombocytopenia (3.0 vs 3.2%), hand-foot syndrome (0 vs 12.9%), diarrhea and skin rash (0 vs 3,2%, respectively). Conclusions: Despite the promising trend, considering the sample was not sized for the statistical study hypothesis, REGO maintenance therapy after 1L chemotherapy did not reach statistically significant results in mPFS1. No significant safety concerns were raised. New study designs following the REGO with ICIs are currently underway. Clinical trial information: NCT03627728 .

Survival impact of KRAS mutation in metastatic colorectal cancer (mCCR) under first-line treatment.

3547 Background: Activating mutations in the MAPK pathway are predictive biomarkers in mCCR and 50% of patients (pts) present KRAS mutations. There is a large spectrum of molecular aberrations with a lack of data regarding tumor side correlations and their impact on treatment response and overall survival. Methods: Retrospective cohort of mCRC pts and KRAS activating mutations treated between 2019-2022 in a tertiary cancer center in Brazil. KRAS gene was analyzed by next-generation sequencing in tumor tissue samples. Electronic medical records were reviewed with case report forms registered in RedCap software. The primary endpoint was Overall survival (OS), estimated using Kaplan-Meir and compared with the log-rank test. Cox proportional models were applied to estimate hazard ratios (HR). Results: We included 490 patients with a mean age of 59 years (y), mostly male, 51.4%. Primary left-side location was present in 65.5% and liver metastasis in 66.7%. The spectrum of KRAS mutations found were G12D (31.2%), G12V (20.2%), G13D (15.1%), G12C (9.4%), G12A (4.9%), G12S (3.5%), and G12R (2%). First line regimen was 5-FU and Oxaliplatin (mFLOX) in 84.9% (n=388), with a median PFS of 9.2 months (95%CI 7.8 - 11.6) and OS of 21 months (95%CI;19-23) in this group. Treatment related outcomes in first-line therapy at first evaluation were 40% partial response, 20.4% stable disease, 30,9% disease progression and 1.3% complete response. G12S mutation was associated with better PFS 18.62 vs. 8.75m compared with other codon mutations (HR:0.52;95%CI 0.28-0.98) and OS NR vs. 21.58m HR (HR:0.48;95%CI;0.24-0.97). G12R was associated with worse PFS 5.31 vs. 9.90 m (HR:2.2;95%CI;1.09-4.47) and OS 17.89 vs. 21.88m (HR:1.61;0.79-3.24). Sideness was not associated with prolonged response or overall survival right-sided tumors 20.72 vs. vs. left-sided tumors 22.14m (HR:1.04;95%CI;0.82-1.31). Conclusions: Specific mutated codons in the KRAS gene impact PFS and OS independently of primary tumor sidedness. G12S mutation demonstrated an improved OS and PFS. [Table: see text]

Oral microbiome sequencing revealed the enrichment of Fusobacterium sp., Porphyromonas sp., Campylobacter sp., and Neisseria sp. on the oral malignant fibroma surface of giant panda.

Microbial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host-microbiota dynamics in various health contexts. In this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma. We observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side. This study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas.