Tumor Side Research Articles

Clinical features and pathogenesis of scoliosis due to spinal astrocytoma.

The aetiology of scoliosis remains unclear. Some studies have focused on the theory of possible muscular imbalance. The role of the spinal cord, which directly innervates the paraspinal muscles, in muscular imbalance has not yet been studied. Spinal astrocytomas often grow on one side of the spinal cord, destroying it asymmetrically. Asymmetrical damage to the spinal cord can lead to asymmetrical changes in paraspinal muscles. The present study investigated the effect of muscular imbalance on scoliosis by observing scoliosis caused by spinal astrocytomas. Patients diagnosed with spinal astrocytomas in a single centre were analysed, and the type and side of the symptoms, sagittal tumour position, scoliosis, end vertebrae and apical vertebrae of scoliosis were recorded. The tumour side was assumed from symptom type and side, and the cross-sectional area of the paraspinal muscles on both sides of the end vertebra was outlined and compared. The incidence of astrocytoma-induced scoliosis was significantly higher in patients with unilateral symptoms. The inferred tumour side was highly consistent with the convex side of scoliosis. The distal vertebral segments of scoliosis were consistent with the spinal cord segments involved in the astrocytomas. The apical vertebrae were more caudal in astrocytoma-induced scoliosis. The cross-sectional area of the multifidus muscle on the convex side of apical-level scoliosis was significantly smaller than that on the concave side. However, no significant differences were observed in the erector spinae muscles. Overall, spinal astrocytomas can cause asymmetric destruction of the corresponding spinal cord segment, resulting in asymmetric atrophy and weakness of the multifidus muscle innervated by the spinal cord segment, thereby causing scoliosis that is convex to the weaker side. This mechanism involves asymmetric lower neuron paralysis of the multifidus muscle. This is a type of scoliosis with several differences from idiopathic scoliosis.

Primary tumour side as a driver for treatment choice in RAS wild-type metastatic colorectal cancer patients: a systematic review and pooled analysis of randomised trials

BackgroundRetrospective subgroup analyses of previous trials in the first-line therapy of RAS wt metastatic colorectal cancer (mCRC) suggested a predictive impact of primary tumour side on the efficacy of anti-epidermal growth factor receptor (EGFR) agents. Recently, new head-to-head trials of doublets/bevacizumab versus doublets/anti-EGFR, PARADIGM and CAIRO5 were presented. Patients and methodsWe searched for phase II and III trials comparing doublet chemotherapy plus an anti-EGFR or bevacizumab as the first-line treatment for RAS wt mCRC patients. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and radical resection rate result in the overall study populations and, according to the primary side, were pooled together in a two-stage analysis with random effects and fixed effect models. The interaction between sidedness and treatment effect was then analysed. ResultsWe identified five trials (PEAK, CALGB/SWOG 80405, FIRE-3, PARADIGM and CAIRO5), including 2739 patients, 77% left- and 23% right-sided. Among patients with left-sided mCRC, the use of anti-EGFRs was associated with higher ORR (74% versus 62%, OR = 1.77 [95% confidence interval {CI} 1.39–2.26–0.88], p < 0.0001), longer OS (hazard ratio [HR] = 0.77 [95% CI 0.68–0.88], p < 0.0001) and not significantly longer PFS (HR = 0.92, p = 0.19). Among patients with right-sided mCRC, the use of bevacizumab was associated with longer PFS (HR = 1.36 [95% CI 1.12–1.65], p = 0.002) and not significantly longer OS (HR = 1.17, p = 0.14). A subgroup analysis confirmed a significant interaction effect between the primary tumour side and treatment arm in terms of ORR (p = 0.02), PFS (p = 0.0004) and OS (p = 0.001). No differences in the radical resection rate were found according to treatment and sidedness. ConclusionsOur updated metanalysis corroborates the role of the primary tumour location in the choice of the upfront therapy for RAS wt mCRC patients, leading to strongly recommend anti-EGFRs in left-sided tumours and to prefer bevacizumab in the right-sided.

Clinicopathological significance and prognostic role of LAG3 + tumor-infiltrating lymphocytes in colorectal cancer; relationship with sidedness

BackgroundIt is well-documented that the interplay between tumor-infiltrating lymphocytes (TILs) and tumor cells is a major determining factor in cancer progression. CD45RO seems to be a reliable indicator for predicting prognosis and disease outcome, along with CD3 and CD8 markers. LAG-3 is another important marker that overexpresses on TILs in a variety of cancers and is associated with disease prognosis; however, its prognostic impact is controversial. Hence, in the present study, we aimed to investigate the presence of CD45RO + , LAG3 + , CD3 + , and CD8 + lymphocytes in CRC tumor tissues and their association with clinicopathological parameters of the disease as well as patients' survival, according to primary tumor locations.MethodsExpression of CD45RO, LAG3, CD3, and CD8 was immunohistochemically assessed in tissue sections of 136 patients with CRC. The percentages of TILs expressing these markers were then separately determined in both invasive margin (IM) and center of tumor (CT). Their associations with clinicopathological factors and patients’ survival were analyzed in the entire cohort and the subgroups of patients with right- and left- rectum tumors.ResultsBased on our observation, CD45RO + and CD3 + cells were the most frequent infiltrated lymphocytes in both CT and IM regions of colon tumor tissue. Whilst, LAG3 + lymphocytes were the least frequent subset in both areas. Statistical analysis indicated that the frequency of CD45RO + TILs was positively associated with advanced TNM stages (III/IV), in the entire cohort and right-sided tumors (P < 0.05). LAG3 + TILs in IM were also increased in tumor tissues with higher T-stages in the entire cohort (P = 0.027). In univariate analysis, high score of CD45RO + TILs in IM was associated with better overall survival in the entire cohort. High score of CD8 + and CD45RO + lymphocytes in IM were also associated with improved survival in patients with right-sided tumors.ConclusionsOur findings generally suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD45RO and LAG3 depends on the primary tumor sides. Our results collectively demonstrated that infiltration of CD45RO + lymphocytes in IM could be an independent prognostic factor in a site-dependent manner.

Three dimensional condylar positional and morphological changes following mandibular reconstruction based on CBCT analysis: a prospective study

ObjectiveThis study aimed to evaluate the condylar positional changes following mandibular reconstruction with preservation of the condylar head using Cone-Beam Computed Tomography (CBCT). Also, to assess joint space changes and the overall volumetric space compared to the preoperative status.MethodologyThis prospective study included 30 patients (60 joints) subjected to unilateral mandibular resection and reconstruction with preservation of the condylar head. The Helkimo index and preoperative (T1), two weeks postoperative (T2), and follow-up CBCTs (T3) after at least six months were gathered and processed to evaluate the condylar position and TMJ joint space using Anatomage Invivo 6. A student’s t-test and repeated-measures ANOVA statistics were used. A P value of less than 0.05 was considered statistically significant.ResultsThirty patients (14 males, 16 females) with a mean age of 40.01 ± 12.7 years (a range of 18.1–62.9 years) were included. On the tumor side, there were significant variances in the vertical and mediolateral condylar positions between the three-time points (T1, T2, T3). Immediately after the operation, the condyles were significantly displaced in a downward direction at T2, which became larger after the last follow-up period (T3) (p = 0.007). The condylar positions at the anteroposterior direction were relatively stable without significant differences between the three times points (p = 0.915). On the non-tumor side, the condylar positions were relatively stable in the mediolateral and anteroposterior positions.In the tumor side, all of the TMJ spaces were significantly increased in size following the mandibular reconstructions (T2 and T3). However, on the non-tumor side, the anterior, posterior, and medial joint spaces were significantly changed postoperatively.ConclusionAfter mandibular reconstruction with condylar preservation, the condylar position and volumetric measurement immediately changed noticeably and continued to be a permanent change over time compared to relatively stable condyles on the non-tumor side. According to Helkimo index, patients become adapted to the postoperative changes without significant differences between the two sides.

Hyaluronic acid-targeted protein capped AMSN for inhibiting tumour growth and side effects by the controlled release of curcumin and doxorubicin

Ample attention has focused on Hyaluronic acid (HA) targeted Soy protein (SOY) capped Aminated Mesoporous Silica (AMSN), a novel combinatorial approach for the effective co-delivery of curcumin (CUR) and doxorubicin (DOX) for colon cancer. CUR was loaded in the inner core of AMSN via electrostatically followed by capping with SOY. HA acts as a targeting ligand and DOX carrier. The modified structural elucidation of drug carrier was done by FT-IR, XRD, DLS, EDX and BET adsorption isotherm. The morphological detection was carried out by FE-SEM, AFM and TEM analyses.The dual drug delivery system (DDDS) having maximum drug loading efficiency of 81.0 % for DOX and 70.0 % for CUR. The pH dependent release study shows maximum release (64.2 % CUR and 80.0 % DOX) at tumour pH. The effective haemolytic activity (<3.0 %) and antioxidant property (>70.0 %) reveal the practical applicability of DDDS. MTT assay shows 25.0 % anticancer activity in DLD-1 human colon cancer cell lines and no toxic to cardiac cells (H9C2), which was further confirmed by apoptosis assay. Material without drug shows < 90.0 % viability in (L929) normal cells confirmed the non-toxic nature and proved the novel potency towards drug delivery applications.

Effect of spatial transcriptomic-derived intrinsic epithelial signatures on immune cell recruitment and behaviour in the microenvironment of colorectal cancer.

251 Background: Colorectal Cancer (CRC) remains a significant healthcare problem. Interest in the role of the Tumour Microenvironment (TME) in progression and metastasis is established, yet much remains to be learned about the mechanism of immune cell recruitment to the TME of primary and metastatic tumours. The Klintrup Makinen (KM) score measures the density of immune infiltrate to the invasive edge of tumours and is associated with good prognosis in primary CRC. Neutrophil infiltration to metastases is a poor prognostic feature suggesting phenotypic differences in the TME at primary and metastatic sites. We set out to examine epithelial determination of the TME in primary CRC. Methods: 180 patient’s primary CRC from a curated TMA underwent deep phenotyping using a multiplex-immunofluorescent panel (DAPI, Panck, CD3 (T cells), FOXP3 (T regulatory cells), CD68 (Macrophages), CD163 (Tumour associated macrophage), CD66b (Neutrophils), KI67). The Nanostring GeoMx Spatial Transcriptomic platform was used to obtain segmented (Tumour: Panck+; TME: Panck-) whole transcriptomic (18000 genes) readout from 54 matched cores from the same TMA. Results: No significant association was demonstrated between immune cell density of any cell types and clinicopathological variables including tumour side, MMR status, N-stage or survival. High KM grade was associated with high CD3 (P = 0.01) and FOXP3 (P = 0.002). Density of all immune cell types were highly corelated. Spatial transcriptomic analysis of the segmented epithelium of patients with high KM grade demonstrated over-expression of known neutrophil chemo-attractant CXCL5 (log2FC 3.76 Adj.P &lt; 0.005). The TME compartments of cores with high CD68 and low CD163 counts were associated with adaptive immune co-ordination with high expression of CXCL13 (log2FC -2.97, Adj.P &lt; 0.005) and CD74 (log2FC -1.42 Adj.P 0.007). IGF2 (log2FC 6.08 Adj.P &lt; 0.005) and LCN15 (log2FC 4.96 Adj.P &lt; 0.005) were globally over-expressed in both TME and epithelium of cores with generalised low immune infiltration. The epithelial compartment neutrophil dense cores also over-expressed IGF2 (log2FC -3.53 Adj.P 0.02). Conclusions: TMAs provide a unique opportunity for broad transcriptomic phenotyping of large numbers of patients simultaneously. The Nanostring GeoMx platform is a flexible tool which can be used in novel ways with other proteomic technologies to drive deeper analysis of the TME. CXCL5 expression in the epithelial compartment drives global immune infiltration to the TME and may be manipulated in different contexts therapeutically through CXCR2 signalling in future.

First-line anti-EGFR or anti-VEGF therapy, tumour sidedness, and survival: Results from the South Australian (SA) Metastatic Colorectal Cancer (mCRC) Registry.

42 Background: The anti-EGFR monoclonal antibodies panitumumab (Pmab) and cetuximab (Cmab) and the anti-VEGF antibody bevacizumab (bev) have demonstrated clinical efficacy in mCRC in combination with first-line chemotherapy. Clinical and molecular characteristics, such as primary tumour sidedness, RAS, BRAF and MMR status are prognostic and predictive biomarkers for response to treatment. Our aim was to compare the survival and tumour characteristics of patients receiving first-line chemotherapy and antibody combinations using the SA mCRC Registry. Methods: This real-world registry has collected data from all patients diagnosed with mCRC in SA prospectively since 2006. We identified patients who had received first-line Pmab, Cmab or bev. Survival was analysed using the Kaplan-Meier method and log-rank test to compare outcomes based on primary tumour location. Results: Of the 5537 patients currently entered onto the registry, 1313 with RAS results available had received first-line anti-EGFR/VEGF antibodies and had colon tumour side recorded. The table summarises median overall survival (mOS) and patient characteristics. Survival was significantly shorter for those with right colon cancers (P &lt; 0.001). There were more high-grade (P &lt; 0.001), KRAS mutant (P = 0.004) and BRAF mutant (P = 0.036) tumours in those with right colon cancers, and a trend towards fewer curative liver resections (P = 0.059). There was no significant difference in mOS seen between Pmab, Cmab or bev for both left (P = 0.14) and right-sided (P = 0.88) primary tumours. Conclusions: There were more high-grade, BRAF and KRAS mutant patients with right colon tumours, and lower rates of liver resection, which may explain the significantly shorter mOS. The survival seen for Pmab and Cmab was almost identical for both right and left primary tumours. When comparing Pmab, Cmab and bev as first-line therapy, there was no significant difference in mOS for both left- and right-sided CRC. [Table: see text]

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases.

Patients who develop early extrahepatic recurrence (EHR) may not benefit from local treatment of colorectal liver metastases (CRLMs). This study aimed to develop a prediction model for early EHR after local treatment of CRLMs using a national data set. A Cox regression prediction model for EHR was developed and validated internally using data on patients who had local treatment for CRLMs with curative intent. Performance assessment included calibration, discrimination, net benefit, and generalizability by internal-external cross-validation. The prognostic relevance of early EHR (within 6 months) was evaluated by landmark analysis. During a median follow-up of 35 months, 557 of the 1077 patients had EHR and 249 died. Median overall survival was 19.5 (95 per cent c.i. 15.6 to 23.0) months in patients with early EHR after CRLM treatment, compared with not reached (45.3 months to not reached) in patients without an early EHR. The EHR prediction model included side and stage of the primary tumour, RAS/BRAFV600E mutational status, and number and size of CRLMs. The range of 6-month EHR predictions was 5.9-56.0 (i.q.r. 12.9-22.0) per cent. The model demonstrated good calibration and discrimination. The C-index through 6 and 12 months was 0.663 (95 per cent c.i. 0.624 to 0.702) and 0.661 (0.632 to 0.689) respectively. The observed 6-month EHR risk was 6.5 per cent for patients in the lowest quartile of predicted risk compared with 32.0 per cent in the highest quartile. Early EHR after local treatment of CRLMs can be predicted.

Renal cell carcinoma T staging: Diagnostic accuracy of preoperative contrast-enhanced computed tomography.

Renal cell carcinoma (RCC) accounts for 1-2% of all malignancies and is the most common renal tumor in adults. Imaging studies are used for diagnosis and staging. Tumor-Node-Metastasis staging strongly affects prognosis and management, while contrast-enhanced computed tomography (CECT) is regarded as a standard imaging technique for local and distant staging. The present study aimed to evaluate the accuracy of CECT for the preoperative staging of RCC by using surgical and pathological staging as the reference methods. This single-center prospective study was conducted between October 2019 and November 2021. The preoperative abdominal CT scans of patients suspected of having RCC were reviewed. Imaging data were collected, including tumor side and size, and perinephric fat invasion. Intraoperative notes were recorded, including the operation type, perinephric fat invasion, renal vein (RV) or inferior vena cava (IVC) tumor extension, and surrounding organ invasion. pathological data were collected on tumor size, RCC type, presence of clear margins, presence of renal capsule or perinephric fat invasion, renal sinus or pelvicalyceal system (PCS) invasion, segmental or main RV extension, and the involvement of Gerota's fascia and nearby organs. Preoperative CECT revealed that 42 out of 59 tumors had a greater maximum diameter than the pathological specimen, with an overall disparity of 0.25 cm. The specificity of CT for the detection of tumor invasion of the perinephric and renal sinus fat and PCS was 95%, and the sensitivity ranged from 80 to 88%. CT had an 83% sensitivity and a 95 specificity in detecting T4 stage cancer, with a 100% specificity for adrenal invasion. The concordance between radiographic and histological results for RV and IVC involvement was high, with specificities of 94 and 98%, and sensitivities of 80 and 100%, respectively. Overall accuracy for correct T staging was 80%. In conclusion, CECT is accurate in the local T staging of RCC, with high sensitivity and specificity for estimating tumor size and detecting extension to nearby structures and venous invasion.

CARCINOMA TESTIS PROFILE IN TERTIARY HOSPITAL

Objective: This study was undertaken to estimate the epidemiological characteristics, histological types, and subtypes of testicular neoplasm according to the WHO classification in our patient group. Material &amp; Methods: This was a retrospective study done over a period of ten years from January 2010 - December 2020 in our institution. Histopathological slides were retrieved and reviewed for tumour. Testicular Neoplasm patients who underwent orchidectomy and chemotherapy clinical data including the patient’s age, tumor location, tumor side, pathological finding, tumor marker, chemotherapy regiment, prognosis, chemotherapy response, and side effect were observed. All the data were analyzed descriptively and using SPSS 17.0. Results: A total of 31 cases of testicular and paratesticular neoplasm were encountered in our study with a mean age of 32.516.2 years. The highest incidence was 15-35 years old (48.3). Scrotum mass was the most frequent clinical presentation (70.96%) and left side became the predominant area (52%). Most of the patients come in late stage T3 (51.61%) and N3 (67.74%) with no metastatic process (70.96). The major pathological finding was Seminoma (64.51%), Teratoma (16.12), Yolk Sac (12.9%), Embryonal, and Mixed (3.22%). AFP, B-HCG, and LDH were elevated in some Seminoma, Teratoma, and Yolk Sac groups. The most wide chemotherapy used was 4 series BEP (87.09%). Patient prognosis highest incidence were Intermediate (70.96%). Most of the patients showed complete response (67.74) of chemotherapy. Nausea, vomiting, alopecia, and mucositis were observed as chemotherapy side effect in all patients. Conclusion: Testicular neoplasm peak incidence appears in young male. Most patients come to health care service in late stage. Seminoma become the highest testicular neoplasm incidence in our study. Elevated tumor markers were found in some patients. Four cycle BEP chemotherapy regiment showed great outcome for these patients.&#x0D; Keywords: Epidemiological, histological, testicular neoplasm.

SENP1 induced protein deSUMO modification increased the chemotherapy sensitivity of endometrial cancer side population cells

Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) μg/ml to (11.55±3.12) μg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.

Tumor Microenvironment and Microvascular Density in Human Glioblastoma

Glioblastoma (GBM) is a very aggressive form of cancer affecting the central nervous system. Although it occurs almost exclusively in the brain, glioblastoma can also appear in the brainstem, cerebellum, and spinal cord. It is characterized by high rates of proliferation, invasion, and necrosis. Moreover, GBM is a highly vascularized tumor and presents resistance to therapy. Recent data indicate that GBM cells are surrounded by a microenvironment (TME) which includes a complex network constituted of cellular/extracellular components and vessels able to influence both tumor growth and angiogenesis. In this retrospective study, we evaluated 30 bioptic specimens of adult patients diagnosed with IDH1 wild type GBM taken at the time of the first diagnosis. Each section has been divided into two experimental zones: the tumor side and the healthy surrounding tissue. We performed a series of immunohistochemical stainings with the purpose of evaluating the presence of total and M2 macrophages, CD4+-, CD8+-lymphocytes, and CD34+ microvessels. In addition, we have also evaluated the percentage of cells expressing bcl6 and p53 to determine any possible correlations with TME. Our data showed a significant increase in the total and M2 type macrophages, of CD4+ and CD8+ lymphocytes, and of CD34+ microvessels in the tumoral area respective to the healthy zone. We also confirmed our previous data showing the higher number of p53 and BCL6+ cells in the tumor area with a positive correlation between BCL6 and CD34+ microvessels. In conclusion, the data that came from this work support the important role played by microenvironment components in GBM progression. These results could contribute to the generation of new specific therapies useful in preventing GBM progression.

The predictive association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas: 4 decades follow up of 719 victims

BackgroundRespiratory diseases are the leading cause of morbidity and mortality in the survivors exposed to Sulfur Mustard (SM). The late abnormalities can be present as chronic bronchitis, tracheobronchial stenosis, asthma, bronchiectasis, airway narrowing, lung fibrosis, and lung cancers. This study aims to investigate the association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas.MethodsWe entered 719 victims exposed to SM during the Iran–Iraq war into our follow-up study in a consensus manner. They were periodically followed with Chest HRCT scans from 2001 to an interval of 2014–2019. The mean year interval between exposure and the last follow-up was 38 years. For confirming the lung cancer in those with evidence of malignancy in their imaging, fine needle aspiration/biopsy and/or surgical intervention were done.ResultsAmong 719 patients, 57% were free from any pathologic findings in their HRCT scan. Among the subjects who had the abnormal radiologic findings, Air Trapping (AT), Lung Fibrosis (LF), Bronchiectasis (B), and the evidence of lung cancer were found in 265 (36.9%), 207 (28.8%), 151 (21.0%), and 42 (5.8%), respectively. Adenocarcinoma (38.1%) was the most common type of cancer. The right lung was involved more than the left one regarding LF, B, and cancer (p value < 0.05). Considering the laterality, a significant correlation was found between the side of LF and B and the tumor side. Furthermore, it was shown that the lung lobes with LF were statistically correlated to tumor-involved lobes. The relative risk of AT and B existence for tumor development was 11.73 [4.87–28.26] and 10.14 [5.12–20.090], respectively. The most predictive finding was LF which caused the risk of developing tumor 17.75 [7.35–42.86] times higher in the patient with this pathology. By each increment of the number of LF and B, the risk of developing tumors increased by 51% and 76%, respectively.ConclusionIn survivors exposed to Sulfur Mustard, those with bronchiectasis and lung fibrosis have a significantly higher risk of developing lung cancers, so a close follow-up of these victims is recommended.Trial registration This study was confirmed by the institutional review board and ethics committee at Shiraz University of Medical Sciences (SUMS) with the ethical code IR.SUMS.MED.REC.1399.637.

The Impact of CD37 Ectoenzyme Expression in Benign and Malignant Colorectal Tumors.

The depth of invasion of colorectal cancer through the bowel wall provided the basis for pathological staging. The establishment of prognostic markers for CRC is important in the search for potential targets for therapeutic intervention. The cell surface nucleotidase (CD73) is an enzyme involved in tumor progression and metastasis. Its main function is to convert adenosine monophosphate (AMP) to adenosine. Preclinical studies suggest that CD73 can be targeted for cancer treatment. This study was designed to investigate the prognostic value of CD73 in malignant and benign colorectal tumors among Iraqi patients and its correlation with clinicopathological features using the immunohistochemistry (IHC) technique. In the current study, 60 cases of formalin-fixed paraffin-embedded (FFPE) tissues of colorectal tumors were collected from the Teaching Laboratories of Baghdad Medical City Teaching Hospital, Baghdad - Iraq & private labs in Baghdad. Of them, 52 were malignant, and 8 of benign cases. In addition, 10 cases of the non-pathological significance of colorectal tissues were used as a control group. This study's results revealed significant differences (P=0.001) in the expression of CD73 between malignant tumors and benign and non-significant pathology groups. The highest expression of CD73 was detected in 76.9% of malignant cases, while in the benign group, only 12.5% of cases showed weak positive expression for this marker. Furthermore, significant differences had been reported in CD73 expression with patients' age groups for malignant (P=0.0335), tumor side (P=0.0409), and tumor grade & stage (P=≤0.01). No significant differences had been seen between CD73 expression with tumor diameter and patients' gender.

The Role of Intraoperative Indocyanine Green (ICG) and Preoperative 3-Dimensional (3D) Reconstruction in Laparoscopic Adrenalectomy: A Propensity Score-matched Analysis.

Laparoscopic adrenalectomy (LA) is considered the "gold standard" treatment of adrenal lesions that are often coincidentally diagnosed during the radiologic workup of other diseases. This study aims to evaluate the intraoperative role of indocyanine green (ICG) fluorescence associated with preoperative 3-dimensional reconstruction (3DR) in laparoscopic adrenalectomy in terms of perioperative outcomes. To our knowledge, this is the first prospective case-controlled report comparing these techniques. All consecutive patients aged≥18 and undergoing laparoscopic transperitoneal adrenalectomy for all adrenal masses from January 1, 2019 to January 31, 2022 were prospectively enrolled. Patients undertaking standard LA and those undergoing preoperative 3D reconstruction and intraoperative ICG fluorescence were matched through a one-on-one propensity score matching analysis (PSM) for age, gender, BMI, CCI score, ASA score, lesion histology, tumor side, and lesion diameter. Differences in operative time, blood loss, intraoperative and postoperative complications, conversion rate, and length of stay were analyzed. After propensity score matching analysis, we obtained a cohort of 36 patients divided into 2 groups of 18 patients each. The operative time and intraoperative blood loss were shorter in patients of the 3DR group ( P =0,004 and P =0,004, respectively). There was no difference in terms of length of stay, conversion rate, and intraoperative and postoperative complications between the 2 groups. The use of intraoperative ICG in LA and preoperative planning with 3DR images is a safe and useful addition to surgery. Furthermore, we observed a reduction in terms of operating time and intraoperative blood loss.

A hint for the obesity paradox and the link between obesity, perirenal adipose tissue and Renal Cell Carcinoma progression

Increasing evidence supports a role for local fat depots in cancer outcomes. Despite the robust positive association of obesity with renal cell carcinoma (RCCa) diagnosis, increased adiposity is inversely related to RCCa oncological outcomes. Here, we sought to ascertain whether imagiologically assessed local fat depots associate with RCCa progression and survival and account for this apparent paradox. A retrospective cohort of renal carcinoma patients elective for nephrectomy (n = 137) were included. Beyond baseline clinicopathological characteristics, computed tomography (CT)-scans at the level of renal hilum evaluated areas and densities of different adipose tissue depots (perirenal, subcutaneous, visceral) and skeletal muscle (erector spinae, psoas and quadratus lumborum muscles) were analyzed. Univariate and multivariable Cox proportional hazards models were estimated following empirical analysis using stepwise Cox regression. Age, visceral adipose tissue (VAT) area and body mass index (BMI) predicted tumour-sided perirenal fat area (R2 = 0.584), which presented upregulated UCP1 expression by 27-fold (P = 0.026) and smaller adipocyte areas, compared with subcutaneous depot. Multivariate analyses revealed that increased area of perirenal adipose tissue (PRAT) on the contralateral and tumour side associate with improved progression-free survival (HR = 0.3, 95CI = 0.1–0.8, P = 0.019) and overall survival (HR = 0.3, 95CI = 0.1–0.7, P = 0.009). PRAT measurements using CT, might become a possible tool, well correlated with other measures of obesity such as VAT and BMI, that will improve determination of obesity and contribute to assess the risk for disease progression and mortality in renal cancer patients. Present data supports the obesity paradox in RCCa, assumed that larger PRAT areas seem to protect from disease progression and death.

NIMG-76. MORPHOLOGIC CHANGES TO THE HIPPOCAMPI FOLLOWING SURGICAL RESECTION AND ADJUVANT CHEMORADIATION IN PATIENTS WITH HIGH GRADE TEMPORAL GLIOMAS

Abstract BACKGROUND The hippocampus is known to remodel in pathologic conditions including epilepsy and Alzheimer’s disease. Literature investigating the effect of high-grade gliomas (HGGs) on the hippocampus following resection and adjuvant chemoradiation are limited; no study has evaluated these effects in tumors exclusively in the temporal lobe. METHODS A retrospective chart review was conducted on 30 patients with temporal HGGs who underwent craniotomy for resection with adjuvant RT and TMZ. Brainlab Elements was used to manually contour bilateral hippocampal gray matter volumes in the subgranular zone using T1-precontrast MRI sequences (1.5 mm thickness or less) pre-resection and at time of most recent follow up. These volumes were compared using a student’s t-test with significance set at p&amp;lt; 0.05. RESULTS Average follow up time was 23.5 months from initial resection. Average pre-treatment hippocampal volumes in this temporal glioma cohort compared to healthy controls from prior studies were 2.93 vs 2.83 cm3 (right, p=0.31) and 2.78 vs 2.76 cm3 (left, p=0.39) respectively. Pre vs post resection right hippocampal volumes in patients with right sided lesions were 2.59 vs 1.75 cm3 (p=.002). Left hippocampal volumes in patients with left sided tumors were 2.99 vs 1.64 cm3 pre and post resection respectively(p=0.0009). No significant differences in hippocampal volumes contralateral to the tumor side were found following treatment (p=0.31 and 0.07 for right and left hippocampi respectively). CONCLUSIONS Temporal gliomas are in close anatomic proximity to the hippocampi also may invade and/or disrupt local circuits which output to the hippocampi. Resection and chemoradiation are correlated with decreased hippocampal volumes ipsilateral to the primary locus of disease. Further characterization of hippocampal subregions, particularly the dentate gyrus, in addition to results of neuropsychiatric testing pre and post treatment are necessary to better elucidate the clinical implications of these morphologic changes and the putative functional networks which underlie them.

Endoscopic transoral resection of metastatic retropharyngeal lymph nodes in nasopharyngeal carcinoma via posteroinferior eustachian tube approach: a single center review study

Objective: To summarize the clinical experience and treatment results of endoscopic transoral resection of metastatic retropharyngeal lymph nodes (MRPLN) in nasopharyngeal carcinoma (NPC) via posteroinferior eustachian tube approach. Methods: The clinical data of 37 patients with NPC who underwent endoscopic transoral surgery via posteroinferior eustachian tube approach for MRPLN in Xuanwu Hospital, Capital Medical University from 2010 to 2020 were analyzed retrospectively. There are 28 males and 9 females, aged from 31 to 72 years. The clinicopathological features such as gender, age, primary tumor stage, stage, side and size of MRPLN were recorded and analyzed. The surgical procedures of endoscopic transoral resection of MRPLN via posteroinferior eustachian tube approach were described. The MRPLN resection, perioperative complications and follow-up results were also summarized. Results: The primary tumors of 37 cases were determined as rT1 stage in 2 cases, rT2 stage in 30 cases and primary T2 stage in 5 cases in this study. There were 33 cases of unilateral MRPLN(89.2%), 4 cases of bilateral ones (10.8%), 36 cases in N1 stage, and 1 case in N3 stage. Single lymph node was detected in 23 cases(62.2%), and 2-5 lymph nodes in 14 cases(37.8%). Endoscopic transoral surgery via posteroinferior eustachian tube approach was completed in all cases. Total MRPLN resection was obtained in 35 cases (94.6%) with one-stage operation, and subtotal resection was achieved in 2 cases whose MRPLN involved the wall of internal carotid artery. No serious complications occurred in the perioperative period. During the follow-up period (median follow-up period 53.1 months), no recurrence of MRPLN was observed in patients who received total resection. And 8 patients (21.6%) died from different causes. Conclusion: Endoscopic transoral surgery via posteroinferior eustachian tube approach for MRPLN is a practicable and effective surgical option, but the long-term effect still needs longer follow-up and summary of bulk cases.

Perioperative outcomes following robot-assisted partial nephrectomy in elderly patients.

To compare perioperative outcomes following robot-assisted partial nephrectomy (RAPN) in patients with age ≥ 70years to age < 70years. Using Vattikuti Collective quality initiative (VCQI) database for RAPN we compared perioperative outcomes following RAPN between the two age groups. Primary outcome of the study was to compare trifecta outcomes between the two groups. Propensity matching using nearest neighbourhood method was performed with trifecta as primary outcome for sex, body mass index (BMI), solitary kidney, tumor size and Renal nephrometery score (RNS). Group A (age ≥ 70years) included 461 patients whereas group B included 1932 patients. Before matching the two groups were statistically different for RNS and solitary kidney rates. After propensity matching, the two groups were comparable for baselines characteristics such as BMI, tumor size, clinical symptoms, tumor side, face of tumor, solitary kidney and tumor complexity. Among the perioperative outcome parameters there was no difference between two groups for operative time, blood loss, intraoperative transfusion, intraoperative complications, need for radical nephrectomy, positive margins and trifecta rates. Warm ischemia time was significantly longer in the younger age group (18.1min vs. 16.3min, p = 0.003). Perioperative complications were significantly higher in the older age group (11.8% vs. 7.7%, p = 0.041). However, there was no difference between the two groups for major complications. RAPN in well-selected elderly patients is associated with comparable trifecta outcomes with acceptable perioperative morbidity.

Practical Implications of KRAS Mutation Status and Sidedness of Primary Tumour in Patients with Colorectal Cancer and Synchronous Liver Metastases: A Subset Analysis of the CoSMIC Study.

Simple SummaryPatients presenting with liver metastases at the time of diagnosis of their colorectal cancer (termed ‘synchronous disease’) have a worse outcome than those whose disease is limited to the primary bowel tumour. There is evidence to show that patients with tumours on the right side of the colon have worse survival. Furthermore, mutations in the KRAS gene have also been shown to adversely affect outcome. This study explores the association between the side of the primary colorectal tumour in patients with synchronous disease and mutations in the KRAS gene on survival. We analyse a specific cohort of patients from the previously published CoSMIC study who presented with colorectal cancer and synchronous liver metastases and who had their colorectal tumour analysed for KRAS mutations. We find that for this cohort, neither mutations in the KRAS gene nor the side of the colon tumour influenced survival.Patients with colorectal cancer presenting with synchronous liver metastases have less favourable outcomes than those with primary-only disease. There is evidence of different genetic mutational signatures according to the sidedness of the primary tumour. KRAS mutations are key driver mutations in colorectal cancer progression. This post hoc analysis of the previously reported CoSMIC inception cohort explores the association between primary tumour sidedness and KRAS mutational status on the outcome of patients with colorectal cancer and synchronous liver metastases. Patients diagnosed with synchronous disease were recruited between April 2014 and March 2017 and, after exclusions, 83 patients undergoing colorectal primary KRAS mutation testing constituted the final study population. Data were collected prospectively on demographic profiles, treatment, and outcomes. Twenty-one patients (25%) had right-sided tumours and 62 (75%) had left-sided tumours, with 46 (55%) and 37 (45%) exhibiting wildtype and mutated KRAS, respectively. There was no difference in distribution of liver metastases by KRAS status (unilobar vs. bi-lobar; p = 0.58; Fisher’s Exact test) and no difference in 5-year survival according to KRAS mutation status (Log-rank test, p = 0.82) or tumour sidedness (p = 0.16). In summary, in this cohort of patients with colorectal cancer and synchronous liver metastases, neither KRAS mutation status nor tumour sidedness influenced survival.