Superficial Squamous Cell Carcinoma Research Articles

Tumor thickness as a novel risk factor for lymph node metastasis by superficial squamous cell carcinoma of head and neck.

Narrow-band imaging combined with magnified endoscopy has enabled the detection of superficial squamous cell carcinoma of the head and neck (SSCCHN) that has been resected with minimally invasive treatment, preserving vocalization and swallowing functions. However, risk factors of lymph node metastasis (LNM) must be identified, as some patients with LNM have a poor prognosis. From an initial 599 patients with 700 lesions who underwent trans-oral surgery in 27 Japanese hospitals (a nationwide registration survey), we enrolled 541 patients with 633 SSCCHNs, as indicated by central pathological diagnoses. All pathological specimens for each patient were examined using 20 pathological factors that are thought to affect the LNM of SSCCHN. In all, 24 (4.4%) of the 568 SSCCHNs exhibited LNM, and all 24 had at least one solitary nest of epithelial neoplastic cells present in the stroma, clearly separated from the intraepithelial carcinoma. Multivariate analysis also showed that tumor thickness (p = 0.0132, RR: 7.85, 95% confidence interval [CI]: 1.54-40.02), and an INFc pattern classified as infiltrating growth (INF) with unclear boundaries between tumor and non-tumor tissues (p = 0.0003, RR: 14.47, 3.46-60.46), and tumor budding (p = 0.0019, RR: 4.35, CI: 1.72-11.01) were significantly associated with LNM. Solitary nests may be indicative of LNM. In addition, tumor thickness was revealed to be a risk factor for LNM in SSCCHNs using pT factors that do not include an invasion depth element because of the anatomical absence of the muscularis mucosae.

Subtotal esophagectomy and concurrent reconstruction with free jejunal flap for primary esophageal cancer after pancreatoduodenectomy.

Pancreatoduodenectomy and subtotal esophagectomy are widely considered the most invasive and difficult surgical procedures in gastrointestinal surgery. Subtotal esophagectomy after pancreatoduodenectomy is expected to be extremely difficult due to complicated anatomical changes, and selecting an appropriate intestinal reconstruction method will also be a difficult task. Therefore, perhaps because the method is considered impossible, there have been few reports of subtotal esophagectomy after pancreatoduodenectomy. A 73-year-old man with a history of pancreatoduodenectomy was diagnosed with superficial thoracic esophageal squamous cell carcinoma. Definitive chemoradiation therapy was recommended at another hospital; however, he visited our department to undergo surgery. We performed the robot-assisted thoracoscopic subtotal esophagectomy. There were some difficulties with the reconstruction: the gastric tube could not be used, the reconstruction was long, and the organs reconstructed in the previous surgery had to be preserved. However, the concurrent reconstruction was achieved with the help of a free jejunal flap and vascular reconstruction. All reconstructions from the previous surgery, including the remnant stomach, were preserved via regional abdominal lymph node dissection. After reconstruction, intravenous indocyanine green showed that circulation in the reconstructed intestines was preserved. On postoperative day 1, no recurrent nerve paralysis was observed during laryngoscopy. The patient could start oral intake smoothly 2weeks after surgery and did not exhibit any postoperative complications related to the reconstruction. The patient was transferred to another hospital on postoperative day 21. Owing to the free jejunal flap interposition method, we safely performed one stage subtotal esophagectomy and concurrent reconstruction, preservation of the remnant stomach, and pancreaticobiliary reconstruction in patients with a history of pancreatoduodenectomy. We believe that this method is acceptable and useful for patients undergoing complicated reconstruction.

Treatment benefit of electrochemotherapy for superficial squamous cell carcinoma: a systematic review and single-arm meta-analysis.

