Surgical Resection Specimens Research Articles

Expressions of NeuroD and GAP43 as diagnostic markers for olfactory neuroblastoma

ObjectiveOlfactory neuroblastoma (ONB) is often difficult to pathologically distinguish from other small round cell tumors (SRCTs) arising in the nasal cavities. Although there are several diagnostic markers used for differential diagnosis of ONB, these molecules are also expressed in various neuronal derived tumors. Here, we examined the expression of NeuroD, GAP43, and olfactory marker protein (OMP) in ONB and non-ONB SRCT to determine their utility in the differential diagnosis of ONB. MethodsTwenty-six patients diagnosed with and treated for ONB at Kobe University Hospital between 1997 and 2017 with formalin-fixed, paraffin-embedded biopsy or surgical resection specimens were included. The expressions of NeuroD, GAP43, and OMP were immunohistochemically examined in these 26 ONB specimens and specimens from 13 SRCTs arising in the nasal cavities for reference. ResultsAmong the 26 ONB samples, focal, patchy, and marked staining for NeuroD was observed in 4, 3, and 9 samples, respectively. Focal, patchy, and marked GAP43 staining was observed in 5, 3, and 11 samples, respectively. Consequently, marked positive staining for either NeuroD or GAP43 was observed in 54% (14/26) of ONBs. Among the 13 SRCTs, marked staining for NeuroD was observed in two small cell carcinomas, one undifferentiated carcinoma, and one neuroendocrine carcinoma, whereas marked positive staining for GAP43 was observed only in one undifferentiated carcinoma. No specimen in this study exhibited OMP staining. ConclusionsOur results suggest possible roles of GAP43 immunostaining in the differential diagnosis of ONB.

Application of immune enhanced organoids in modeling personalized Merkel cell carcinoma research

Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous cancer, with incidence of less than 1/100,000, low survival rates and variable response to chemotherapy or immunotherapy. Herein we explore the application of patient tumor organoids (PTOs) in modeling personalized research in this rare malignancy. Unsorted and non-expanded MCC tumor cells were isolated from surgical specimens and suspended in an ECM based hydrogel, along with patient matched blood and lymph node tissue to generate immune enhanced organoids (iPTOs). Organoids were treated with chemotherapy or immunotherapy agents and efficacy was determined by post-treatment viability. Nine specimens from seven patients were recruited from December 2018-January 2022. Establishment rate was 88.8% (8/9) for PTOs and 77.8% (7/9) for iPTOs. Histology on matched patient tissues and PTOs demonstrated expression of MCC markers. Chemotherapy response was exhibited in 4/6 (66.6%) specimens with cisplatin and doxorubicin as the most effective agents (4/6 PTO sets) while immunotherapy was not effective in tested iPTO sets. Four specimens from two patients demonstrated resistance to pembrolizumab, correlating with the corresponding patient’s treatment response. Routine establishment and immune enhancement of MCC PTOs is feasible directly from resected surgical specimens allowing for personalized research and exploration of treatment regimens in the preclinical setting.

Feasibility and outcomes of laparoscopic proximal gastrectomy with Kamikawa double-flap reconstruction for upper - third gastric cancer

Abstract Introduction: Laparoscopic Proximal Gastrectomy (LPG) is a priority selection for early cancer, submucosal tumor in the cardia location. However, the optimal method for reconstruction of intestinal circulation is still debated, especially regarding post-operative life quality. This study aimed to evaluate the feasibility, result and post-operativequality of life ofa LPG with double-flap technique for reconstruction of digestive tract using Kamikawa technique - double flap (DFT). Patients and method: A retrospective study was performed on 18 patients with early cancer, submucosal tumors in the 1/3 upper or cardia location undergoing LPG – DFT Kamikawa technique 5/2018 to 4/2022 at Digestive Surgery Department, University Medical Center, HCMC. We evaluated clinical data and operation results. Results: Median age was 52 years. The operating time was 265 minutes, and the mean time to perform anastomosis was 85 minutes. There were 4 with early-stage adenocarcinoma, 10 patients with GIST, and 4 with leiomyoma. All cases were free of cancer cells in the surgical resection specimens. There were no intraoperative complications or postoperative complications. There was no postoperative mortality. The mean follow-up time was 20,3 months. Quality of life improved over time: the scores at 6, 12, and 24 months were: 25.7 ± 11.6, 21.3 ± 6.2, and 19.6 ± 3.9, respectively. The average hospital stay was 6,3 days. Conclusions: LPG –DFT by Kamikawa technique is safe, feasible and patients quality of life were acceptable. Keywords: Gastric cancer, proximal gastrectomy, double-flap reconstruction, Kamikawa

Proposal of novel staging system CNM (Crohn's primary site, nodes, mesentery) to predict postoperative recurrence of Crohn's disease.

After oncologic resection, histological grading and staging of the tumor give important prognostic information about the future risk of recurrence and hence influence the subsequent management plan. Several studies and their meta-analysis have shown that various histological features (e.g., microscopic positive resection margins, plexitis, granuloma, mesenteric inflammatory activity) can predict postoperative clinical/endoscopic/surgical recurrence after resection in Crohn's disease (CD). Inclusion of mesentery in surgical resection specimens has been shown to reduce surgical recurrence after ileocolonic resection in CD. However, there is no uniform histopathological staging system for risk stratification in postoperative CD to systematically predict postoperative recurrence. This is because the prediction to date is based on clinical characteristics (smoking status, disease phenotype, surgical history). Histopathological predictors are still not adopted in routine clinical practice due to the lack of a uniform staging system, heterogeneity of published studies and lack of standardized definition of histological features. In this article, we attempted to incorporate all such histological features in a single histological staging system CNM (Crohn's primary site [resection margin positivity, plexitis, granuloma, depth of infiltration], nodes [presence of granuloma], mesentery [involved or not]) in surgical resection specimen in CD. The proposed CNM classification would help to enable systematic reporting, design future clinical trials, stratify postoperative recurrence risk and choose appropriate postoperative prophylaxis.

Mediastinal Staging with Endobronchial Ultrasound in Early-Stage Non—Small Cell Lung Cancer: Is It Necessary?

Herein we examine the need for minimally invasive mediastinal staging for patients with early-stage non-small cell lung cancer (NSCLC) using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Early NSCLC, stages 1 and 2, has a 5-year survival rate between 53 and 92%, whereas stages 3 and 4 have a 5-year survival of 36% and below. With more favorable outcomes in earlier stages, greater emphasis has been placed on identifying lung cancer earlier in its disease process. Accurate staging is crucial as it dictates both prognosis and therapy. Inaccurate staging can adversely impact surgical candidacy (if falsely "over-staged") or lead to inadequate treatment (if "under-staged"). Clinical staging utilizes noninvasive methods to evaluate the anatomic extent of disease; however, it remains controversial whether mediastinal staging of early NSCLC with radiological exams alone is sufficient. EBUS-TBNA has altered the landscape of invasive mediastinal staging and is a crucial component to improving confidence in lung cancer staging, specifically in early NSCLC. Radiographic occult lymph node metastasis identified upon review of surgical resection specimens of early NSCLC may support the argument to perform EBUS-TBNA in all cases of early-stage disease. Other data suggest that EBUS-TBNA could be spared in cases of peripheral cT1aN0 and cT1bN0 for which surgical resection with lymph node dissection is planned. By reviewing reported EBUS-TBNA outcomes in patients with early NSCLC, we aim to emphasize the necessity of staging with EBUS in this population.

Primary Osseous Leiomyosarcoma with Vertebral and Nodal Metastasis in a Young Woman: A Rare Case Report.

Introduction. Primary leiomyosarcoma of bone is rarely described in the literature. In young patients, the clinical and radiological features may mimic relatively common tumours like osteosarcoma. Vertebral and nodal metastasis from osseous leiomyosarcoma is extremely uncommon. Case presentation. A 25-year-old female presented with progressively increasing pain and swelling of the right knee. Clinical and radiological features were suggestive of osteosarcoma. Pre-operative biopsy showed a malignant spindle cell tumour. The surgical resection specimen showed features of leiomyosarcoma of the right proximal tibia. On further evaluation, the patient was found to have an L3-L4 vertebral lesion and histopathological evaluation showed a similar tumour. After 11 months of initial presentation, the patient had axillary lymph node metastasis. Conclusion. Primary osseous leiomyosarcoma should be considered as a differential diagnosis even in young patients presenting with meta-diaphyseal expansile malignant bony lesions. Histology and ancillary studies can confirm the diagnosis.

The Deubiquitinase USP13 Maintains Cancer Cell Stemness by Promoting FASN Stability in Small Cell Lung Cancer.

USP13 is significantly amplified in over 20% of lung cancer patients and critical for tumor progression. However, the functional role of USP13 in small cell lung cancer (SCLC) remains largely unclear. In this study, we found that the deubiquitinase USP13 is highly expressed in SCLC tumor samples and positively associated with poor prognosis in multiple cohorts. In vitro and in vivo depletion of USP13 inhibited SCLC cancer stem cells (CSCs) properties and tumorigenesis, and this inhibitory effect was rescued by reconstituted expression of wide type (WT) USP13 but not the enzyme-inactive USP13 mutant. Mechanistically, USP13 interacts with fatty acid synthase (FASN) and enhances FASN protein stability. FASN downregulation suppresses USP13-enhanced cell renewal regulator expression, sphere formation ability, and de novo fatty acids biogenesis. Accordingly, we found FASN expression is upregulated in surgical resected SCLC specimens, positively correlated with USP13, and associated with poor prognosis of SCLC patients. More importantly, the small molecule inhibitor of FASN, TVB-2640, significantly inhibits lipogenic phenotype and attenuates self-renewal ability, chemotherapy resistance and USP13-mediated tumorigenesis in SCLC. Thus, our study highlights a critical role of the USP13-FASN-lipogenesis axis in SCLC cancer stemness maintenance and tumor growth, and reveals a potential combination therapy for SCLC patients.

Anaplasia and multinucleation in metastases of oropharyngeal squamous cell carcinoma is associated with poorer outcomes.

The presence of tumor cell anaplasia and multinucleation (A/M) in oropharyngeal squamous cell carcinoma (OPSCC) has recently been found to be associated with increased disease recurrence and poorer disease-specific survival, regardless of human papillomavirus status. We studied the detection of A/M in cytology specimens. We performed a comprehensive data search for all patients with OPSCC diagnosed and treated at Northwestern Memorial Hospital between January 2013 and April 2020. All cytology and histopathologic slides were reviewed for the presence of A/M in patients with both surgical resection or biopsy specimens and fine needle aspiration cytology of a metastatic site. A total of 87 patients were identified with both surgical and cytology specimens available for review. A/M was identified in 21 cytology specimens and 14 surgical specimens. Cytologic A/M was seen in 11 of the 14 patients (78.5%) with corresponding histologic A/M and in 10 of the 73 patients (13.7%) without histologic A/M. Disease-specific survival was significantly worse for the patients with cytologic A/M regardless of the presence of histologic A/M (P = 0.0064) and for the patients with cytologic A/M only (P = 0.0271). In patients with p16-positive/human papillomavirus-associated carcinoma, disease-specific survival was significantly worse for the patients with both histologic and cytologic A/M (P=0.0305). A/M can be reliably identified in cytology specimens among all the various stains and preparations, irrespective of the primary tumor histologic type. Identification of A/M on cytology specimens could indicate more aggressive clinical behavior and help guide patient management.

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Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment

PurposesProgrammed death-ligand 1 (PD-L1) testing is performed mainly on biopsy specimens in patients with advanced lung cancer. It is questionable whether the small amount of tissue analysed in biopsies may represent the true PD-L1 expression of a tumour.MethodsIn this retrospective study, PD-L1 expression on tumour cells derived from bronchoscopy brush cytology, endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA), endobronchial biopsy, transbronchial biopsy (TBB) and computed tomography (CT)-guided transthoracic biopsy was compared to the PD-L1 expression of the corresponding surgical resection in lung cancer patients with regard to neoadjuvant treatment in-between.ResultsA quantitative comparison between the diagnostic biopsy of the primary tumour with corresponding resected surgical specimens in a total of 113 lung cancer patients (60% male, mean age 65 ± 9 years) revealed a statistically significant correlation of PD-L1 expression on tumour cells (r = 0.58, p< 0.001), for patients without neoadjuvant treatment in-between and for patients who underwent neoadjuvant treatment (both p < 0.001). Using a cut-off value of ≥ 50% PD-L1 TPS for comparing the biopsy samples and resected specimens, the concordance rate was 78% with a Cohen’s Kappa of 0.45.ConclusionA statistically significant concordance for PD-L1 expression on tumour cells between biopsies from primary lung tumour and resected specimen was found, but of uncertain clinical accuracy. The use of a cut-off value of ≥ 50% PD-L1 TPS resulted only in a moderate agreement. Therefore, the interpretation of the PD-L1 determined form biopsy specimens status should only be considered with caution for treatment decisionsQuery.

Abstract 1480: miR-21 as a post-transcriptional regulator of pancreatic ductal adenocarcinoma (PDAC) tumorigenesis

Abstract Introduction: MicroRNAs are short non-coding RNAs that are frequently dysregulated across cancers. Specifically, microRNA-21 (miR-21) is a known oncomir overexpressed in pancreatic adenocarcinoma (PDAC) that regulates multiple gene targets downstream of KRAS, the site of the primary driver mutation in PDAC. Past efforts to target mutant KRAS have been limited by compensatory activation of other growth pathways and treatment-related toxicity. Inhibiting miR-21 expression is a novel therapeutic strategy to target KRAS effector function through post-transcriptional regulation. We previously demonstrated that systemic inhibition of miRNA-21 (miR-21) intercepts tumorigenesis in the transgenic KrasG12D/+;Trp53R172H/+;Pdx-1-Cre (KPC) mice without causing overt toxicity. Our major goal was to verify the translation of the previous findings to human models and examine the mechanistic implications of miR-21 inhibition in PDAC. Experimental Procedures: Using publicly available data from a cohort of patients with PDAC in The Cancer Genome Atlas (TCGA), we performed differential expression analysis of miR-21 and KRAS-related gene targets as well as gene set enrichment analysis of oncogenic pathways identified by the Molecular Signatures Database (MSigDB). Concurrently, de-novo patient-derived organoid (PDO) models were generated from core biopsies and surgical resection specimens. To evaluate the effects of miR-21 inhibition on KRAS pathway activity in a human model system, we selected 6 PDO cell lines and determined miR-21 gene expression by quantitative PCR at baseline and after knockdown using a lentiviral construct. Results: Analysis of TCGA PDAC cohort identified heterogeneous endogenous expression of miR-21, which was validated ex vivo in our PDO model system. Gene set enrichment analysis revealed enrichment of gene sets associated with KRAS dependency, MEK, AKT, and MTOR signaling in patients with higher endogenous miR-21 expression. MiR-21 knockdown in PDO cell lines was stable at multiple intervals following lentiviral transduction. Further, expression of PDCD4, a tumor suppressor gene and target of miR-21 downstream of KRAS, was enhanced in PDO lines following miR-21 inhibition. Conclusions: We previously demonstrated that miR-21 appears to be an early and reliable molecular marker of pancreatic neoplasia and that systemic inhibition in a murine model intercepts PDAC tumorigenesis. We now demonstrate in human models that higher miR-21 expression is associated with enrichment of gene sets downstream of KRAS. Additionally, knocking down miR-21 expression enhances the expression of gene targets with tumor suppressor function, notably PDCD4. This suggests that modulating miR-21 expression subsequently modulates the expression of gene targets with critical cell regulatory functions and provides additional insight into novel therapeutic targets. Citation Format: Jacquelyn W. Zimmerman, Daniel H. Shu, Richard A. Burkhart, Joseph Tandurella, Elana J. Fertig, Elizabeth M. Jaffee. miR-21 as a post-transcriptional regulator of pancreatic ductal adenocarcinoma (PDAC) tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1480.

Abstract 1727: CD8+ T cells in the invasive margin combined with FOXP3+ T cells in the tumor center significantly associate with survival in resectable gastric cancer, a post-hoc analysis of the Dutch D1/D2 trial

Abstract Introduction: In gastric cancer, studies of tumor infiltrating lymphocytes as a prognostic biomarker show contradictory results. These results may be caused by use of variable immunohistochemistry (IHC) quantification techniques, different marker selections and particularly inconsistency in the evaluated tumor regions. To overcome these issues, we performed a comprehensive digital image analysis of 5 immune cell markers for their prognostic value in a cohort of gastric cancer patients who were treated with surgery only in the Dutch D1/D2 trial. Methods: All available surgical resection specimens of gastric cancer patients were included in this study (N=251). IHC for T-cell markers CD3, CD45RO, CD8, FOXP3 and Granzyme B was performed on serial slides. After manual annotation of the tumor area, an invasive margin was defined as 0.5 mm into the tumor still containing tumor cells (inner margin, IM) and 0.5 mm outside of the tumor not containing tumor cells (outer margin, OM). The density of positive immune cells (cells/mm2) was digitally quantified using QuPath for each 0.5x0.5 mm2 square across tumor center (TC), IM and OM, separately. A classification and regression tree (CART) model was employed to identify an optimal combination of prognostic markers from the continuous immune cell density variables with cancer specific survival (CSS) as outcome. Results: The CART decision tree identified CD8 OM (≥798 cells/mm2) as most dominant prognostic factor, followed by FOXP3 TC (≥20 cells/mm2) in the CD8 OM low subset. This resulted in 3 CART branches in the decision tree: CD8 OM high with best prognosis, CD8 OM low/FOXP3 TC high with intermediate prognosis, and CD8 OM low/FOXP3 TC low with worst prognosis (Log-rank P-value &amp;lt;0.0001). The CD8 OM high branch was enriched in EBV+ (38.2%) and MSI-high (17.6%) tumors, compared to the other two branches with poorer prognosis (4.2% and 3.4% for EBV+, 7.9% and 8.4% for MSI-high). The CART model was an independent predictor of CSS in a multivariable cox-regression (HR branch 2 vs 1: 4.87, 95% CI 1.96-12.07 and HR branch 3 vs 1: 7.97, 95% CI 3.20-19.86), which included T stage, N stage, Lauren subtype, EBV-status and MSI-status. The performance of the CART model was assessed by 5-fold cross-validation, where 4 out of 5 models reached a P-value &amp;lt; 0.05 (Likelihood-Ratio test). Conclusions: The OM in gastric cancer contains previously overlooked important prognostic information valuable for immune biomarker studies. The combination of CD8 OM and FOXP3 TC is identified as strongest prognostic factor in the risk stratification of resectable gastric cancer, and is independent of T stage, N stage, EBV-status, MSI-status and Lauren subtype. Moreover, high T-cell densities found in a proportion of EBV-/MSS tumors support further investigation of response to immunotherapy in these subgroups. Citation Format: Tanya T. Soeratram, Hedde D. Biesma, Jacqueline M. Egthuijsen, Elma Meershoek-Klein Kranenbarg, Henk H. Hartgrink, Cornelis J. van de Velde, Erik van Dijk, Yongsoo Kim, Bauke Ylstra, Hanneke W. van Laarhoven, Nicole C. van Grieken. CD8+ T cells in the invasive margin combined with FOXP3+ T cells in the tumor center significantly associate with survival in resectable gastric cancer, a post-hoc analysis of the Dutch D1/D2 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1727.

Management of residual nonretroperitoneal disease in nonseminomatous germ-cell tumors (NSGCT).

5034 Background: The management of NSGCT patients (pts) with post-chemotherapy residual non-retroperitoneal disease (RP) remains unsettled. Decisions for surveillance vs surgical resection are commonly steered by pathology from retroperitoneal lymph node dissection (RPLND). Data is limited in pts who do not require RPLND (normal or normalized RP post-chemo). Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT who completed first-line chemotherapy and had residual extra-RP disease without residual RP disease. Pts with post-chemo non-RP surgical resection were included. Results: 134 pts met eligibility. Median age at diagnosis was 28.6 (range, 16.2-51.5). Primary tumor predominant histology was embryonal (35.1%), mixed (25.4%), seminoma (2.2%), yolk sac (9.7%), choriocarcinoma (15.7%), teratoma (11.2%). 76 pts (56.7%) had teratoma in the primary tumor. Metastatic sites at diagnosis were RP (15.7%), mediastinal LN (8.2%), lung (28.4%), liver (11.2%), bone (6.7%), brain (21.6%). Those with RP mets at diagnosis had normalization of RP nodes after chemo. IGCCCG risk was good in 57, intermediate in 21, and poor in 56 pts. Median pre-chemo AFP was 66 (0.9-467,000). hCG was 960.5 (0.5-1,300,000). First-line chemo was BEPX4 in 68, BEPx3 in 29, EPX4 in 10, VIPX4 in 9, and other in 18 pts. All pts had surgical resection of non-RP disease. None had RPLND. 84 pts had lung nodule resection, 16 had mediastinal LN, 8 had cervical LN, 5 had liver, 6 had bone, and 20 had brain met resection. Of the 76 pts with teratomatous elements in the orchiectomy, 41 (53.9%) had teratoma and 24 (31.6%) had non-teratoma GCT in post-chemo non-RP surgical specimens. Of the 58 pts without teratoma in the orchiectomy, 9 (15.5%) had teratoma and 34 (58.6%) had non-teratoma GCT in the non-RP surgical resection specimens. Teratoma in the orchiectomy was a predictor of non-RP teratoma (Fisher’s exact test P&lt;0.0001). Conclusions: The presence of teratoma in orchiectomy predicts teratoma in residual post-chemo non-RP disease in pts who do not undergo RPLND. The absence of teratoma in orchiectomy should not preclude resection of residual non-RP disease given a subset of patients had persistent GCT. [Table: see text]

Application of near infrared fluorescence imaging in detection of residual cancer in oral squamous cell carcinoma

Objective: Local recurrence is the main cause of treatment failure in patients with oral squamous cell carcinoma (OSCC). This study was proposed to investigate the feasibility of near infrared fluorescence (NIF) via indocyanine green (ICG) for monitoring surgical marginal in operation for OSCC patients. Methods: In 35 patients with OSCC treated surgically in the Department of Oral and Maxillofacial Surgery, Nanjing University School of Medicine, from January 2019 to June 2020, ICG (0.75 mg/kg) was administered intravenously via elbow vein at (12±1) hours before surgery, and NIF was performed intraoperatively on the surgical field and the cut edge of the surgically excised specimen, and fluorescence intensity was measured for OSCC tissue and normal oral mucosa, abnormal fluorescence signals were taken and subjected to rapid cryopathological examination. Correlation between NIF tumor boundary grading and pathological tumor boundary grading was analyzed by Spearman correlation analysis. Results: Clear ICG NIF was obtained for tumor lesions in all 35 patients, with a positive rate of 100%. The fluorescence intensity of OSCC tissue was (412.73±146.56) au, which was higher than that of normal oral mucosa tissue [(279.38±82.56) au, P<0.01]. Abnormal fluorescence signals were detected at the tumor bed and the cut edge of the surgical resection specimen in 4 patients, of which 2 cases were pathologically confirmed as cancer cell residue and 2 cases as inflammatory cell infiltration. The rate of positive detection of cut margins using ICG NIF technique in OSCC was 5.7% (2/35). Twenty of the 35 OSCC patients had grade 1, 11 of grade 2, and 4 of grade 3 tumor borders revealed by NIF of surgical resection specimens, which was positively correlated with pathological tumor border (r=0.809, P<0.001). Conclusions: ICG NIF technique can effectively detect the residual cancer cells at the incision margin, which is of great clinical value in reducing local recurrence of OSCC after surgery due to intraoperative cancer residue.

Quality of resection margin with patient specific instrument for bone tumor resection

BackgroundPatient Specific Instruments (PSI) is currently a proven technique for bone tumor resection. In a previous publication, we analyzed the quality of margin resection of pelvic sarcoma resections with the use of PSI (by pathologic evaluation of the margins). In this new study, we compare preoperative resection planning and actual resection margins by MRI analysis of the resection specimens. MethodsBetween 2011 and 2020, 31 patients underwent bone tumor resection with the use of PSI. Preoperatively, the margins were planned with a software and PSI were made according to these margins. Postoperatively, the surgical resection specimens were analyzed with MRI. Resection margins were measured with the same software used in the preoperative planning. ResultsAll margins were safe (free of tumor). The differences between preoperative planned margins and the obtained ones were within the range −5 to +5 mm. The correlation between planned margin and the obtained one was excellent (R2 = 0.841; p < 0.0001). ConclusionsThis study demonstrates the accuracy of PSI. In our series, all resection margins were safe. A minimal 5 mm-margin has to be planned but a larger sample is needed to give recommendations.

Lymph node yield in colorectal cancer specimens and its impact on pathological staging: Does number matter?

Regional lymph node involvement is an important predictor of outcome in colorectal cancer (CRC). The lymph node yield in resected specimens varies from case to case. To assess whether clinicopathologic factors have an impact on the number of lymph nodes harvested from surgical resection specimens of CRCs To assess whether the total number of lymph nodes retrieved has a bearing on the positivity of lymph nodes and hence the N category. All resection specimens of treatment naïve CRC received in the department of pathology during a 2 year period (2017-2019) were reviewed. The lymph node yield was correlated with age, sex, type of surgical procedure, length of resected segment, tumor location, histological type and grade, T and N categories. The statistical tests used were Spearman rank, Mann-Whitney U, Kruskal-Wallis, and Chi-square tests. A total of 51 resections were studied. The mean age was 59.64 years with 72.55% being male. About 76.47% were hemicolectomies and 23.52% were rectosigmoid surgeries. The lymph node yield ranged from 0 to 38, the mean being 12.67. None of the parameters studied had a significant correlation with the lymph node yield except histological grade, specimens with higher-grade tumors yielding more number of nodes (P = 0.0242). There was no significant correlation between node positivity and the average number of lymph nodes (P = 0.0883). There was no significant correlation between total yield in cases with ≥12 lymph nodes and N category (P = 0.180). Furthermore, there was no significant correlation between total yield in node-positive cases with ≥12 lymph nodes and N category (P = 0.216). There was no significant difference in the sizes of the lymph nodes in node-positive and negative cases (P = 0.3930 and 0.2355, respectively). Among the parameters affecting lymph node yield, the current study found a significant correlation between histological grade and lymph node yield. There was no significant difference in the size of lymph nodes between node-positive and negative cases. The total lymph node yield did not have a bearing on node positivity and this shows that a lower lymph node yield may be accepted as adequate after thorough examination of the specimen.

Malignant mesothelioma: Cytological features

A malignant mesothelioma arises from the serosal surface of the pleural, peritoneal, or pericardial cavity. Although rare, with development of diagnostic techniques, the frequency of this tumor has been increasing. Malignant mesothelioma is classified into three types; epithelioid, sarcomatoid, and biphasic. It is especially important to differentiate epithelioid type from reactive mesothelial cells and another type of carcinoma, with a definitive diagnosis usually obtained based on examination of tissue biopsy or surgical resection specimens.

Optimal Preservations of Cytological Materials Using Liquid-Based Cytology Fixatives for Next-Generation Sequencing Analysis

Introduction: Molecular targeted therapies have been established for various diseases, including cancers, and there is an increasing need for molecular testing on cytology specimens. The aim of this study was to determine the optimal preservation methods of liquid-based cytology (LBC) materials for molecular testing. Methods: Cytological samples from 35 surgical resected non-small cell lung carcinoma specimens were obtained between June 2016 and June 2021. The samples were fixed in CytoRich™ red Preservative and stored at 4°C. One week later, three tubes were prepared from each specimen sample and divided into the following groups: the SurePath™ group (continued storage at 4°C), Frozen (Fr) group (stored at −80°C after centrifugation), and LBC-Cell Block (LBC-CB) group (generation of paraffin-embedded CB and storage at 4°C). Samples from 5 patients were used for the time course analysis, and we performed evaluations on these samples at 1, 3, 6, 12, 24, and 36 months. The concentrations and purities of extracted DNA and RNA were measured. The double-stranded DNA (dsDNA) and RNA concentrations were also measured by a fluorometer. The DNA and RNA integrities were quantified by the DNA and RNA integrity number. Results: Evaluation of samples was performed at baseline and the six timepoints. In the LBC-CB group, DNA and dsDNA concentrations were higher rather than those in the other groups. The RNA concentration of the LBC-CB group was relatively high compared with those of the other groups at the 36-month timepoint. The Fr group maintained higher DNA quality compared with the other groups over 3 years. The LBC-CB group maintained a higher RNA quality than the other groups until 24 months. Conclusion: LBC-CB preparation is an effective method to maintain DNA/RNA quality and quantity in long-duration preservation for eventual molecular testing. Therefore, LBC-CB may have applications on preanalytical stage for molecular genomic testing such as next-generation sequencing.

Depth of Invasion as Tumor Indicator in Cervical Lymph Node Metastasis in OSCC

Squamous cell carcinoma of oral cavity is the 6th common cancer of the world and a major source of malignancy around the world. The best prognostic indicators for the occult lymph node metastasis are tumor depth of invasion and lymph node biopsies.&#x0D; SAMPLE ABSTRACT:&#x0D; Aims:. This study was conducted to assess the association of tumor depth of invasion and lymph nodes metastasis in oral cancer diagnosis at its initial stage.&#x0D; Study design: Cross-Sectional Study design.&#x0D; Place and Duration of Study:. Ziauddin Hospital, North Nazimabad campus, Karachi. January 2021 to January 2022.&#x0D; Methodology: This Cross sectional study was conducted at the Ziauddin hospital, North nazimabad after Ziauddin University Ethical Review Committee approval (Reference&#x0D; Code: 0330618FAOM).140 biopsied surgical resection specimen slides were included the slides were evaluated by 3 investigators.&#x0D; Results: . The mean age of 140 OSCC was found to be 46.87 ± 12.25 years. 80.7% of study population comprised of males. 50% of patients had T4 stage. Moderately differentiated grade (89.3%) was the most predominnant grade observed in this study. on the basis of DOI the patients were divided into 2 groups. One Group with Depth of invasion upto 4 mm and second group with Depth of invasion &gt;4 mm. depth of invasion above 4 mm was found in 82.1% and without nodal metastasis(40.7%). The mean tumor size was was found to be 4.36± 2.433 mm and tumor thickness was 1.95±1.48 mm. and the most common anatomical site was found to be buccal mucosa (73.6%). T Stage and Nodal status,Tumour thicknes showed significant association with depth of invasion with p values 0.001, 0.023 and 0.002 respectively.&#x0D; Conclusion: The tumor depth of invasion is found to be an important variable that can be related with metastasis in Oral cancer as our study showed its significant association with lymph node meatastasis.

Transvaginal Colour Doppler Ultrasound Study of Uterine Tumours with Histopathological Correlation

A cross-sectional study was conducted in the Department of Radiology &amp; Imaging, in collaboration with the Department of Obstetrics &amp; Gynaecology, in Dhaka Medical College Hospital and Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh, between July 2010 and March 2012, to evaluate the diagnostic usefulness of transvaginal color doppler ultrasonography (TVCDU) in differentiating benign and malignant uterine tumours. A total of fifty women, diagnosed as having uterine tumours both clinically and using ultrasound, participated in the study. They were evaluated preoperatively using TVCDU. All the study participants underwent surgical operation and resected specimens were sent for histopathological examination. Histopathology reports were correlated with the of colour Doppler findings. The mean age of the patients was 47.72±8.79 years. Major complaints were menorrhagia (58%), dysmenorrhoea (50%) and lump in the lower abdomen (48%). Neovascularization was found in 16(32%) cases. The mean resistance index and pulsatility index were much lower in malignant tumours than that of the benign counterpart (0.35±0.03 vs. 0.67±0.01 and 0.65±0.14 vs. 1.35±0.11 respectively); the difference was statistically significant (P&lt;0.001). The sensitivity, specificity, positive and negative predictive values of TVCDU were found 86.7%, 97.14%, 92.85% and 94.4% respectively. Overall diagnostic accuracy was 94%. To summarize, blood flow characteristics of benign and malignant uterine tumours, as evident on color Doppler imaging, have distinct diagnostic value. Hence, transvaginal colour Doppler ultrasound examination can be used as an easily available, efficient, and non-invasive diagnostic modality in differentiation of uterine tumours, which can be histologically confirmed later.&#x0D; CBMJ 2021 January: vol. 10 no. 02 P: 105-110