Tumor Margin Research Articles

Clinicopathological characteristics and prognosis of combined hepatocellular cholangiocarcinoma

There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

First experience using a plate for fixing histological specimens of parotid salivary gland tumors

Relevance. Accurately assessing all resection margins during the removal of parotid salivary gland tumors is crucial due to the risk of recurrence and the potential for benign processes to become malignant over time. Macroscopic specimens obtained during these surgeries are sent to the pathology laboratory in containers filled with fixative solution. During fixation, the soft tissue fragments, typically round in shape, can alter their configuration because of the tissue's heterogeneity. This can create challenges for the pathologist in properly orienting the surgical specimen, which in turn complicates the precise evaluation of the resection margins.Materials and methods. To address this issue, the "Plate for fixing histological specimens of parotid salivary gland tumors" (patented) was developed. Twenty cases of its clinical use were analyzed: the surgical material (parotid gland tissue containing a tumor) was sent to the pathology department, fixed on this plate to preserve its original anatomical orientation. A macroscopic and histological evaluation of the neoplasms was then carried out, with special attention given to the accurate identification of all resection margins. In all 20 clinical cases, the use of this invention improved the convenience for the pathologist in handling the excised tissue block by standardizing the method and clearly identifying the resection margins.Conclusion. The application of this invention enhances the accuracy of marking and evaluating the resection margins in parotid gland tumors.

Profiling mRNA and miRNA expression variations associated with cyclin-dependent kinase pathway in the low-grade luminal early breast cancer.

Luminal A and B subtypes of breast tumors have fluctuated in proliferation rates, which arise from cell cycle dysregulation in cancer. Besides, microRNAs can regulate various cell processes through integration with mRNA. miRNAs that target the cell cycle are significant because of their prediction capability of prognosis. The objective of this study is to discover the integration between miRNA-mRNA and miRNA-miRNA related to cyclin-dependent kinase. Thirty-four pairs of human primary breast cancer and tumor margin samples from luminal breast cancer patients were investigated to assess the expression levels of CCND1, E2F1, miR-124, miR-503, miR-449a, and miR-449b. Afterward, the expression levels of mRNAs and miRNAs were investigated by real-time PCR. Statistical analysis was conducted to compare the expression levels between breast cancer and corresponding normal tissues. The protein expressions of E2F1 and CCND1 were verified by western blotting. Further, the correlation between mRNAs and miRNAs was calculated. E2F1 was significantly increased in both luminal A and B patients, while CCND1 was upregulated only in luminal B. Significant differences in all miRNAs were detected in both luminal A and B biopsy specimens (p < 0.0001). The correlation analysis revealed a positive strong correlation between miR-124 and E2F1 in luminal A patient. Moreover, the correlation test confirmed the ability of miR-449a to increase the CCND1 gene in luminal B subtypes. Also, miRNA correlation exhibited the miRNA-miRNA interaction in luminal breast cancer. This study demonstrated the novel miRNA-mRNA and miRNA-miRNA interactions, providing new insights into the molecular integration in luminal A and B patients. The authors propose that this research could contribute to introducing valuable biomarkers for luminal cancerous cells.

Targeted blood-brain barrier penetration and precise imaging of infiltrative glioblastoma margins using hybrid cell membrane-coated ICG liposomes

Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.Graphical abstract

6436 Adrenal Venous Congestion Clinically Mimicking Carcinoma In A Large Degenerated Adrenocortical Adenoma

Abstract Disclosure: K. Ishiwata: None. S. Suzuki: None. S. Watanabe: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None. Introduction: A large heterogenous adrenal tumor is often malignant. Only eight reported cases of adrenal adenoma harboring hemorrhage or venous thrombosis have been reported but their details not. We encountered a case of large degenerated adrenocortical adenoma harboring adrenal venous congestion mimicking adrenocortical carcinoma. Case: Adrenal tumor was incidentally detected in a 71-year-old woman with a history of hypertension, dyslipidemia, and osteoporosis in her regular health check-up. Abdominal CT and MRI demonstrated a heterogenous mass measuring 7.6 cm with peripheral enhancement in the left adrenal gland. [1]3[1]I-adosterol scintigraphy revealed accumulation only in the left tumor margins with no accumulation in [1]8F-FDG-PET scan. Results of endocrinologic evaluation were consistent with subclinical Cushing syndrome. The large size and heterogeneous nature of the mass clinically suggested adrenocortical malignancy, and left laparoscopic adrenalectomy was subsequently performed. The resected left adrenal lesion was encapsulated and measured 6.5 x 6.3 x 5.8 cm appearing almost black and partially yellow on the cut surface. Microscopically, the nodule was composed of SF-1 positive, clear cortical cells with abundant hyaline stroma containing numerous dilated veins with CD31/34-positive endothelial cells, and no foci of necrosis or hemorrhage were detected. The tumor cells above were positive for steroidogenic enzymes including CTP17, HSD3β and CYP11B1 but negative for CYP11B2. Ki-67 labeling index was &amp;lt;2% in the tumor. The criteria of Weiss (0 out of 9) revealed that the tumor was cortisol-producing adrenocortical adenoma. Discussion: In this case, clusters of SF1-positive cortisol producing adrenocortical adenoma cells were present in the hyalinized stroma containing many dilated blood vessels. These findings indicated that those histological features were caused by ischemic degeneration due to intratumoral circulatory disturbance, which clinically simulated adrenocortical carcinoma. Conclusion: We have experienced a very rare case of cortisol-producing adrenocortical adenoma with adrenal venous congestion, resulting in marked enlargement of the lesion. Presentation: 6/3/2024

Spinal chordoma and chondrosarcoma treatment experiences - a 20-year retrospective study from databases of two medical centers

The research retrospectively analyzed cases of spinal chordoma and chondrosarcoma involving patients who received treatment at the two hospitals between 2001 and 2023. Among the 48 patients studied (39 chordoma and 9 chondrosarcoma cases), the average age was 53.9 ± 15.8 years, with a range of 17 to 86 years. Out of these patients, 43 underwent excision surgery and were categorized based on tumor margin into negative (R0) or microscopically positive (R1) margin (n = 14) and macroscopically positive (R2) margin (n = 29) groups. The mean overall survival (OS) for R0/R1 and R2 groups was 156.5 ± 19.3 and 79.2 ± 11.9 months, respectively (p value = 0.012). The mean progression-free survival (PFS) for R0/R1 and R2 was 112.9 ± 24.4 and 25.5 ± 5.5 months (p value < 0.001). The study showed that regardless of whether patients in the R0/R1 or R2 groups received radiation therapy (RT) or not, there was no significant improvement in OS or PFS. Specifically, the OS and PFS for the RT only group were 75.9 ± 16.6 and 73.3 ± 18.0 months. In conclusion, the recommended treatment approach for spinal chordoma and chondrosarcoma remains en bloc resection surgery with an appropriate margin. Patients who are unsuitable for or decline surgery may find a beneficial disease control rate with traditional external beam photon/proton therapy.

Novel imaging techniques for tumor margin detection in basal cell carcinoma: a systematic scoping review of FDA and EMA-approved imaging modalities.

Mohs micrographic surgery (MMS) is the gold standard for removing basal cell carcinomas (BCCs) due to its ability to guarantee 100% margin evaluation through frozen section histopathology, offering the highest cure rate among current treatments. However, noninvasive imaging technologies have emerged as promising alternatives to clinical assessment for defining presurgical margins. This systematic scoping review examines the efficacy of these imaging modalities, focusing on those approved for clinical use by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A systematic search of EMBASE, Scopus, PubMed, and the Cochrane Public Library databases identified 11 relevant studies out of 2123 records, encompassing 644 lesions across five imaging techniques. The findings suggest that dermoscopy, high-frequency ultrasound (HFUS), optical coherence tomography (OCT), line-field optical coherence tomography (LC-OCT), and reflectance confocal microscopy (RCM) show potential in detecting BCC margins, which could enhance MMS by providing better preoperative planning, informing patients of expected defect size, aiding in reconstruction decisions, and reducing overall procedure costs. This review discusses the benefits and limitations of each technique, offering insights into how these innovations could influence the future of BCC management. Emerging imaging techniques could enhance MMS by improving BCC margin assessment and reducing costs. Their adoption will depend on price and ease of use.

Cancer-associated foam cells hamper protective T cell immunity and favor tumor progression in human colon carcinogenesis

BackgroundColorectal cancer (CRC) remains a significant healthcare burden worldwide, characterized by a complex interplay between obesity and chronic inflammation. While the relationship between CRC, obesity and altered lipid metabolism is...

