Endoscopic Treatment of Early Barrett's Adenocarcinoma and Dysplasia: Focus on Submucosal Cancer.

BACKGROUND/AIMS: Eradication of early Barrett's neoplasia by endoscopic resection and radiofrequency ablation is safe and effective. In T1b adenocarcinoma, standard of care remains controversial. We investigated the therapeutic outcome between high-grade dysplasia (HGD)/mucosal adenocarcinoma and submucosal adenocarcinoma in Barrett's patients. We hypothesised similar outcome in low-risk (LR) T1b compared to T1a/HGD. METHODS: Patients with endoscopically treated Barrett's esophagus were included in a Swiss tertiary center cohort study. Primary outcome parameter was complete eradication of early neoplasia. Secondary outcome parameters were recurrence-free survival and safety of endoscopic treatment. RESULTS: Forty-eight patients (1 female) with median Barrett's length C4M6 and mean age of 66 years were included. Complete endoscopic eradication of HGD/T1a was achieved in 33 out of 35 and in 11 out of 13 T1b adenocarcinoma. During a median follow-up of 41 (interquartile range 28-63) months no systemic recurrence was observed in endoscopically treated HGD/T1a and LR -T1b and one in a high-risk T1b adenocarcinoma after surgery. Local recurrences were amenable to surgical or endoscopic re-treatment. No lymphnode metastasis was detected in initial staging with esophageal endosonography/positron emission tomography-CT. CONCLUSION: Comparable endoscopic eradication and recurrence rate were observed in HGD/T1a and LR T1b adenocarcinoma. Carefully selected LR T1b cancer may receive endoscopic treatment in an expert center without any negative impact on recurrence.

[Endoscopic therapy of esophageal diseases]. / Endoskopisch-interventionelle Therapie von Ösophaguserkrankungen.

The esophagus is one of the areas of the gastrointestinal tract, for which therapeutic concepts have changed the most over the last two decades. The most decisive advance is the development of endoscopic resection techniques for early esophageal carcinomas. These methods provide excellent short- and long-term results combined with very low morbidity and negligible mortality rates in comparison with surgical esophagectomy, especially in case of mucosal Barrett's adenocarcinoma. In addition, the endoscopic myotomy techniques in Zenker's diverticulum and spastic achalasia are new, attractive endoscopic treatment modalities.

Surgical therapy of ground-glass opacities.

Ground glass opacities, also known as GGOs, are detected on computed tomography (CT) scans as hazy areas if increased attenuation in the lung, and my represent a variety of pulmonary processes. Natural history of GGOs and their clinical implications are not yet fully understood. Controversies associated with the management of GGOs surround their histological classification, malignant potential, indications, timing, and type of intervention. Herein we discuss the principles and role of surgical therapy for ground glass opacities.

Experience Sharing in Pathological Diagnosis of Early Adenocarcinoma of the Lung.

Background: In daily work, there are still many pathologists who have difficulty handling the diagnosis of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma, and the boundaries are not clear enough. Sometimes, the diagnosis is difficult, and there is sometimes poor reproducibility between different pathologists. Accurate diagnosis and differential diagnosis require a certain amount of experience. Methods: During the COVID-19 pandemic, we collected a large number (n = 381) of specimens of early lung adenocarcinoma, most of which (n = 356) were solitary lesions and 25 were multifocal lesions. There were 78 nodules in multifocal lesions, total 434 nodules. We summarized very careful microscopic observation and comparative analysis on all frozen and paraffin sections collected from many early lung adenocarcinoma specimens, continuously summarizing our experience. Results: Based on the World Health Organization's 2021 classification and diagnostic criteria for lung adenocarcinoma, new perspectives have been proposed on how to distinguish between atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma. In particular, new perspectives have been proposed on how to identify invasive aspects, and there are also some new perspectives on early lung mucinous lesions. Conclusion: Atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma all have corresponding morphological diagnostic criteria, but the morphological boundaries are sometimes not easy to determine and require some experience accumulation. The intraoperative frozen pathological diagnosis of early adenocarcinoma of the lung needs to be closely combined with imaging examination, and has very rich morphological experience.

Solid histological component of adenocarcinoma might play an important role in PD-L1 expression of lung adenocarcinoma.

BACKGROUND: In this study we aimed to clarify the PD-L1 positive expression in lung adenocarcinoma, including various adenocarcinoma subtypes paying particular attention to its component. METHODS: A total of 307 lung adenocarcinoma patients who underwent lobectomy or segmentectomy, as well as systematic lymph node dissection (ND2a), from February 2008 to March 2020 at our hospital, were enrolled into the study. A final diagnosis of adenocarcinoma was obtained from the resected lung specimens of all 307 patients to determine the histological type, adenocarcinoma subtype, and component of adenocarcinoma by ethics of 5%. PD-L1 was immunohistochemically stained using the murine monoclonal antibody clone 22C3. RESULTS: When PD-L1 expression-positive was defined by tumor proportion score (TPS) ≥1%, the positive cases were 6/33 in adenocarcinoma (Ad) in situ (AIS), 2/26 in minimally invasive Ad (MIA), 12/60 in lepidic predominant Ad (LPA), 44/91 in papillary predominant Ad (PPA), 24/49 in acinar predominant Ad (APA), 23/28 in solid predominant Ad (SPA), 4/7 in micropapillary predominant Ad (MPA), and 0/13 in invasive mucinous Ad (IMA). In the high proportion group (APA, PPA, SPA, and MPA) of PD-L1 expression, SPA was the only subtype which was statistically significant when both PD-L1 expression-positive was defined by TPS ≥ 1% (p < 0.0001) and TPS â‰§ 50% (p < 0.0001). We then considered the solid component. We investigated 279 cases of the other subtype group excluding SPA. The group containing a solid component (≥5%) tended to be PD-L1 expression-positive both when defined by TPS ≥1% (p < 0.0001) and TPS â‰§50% (p = 0.0049). CONCLUSIONS: The PD-L1 expression tended to be positive when a solid component was confirmed (≥5%) in specimens of lung adenocarcinoma patients.

Artificial Intelligence in the Management of Barrett's Esophagus and Early Esophageal Adenocarcinoma.

Esophageal adenocarcinoma is increasing in incidence and is the most common subtype of esophageal cancer in Western societies. The stepwise progression of Barrett´s metaplasia to high-grade dysplasia and invasive adenocarcinoma provides an opportunity for screening and surveillance. There are important unresolved issues, which include (i) refining the definition of the screening population in order to avoid unnecessary invasive diagnostics, (ii) a more precise prediction of the (very heterogeneous) individual progression risk from metaplasia to invasive cancer in order to better tailor surveillance recommendations, (iii) improvement of the quality of endoscopy in order to reduce the high miss rate for early neoplastic lesions, and (iv) support for the diagnosis of tumor infiltration depth in order to guide treatment decisions. Artificial intelligence (AI) systems might be useful as a support to better solve the above-mentioned issues.

Current Trends in Endoscopic Diagnosis and Treatment of Early Esophageal Cancer.

Diagnosis of esophageal adenocarcinoma mostly occurs in the context of reflux disease or surveillance of Barrett's metaplasia. Optimal detection rates are obtained with high definition and virtual or dye chromoendoscopy. Smaller lesions can be treated with endoscopic mucosal resection. Endoscopic submucosal dissection (ESD) is an option for larger lesions. Endoscopic resection is considered curative (i.e., without significant risk of lymph node metastasis) if histopathology confirms en bloc and R0 resection of a well-differentiated (G1/2) tumor without infiltration of lymphatic or blood vessels and the maximal submucosal infiltration depth is 500µm. Ablation of remaining Barrett's metaplasia is important, to reduce the risk of metachronous cancer. Esophageal squamous cell cancer is associated with different risk factors, and most of the detected lesions are diagnosed during upper gastrointestinal endoscopy for other indications. Virtual high definition and dye chromoendoscopy with Lugol's solution are used for screening and evaluation. ESD is the preferred resection technique. The criteria for curative resection are similar to Barrett's cancer, but the maximum infiltration depth must not exceed lamina propria mucosae. Although a submucosal infiltration depth of up to 200 µm carries a substantial risk of lymph node metastasis, ESD combined with adjuvant chemo-radiotherapy gives excellent results. The complication rates of endoscopic resection are low, and the functional outcomes are favorable compared to surgery.

Chondroid gastrointestinal stromal tumor in the stomach with early adenocarcinoma.

OBJECTIVE: To explore the pathologic features of gastric chondroid gastrointestinal stromal tumors. METHODS: The clinicopathologic data of one case of gastric chondroid gastrointestinal stromal tumor were collected and the features were analyzed by literature review. RESULTS: The male patient was 64 years old and had suffered from upper abdominal fullness discomfort without obvious cause for 5 years. Gastroscopic examination showed a rough area located in the lesser curvature of the gastric antrum, measuring 6 cm × 4 cm. CT scan showed the stomach wall was unevenly thick at the gastric antrum and stomach outlet. Multiple enlarged lymph nodes were seen nearby. The biopsy pathology showed adenocarcinoma of gastric antrum. The patient underwent laparoscopic gastrectomy and gastric chondroid gastrointestinal stromal tumor was found with adenocarcinoma of the stomach. Asp842Val mutation was found in the PDGFRα 18 exon. CONCLUSION: Gastric chondroid gastrointestinal stromal tumors are rare and low risk. Tumor cells express CD117 and Asp842Val mutation in the PDGFRα 18 exon revealed by genetic sequencing suggesting this kind of tumor might be resistant to imatinib.

PD-L1 Expression in Non-Small-Cell Lung Cancer Including Various Adenocarcinoma Subtypes.

PURPOSE: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell lung cancer (NSCLC), including adenocarcinoma subtypes. METHODS: In all, 90 NSCLC specimens containing various adenocarcinoma subtypes, in addition to squamous cell carcinoma and large-cell carcinoma were selected. PD-L1 was immunohistochemically stained by murine monoclonal antibody clone 22C3. RESULTS: When PD-L1-positive expression was defined by tumor proportion score (TPS) ≥1%, the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma, 6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males, smokers, advanced pathologic stages, positive vessel invasion, and positive lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive expression was a significantly worse prognostic factor in univariate analysis for recurrence-free survival (RFS). CONCLUSION: PD-L1-positive tumors were frequent in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC patients.

Endoscopic management of dysplasia and early oesophageal cancer.

In the past decade there have been technological advances in Endoscopic Eradication Therapy (EET) for the management of patients with oesophageal neoplasia and early cancer. Multiple endoscopic techniques now exist for both squamous and Barrett's oesophagus associated neoplasia or early cancer. A fundamental aspect of endotherapy is removal of the target lesion by endoscopic mucosal resection, or endosopic submucosal dissection. Residual tissue is subsequently ablated to remove the risk of recurrence. The most validated technique for Barrett's oesophagus is radiofrequency ablation, but other techniques such as hybrid-APC and cryotherapy also show good results. This chapter will discuss the evolution of EET, and which patients are most likely to benefit. It will also explore the evidence behind the success of different techniques and provide practical advice on how to carry out the endoscopic techniques with a focus on radiofrequency ablation and endoscopic mucosal resection in particular.

Diagnosis and treatment of superficial esophageal cancer.

Endoscopy allows for the screening, early diagnosis, treatment and follow up of superficial esophageal cancer. Endoscopic submucosal dissection has become the gold standard for the resection of superficial squamous cell neoplasia. Combinations of endoscopic mucosal resection and radiofrequency ablation are the mainstay of the management of Barrett's associated neoplasia. However, protruded, non-lifting or large lesions may be better managed by endoscopic submucosal dissection. Novel ablation tools, such as argon plasma coagulation with submucosal lifting and cryoablation balloons, are being developed for the treatment of residual Barrett's esophagus, since iatrogenic strictures still hamper the development of extensive circumferential resections in the esophagus. Optimal surveillance modalities after endoscopic resection are still to be determined. The assessment of the risk of lymph-node metastases, as well as of the need for additional treatments based on qualitative and quantitative histological criteria, balanced to the patient's condition, requires a dedicated multidisciplinary team decision process. The need for trained endoscopists, expert pathologists and surgeons, and specialized multidisciplinary meetings underlines the role of expert centers in the management of superficial esophageal cancer.

Epidermal growth factor receptor mutations in adenocarcinoma in situ and minimally invasive adenocarcinoma detected using mutation-specific monoclonal antibodies.

OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation rates in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) were studied using both DNA analysis and mutation-specific immunohistochemistry. MATERIALS AND METHODS: The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used to detect mutations in exons 18, 19, 20, and 21 of the EGFR gene in DNA samples extracted from paraffin-embedded tissue sections. Simultaneously, immunohistochemical analysis with two EGFR mutation-specific monoclonal antibodies was used to identify proteins resulting from an in-frame deletion in exon 19 (E746_A750del) and a point mutation replacing leucine with arginine at codon 858 of exon 21 (L858R). RESULTS: Forty-three tumors (22 AIS and 21 MIA) were examined. The EGFR mutation rate in AIS detected by DNA analysis was 27.3% (L858R, 5/22; exon 19 deletion,1/22), whereas that detected in MIA was 42.9% (L858R,4/21; exon 19 deletion,5/21). Mutations detected by immunohistochemical analysis included 22.7% (L858R, 4/22; exon 19 deletion, 1/22) in AIS and 42.9% (L858R, 4/21; exon 19 deletion, 5/21) in MIA. Although some results were contradictory, concordant results were obtained using both assays in 38 of 43 cases (88.4%). CONCLUSION: DNA and immunohistochemical analyses revealed similar EGFR mutation rates in both MIA and AIS, suggesting that mutation-specific monoclonal antibodies are useful to confirm DNA assay results.