Subdivision of pT1N0 (American Joint Committee on Cancer 8th edition) distal cholangiocarcinoma for adjuvant chemotherapy consideration.

BACKGROUND: The adjuvant S-1 trial affirmed adjuvant chemotherapy for biliary tract cancer but excluded pT1N0 distal cholangiocarcinoma (DCC) according to the seventh edition of the American Joint Committee on Cancer (AJCC) classification. The introduction of tumor depth of invasion (DOI) for T-classification in the eighth edition complicates identifying DCC patients less likely to benefit from adjuvant chemotherapy. METHODS: Our cohort consisted of 185 patients with DCC who underwent pancreaticoduodenectomy between 2002 and 2019. We compared clinicopathological factors and survival outcomes between pT1N0 patients in the seventh edition and those in the eighth edition. New DOI cutoffs for subdividing pT1N0 (8th edition) patients were evaluated to identify patients less likely to benefit from adjuvant chemotherapy. RESULTS: Transitioning to the eighth edition increased in pT1N0 cases from eight to 46. The 5-year cumulative recurrence rates of them were 14.3% for the seventh edition and 28.3% for the eighth edition. We proposed a DOI cutoff of <2 mm, at which the 5-year cumulative recurrence rate was 11.5%. CONCLUSION: The eighth AJCC classification revealed that a significant proportion of pT1N0 DCC patients were at risk for recurrence. A DOI cutoff of <2 mm may be considered to potentially improve patient selection for adjuvant chemotherapy.

Tumor cell enrichment by tissue suspension improves sensitivity to copy number variation in diffuse gastric cancer with low tumor content.

The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with sporadic tumor cells, low tumor content prevents the accurate detection of somatic alterations using targeted sequencing. To efficiently identify CNVs, we performed tumor cell enrichment using tissue suspensions of formalin-fixed paraffin-embedded (FFPE) tissue sections with low tumor cell content. Tumor-enriched and residual fractions were separated from FFPE tissue suspensions of intestinal and diffuse-type gastric cancers containing sporadic tumor cells, and targeted sequencing was performed on 225 cancer-related genes. Sequencing of a targeted panel of cancer-related genes using tumor-enriched fractions increased the number of detectable CNVs and the copy number of amplified genes. Furthermore, CNV analysis using the normal cell-enriched residual fraction as a reference for CNV scoring allowed targeted sequencing to detect CNV characteristics of diffuse-type gastric cancer with low tumor content. Our approach improves the CNV detection rate in targeted sequencing with tumor enrichment and the accuracy of CNV detection in archival samples without paired blood.

Non-contrast-enhanced breast MRI for evaluation of tumor volume change after neoadjuvant chemotherapy.

PURPOSE: Three-dimensional contrast-enhanced magnetic resonance imaging (3D-Ce-MRI) is a most powerful tool for evaluation of neoadjuvant chemotherapy (NAC). However, the use of contrast agent is invasive, expensive, and time consuming, Thus, contrast agent-free imaging is preferable. We aimed to investigate the tumor volume change after NAC using maximum intensity projection diffusion-weighted image (MIP-DWI) and 3D-Ce-MRI. METHOD: We finally enrolled 55 breast cancer patients who underwent NAC in 2018. All MRI analyses were performed using SYNAPSE VINCENT® medical imaging system (Fujifilm Medical, Tokyo, Japan). We evaluated the tumor volumes before, during, and after NAC. Tumor volume before NAC on 3D-Ce-MRI was termed Pre-CE and those during and after NAC were termed Post-CE. The observer raised the lower end of the window width until the tumor was clearly visible and then manually deleted the non-tumor tissues. A month thereafter, the same observer who was blinded to the 3D-Ce-MRI results randomly evaluated the tumor volumes (Pre-DWI and Post-DWI) using MIP-DWI with the same method. Tumor volume change between ΔCE (Pre-CE - Post-CE/Pre-CE) and ΔDWI (Pre-DWI - Post-DWI/Pre-DWI) and the processing time for both methods (Time-DWI and Time-CE) were compared. RESULTS: We enrolled 55 patients. Spearman's rho between ΔDWI and ΔCE for pure mass lesions, and non-mass enhancement (NME) was 0.89 (p < 0.01), 0.63(p < 0.01) respectively. Time-DWI was significantly shorter than Time-CE (41.3 ± 21.2 and 199.5 ± 98.3 respectively, p < 0.01). CONCLUSIONS: Non-contrast-enhanced Breast MRI enables appropriate and faster evaluation of tumor volume change after NAC than 3D-Ce-MRI especially for mass lesions.

Cumulative incidence and risk factors for recurrence of upper tract urothelial carcinoma in patients undergoing radical cystectomy.

Objectives: This study aimed to evaluate the cumulative incidence of upper tract urothelial carcinoma (UTUC) recurrence and identify its risk factors in patients who underwent radical cystectomy (RC). Patients and methods: We performed RC on 385 patients between September 2002 and February 2020. After excluding 20 patients-13 with simultaneous nephroureterectomy, 6 with distal ureteral stump positivity and 1 with urachal cancer-365 patients were included in the analysis. To predict UTUC recurrence, we examined the cancer extension pattern in cystectomy specimens and categorized them into three types: cancer located only in the bladder (bladder-only type), cancer extending to the urethra or distal ureter (one-extension type) and cancer extending to both the urethra and distal ureter (both-extension type). We determined hazard ratios for UTUC recurrence for each covariate, including this cancer extension pattern. Results: Of the 365 patients, 60% had the bladder-only type, 30% had the one-extension type and 10% had the both-extension type. During a median follow-up period of 72 months for survivors, UTUC recurred in 25 of the 365 patients, with cumulative incidences of 3.7% at 5 years and 8.3% at 10 years. The median interval from cystectomy to recurrence was 65 months (interquartile range: 36-92 months). In the multivariate analysis, the extension pattern was a significant predictor of UTUC recurrence. The hazard ratios for UTUC recurrence were 3.12 (95% confidence interval [CI] = 1.15-8.43, p = 0.025) for the one-extension type and 5.96 (95% CI = 1.98-17.91, p = 0.001) for the both-extension type compared with the bladder-only type. Conclusions: The cancer extension pattern in cystectomy specimens is predictive of UTUC recurrence. A more extensive cancer extension in cystectomy specimens elevates the risk of subsequent UTUC recurrence. Intensive long-term monitoring is essential, particularly for patients with the both-extension type.

Efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma.

The efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) is unclear. This study aimed to evaluate the efficacy of second-line chemotherapy in patients with pulmonary LCNEC. We retrospectively reviewed patients with pulmonary LCNEC or possible LCNEC (pLCNEC) who received platinum-based chemotherapy as the first-line treatment. Among these patients, we evaluated the efficacy of second-line treatment by comparing patients with small cell lung cancer (SCLC group). Of the 61 patients with LCNEC or pLCNEC (LCNEC group) who received first-line chemotherapy, 39 patients were treated with second-line chemotherapy. Among the 39 patients, 61.5% received amrubicin monotherapy. The median progression-free survival (PFS) and overall survival (OS) in the LCNEC groups were 3.3 and 8.3 months, respectively. No significant differences in the PFS (hazard ratio [HR]: 0.924, 95% confidence interval [CI] 0.647-1.320; P = 0.664) and OS (HR: 0.926; 95% CI 0.648-1.321; P = 0.670) were observed between the LCNEC and SCLC groups. In patients treated with amrubicin, the PFS (P = 0.964) and OS (P = 0.544) were not different between both the groups. Second-line chemotherapy, including amrubicin, may be considered as a treatment option for patients with pulmonary LCNEC.

Genetic and Immunological Characterization of Brain Metastases from Solid Cancers.

BACKGROUND/AIM: Brain metastasis, a leading cause of cancer death, is a clinical challenge. Recently, genetic characterization of brain metastatic lesions based on next generation sequencing-based advanced technologies, such as single-cell RNA sequencing, has been performed to develop novel efficient therapies. The present study aimed to investigate brain-metastasis-specific biomarkers as well as relevant prognostic factors. PATIENTS AND METHODS: The genetic profiles and expression levels of immune response-associated genes and 820 cancer-associated genes were compared between primary cancer lesions and metastatic cancer lesions obtained from nine cancer patients at the Shizuoka Cancer Center. Cytokine and chemokine marker genes were analyzed via quantitative PCR. T-cell receptor (TCR) repertoire profiling was performed for the same patients. For survival analysis, survival data of 52 cancer patients with brain metastases were utilized. RESULTS: Comparison of driver mutation profiling between primary and metastatic lesions revealed shared core mutations in both lesions and a few new mutations in metastatic lesions. A high tumor mutation burden (TMB) was detected in metastatic lesions. Volcano plot analysis revealed specific features of the metastatic tumor microenvironment, such as cancer signaling promotion and immune suppression due to decreased immune cell infiltration. Survival analysis revealed that three genes, the TREML2 gene, the BTLA gene on activated microglia and the CERS2 gene on metastatic tumor, were potent prognostic factors. CONCLUSION: High TMB in metastatic lesions indicates potential benefit from immune checkpoint inhibitor usage for brain metastasis and TREML2 and BTLA are factors associated with poor prognosis. Activated microglia may be novel targets for the treatment of brain metastasis.

Pathologic significance of peribiliary capillary plexus in gallbladder neoplasm.

AIMS: Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP. MATERIALS AND METHODS: High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls. RESULTS: In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion). CONCLUSION: A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.

Brain Metastasis of Non-small Cell Lung Cancer After Disease-Free Survival of 5 years: Case Series and Comprehensive Literature Review.

BACKGROUND: In the treatment of nonsmall cell lung cancer (NSCLC), a disease-free survival of 5 years is a criterion for cure. This study aimed to evaluate the characteristics and outcomes of patients with brain metastases of NSCLC after a disease-free survival of 5 years (late recurrent brain metastasis [LRBM]). METHODS: We reviewed 1281 consecutive patients with brain metastasis of lung cancer at a single institute between November 2014 and December 2022. Relevant articles were retrieved from PubMed. Only peer-reviewed journals published in English were included. RESULTS: Six patients (0.47%) showed LRBM. Three were male. The median age at lung cancer diagnosis was 45 years. The histological diagnosis of all patients was adenocarcinoma. Driver gene mutations were observed in five patients. The median latency period from lung cancer treatment to the development of brain metastasis was 13 years. All patients had no metastasis to any other organs and underwent craniotomies. The median follow-up duration after craniotomy was 3.5 years. No local intracranial recurrences were observed. Three patients had distant intracranial recurrences at 7, 2, and 0.6 years after craniotomy. Five patients survived for 8, 4, 3, 2, and 0.3 years after craniotomy. One patient experienced re-recurrence in the lung 4 years after craniotomy and died 3.7 years later. In our systematic review, only six studies described LRBM of NSCLC. CONCLUSIONS: LRBM is rare in patients with NSCLC. In our institution, many of these patients harbored driver gene mutations, and achieved long-term survival with aggressive local therapy. Multicenter analysis is mandatory.

