Deep Invasion Research Articles

Re-evaluation of the role of endoscopic submucosal dissection in the treatment of early gastric cancer based on additional gastrectomy results.

Endoscopic submucosal dissection (ESD) plays a pivotal role in treating early gastric cancer (EGC). Some patients require additional gastrectomy because of non-curative ESD. This study aimed to analyze the clinical factors associated with non-curative ESD and to re-evaluate the role of ESD according to its indication criteria. Altogether, 134 patients who had undergone additional gastrectomy with lymphadenectomy for non-curative ESD based on the pathological results of ESD specimens were included. Their data including pre-ESD diagnosis, reasons for requesting additional gastrectomy, and surgical outcomes were analyzed retrospectively. Of the 134 patients with EGC in the final pathology of ESD specimens, 56 underwent staging ESD for a diagnostic approach, of whom 28 were diagnosed with atypical glands and 28 with high-grade dysplasia (HGD) prior to ESD. The remaining 78 patients of the 134 were identified to have EGC and received ESD for therapy. Based on the pathological results of ESD specimens, additional gastrectomy was commissioned with non-curative ESD because of one or more causes such as deep submucosal invasion, lymphatic invasion, positive vertical margin, undifferentiated histology, positive lateral margin, and venous invasion. Regarding surgical specimens, 13 patients had lymph node metastasis (LNM) and 9 had local residual tumor; one of them had both LNM and a local residual tumor. In patients with atypical glands, 4 had LNM and 3 had a local residual tumor; one of them had both LNM and a local residual tumor, and then died of multiple organ metastasis. In patients with HGD, 4 had LNM and 1 had a local residual tumor. Additionally, 4 patients who were absolutely indicated for ESD had LNM, of whom 2 had atypical glands, and the other 2 had HGD. Similarly, in 6 patients with a local residual tumor absolutely indicated for ESD, 2 had atypical glands and 1 had HGD. Positive vertical margin, lymphatic invasion, and deep submucosal invasion were identified as independent risk factors for LNM. ESD may play diagnostic and therapeutic roles in determining the optimal treatment of EGC when the diagnosis is equivocal or insufficient in endoscopic assessments for gastric cancer screening.

Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer: Does Submucosal Invasion Depth Really Matter?

After endoscopic resection of colorectal cancer with submucosal invasion (pT1 CRC), additional surgical treatment is recommended if deep submucosal invasion (DSI) is present. This study aimed to further elucidate the risk factors for lymph node metastasis (LNM) in patients with pT1 CRC, especially the effect of DSI on LNM. Patients with pT1 CRC who underwent lymph node dissection were selected. The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM. The submucosal invasion depth (SID) was measured via 4 methods and analyzed with 3 cut-off values. Twenty-eight of the 239 patients presented with LNM (11.7%), and the independent risk factors for LNM included high histological grade (P=0.003), lymphovascular invasion (LVI) (P=0.004), intermediate to high budding (Bd 2/3) (P=0.008), and cancer gland rupture (CGR) (P=0.008). Moreover, the SID, width of submucosal invasion (WSI), and area of submucosal invasion (ASI) were not significantly different. When one, two, three or more risk factors were identified, the LNM rates were 1.1% (1/95), 12.5% (7/56), and 48.8% (20/41), respectively. Indicators such as the SID, WSI, and ASI are not risk factors for LNM and are subjective in their measurement, which renders them relatively inconvenient to apply in clinical practice. In contrast, histological grade, LVI, tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant. It would be prudent to focus on these histological factors rather than subjective measurements.

Sentinel node mapping decreases the risk of failed detection of isolated positive para-aortic lymph node in endometrial cancer

BackgroundIsolated positive para-aortic lymph node metastasis in endometrial cancer is an uncommon event, ranging from 1% to 3%.ObjectiveOur aim was to evaluate the impact of sentinel lymph node (SLN) mapping...

Imaging colonic polyps in 2024.