Treating aggressive superficial squamous cell carcinoma (SCC) poses challenges due to invasiveness. Palliative care is recommended for inoperable cases with extensive tumors near vital organs, risking disfigurement or functional impairment. Electrochemotherapy (ECT) is an emerging cutaneous tumor treatment, but its efficacy against superficial SCC remains uncertain. This study conducts a systematic review and single-arm meta-analysis to evaluate ECT's effectiveness against superficial SCC and provide current evidence for clinical practice. Embase, PubMed and Cochrane Library were searched for studies up to May 2023. The random effects model analyzed complete response (CR) and partial response (PR), with subgroup assessment based on drug dosage, treatment response evaluation, tumor size, primary/recurrent status, and tumor location. Ten studies involving 162 patients and 208 tumors were included. Pooled CR and PR rates for ECT-treated superficial SCC were 66.5% (95% CI 48.4%-82.5%; I2 = 84%) and 20.3% (95% CI 10.5%-32.3%; I2 = 70%), respectively. Subgroup analysis indicated ECT's superiority in treating primary tumors (PR: 70%, CR: 30%) and tumors ≤ 3cm (PR: 81.3%, CR: 10.1%) compared to recurrent tumors (PR: 56.7%, CR: 36.5%) and tumors > 3cm (PR: 45.2%, CR: 34.4%). This single-arm meta-analysis confirms ECT's efficacy against superficial SCC, especially in primary tumors and those ≤ 3cm in diameter. The study highlights the impact of tumor location and response evaluation on ECT's benefits, warranting further investigation through additional research.

Efficacy of endoscopic surveillance for pharyngeal mucosa during endoscopic resection for pharyngeal carcinoma: a multicenter prospective study.

Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.

Submucosal gland differentiation and implications in esophageal basaloid squamous cell carcinomas.

Esophageal basaloid squamous cell carcinoma (BSCC) is a heterogenous entity with multilineage differentiation. It lacks systematical analysis on submucosal gland differentiation (SGD) due to the histological diversity and low incidence of esophageal BSCC. This study aims to find the correlation of SGD and clinicopathological features. A total of 152 esophageal BSCCs were separated into three histological groups: pure, mixed, and borderline group. The clinicopathological features were compared between different groups. The prevalence of SGD was also compared between cases of different groups. A panel of antibodies were used to identify SGD. The pure group differed from the mixed and borderline groups in many aspects, lymph node metastasis (LNM), cancer embolus, perineural invasion, and advanced stage occurred less frequently in the pure group (P<0.01). The pure group had a better but statistically insignificant overall survival (P=0.097). The squamous cell carcinoma (SCC) component or focal squamous differentiation was present in metastatic lymph nodes in almost all mixed BSCCs (95.7%, 22/23) with LNM. The LNM rate of superficial (T1b) BSCCs (17.6%, 6/34) was comparable to that of superficial (T1b) SCCs (18.5%, 57/308). However, LNM exclusively occurred in superficial mixed (3/5) and borderline (3/10) BSCCs. The IHC results demonstrated a prevalence of SGD in pure group (77%, 43/56). SGD is considered to be a favorable factor, while the squamous differentiation or invasive SCC component is an adverse factor in esophageal BSCCs. Refinement of classification is a promising way to improve patient management.

Diagnostic Performance of a Novel Ultra-Thin Endoscopy under Narrow-Band Imaging for Superficial Squamous Cell Carcinoma of the Pharynx and Esophagus

This study aimed to evaluate the diagnostic utility of the ultra-thin endoscope (UTE) for superficial squamous cell carcinoma (SSCC) compared to magnifying endoscopy (ME) under narrow-band imaging. Participants underwent endoscopic examination, and images of pharyngeal and esophageal SCCs, as along with suspicious SSCC lesions, were collected using UTE and ME on the same day. Three image catalogs (UTE, ME-1, and ME-2) were created and reviewed by three expert endoscopists. ME-1 and ME-2 contained the same endoscopic images. The primary endpoint was the intra-observer agreement for diagnosing SCC. Eighty-six lesions (SCC = thirty-nine, non-SCC = forty-seven) in 43 participants were identified. The kappa values for the intra-observer agreement between UTE and ME-1 vs. the control (ME-1 vs. ME-2) were 0.74 vs. 0.84, 0.63 vs. 0.76, and 0.79 vs. 0.88, respectively. The accuracies for diagnosing SCC by UTE and ME-1 were 87.2% vs. 86.0%, 78.0% vs. 73,2%, and 75.6 vs. 82.6%, respectively, with no significant differences (p &gt; 0.05). The rates of lesions that were diagnosed with confidence by UTE and ME-1 were 30.2% vs. 27.9%, 55.8% vs. 62.8%, and 58.1% vs. 55.8%, respectively. UTE demonstrates substantial diagnostic performance for SSCC in the pharynx and esophagus.

Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial

Despite the usefulness of white light endoscopy (WLE) and non-magnified narrow-band imaging (NBI) for screening for superficial oesophageal squamous cell carcinoma and precancerous lesions, these lesions might be missed due to their subtle features and interpretation variations among endoscopists. Our team has developed an artificial intelligence (AI) system to detect superficial oesophageal squamous cell carcinoma and precancerous lesions using WLE and non-magnified NBI. We aimed to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. We did a multicentre, tandem, double-blind, randomised controlled trial at 12 hospitals in China. Eligible patients were aged 18 years or older and underwent sedated upper gastrointestinal endoscopy for screening, investigation of gastrointestinal symptoms, or surveillance. Patients were randomly assigned (1:1) to either the AI-first group or the routine-first group using a computerised random number generator. Patients, pathologists, and statistical analysts were masked to group assignment, whereas endoscopists and research assistants were not. The same endoscopist at each centre did tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-first group, the endoscopist did the first examination with the assistance of the AI system and the second examination without it. In the routine-first group, the order of examinations was reversed. The primary outcome was the miss rate of superficial oesophageal squamous cell carcinoma and precancerous lesions, calculated on a per-lesion and per-patient basis. All analyses were done on a per-protocol basis. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100052116) and is completed. Between Oct 19, 2021, and June 8, 2022, 5934 patients were randomly assigned to the AI-first group and 5912 to the routine-first group, of whom 5865 and 5850 were eligible for analysis. Per-lesion miss rates were 1·7% (2/118; 95% CI 0·0-4·0) in the AI-first group versus 6·7% (6/90; 1·5-11·8) in the routine-first group (risk ratio 0·25, 95% CI 0·06-1·08; p=0·079). Per-patient miss rates were 1·9% (2/106; 0·0-4·5) in AI-first group versus 5·1% (4/79; 0·2-9·9) in the routine-first group (0·37, 0·08-1·71; p=0·40). Bleeding after biopsy of oesophageal lesions was observed in 13 (0·2%) patients in the AI-first group and 11 (0·2%) patients in the routine-first group. No serious adverse events were reported by patients in either group. The observed effect of AI-assisted endoscopy on the per-lesion and per-patient miss rates of superficial oesophageal squamous cell carcinoma and precancerous lesions under WLE and non-magnified NBI was consistent with substantial benefit through to a neutral or small negative effect. The effectiveness and cost-benefit of this AI system in real-world clinical settings remain to be further assessed. National Natural Science Foundation of China, 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University, and Chengdu Science and Technology Project. For the Chinese translation of the abstract see Supplementary Materials section.

Invasive features of superficial oesophageal squamous cell carcinoma-analysis of risk factors for lymph node metastasis.

There are currently no studies that have examined the clinicopathological factors in detail, including the histological images of the invasive front, and the risk of lymph node metastasis (LNM) in superficial oesophageal squamous cell carcinoma (SESCC). This study aimed to develop an algorithm that contributes to a better assessment of the risk of LNM and recurrence in SESCC. Clinicopathological factors, such as submucosal (SM) invasion distance, were examined in 88 surgically resected cases of SESCC. An SM invasion distance of 600μm was the statistically best customer value for LNM (p = 0.0043). To obtain a histological image of the invasive front, we evaluated modified tumour budding (MBD) by modifying the number of tumour foci constituent cells and foci in tumour budding. We also evaluated the smallest number of tumour foci. Using these factors, we developed an algorithm to predict the risk of LNM. The best algorithm was created using an SM invasion distance of 600μm and an index of 5 or more foci consisting of five or fewer tumour cells in the MBD (MBD5 high-grade ≥ 5), which was also significantly associated with recurrence-free survival (p = 0.0305). Further study of the algorithm presented in this study is expected to improve the quality of life of patients by selecting appropriate additional treatments after endoscopic resection and appropriate initial treatment for SESCC.

Analysis of white-light imaging-based features predictive for determination of lesion depths of superficial flat esophageal squamous cell carcinoma: a retrospective multicenter study from China