Gastric inflammatory myofibroblastic tumor: a case report.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) of the stomach is an uncommon mesenchymal neoplasm. We present a case of gastric submucosal tumor (SMT) where the final diagnosis was IMT. CASE PRESENTATION: A 69-year-old man presented with a 24-mm SMT on the posterior wall of the middle third of the stomach that was detected by screening upper gastrointestinal endoscopy. Abdominal contrast-enhanced computed tomography showed that the tumor was well-enhanced. Although endoscopic ultrasonography-guided biopsy was performed, the histological diagnosis was not confirmed preoperatively. Since the tumor was clinically suspected to be a gastrointestinal stromal tumor, we performed gastric wedge resection by laparoscopic-endoscopic cooperative surgery. Pathologically, proliferative spindle cells with a positive reaction for smooth muscle actin, negativity for c-kit, desmin, s-100, CD34, STAT-6, ß-catenin and anaplastic lymphoma kinase 1 were identified. Hence, the tumor was finally diagnosed as an IMT originating from the stomach. CONCLUSIONS: When an SMT of the stomach is identified, the possibility of gastric IMT should be considered.

Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment.

BACKGROUND/AIM: Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers. PATIENTS AND METHODS: Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis. RESULTS: Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers. CONCLUSION: These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.

A novel low-power pure-cut hot snare polypectomy for 10-14 mm colorectal adenomas: An ex vivo and a clinical prospective feasibility study (SHARP trial).

BACKGROUND AND AIM: Hot snare polypectomy using blend or coagulation current is widely used; however, it causes deeper tissue heat injury, leading to adverse events. We hypothesized that hot polypectomy using low-power pure cut current (PureCut, effect 1 10 W) could reduce deeper tissue heat injury. We conducted animal experiments to evaluate the deeper tissue heat injury and conducted a prospective clinical study to examine its cutting ability. METHODS: In a porcine rectum, hot polypectomy using Blend current (EndoCut, effect 3 40 W) and low-power pure cut current was performed. The deepest part of heat destruction and thickness of the non-burned submucosal layer were evaluated histologically. Based on the results, we performed low-power pure cut current hot polypectomy for 10-14 mm adenoma. The primary endpoint was complete resection defined as one-piece resection with negative for adenoma in quadrant biopsies from the defect margin. RESULTS: In experiments, all low-power pure-cut resections were limited within the submucosal layer whereas blend current resections coagulated the muscular layer in 13% (3/23). The remaining submucosal layer was thicker in low-power pure cut current than in blend current resections. In the clinical study, low-power pure-cut hot polypectomy removed all 100 enrolled polyps. For 98 pathologically neoplastic polyps, complete resection was achieved in 84 (85.7%, 95% confidence interval, 77-92%). The lower limit of the 95% confidence interval was not more than 15% below the pre-defined threshold of 86.6%. No severe adverse events occurred. CONCLUSIONS: A novel low-power pure-cut hot polypectomy may be feasible for adenoma measuring 10-14 mm. (UMIN000037678).

An autopsy case of primary gliosarcoma with multiple extracranial metastases: pathology after administration of bevacizumab and genetic profile.

Gliosarcoma (GS), a morphological variant of glioblastoma, pathologically shows a biphasic pattern with gliomatous and sarcomatous components. It has been reported that GS has much higher metastatic capacity than glioblastoma. A few reports on the pathology of the extracranial metastasis of GS have shown that metastatic lesions had a sarcomatous component alone or a mixture of gliomatous and sarcomatous ones. Therefore, it is considered that GS tends to disseminate hematogenously due to its mesenchymal sarcomatous component. Herein, we report an autopsy case of GS with multiple extracranial metastases treated by craniotomy, radiotherapy, and bevacizumab. In this case, metastatic lesions at autopsy contained a gliomatous component alone, but no sarcomatous component. In addition, the sarcomatous component disappeared from the intracranial lesion at autopsy after the administration of bevacizumab. In this report, we discuss the clinical course and pathological findings at the initial state, recurrence, and autopsy, including the results of whole-genome analysis.

A Primary Intraosseous Meningioma: A Rare Case of Malignancy with High Proliferative Ability.

Primary intraosseous meningioma (PIM) is a rare tumor that arises in the skull. Histopathologically, it is generally described as a slow-growing, benign lesion. However, on rare occasions, PIM presents as a malignancy with high proliferative ability, which requires maximal resection, adjuvant radiotherapy, and subsequent careful follow-up. Because of the rarity of such cases, they present a diagnostic challenge with unusual pathological findings. Herein, we report a case of a primary intraosseous anaplastic meningioma with extensive invasion inside and outside the skull, along with the results of whole-genome analysis. Histopathological diagnosis was a World Health Organization grade 3 anaplastic meningioma. In the literature, only two cases of anaplastic PIM have been reported, so its characteristics and treatment are poorly understood. Our patient was successfully treated with tumor resection, followed by intensity-modulated radiation therapy. Follow-up imaging studies revealed no recurrence or distant metastasis, including to lung, liver, and bone, at 8 months after the surgery.

Prognostic significance of tumor microenvironment assessed by machine learning algorithm in surgically resected non-small cell lung cancer.

BACKGROUND: A methodology to assess the immune microenvironment (IME) of non-small cell lung cancer (NSCLC) has not been established, and the prognostic impact of IME factors is not yet clear. AIMS: This study aimed to assess the IME factors and evaluate their prognostic values. METHODS AND RESULTS: We assessed CD8+ tumor-infiltrating lymphocyte (TIL) density, forkhead box protein P3+ (Foxp3+ ) TIL density, and programmed death receptor ligand-1 (PD-L1) tumor proportion score (TPS) using a machine-learning algorithm in whole-slide imaging (WSI). We dichotomized patients according to TIL density or TPS and compared their clinical outcomes. Between September 2014 and September 2015, 165 patients with NSCLC were enrolled in the study. We assessed IME factors in the epithelium, stroma, and their combination. An improvement in disease-free survival (DFS) was observed in the high CD8+ TIL density group in the epithelium, stroma, and the combination of both. Moreover, the group with high PD-L1 TPS in the epithelium showed better DFS than that with low PD-L1 TPS. In the multivariate analysis, the CD8+ TIL density in the combination of epithelium and stroma and PD-L1 TPS in the epithelium were independent prognostic factors (hazard ratio [HR] = 0.43; 95% confidence interval [CI] = 0.26-0.72; p = .001, HR = 0.49; 95% CI = 0.30-0.81; p = .005, respectively). CONCLUSION: Our approach demonstrated that the IME factors are related to survival in patients with NSCLC. The quantitative assessment of IME factors enables to discriminate patients with high risk of recurrence, who can be the candidates for adjuvant therapy. Assessing the CD8+ TIL density in the combination of epithelium and stroma might be more useful than their individual assessment because it is a simple and time-saving analysis of TILs in WSI.

ERBB2-Mutant Gastrointestinal Tumors Represent Heterogeneous Molecular Biology, Particularly in Microsatellite Instability, Tumor Mutation Burden, and Co-Mutated Genes: An In Silico Study.

During recent years, activating mutations in ERBB2 have been reported in solid tumors of various organs, and clinical trials targeting ERBB2-mutant tumors have been conducted. However, no effective treatment has been established for gastrointestinal tumors targeting ERBB2 mutations. ERBB2-mutant tumors have a higher tumor mutation burden (TMB) and microsatellite instability (MSI) than ERBB2 non-mutant tumors, but not all ERBB2-mutant tumors are TMB- and MSI-high. Thus, a more detailed classification of ERBB2-mutant tumors based on the underlying molecular mechanisms is required. Herein, we classified ERBB2 mutations into three groups-group 1: both ERBB2 mutations and amplifications; group 2: ERBB2 mutations annotated as putative driver mutations but without amplifications; group 3: ERBB2 mutations annotated as non-driver mutations (passenger mutations or unknown significance) and those that were not amplified in gastrointestinal tumors. Esophageal adenocarcinoma, gastric cancer, and colorectal cancer presented significantly higher MSI and TMB in the ERBB2-mutant group than in the ERBB2-wild-type group. The proportions of TMB- and MSI-high tumors and frequency of co-mutated downstream genes differed among the groups. We identified TMB- and MSI-high groups; this classification is considered important for guiding the selection of drugs for ERBB2-mutant tumors with downstream genetic mutations.