Screening colonoscopy and polypectomy are the cornerstone in decreasing the incidence and mortality of colorectal cancer. Despite the low incidence of colorectal cancer in India, there has been a rising trend in the incidence of colonic polyps and cancer over the last decade. It is, hence, imperative that we are well equipped in themanagement of colonic polyps. Adequate training in thedetection and characterization of polyps to aid in their management is necessary. Detection of polyps can be increased by adhering to the standards of colonoscopy, including good bowel preparation, cecal intubation rate, adequate withdrawal time and use of distal attachment devices. A detected polyp needs optimal characterization to predict histology in real time and decide on the management strategies. Characterization of the polyps requires high-definition-white light endoscopy and/or image-enhanced endoscopy (dye based or digital). Various factors that helpin predicting histology include size, location and morphology of the polyp and the pit pattern, vascular and surface pattern of the polyp. Polyps can be differentiated as neoplastic or non-neoplastic with reasonable accuracy with the above features. Prediction of advanced pathology including high-grade dysplasia and deep sub-mucosal invasion is essential, as it helps indeciding if the lesion is amenable to endotherapy and the technique of endoscopic resection. Adequate training in image-enhanced endoscopy is necessary to assess advanced pathology in polyps. Technology pertaining to image-enhanced endoscopy includes narrow banding imaging and blue laser imaging; newer variations are being introduced every few years making it necessary to be abreast with growing information. The recent advances in gastrointestinal (GI) endoscopy with the advent of endocytoscopy and artificial intelligence seem promising and are predicted to be the future of GI endoscopy.

Spatial proteomics and transcriptomics of the maternal-fetal interface in placenta accreta spectrum

In severe Placenta Accreta Spectrum (PAS), trophoblasts gain deep access in the myometrium (placenta increta). This study investigated alterations at the fetal-maternal interface in PAS cases using a systems biology approach consisting of immunohistochemistry, spatial transcriptomics and proteomics. We identified spatial variation in the distribution of CD4+, CD3+ and CD8+ T-cells at the maternal-interface in placenta increta cases. Spatial transcriptomics identified transcription factors involved in promotion of trophoblast invasion such as AP-1 subunits ATF-3 and JUN, and NFKB were upregulated in regions with deep myometrial invasion. Pathway analysis of differentially expressed genes demonstrated that degradation of extracellular matrix (ECM) and class 1 MHC protein were increased in increta regions, suggesting local tissue injury and immune suppression. Spatial proteomics demonstrated that increta regions were characterised by excessive trophoblastic proliferation in an immunosuppressive environment. Expression of inhibitors of apoptosis such as BCL-2 and fibronectin were increased, while CTLA-4 was decreased and increased expression of PD-L1, PD-L2 and CD14 macrophages. Additionally, CD44, which is a ligand of fibronectin that promotes trophoblast invasion and cell adhesion was also increased in increta regions. We subsequently examined ligand receptor interactions enriched in increta regions, with interactions with ITGβ1, including with fibronectin and ADAMS, emerging as central in increta. These ITGβ1 ligand interactions are involved in activation of epithelial–mesenchymal transition and remodelling of ECM suggesting a more invasive trophoblast phenotype. In PAS, we suggest this is driven by fibronectin via AP-1 signalling, likely as a secondary response to myometrial scarring.

Clinical Features and Surgical Outcomes of Jugulotympanic Paraganglioma

Introduction: Jugulotympanic paraganglioma (JTP) refers to paraganglioma arising from jugular bulb, which can invade surrounding structures such as the bones, blood vessels, meninges, and cranial nerves. The authors conducted a study to find surgical indications to avoid a serious cranial nerve complications by analyzing the medical records of patients who underwent surgical management for JTP. Methods: We performed a single-institution, retrospective review of patients who underwent resection of JTP from 2004 to 2022. Patients underwent either Fisch infratemporal fossa approach type A (ITFA-A) or modification of ITFA-A with partial rerouting of the facial nerve. Preoperative and postoperative lower cranial nerve (LCN) function and facial function using the House-Brackmann (H-B) grade were evaluated. Results: The study included 19 patients with a mean age of 43.1 years (standard deviation [SD], 16.1 years). The average tumor size was 28.6 mm (SD 12.6 mm). In patients with Fisch classes C1 and C2 tumors, there were 3 and 11 patients, respectively. Gross total tumor removal (GTR) was performed in all patients with classes C1 and C2. GTR was achieved in 2 out of the 5 patients with class C3 tumor. Seventeen patients underwent ITFA-A and 2 patients underwent partial rerouting. Facial function before surgery was normal in all but 3 cases. Among 16 patients with preoperative normal facial function, 13 had H-B grade I to II and 3 had H-B grade III at 1 year after surgery. Total and partial rerouting did not significantly affect facial function immediately after surgery or at the postoperative 1-year evaluation (p = 1.00). Preoperative LCN function was normal in all patients. LCN palsy lasting more than 1 year occurred in 7 patients after surgery. Patients with Fisch class C1 tumor did not develop postoperative LCN palsy. Among the patients with class C2 tumor, none of 5 patients with medial invasion depth less than 9.5 mm developed LCN palsy, whereas 5 of 6 patients (83.3%) with invasion depth of 9.5 mm or greater developed LCN palsy (p = 0.02). Conclusion: JTPs with deep medial invasion should be managed conservatively to prevent LCN palsy.

Clinicopathological Characteristics and Lymph Node Metastasis Rates in Early Gastric Lymphoepithelioma-Like Carcinoma: Implications for Endoscopic Resection.

Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa. We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy. Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively. Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM.

356. TUMOUR BURDEN CORRELATES WITH THE RISK OF RECURRENCE AFTER PIECEMEAL ENDOSCOPIC RESECTION OF EARLY-STAGE ADENOCARCINOMA IN BARRETT’S OESOPHAGUS

Abstract Background Endoscopic resection (ER) is curative for Barrett’s oesophagus-related early-stage oesophageal adenocarcinoma (EAC) without high-risk features, such as lymphovascular invasion (LVI), positive margins (R1), and deep submucosal invasion (T1bsm2-3). Piecemeal endoscopic mucosal resection (pEMR), often used for lesions larger than 15mm, prevents assessment of lateral margins and therefore complicates precise risk estimation for residual EAC at the first post-ER endoscopy. Thus, we investigated alternative clinical factors that could potentially be used to assess the risk for residual and recurrent EAC post-ER. Methods We performed a longitudinal cohort study of patients who underwent ER between 2006-2023. Inclusion criteria were: T1a or well/moderately differentiated T1bsm1 EAC; LVI-, and R0 resection. ER was categorised as pEMR (n=106) or en-bloc ER (n=22 en-bloc EMR, n=9 endoscopic submucosal dissection). The primary outcome was residual EAC at first post-ER endoscopy. Secondary outcomes were residual HGD at first post-ER endoscopy, EAC and HGD recurrence at any post-ER endoscopy, and remission of EAC, HGD and intestinal metaplasia (IM) at latest endoscopy. Multivariate logistic regression, receiver operating characteristics, chi-squared, and Kaplan Meier analyses were performed to investigate possible associated risk factors. Results Rates of EAC/HGD recurrence were higher post-pEMR versus en-bloc ER (p=0.019), with residual EAC at first post-ER endoscopy accounting for 34% of post-pEMR recurrence. The percentage of pEMR specimens with EAC (p=0.022) and T1bsm1 staging (p=0.013) were independent risk factors for residual EAC at first post-pEMR endoscopy (Table 1). A 53.5% cut-off of involved pEMR specimens was identified as the optimal threshold for residual EAC prediction (specificity=0.68, sensitivity=0.67). Indeed, residual (p=0.012) and recurrent (p=0.00077) EAC rates were higher when EAC involvement was >53.5%. However, rates of EAC (p=0.13), HGD (p=0.19) and IM (p=0.76) remission were unaffected by high EAC burden. Conclusions High burden of EAC on pEMR specimens correlates with increased risk of residual and recurrent EAC at post-pEMR endoscopy. Post-pEMR site check is recommended prior to endoscopic ablation, particularly in patients where more than 50% of pEMR specimens show EAC and in cases of flat subtle lesions. This will ensure eradication of any residual disease and high success rates for treatment of early EAC using endotherapy.

Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer

ObjectiveWe assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease.MethodsPatients diagnosed with stage...

A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50years) and intervals (2/5/10years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20mm in size, and the deep submucosal invasion rate was less than 30%. A mathematical simulation model revealed that screening every 5years starting at 45years of age could efficiently assist in identifying HpNGNs at an early stage.

Impact of adjuvant treatments and risk factors on survival in 2023 FIGO stage IIB endometrial cancer patients: Turkish Gynecologic Oncology Group Study

ObjectiveThe aim of this study was to investigate the impact of adjuvant treatments, factors influencing recurrence, and survival data in patients with 2023 International Federation of Gynecology and Obstetrics (FIGO)...

Endoscopic Resection of Stage T1 Colorectal Adenocarcinoma Followed by Surgical Intervention: a Single-center Retrospective Study

BackgroundDomestic and international guidelines recommend endoscopic resection for stage T1 colorectal adenocarcinoma with indications. However, completion surgery remains imperative for patients exhibiting high-risk factors subsequent to endoscopic procedures.ObjectiveTo investigate the evidence, pathological features, and surgical outcomes of completion surgery in patients with T1 colorectal adenocarcinoma following endoscopic resection.MethodsWe retrospectively collect data on the clinical features and treatment outcomes of patients with stage T1 colorectal adenocarcinoma who underwent endoscopic resection followed by surgical resection and those who initially completed surgical intervention at Peking University International Hospital between January 2019 and October 2022, with the aim of assessing the necessity and feasibility of surgical intervention.ResultsSeventeen patients (Group A) with high-risk factors following endoscopic procedure, especially with deep submucosal invasion and vascular or lymphatic invasion, experienced further surgical resection. The median interval between endoscopic resection and completion surgery was 23.71 days ± 15.89. Sixteen patients (Group B) underwent radical resection without any prior interventions. The surgical approach involves integration of laparoscopy and colonoscopy for precise localization and quantitative diagnosis, followed by radical surgery. The two groups demonstrated significant differences statistically with reference to tumor diameter (1.65 cm ± 0.77 vs 3.36 cm ± 1.39, P = 0.000) and the attainment of standard lymph node count (cases of detected lymph nodes larger than or equal to 12, 5 vs 12, P = 0.015). Postoperative complications and hospital stay manifested no significant disparity statistically in two groups. Patients who underwent completion surgery had no inferior outcomes compared with those who underwent direct surgery in terms of 5-year disease-free survival (Log rank test: P = 0.083, Breslow test: P = 0.089). The two groups also exhibited no significant differences statistically in the context of overall survival (Log rank test: P = 0.652, Breslow test: P = 0.758).ConclusionCompletion surgery is a safe and feasible treatment option for T1 colorectal adenocarcinoma patients with high-risk factors, particularly those with deep submucosal invasion and vascular or lymphatic invasion following endoscopic treatment. Furthermore, subsequent treatment should be chosen based on a comprehensive analysis of the patient’s history of abdominal surgery, willingness, and pathological features.

Diagnostic utility of apparent diffusion coefficient in preoperative assessment of endometrial cancer: are we ready for the 2023 FIGO staging?

BackgroundAlthough endometrial cancer (EC) is staged surgically, magnetic resonance imaging (MRI) plays a critical role in assessing and selecting the most appropriate treatment planning. We aimed to assess the diagnostic performance of quantitative analysis of diffusion-weighted imaging (DWI) in preoperative assessment of EC.MethodsProspective analysis was done for sixty-eight patients with pathology-proven endometrial cancer who underwent MRI and DWI. Apparent diffusion coefficient (ADC) values were measured by two independent radiologists and compared with the postoperative pathological results.ResultsThere was excellent inter-observer reliability in measuring ADCmean values. There were statistically significant lower ADCmean values in patients with deep myometrial invasion (MI), cervical stromal invasion (CSI), type II EC, and lympho-vascular space involvement (LVSI) (AUC = 0.717, 0.816, 0.999, and 0.735 respectively) with optimal cut-off values of ≤ 0.84, ≤ 0.84, ≤ 0.78 and ≤ 0.82 mm2/s respectively. Also, there was a statistically significant negative correlation between ADC values and the updated 2023 FIGO stage and tumor grade (strong association), and the 2009 FIGO stage (medium association).ConclusionsThe preoperative ADCmean values of EC were significantly correlated with main prognostic factors including depth of MI, CSI, EC type, grade, nodal involvement, and LVSI.

Clinicopathological association of CD93 expression in gastric adenocarcinoma

AimsCD93 was recently identified as a promising therapeutic target for angiogenesis blockade in various tumors. Herein, we aimed to investigate the expression and clinicopathological significance of CD93 in gastric adenocarcinoma.MethodsThe gene expression of CD93 gastric adenocarcinoma was assessed using The Cancer Genome Atlas (TCGA) dataset. We then analyzed CD93 expression in 404 cases of gastric adenocarcinoma using immunohistochemistry. Clinicopathological associations and prognostic implications of CD93 expression were further investigated.ResultsUsing the TCGA dataset, we observed a significantly elevated CD93 gene expression in gastric adenocarcinoma compared to normal gastric tissues. The immunohistochemistry assay revealed a highly variable CD93 expression among patients with gastric adenocarcinoma, consistently demonstrating higher intratumor expression than in adjacent normal tissues. Notably, CD93 was predominantly expressed on the membrane of CD31+ vascular endothelial cells. Furthermore, patients with higher CD93 expression demonstrated significantly poorer overall survival. Accordingly, higher CD93 expression was associated with deeper invasion and a higher possibility of lymph node metastasis and developing tumor thrombus. Cox proportional hazards regression suggested CD93 expression was an independent predictor for the prognosis of patients with gastric adenocarcinoma.ConclusionsOur study revealed a significantly higher CD93 expression in gastric adenocarcinoma when compared with adjacent normal gastric tissues, and demonstrated its predominant expression on vascular endothelial cells. Our findings also highlighted the clinicopathological significance of CD93 in gastric adenocarcinoma, shedding light on a potential therapeutic target.

Clinical significance of lympho-vascular space invasion in different molecular subtypes of endometrial carcinoma

Objective: To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes. Methods: A total of 258 patients diagnosed EC undergoing surgery in Peking University People's Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative. Results: (1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences (χ2=7.79, P=0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P<0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all P<0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P<0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; χ2=12.15, P<0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; χ2=3.94, P=0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both P>0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both P<0.05). (4) Lymph node metastasis (HR=6.93, 95%CI: 1.15-41.65; P=0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression (HR=0.04, 95%CI: 0.01-0.14;P<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions: LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.

Therapeutic indications for antibody-drug conjugates estimated from HER2 and p53 expressions in endometrial carcinoma

ObjectiveWhile human epidermal growth factor receptor 2 (HER2) is upregulated in endometrial carcinoma—especially in the p53 aberrant type— conventional anti-HER2 therapy is not typically used for this cancer type. Recently, HER2-targeted antibody-drug conjugates have shown antitumor effects against HER2 low-expressing cancers. Therefore, we analyzed the clinicopathological characteristics of HER2-positive endometrial carcinomas including those with low expression, as well as the prognostic significance of p53 and HER2 co-expression. MethodsImmunohistochemistry for HER2 and p53 was performed in 530 patients with endometrial carcinoma; 124 cases (23%) were HER2-positive. ResultsOf the HER2-positive cases, >50% were 1+. A high prevalence of HER2 expression was observed in serous (64%), clear-cell (73%), and mixed (64%) carcinomas. Notably, 19% of endometrioid carcinomas were HER2-positive. HER2 positivity was significantly associated with age ≥60 years, high-grade histological subtype, deep myometrium invasion, stage III/IV, recurrence, and death. Univariate analysis showed that HER2-positive cases had reduced progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.012). However, after adjusting for stage, HER2 positivity was not associated with survival. In the early stage, co-expression of HER2-positive and p53 aberrant types was associated with shorter PFS (p < 0.001) and OS (p < 0.001) compared with at least one negative result. Multivariate analysis of PFS showed HER2 and p53 co-expression (hazard ratio, 1.891; 95% confidence interval, 1.183–5.971, p = 0.008) as an independent prognostic factor. ConclusionsThis study presents detailed clinicopathological characteristics and the prognostic impact of HER2-positivity in endometrial carcinomas. HER2-targeted antibody-drug conjugate therapy may be broadly applicable to endometrial carcinoma.

Urothelial Carcinoma with Trophoblastic Differentiation-A Report with Review.

Urothelial carcinoma with trophoblastic differentiation is a rare type of urothelial carcinoma that poses a diagnostic challenge. A 50-year-old man presented with hematuria for 4 months duration. Ultrasonography examination showed polypoidal lesions along the right lateral wall and near the right vesicoureteric junction of the urinary bladder. The transurethral resection of the bladder tumor (TURBT) specimen showed marked necrosis and urothelial tumor cells arranged in nests, sheets, and papillae, admixed with multinucleated large cells. Deep muscle and extensive lymphovascular invasion were noted. The tumor cells were diffuse immunopositive for GATA3 and focal positive for p63 and SALL4. Large multinucleated tumor cells were immunopositive for β-hCG, GATA3, inhibin-α, and PLAP, focally positive for SALL4 while negative for p63. The patient denied further treatment and succumbed to the disease after 8 months of the TURBT procedure. We report a rare invasive urothelial carcinoma with trophoblastic differentiation and discuss the differential diagnosis and literature review.

Role of androgen receptor expression in the metastatic potential of colorectal carcinoma

Background The prevalence of colorectal cancer (CRC) is widespread and associated with significant morbidity and deaths. In CRC, hormone receptors, such as androgen receptors (AR), are pathologically modified. Additional research is required to understand better its function and predictive and therapeutic value in CRC metastatic potential. Objective To assess the AR status in CRC primary tumors and metastatic lymph nodes. Methods Tissue microarray and immunohistochemical techniques were applied to 75 CRC cases with lymph node (LN) metastases. We correlate the results with all relevant clinicopathological indicators of prognostic relevance. Results and conclusion Out of the 75 cases that were analyzed, 16% of CRC primaries and 12% of LN metastases had nuclear AR that was focally positive. AR expression was significantly correlated with advanced age, conventional non-mucinous histology, lower grade, and arousal on top of adenoma. A deeper invasion was likewise linked to AR expression; however, this association was not statistically significant. AR expression has a positive prognostic influence since the median overall and disease-free survival of cases with positive AR expression in either primary carcinomas or LN metastases were significantly higher than that of cases with negative expression in both primary and LN metastases. We assume that AR expression in CRC has a positive prognostic influence.

Outcomes of noncurative endoscopic submucosal dissection for T1 colorectal cancer: Prospective, multicenter, cohort study in Japan.

This study investigated the incidence of lymph node metastasis and long-term outcomes in patients with T1 colorectal cancer where endoscopic submucosal dissection (ESD) resulted in noncurative treatment. It is focused on those with deep submucosal invasion, a factor considered a weak predictor of lymph node metastasis in the absence of other risk factors. This nationwide, multicenter, prospective study conducted a post-hoc analysis of 141 patients with T1 colorectal cancer ≥20 mm where ESD of the lesion resulted in noncurative outcomes, characterized by poor differentiation, deep submucosal invasion (≥1000 μm), lymphovascular invasion, high-grade tumor budding, or positive vertical margins. Clinicopathologic features and patient prognoses focusing on lesion sites and additional surgery requirements were evaluated. Lymph node metastasis incidence in the low-risk T1 group, identified by deep submucosal invasion as the sole high-risk histological feature, was assessed. Lymph node metastasis occurred in 14% of patients undergoing additional surgery post-noncurative endoscopic submucosal dissection for T1 colorectal cancer. In the low-risk T1 group, in the absence of other risk factors, the frequency was 9.7%. The lymph node metastasis rates in patients with T1 colon and rectal cancers did not differ significantly (14% vs. 16%). Distant recurrence was observed in one patient (2.3%) in the ESD only group and in one (1.0%) in the additional surgery group, both of whom had had rectal cancer removed. The risk of lymph node metastasis or distant occurrence was not negligible, even in the low-risk T1 group. The findings suggest the need for considering additional surgery, particularly for rectal lesions (Clinical Trial Registration: UMIN000010136).

Assessment of postoperative therapy de-escalation for early-stage, intermediate-risk cervical cancer

ObjectiveThe objective of this study was to assess the oncologic outcome of surgically-treated patients with early-stage, intermediate-risk cervical cancer according to postoperative therapy modality.MethodsThis retrospective cohort study queried the Japanese...