ObjectivesEndoscopic diagnosis of invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by white-light imaging (WLI) modality remains difficult. This study aims to clarify WLI-based features which are predictive for invasion depth of SESCC.MethodsA two-phase study was performed by enrolling 1288 patients with 1396 SESCC lesions. Endoscopic appearances, clinical characteristics and post-operative pathological outcomes were collected and reviewed. The association between lesion features and invasion depth were analyzed. A predictive nomogram was constructed for prediction of invasion depth.ResultsAmong 1396 lesions in derivation and validation cohort, 1139 (81.6%), 194 (13.9%) and 63 (4.5%) lesions were diagnosed as lesions confined into the intraepithelium or the lamina propria mucosa (T1a-EP/LPM), lesions invading the muscularis mucosa (T1a-MM) or superficial submucosa (T1b-SM1) and tumor with moderate invasion into the submucosa or deeper submucosal invasion (≥ T1b-SM2), respectively. Lesion length > 2 cm (p < 0.001), wider circumferential extension (p < 0.001, 0.002 and 0.048 for > 3/4, 1/2–3/4 and 1/4–1/2 circumferential extension, respectively), surface unevenness (p < 0.001 for both type 0-IIa/0-IIc lesions and mixed type lesions), spontaneous bleeding (p < 0.001), granularity (p < 0.001) and nodules (p < 0.001) were identified as significant factors predictive for lesion depth. A nomogram based on these factors was constructed and the values of area under the Receiver Operating Characteristics curve were 0.89 and 0.90 in the internal and external patient cohort.ConclusionsOur study provides six WLI-based morphological features predicting for lesion depth of SESCC. Our findings will make endoscopic evaluation of invasion depth for SESCC more convenient by assessing these profiles.

Staging Accuracy and Lymph Node Involvement in Superficial Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus—a Multicenter Case Series Analysis

AbstractAt an early stage, esophageal cancer can be removed surgically or endoscopically. T1a tumors are removed by endoscopic resection, whereas T1b tumors are preferably surgically removed (esophagectomy) due to possible lymph node involvement. However, the diagnostic tools (endoscopic ultrasonography (EUS) and CT/PET-CT) used to distinguish between T1a and T1b tumors and to detect malignant lymph nodes are imprecise. This study aimed to review the accuracy of preoperative locoregional staging in superficial esophageal cancer in a Danish setting. This was a retrospective, multicenter study including patients with a cT1 esophageal tumor, both adenocarcinoma and squamous cell carcinoma. Patients receiving neoadjuvant treatment were excluded. Results from the preoperative diagnostics tools were compared with the pathology report to determine the diagnostic accuracy. Sixty-eight patients were included, 34 patients underwent esophagectomy, and 34 patients underwent endoscopic resection. The positive predictive value (PPV) of PET-CT (or CT) (when staged as a T1 tumor) was 77% (95%CI: 0.59–0.88), and the PPV of EUS (when staged as a T1a or T1b tumor) was 52% (95%CI: 0.32–0.72) and 60% (95%CI: 0.36–0.82), respectively. Six patients had malignant lymph nodes in the surgical specimen; none of them was identified before surgery. In conclusion, neither CT/PET-CT nor EUS is a precise tool to distinguish mucosal from submucosal esophageal tumors. Furthermore, in superficial malignant lesions, lymph node involvement is rare, but when present, it is rarely detected before surgery. To improve staging accuracy, all patients with cT1 tumors could be referred for a diagnostic endoscopic resection prior to possible other treatments.

Long-term outcome of cervical lymph node metastasis in superficial pharyngeal squamous cell carcinoma after endoscopic submucosal dissection

Superficial pharyngeal squamous cell carcinoma (PSCC) has received increasing attention as a therapeutic target in the GI field with recent innovations in endoscopic submucosal dissection (ESD). However, there are currently no defined criteria for the application of ESD to superficial PSCC. One of the problems encountered during follow-up after ESD is cervical lymph node metastasis (LNM). Identifying the clinicopathologic predictors of cervical LNM can help to provide a basis for the refinement of therapeutic strategies for superficial PSCC. The risk of cervical LNM was evaluated in 331 patients with superficial PSCC who underwent initial ESD between 2008 and 2021. Since tumor size, rather than depth, is the dominant factor in the current TNM classification for PSCC, the correlation between tumor size and thickness was investigated. The median follow-up period was 4.8 years. The cumulative 5-year cervical LNM rate was 6.1%. Multivariate Cox proportional hazards regression analysis identified tumor thickness≥1000 μm and lymphatic invasion as significant independent predictors. Among 204 cases with subepithelial invasion, both factors were also revealed to be significant independent predictors, suggesting that tumor thickness was superior to tumor size in predicting cervical LNM. Despite the positive correlation between tumor thickness and size, there was noticeable variability in the values (R= .20), and the current staging was inadequate to identify groups at high risk for cervical LNM. Tumor thickness and lymphatic invasion are validated as significant independent predictors for cervical LNM and can be useful indicators to optimize the therapeutic strategies for superficial PSCC.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Long‑term prognosis and comprehensive endoscopic treatment strategy for esophageal cancer, including salvage endoscopic treatment after chemoradiation therapy.