Desmin immunostaining is effective for improving interobserver variability in the depth assessment of the submucosal invasion of colorectal cancers.

Tumor depth evaluation is essential for pathological tumor staging because it affects clinical management as an independent risk factor for lymph node metastasis in colorectal cancers. However, poor interobserver variability of invasion depth has been reported. This study aimed to clarify the effectiveness of desmin immunostaining in the histological diagnosis of colorectal cancer. Overall, 63 sets of slides of colorectal cancer stained with hematoxylin and eosin (H&E) and desmin were prepared and independently reviewed by four examiners. After reviewing the desmin-stained slides, the interobserver variability of H&E slides alone was significantly improved for all examiners. For the assessment of Tis vs. T1, the sensitivity and accuracy were significantly improved for all examiners by combining H&E and desmin immunostaining. For the diagnosis of T1b vs. Tis or T1a, specificity and accuracy were significantly improved by adding desmin immunostaining. Ancillary desmin staining to assess submucosal invasion in colorectal cancers significantly improved interobserver agreement, led to efficient screening of T1 cancers, and reduced excessive T1b diagnoses. The combination of desmin immunostaining and H&E staining is highly recommended for diagnosing invasive colorectal cancer.

Molecular profiling of gastric neuroendocrine carcinomas.

Gastric neuroendocrine carcinoma (G-NEC) usually has NEC and adenocarcinoma components and is considered to have a common origin in gastric adenocarcinoma because common pathogenic mutations are shared. However, G-NEC without adenocarcinoma also exists, and it may have a different mechanism of tumorigenesis. We aimed to elucidate the tumorigenesis of G-NEC by focusing on the proportion of NEC components. Thirteen patients with G-NEC were included in this study. Comprehensive genetic analysis using whole-exome sequencing was performed. G-NEC without an adenocarcinoma component was defined as pure NEC. TP53 was detected as the most frequent gene mutation (85% of the patients), independent of classification. RB1, KMT2C, LTBP1, and RYR2 mutations were identified in two of three pure NEC patients but were not detected in other G-NEC patients. Pure NEC has different somatic mutation profile than other NECs. This study provides insights into the mechanism of tumorigenesis in G-NEC.

Local recurrence risk of esophageal squamous cell carcinoma due to intralesional damage during endoscopic submucosal dissection.

BACKGROUND AND AIM: It is unclear whether additional treatment should be considered given the recurrence risk after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) when the vertical margin is positive or unclear (VM1/VMX) due to intralesional damage. This study aimed to elucidate the local recurrence risk of ESCC caused by intralesional damage during ESD. METHODS: Among consecutive patients with pT1a ESCCs initially treated by ESD at our institution between January 2006 and December 2018, ESCCs diagnosed as VM1/VMX were retrospectively reviewed. Exclusion criteria were piecemeal resection and any additional treatment after ESD. Intralesional damage included the following three types: a macroscopic hole inside the lesion, an incision from the lateral margin of the specimen into the lesion, and crushing injury or burn effect into the deepest area of the lesion without an obvious hole. The local recurrence rate after ESD was primarily analyzed. RESULTS: Of 1174 pT1a ESCCs initially treated using ESD, 22 lesions were histopathologically diagnosed as VM1/VMX due to intralesional damage (1.9%; 95% confidence interval [CI], 1.2-2.8%). At a median follow-up period of 60.0 (interquartile range, 15.0-84.0) months, no local recurrence was observed (0.0%; 95% CI, 0.0-13.3%) among 21 lesions finally evaluated. CONCLUSIONS: The impact of intralesional damage during ESD for ESCC on local recurrence might be negligible. Follow-up without additional treatment may be acceptable even if intralesional damage occurs and results in VM1/VMX after ESD for pT1a ESCCs.