Prospective selective embedding of radical prostatectomy specimens is not inferior to full embedding regarding established and new prognostic parameters.

The histopathological examination of radical prostatectomy specimens is essential for assessing critical tumor characteristics, including stage, grade, and margins, all of which impact patient prognosis. However, the extent of embedding the prostate has long been a subject of debate, with some advocating partial/selective embedding and others favoring complete embedding. This study establishes a standardized and time-efficient protocol for processing radical prostatectomy specimens with limited embedding while maintaining diagnostic accuracy. Two hundred twenty-six prostatectomy specimens were analyzed, and the results of a highly standardized selective embedding protocol, systematically embedding the apex, the base, the transition to the seminal vesicles, and selected horizontal sections, were compared with full embedding as the gold standard. Non-inferiority testing was conducted by one-sided binomial tests and Pearson-Clopper confidence intervals. Selective embedding provided consistent and accurate diagnostic information with up to 90-98% concordance in pT, margins, ISUP-grade groups, and presence of IDC-P and cribriform tumor growth. In summary, this study establishes an economical standardized protocol for selective embedding of radical prostatectomy specimens with only minimal loss of information.

Association of Collagen Changes in Distal Anastomotic Margin and Anastomotic Stenosis after Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Neoadjuvant chemoradiotherapy (nCRT) for rectal cancer can lead to structural changes in collagen in the tumor microenvironment and increase the risk of postoperative anastomotic stenosis (AS). However, the quantitative relationship between AS and collagen has not been defined. This study is to quantitatively analyze the collagen features in rectal cancer and explore the relationship between the changes of collagen and postoperative anastomotic stenosis after nCRT. This is a retrospective study. A total of 371 patients with rectal cancer were included. Collagen features in the resection margin of rectal cancer anastomosis was extracted by multiphoton imaging. The least absolute shrinkage operator logistic regression was performed to select features related to AS and the collagen score (CS) was constructed. Area under the receiver operating curve (AUROC) and decision curve analysis were performed to evaluate the discrimination and clinical benefit of the nomogram. The probability of AS was 23% in the training cohort and 15.9% in the validation cohort. In the training cohort, the distance between tumor and resection margin, anastomotic leakage and CS were independent risk factors for postoperative AS in univariate and multivariate analyses. A nomogram was constructed based on these results. The prediction nomogram showed good discrimination (AUROC 0.864; 95% CI 0.776 to 0.952) and was validated in the validation cohort (AUROC 0.918; 95% CI 0.851 to 0.985). CS is an independent risk factor for AS in rectal cancer after nCRT. The predictive model based on CS can predict the occurrence of postoperative AS.

The Prognostic Impact of Minimally Invasive Esophagectomy on Survival After Esophagectomy Following a Delayed Interval After Chemoradiotherapy: A Secondary Analysis of the DICE Study.

To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12wk) following chemoradiotherapy (CRT). Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival. This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches. A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate ( P =0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI: 1.14-2.5) and propensity-matched analysis ( P =0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50Gy dose groups (HR=1.9; 95% CI: 1.2-3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1-2.2). MIE was associated with improved overall survival compared with OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

Development and validation of a machine-learning model for preoperative risk of gastric gastrointestinal stromal tumors

BackgroundGastrointestinal stromal tumors (GISTs) have malignant potential, and treatment varies according to risk. However, no specific protocols exist to preoperatively assess the malignant potential of gastric stromal tumors (gGISTs). This study aimed to use machine learning (ML) to develop and validate clinically relevant preoperative models to predict the malignant potential of gGISTs. MethodsWe screened patients diagnosed with gGISTs at the Affiliated Hospital of North Sichuan Medical College. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to identify risk factors. Subsequently, an ensemble of ML models was deployed to determine the optimal classifier. Additionally, we harnessed SHapley Additive exPlanations (SHAP) for tailored risk profiling. ResultsWe enrolled 318 patients with gGISTs. Utilizing LASSO regression and multifactorial logistic regression, we analyzed the training dataset, revealing that the presence of endoscopic ultrasound (EUS) high-risk features, tumor border clarity, tumor diameter, and monocyte-to-lymphocyte ratio (MLR) were significant predictors of high malignancy risk in gGIST. As determined by our ML approach, the logistic classification model demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.919 and 0.925 for the training and test sets, respectively. Furthermore, decision curve analysis substantiated the clinical relevance of the model. ConclusionHigh-risk EUS features, ill-defined tumor margins, larger tumor diameters, and elevated MLR independently predicted heightened malignant potential in gGIST. We developed logistic regression models based on these factors, which were further interpreted using the SHAP methodology. This analytical approach facilitated personalized therapeutic decision-making for diverse patient populations.

A prospective observational study on functional outcomes and condition-specific quality of life after intersphincteric resection for low rectal cancer

Objective: To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires. Methods: A prospective observational study was conducted in the Characteristic Medical Center of the People's Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS). Results: A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge(M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703,P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781,P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that "emptying difficulties" and "dissatisfaction with the bowels" were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952,P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score (rs=-0.72, P<0.01). Conclusions: Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

Contribution of Immunoscore to Survival Prediction in Pancreatic Ductal Adenocarcinoma.

The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated as a prognostic factor in colorectal cancer after surgical resection of malignancy, but knowledge on their role in pancreatic cancer is lacking. The Immunoscore (IS) assesses TILs at the core of the tumor (CT) and invasive margin (IM) and is being evaluated as a new concept in tumor immunity. The aim of this study was to evaluate the relationship between IS and prognosis in PDAC. The IS was analyzed by immunohistochemistry using surgical tissue blocks from 131 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgery to investigate the relationship between immune cell infiltration into the tumor and prognosis in PDAC. A high IS in both CT and IM of the tumor was significantly associated with prolonged overall survival (OS) (p<0.01) and relapse-free survival (RFS) (p<0.01). In multivariate logistic regression models adjusted for clinical pathology data, IS predicted survival and recurrence (p<0.01 and p<0.01, respectively). Moreover, in patients who received preoperative chemotherapy, a high IS was statistically significantly associated with longer OS and RFS (p<0.01 and p<0.01, respectively). The immunohistochemically assessed IS might be a useful prognostic marker for patients with PDAC who underwent primary tumor resection.

Clinicopathological differences between classical schwannomas and cellular schwannomas in the retroperitoneum.

This study aimed to compare clinical and pathological features of retroperitoneal classical schwannomas and cellular schwannomas. A total of 64 cases of retroperitoneal classical schwannoma and 48 cases of cellular schwannoma were studied. Histopathological analysis was performed using hematoxylin and eosin staining and immunohistochemistry. Retroperitoneal cellular schwannomas exhibited 100% (48/48) and 75% (36/48) positive expression for glial fibrillary acidic protein (GFAP) and cytokeratins (CK), respectively. Classical schwannomas showed rates of 6.25% (4/64) and 15.63% (10/64), respectively (P < .05). In classic schwannomas, 85.9% (55/64) showed a reticular pattern of positive anti-CD34 staining around tumor margins and subcapsular areas vs 52.1% (25/48) in cellular schwannomas (P < .05). Cellular schwannomas exhibited more mitotic figures than classical schwannoma (P < .05). The recurrence rate of cellular schwannomas was 10.42% (5/48), while that of classical schwannomas was 1.56% (1/64) (P < .05). Retroperitoneal cellular schwannomas commonly express GFAP and CK compared to classical schwannomas, suggesting that cellular schwannoma may originate from unmyelinated Schwann cells, while classical schwannoma may originate from myelinated Schwann cells. Anti-CD34 staining patterns may be used to distinguish between the 2 types. Retroperitoneal cellular schwannomas also show higher mitotic activity and are more prone to recurrence.

Peptide-mediated targeting of Quantum Dots in a 3D model of head and neck cancer

BackgroundOral squamous cell carcinoma (OSCC) treatment mainly relies on surgery. The status of surgical margin is a major prognostic factor for patients as positive margins are associated with lower survival. However, the anatomical particularities of this area complicate margin establishment. Fluorescence guided surgery (FGS) could be employed as an intraoperative technique to improve tumor resection and margin investigation. Quantum dots (QDs) serve as ideal contrast agents in this technique due to their brightness and stability. Since αVβ6 integrin is overexpressed in OSCC, coupling QDs with A20FMDV2 peptide (QDs-A20) targeting the αVβ6 integrin constitute a real opportunity. This study investigates the accumulation of QDs-A20 in 2D and 3D tongue cancer models, as well as QDs coupled to a scrambled version of this peptide (QDs-Scr) or without peptide (QDs-SPP), for imaging purposes. MethodsCdSeCdS/ZnS quantum dots were coated with sulfobetaine polymers (QDs-SPP) and conjugated to A20FMDV2 peptide (QDs-A20) or its scrambled version (QDs-Scr). Two-dimensional (2D) and three-dimensional (3D) tongue cancer cells HSC-3 were employed to test the effectiveness of intracellular accumulation of all types of QDs. Targeting ability of each QDs was assessed by flow cytometry, while the depth of penetration into cancerous spheroids was assessed by fluorescence microscopy. ResultsQDs coating with sulfobetaines polymers (QDs-SPP) completely prevented their internalization by HSC-3 cells in 2D and 3D models, making QDs stealthy and preventing their non-specific accumulation. Conversely, peptides conjugated QDs (QDs-A20 & QDs-Scr) labeled HSC-3 monolayers and managed to label spheroid periphery up to 23 µm deep. However, no difference in accumulation was found between these two QDs whereas only A20 peptide could potentially target αVβ6 integrin. It appears that peptide conjugation increased QDs zeta potential, promoting their adsorption and subsequent endocytosis by cells, independently from αVβ6 integrin. ConclusionsThe present study highlighted the impact of peptide conjugation on QDs internalization in 2D and 3D tongue cancer cell models. QDs-SPP were stealthy and did not accumulate in cells. Peptides conjugated QDs could be used as contrast agents, but in a passive targeting approach. Modifications to surface chemistry are required to target αVβ6 integrin through active targeting. This study also highlights the need for controls such as scrambled peptides, the absence of which can lead to misinterpretation of results.

Tumor-infiltrating immune cell profiles and changes associate with additional trastuzumab in preoperative chemotherapy for patients with HER2-positive gastric cancer

BackgroundHER2(+) gastric cancer (GC) can benefit from trastuzumab. However, the impact of additional trastuzumab in preoperative treatment on immune cells remains largely unknown.MethodsIn cohort I, immune cells were detected by immunohistochemistry in 1321 patients. Then 88 HER2(+) patients received preoperative therapy were collected as cohort II. Immune cell profiles and changes were analyzed in paired pre- and post-operative specimens using multiple immunohistochemistry staining.ResultsIn the treatment-naive GC patients (n = 1002), CD3+ and CD8+ T cell infiltration was significantly lower in the HER2(+) GC patients together with higher FoxP3+ T cells compared with HER2(−). However, FoxP3+ T and CD20+ B cell infiltration was significantly higher in HER2(+) GC after neoadjuvant chemotherapy (n = 319). The trastuzumab-exposed group had higher CD8+ T and lower FoxP3+ T cell infiltration and CD8+ T cell was even more significant in responders. Additionally, tertiary lymphoid structure (TLS) density increased in invasion margin of residual tumors. Patients with lower TLS in the tumor core or lower FoxP3+ T cells had better overall survival in the trastuzumab-exposed group.ConclusionAddition of trastuzumab modulates the immune microenvironment, suggesting the potential mechanism of the favorable outcome of anti-HER2 therapy and providing a theoretical rationale for the combinational immunotherapy in resectable HER2(+) GC patients.

Deep learning-enabled fluorescence imaging for surgical guidance: in silico training for oral cancer depth quantification.

Oral cancer surgery requires accurate margin delineation to balance complete resection with post-operative functionality. Current in vivo fluorescence imaging systems provide two-dimensional margin assessment yet fail to quantify tumor depth prior to resection. Harnessing structured light in combination with deep learning (DL) may provide near real-time three-dimensional margin detection. A DL-enabled fluorescence spatial frequency domain imaging (SFDI) system trained with in silico tumor models was developed to quantify the depth of oral tumors. A convolutional neural network was designed to produce tumor depth and concentration maps from SFDI images. Three in silico representations of oral cancer lesions were developed to train the DL architecture: cylinders, spherical harmonics, and composite spherical harmonics (CSHs). Each model was validated with in silico SFDI images of patient-derived tongue tumors, and the CSH model was further validated with optical phantoms. The performance of the CSH model was superior when presented with patient-derived tumors ( ). The CSH model could predict depth and concentration within 0.4mm and , respectively, for in silico tumors with depths less than 10mm. A DL-enabled SFDI system trained with in silico CSH demonstrates promise in defining the deep margins of oral tumors.

Matrix Metallopeptidase 9 Expression in Tumoral and Marginal Tissues of Cholesteatoma

Background: Cholesteatoma, a serious, expanding otolaryngologic condition, is challenging to otolaryngologists worldwide. The purpose of the present study was to evaluate the expression of MMP-9 gene in cholesteatoma patients. Methods: In this study, 40 samples of tumor tissue and 40 samples as control of tumor margins of patients with cholesteatoma were examined. Quantitative real-time polymerase chain reaction (PCR) was used for detection of the MMP-9 gene expression levels in cholesteatoma and control group. expression changes were calculated by ΔCT formula and data were analyzed by GraphPad Prism 8. Results: MMP-9 expression level in case group was significantly higher than the control group (P=0.0011). ROC analysis for the MMP-9 gene expression level that discriminates Cholesteatoma tumoral tissue from healthy tissues revealed a sensitivity of 67.5 % and a specificity of 84.62% with an area under the curve (AUC) value of 0.75 (P&lt;0.001). Conclusion: The results indicated that MMP-9 is overexpressed in cholesteatoma tumoral tissues group compared to the healthy tissues. Based on AUC value of RUC curve analysis of MMP-9 expression level could be helpful in diagnosis of tumoral tissue form healthy tissue.

Retroperitoneal Approach to D3-Lymph Node Dissection With Left Colic Artery Preservation in the Treatment of Sigmoid Cancer.

Laparoscopic approaches and robot-assisted operations are used for colorectal cancer surgery because of their minimal invasiveness.1 However, changes in intra-abdominal pressure during laparoscopy can lead to cardiovascular complications in compromised patients;2 obesity and intraabdominal adhesions may further interfere with laparoscopic procedures. The retroperitoneal approach may facilitate minimally invasive surgery, even in patients with comorbidities. The technique for high ligation of the inferior mesenteric artery has been described in left colonic surgeries.3 However, complete termination of the blood supply through this artery may lead to a higher frequency of anastomotic leakage.4. We present a novel retroperitoneal approach for D3-lymph node dissection with low ligation of the inferior mesenteric artery and preservation of the left colic artery. This method can reduce the duration of laparoscopic procedures for compromised patients and meet the standards for extended lymph node dissection with tumor-specific mesocolic excision.5,6. The procedure started with the installation of a paraumbilical optical trocar to introduce a 30-degree optical system. The SILS™ Port (Covidien, Medtronic) was inserted into the retroperitoneal space via a 4-cm incision, made 2 cm below and parallel to the anterior superior iliac spine in the left flank under the control of the optical system. The horizontal aspect of the duodenum served as the cranial landmark during interfascial dissection, with the dissection proceeding in a cranial and medial direction. During the dissection, the left ureter was the primary landmark, passing medial to the gonadal vessels and Gerota's fascia.The aorta was exposed medially and the inferior mesenteric artery was identified. The inferior mesenteric artery was skeletonized from its origin until the branching of the left colic artery and the sigmoid artery. The left colic artery was skeletonized until the passage of the inferior mesenteric vein, and the apical lymphatic nodes with mesocolic tissue were mobilized and excised. The inferior mesenteric artery was cut below the left colic artery.The final step was performed laparoscopically. The parietal fascia along Toldt's line was cut laterally to complete the mesocolon excision. The parietal fascia was cut along the right side of the aorta to free the mesocolonic medial border. The sigmoid mesocolon was dissected at the proximal and distal resection margins.Following mobilization, the colon was cut 10 cm distal to the tumor margin using a linear stapler. The specimen was then extracted using an SILS incision. The sigmorectal anastomosis was made. Atypical hepatic resection was performed using two additional trocars. The incidence of pain syndrome in the early postoperative period was low. Blood loss reached 100 mL. The duration of the surgery was 300 min. The retroperitoneal step took 63 min. Metastases were observed in 7 of the 41 harvested lymph nodes. The patient was discharged on the 8th postoperative day. The retroperitoneal technique can be safely performed. Anatomical structures are readily accessible and easily visualized with this approach after special training, enabling extended lymph node dissection.