Endoscopic submucosal dissection (ESD) is the first treatment option for superficial squamous cell carcinoma of the esophagus (SSCE). Salvage endoscopic treatment for recurrent advanced esophageal cancer after chemoradiotherapy (CRT) has been reported. However, there are few reports on long-term prognosis after salvage endoscopic treatment in Japan. The present study investigated long-term treatment results after conventional ESD for SSCE and after salvage endoscopic treatment for locally recurrent lesions after CRT. Outcomes of esophageal ESD were retrospectively investigated at Nagasaki University Hospital and long-term prognosis after salvage endoscopic treatment for locally recurrence lesions after CRT was examined. The en-bloc curative resection rate was 89.5% (606/676) for conventional ESD. The 5-year cause-specific survival rate (CSS) was 98.5%. A total of 77 patients underwent salvage endoscopic treatment [ESD or photodynamic therapy (PDT)] for locally recurrent lesions after CRT. The 3-year CSS was 81.3 and 77.1% for salvage ESD and salvage PDT, respectively. SSCE management using ESD yielded high en-bloc curative resection and survival rates. Overall, establishing salvage endoscopic treatment made long-term control of the underlying disease possible, while also maintaining the quality of life for patients with recurrent advanced esophageal cancer deeper than patients with T1b who underwent CRT and patients with recurrence after additional CRT following ESD.

Efficacy of Organ Preservation Strategy by Adjuvant Chemoradiotherapy after Non-Curative Endoscopic Resection for Superficial SCC: A Multicenter Western Study.

In case of high risk of lymph node invasion after endoscopic resection (ER) of superficial esophageal squamous cell carcinoma (SCC), adjuvant chemoradiotherapy (CRT) can be an alternative to surgery. We assessed long-term clinical outcomes of adjuvant therapy by CRT after non-curative ER for superficial SCC. We performed a retrospective multicenter study. From April 1999 to April 2018, all consecutive patients who underwent ER for SCC with tumor infiltration beyond the muscularis mucosae were included. A total of 137 ER were analyzed. The overall nodal or metastatic recurrence-free survival rate at 5 years was 88% and specific recurrence-free survival rates at 5 years with and without adjuvant therapy were, respectively, 97.9% and 79.1% (p = 0.011). Independent factors for nodal and/or distal metastatic recurrence were age (HR = 1.075, p = 0.031), Sm infiltration depth > 200 µm (HR = 4.129, p = 0.040), and the absence of adjuvant CRT or surgery (HR = 11.322, p = 0.029). In this study, adjuvant therapy is associated with a higher recurrence-free survival rate at 5 years after non-curative ER. This result suggests this approach may be considered as an alternative to surgery in selected patients.

Multi-institutional questionnaire on treatment strategies for superficial entire circumferential esophageal squamous cell carcinoma.

Recent innovations in prophylactic treatment with steroids have overcome the issue of esophageal stricture after endoscopic submucosal dissection (ESD), except in entire circumferential esophageal squamous cell carcinoma (EC-ESCC). Current Japanese guidelines weakly recommend performing ESD for clinical epithelial/lamina propria EC-ESCC with a longitudinal extension <50 mm upon implementing prophylactic treatment against stricture. However, the accurate indications for ESD in EC-ESCC remain unknown, and strategies differ among institutions. The aim of this study was to understand the initial treatment strategy for EC-ESCC and prophylactic treatment after ESD against esophageal stricture. A questionnaire survey was conducted across 16 Japanese high-volume centers on the initial treatment for EC-ESCC according to the invasion depth and longitudinal extension, and prophylactic treatment against stricture. ESD was performed as the initial treatment not only in clinical epithelial/lamina propria lesions <50 mm (88-94% of institutions), but also in clinical epithelial/lamina propria ≥50 mm (44-50% of institutions) and clinical muscularis mucosae/SM1 (submucosal invasion depth invasion within 200 μm) lesions <50 mm (56-75% of institutions). Regarding prophylactic treatment against esophageal stricture, although there was a common point of local steroid injection, the details and administration of other treatments varied among institutions. As ESD was performed with expanded indications for EC-ESCC than those recommended by the guidelines in more than half of the institutions, the validity of ESD for expanded EC-ESCC needs to be clarified. For that, it is necessary to prospectively collect short- and long-term outcomes after ESD and other treatments, including esophagectomy or chemoradiotherapy.

Efficacy of endoscopy under general anesthesia for the detection of synchronous lesions in oro-hypopharyngeal cancer.

Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p<0.001). The lesions that were newly detected on endoscopy under general anesthesia were small and characterized by few changes in color and surface ruggedness. Endoscopy under general anesthesia for superficial squamous cell carcinoma is helpful for detecting multiple synchronous lesions.

Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma

BackgroundAlthough the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects.ResultsHerein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them.ConclusionThe current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.Graphical

Clinical outcomes of endoscopic submucosal dissection for superficial circumferential esophageal squamous cell carcinoma

Our aim was to elucidate the clinical outcomes of endoscopic submucosal dissection (ESD) for superficial circumferential esophageal squamous cell carcinoma (cESCC). Consecutive patients who underwent ESD for cESCC between 2009 and 2020 were retrospectively reviewed. Short-term outcomes were en-bloc resection, R0 resection, procedure time, and adverse events, whereas long-term outcomes were overall survival (OS), disease-specific survival (DSS), cumulative recurrence rate (CRR), and clinical course. Fifty-two patients with 52 cESCCs (median tumor length, 5.0 cm; interquartile range [IQR], 4.0-6.3) were evaluated. The en-bloc resection and R0 resection rates were 100% (95% confidence interval [CI], 94.4-100) and 69.2% (95% CI, 54.9-81.3), respectively. The median procedure time was 112 minutes (IQR, 87-162). Intraoperative perforations and delayed bleeding occurred in 4 (7.7%) and 1 (1.9%) patients, respectively. Among the 42 patients who underwent ESD alone, 36 (85.7%) experienced esophageal strictures. Within a median follow-up of 49.1 months (IQR, 25.7-74.7), the 4-year OS, DSS, and CRR were 86.2% (95% CI, 71.6-93.6), 95.5% (95% CI, 83.1-98.9), and 11.5% (95% CI, 4.1-23.1), respectively. There was no significant difference in the OS between patients with low-risk cESCC (pT1a, negative lymphovascular invasion, and negative vertical margin) and high-risk lesions, regardless of undergoing additional treatment (P= .93). In 31 patients with low-risk cESCC who were treated with ESD alone, the 4-year OS, DSS, and CRR were 93.2%, 100%, and 0%, respectively. ESD is a highly curative treatment for cESCC with favorable long-term outcomes, especially in low-risk patients. Stricture-prevention techniques should be improved to optimize the benefits of ESD for cESCC.

Clinical features of superficial esophagus squamous cell carcinoma according to alcohol-degrading enzyme ADH1B and ALDH2 genotypes.

Inactivated alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are related to esophageal carcinogenesis. We aimed to clarify the clinical features associated with the alcohol-degrading enzyme genotypes, ADH1B and ALDH2. We also investigated the risk factors for metachronous esophageal squamous cell carcinoma (ESCC) and head and neck SCC (HNSCC). We conducted a single-center, retrospective study including patients with ESCC treated by endoscopic resection. Patients were recruited between October 2020 and September 2021. Buccal mucosal swabs were obtained from them to analyze the genetic polymorphisms affecting ADH (ADH1B) and ALDH (ALDH2) activity. Patients were categorized into three groups: both inactivated = double-inactivated group; inactivated ADH1B or ALDH2 = single-inactivated group; and both activated = activated group. Among the 297 enrolled patients, patients in the double-inactivated group were significantly younger (P < 0.001) and 60% of them were ≤ 50years old. This group also had more ESCCs located in the upper esophagus (P < 0.001) and more simultaneous multiple ESCCs (P = 0.044). More than half of the patients had multiple Lugol-voiding lesions (LVLs) (P < 0.001) and heavy alcohol consumers (P = 0.012). Metachronous ESCC and HNSCC were more common in the double-inactivated group (P < 0.001, P = 0.001). Multivariate analysis identified located in the upper esophagus, multiple LVLs and history of HNSCC as risk factors for metachronous ESCC. Activation patterns of alcohol-metabolizing enzymes were related to age at ESCC onset, lesion location, and metachronous ESCC and HNSCC. Different approaches to the prophylaxis and treatment of esophageal cancer should be considered, depending on the enzyme activity pattern.

Superficial spreading cervical squamous cell carcinoma in situ involving the endometrium: a case report and review of the literature

BackgroundThe spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer.Case presentationWe present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months’ duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery.ConclusionsSquamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease.