Clinical usefulness of hybrid endoscopic submucosal dissection for T1b colorectal carcinomas ≤20 mm to ensure adequate vertical margins.

Objective: To evaluate endoscopic resection strategies for cT1b colorectal carcinomas (CRCs) ≤20 mm to determine strategies that enable adequate vertical margins (VMs). Methods: We enrolled 128 consecutive patients with cT1b colorectal carcinomas ≤20 mm resected by endoscopic mucosal resection or hybrid endoscopic submucosal dissection (ESD). Tumor lifting conditions after submucosal injection were classified into type A (lifting, soft dome-like), type B (lifting, hard trapezoid-like), and non-lifting (positive non-lifting sign). Predictors of positive VMs (VM 1) and adequate VMs were identified. Results: All non-lifting tumors were resected by hybrid ESD and VMs were ≥500 µm. Vertical margin 1 tumors were only found in the endoscopic mucosal resection group, in which, the proportion of type B tumors with VM 1 was significantly higher than that of tumors with negative VMs (p < 0.01). Type A tumors showed no significant between-group differences. Among type B tumors, the proportion of VMs ≥500 µm was significantly higher (p < 0.01) and the VM distance was significantly longer (p < 0.01) in the hybrid ESD group than in the endoscopic mucosal resection group. Conclusions: Hybrid ESD can be selected for type B tumors to ensure adequate VMs.

Comparative analyses of short- and long-term outcomes between endoscopic submucosal dissection and endoscopic laryngo-pharyngeal surgery for superficial pharyngeal carcinomas.

Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

Clinical usefulness and acceptability of small-bowel capsule endoscopy with panoramic imaging compared with axial imaging in Japanese patients.

Objectives: We aimed to evaluate the usefulness and acceptability of CapsoCam Plus (CapsoCam) in Japanese patients. Methods: This retrospective single-center study enrolled 930 patients with suspected small-bowel bleeding (SSBB) who underwent capsule endoscopy. Thirty-three patients using CapsoCam and PillCam SB3 (SB3) were matched using propensity score matching. The diagnostic yield and the acceptability of CapsoCam were evaluated. Results: There was no SSBB case where capsule endoscopy was performed within 48 h of bleeding. CapsoCam had a significantly higher observation rate of the entire small bowel (97% vs. 73%, p = 0.006) and Vater's papilla (82% vs. 15%, p < 0.001) than SB3. The reading time of CapsoCam was significantly longer than that of SB3 (30 vs. 25 min, p < 0.001), and CapsoCam's time from the capsule endoscopy swallowing to read completion was longer than that of SB3 (37 vs. 12 h, p < 0.001). The two groups showed no difference in the capsule endoscopy findings according to the P classification. Notably, 85% of the patients using CapsoCam reported examination distress as "not at all" or "almost not," and 94% reported swallowing difficulty as "very easy" or "easy." Conclusions: CapsoCam took time to read; however, it is a well-tolerated examination with a high observation rate of Vater's papilla and entire small-bowel mucosa. Detectability of bleeding sources was comparable in both modalities for cases of occult SSBB and overt SSBB more than 48 h after bleeding. CapsoCam is a useful modality for patients with SSBB.

Genetic Analysis of Biopsy Tissues from Colorectal Tumors in Patients with Ulcerative Colitis.

BACKGROUND/OBJECTIVES: Colorectal neoplasia developing from ulcerative colitis mucosa (CRNUC) can be divided into ulcerative colitis-associated neoplasia (UCAN) and non-UCAN; however, it is often difficult to distinguish UCAN from non-UCAN during a biopsy diagnosis. We investigated whether a genomic analysis could improve the diagnostic accuracy of UCAN using biopsy specimens. METHODS: In step 1, 14 CRNUCs were used to examine whether the genomic landscape of biopsy and resection specimens matched. In step 2, we investigated the relationship between the genomic landscapes and the pathological diagnosis of 26 CRNUCs. The cancer genome was analyzed by deep sequencing using a custom panel of 27 genes found to be mutated in our previous CRNUC analysis. RESULTS: In step 1, of the 27 candidate genes, 14 were mutated. The concordance rate of the pathogenic mutations in these 14 genes between the biopsy and resection specimens was 29% (4/14), while that of the pathogenic mutations in TP53 and KRAS was 79% (11/14). In step 2, the pathological diagnosis of biopsy specimens using only hematoxylin and eosin (HE) staining had a sensitivity of 33% and an accuracy of 38% for UCAN diagnosis. On the other hand, the combination of the HE pathology and p53 immunohistochemical staining had a sensitivity of 73% and an accuracy of 85% for UCAN diagnosis, while the combination of HE staining and a TP53 mutation had a sensitivity of 87% and an accuracy of 88% for UCAN diagnosis. CONCLUSIONS: An evaluation of TP53 mutations in biopsy specimens may be useful for diagnosing UCAN. However, further studies with larger sample sizes are required before this can be applied in clinical practice.

A case of esophageal squamous cell carcinoma with epidermization showing a unique morphology.

An 80-year-old woman with a history of endoscopic balloon dilation for esophageal stricture caused by accidental ingestion of caustic soda during infancy presented with dysphagia. Upper gastrointestinal endoscopy revealed a 10-cm-long, highly white, elevated lesion with a feathered appearance. This lesion was determined to be the cause of dysphagia and was completely resected via endoscopic submucosal dissection. Histopathological examination revealed a thick keratin layer on the surface of the stratified squamous epithelium, with a prominent granular layer underneath and some areas showing nuclear atypia. The lesion was diagnosed as a well-differentiated squamous cell carcinoma, pT1a-LPM, derived from epidermoid metaplasia. Cancer genome analysis revealed mutations in TP53 as well as amplification of MYC, FGFR1, chromosome 7, and chromosome 20q. This case suggests that epidermoid metaplasia caused by chronic irritation from an esophageal stricture may have been exacerbated by the dilation procedure.

A case of colon cancer implanted on endoscopic resection ulcer certified by cancer genomic testing.

A 90 year-old man underwent endoscopic mucosal resection for lesions in the descending and sigmoid colons as well as endoscopic submucosal dissection (ESD) for a lesion in the rectal peritoneal reflection (Ra) 1 month before undergoing laparoscopic resection and D3 dissection for advanced cancer in the descending colon. One year later, he underwent a surveillance colonoscopy, and advanced colorectal cancer was detected on the ESD scar. The history suggested that this newly detected recurrent colorectal neoplasm on the ESD scar may have originated from cancer cells derived from the descending colon cancer that were implanted in the ESD ulcer, thereby initiating a new colorectal neoplasm. Cancer genomic testing further indicated that three of the four pathogenic variants detected in the recurrent colorectal neoplasm were consistent with pathogenic variants of descending colon cancer. This finding strongly supports our contention that cancer cells derived from the descending colon cancer were implanted in the post-ESD ulcer of the rectal Ra and proliferated, forming the recurrent colorectal neoplasm. This case report highlights the potential for tumor cell implantation on endoscopic resection ulcers and the utility of cancer genomic testing in validating this phenomenon.

Zoster Sine Herpete Affecting Multiple Lower Cranial Nerves Presenting Severe Dysphagia in a Patient with Parkinson's Disease.

We report the case of a 74-year-old woman with Parkinson's disease (PD) who developed acute dysphagia, dysarthria, and hoarseness. A neurological examination and nasopharyngeal fiberscopy revealed paralysis of the left glossopharyngeal, vagus, and hypoglossal nerves. No skin rash was observed. Cerebrospinal fluid testing showed lymphocytic pleocytosis, and an elevated varicella-zoster virus (VZV) IgG antibody index. She was diagnosed with zoster sine herpete unilaterally affecting multiple lower cranial nerves. Although dysphagia is common in patients with PD, acute exacerbations of dysphagia require careful investigation of various potential causes, including VZV infection.

WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases with p53 Mutations.

Inhibition of WEE1, a key regulator of the G2/M checkpoint of the cell cycle, induces apoptosis by initiating mitosis without repairing DNA damage. However, the effects of WEE1 inhibitors on the tumor immune microenvironment in colorectal cancer (CRC) remain unclear. Here, we investigated the association between WEE1 expression and CRC clinicopathological features using surgically resected CRC specimens and assessed the antitumor effects of a WEE1 inhibitor using CRC cell lines and orthotopic transplantation mouse models. WEE1 expression was not correlated with the clinicopathological features of CRC. The WEE1 inhibitor suppressed cell proliferation in a concentration-dependent manner in all CRC cell lines. It also increased the percentage of cells in the G2/M phase and apoptotic cells, especially in cell lines with p53 mutations, but did not alter these cell percentages in most p53 wild-type cell lines. In the orthotopic mouse model of CRC, tumor volume was significantly reduced in the WEE1 inhibitor-treated group compared to that in the control group. RNA sequencing and immunohistochemistry analyses of mouse tumors revealed that treatment with the WEE1 inhibitor activated tumor immunity and suppressed stromal reactions. These results demonstrate the potential antitumor effects of WEE1 inhibitors in CRC, particularly in patients with p53 mutations.

Clinicopathologic Features of Early Gastric Cancer after Heli-cobacter pylori Eradication in Japanese Patients: Comparative Study between Early (<10 Years) and Late (>10 Years) Onset.

BACKGROUND/OBJECTIVES: Eradication therapy for Helicobacter pylori gastritis was approved for insurance coverage by the Japanese government in 2013. Since then, the incidence of gastric cancer discovered after eradication (GCAE) has increased. However, there are only a few reports of GCAE diagnosed more than 10 years after eradication. We investigated the clinicopathological characteristics of early-stage GCAE, including histological types and the interval from eradication to diagnosis. METHODS: Overall, 379 patients with a total of 448 GCAE lesions treated with endoscopic resection or surgery at our hospital between January 2015 and December 2021 were assessed, and 315 patients with a known interval from eradication to diagnosis of GCAE with a total of 354 lesions were included. We classified the cases into two groups: differentiated-type GCAE (D-GCAE; 279 patients, 318 lesions) and undifferentiated-type GCAE (UD-GCAE; 36 patients, 36 lesions). RESULTS: Smoking and a mild-to-moderate degree of atrophy were risk factors associated with differentiated-type gastric cancer occurring more than 10 years after H. pylori eradication. Additionally, the rate of a mixture of histological types with relatively high malignant potential was significantly higher in UD-GCAE presenting more than 10 years after eradication group than those presenting within 10 years after eradication.

Stable Antiaromatic [16]Triphyrin(2.1.1) with Core Modification: Synthesis Using a 16π Electrocyclic Reaction.

Antiaromatic porphyrinoids have attracted significant attention owing to their unique electronic properties and potential applications. However, synthesis of antiaromatic contracted porphyrinoids is challenging owing to the inherent instability associated with smaller ring sizes. In this study, we report the synthesis and characterization of the first stable trioxa[16]triphyrin(2.1.1), a novel 16π antiaromatic contracted porphyrinoid. We utilized a core modification approach to stabilize the [16]triphyrin(2.1.1). X-ray crystallographic analysis revealed a nearly planar structure. Electrochemical studies demonstrated reversible oxidation behavior and a small HOMO-LUMO gap, which was consistent with its antiaromatic nature. Chemical oxidation yielded an aromatic [14]triphyrin(2.1.1) dication, highlighting the antiaromaticity-aromaticity switching capability of this system. This synthesis involved the discovery of a key intermediate, dihydrotrioxatriphyrin(2.1.1), which underwent oxidative dehydrogenation to yield the target compound. Theoretical calculations suggested that dihydrotrioxatriphyrin(2.1.1) formed via a rare 16π electrocyclic reaction. The successful synthesis and characterization of this stable trioxa[16]triphyrin(2.1.1) underscores the potential of the core modification strategies for the rational design of novel antiaromatic systems with tunable properties. Moreover, the discovery of the rare 16π electrocyclic reaction advances the understanding of high-order pericyclic processes and may inspire new synthetic strategies for complex macrocyclic compounds.

Predictive factors of portal hypertensive enteropathy exacerbations based on long-term outcomes.

BACKGROUND: Portal hypertensive enteropathy (PHE) is a small-bowel lesion observed in patients with portal hypertension. The clinical significance of endoscopic findings in PHE remains unclear. We aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings in patients with PHE based on long-term outcomes. METHODS: This retrospective study enrolled 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23-87) followed for > 3 years using capsule endoscopy (CE) between February 2009 and May 2023. We evaluated the clinical factors affecting PHE exacerbations and the effects of PHE exacerbations on gastrointestinal bleeding by comparing exacerbated and unchanged PHE groups. RESULTS: Overall, 3 (5%) patients showed improvement, 33 (60%) remained unchanged, and 19 (35%) showed exacerbation on follow-up CE. In the exacerbated group, the rates of worsened fibrosis-4 index, exacerbated esophageal varices, and exacerbated portal hypertensive gastropathy were significantly higher than those in the unchanged group (21%, 32%, and 42% vs. 3%, 6%, and 12%, respectively; P < 0.05), and the rate of splenectomy was significantly lower in the exacerbated group than in the unchanged group (5% vs. 39%, respectively; P < 0.01). In multivariate analysis, exacerbation of esophageal varices and absence of splenectomy were significantly associated with PHE exacerbation. The rate of gastrointestinal bleeding after follow-up CE was significantly high in the exacerbated group (log-rank, P = 0.037). CONCLUSIONS: Exacerbation of esophageal varices and splenectomy were significantly associated with exacerbation of PHE. Exacerbated PHE requires specific attention to prevent gastrointestinal bleeding.

Management of T1 Colorectal Cancer.

BACKGROUND: Approximately 10% of patients with submucosal invasive (T1) colorectal cancer (CRC) have lymph node metastasis (LNM). The risk of LNM can be stratified according to various histopathological factors, such as invasion depth, lymphovascular invasion, histological grade, and tumor budding. SUMMARY: T1 CRC with a low risk of LNM can be cured by local excision via endoscopic resection (ER), whereas surgical resection (SR) with lymph node dissection is required for high-risk T1 CRC. Current guidelines raise concern that many patients receive unnecessary SR, even though most patients achieve a radical cure. Novel diagnostic techniques for LNM, such as nomograms, artificial intelligence systems, and genomic analysis, have been recently developed to identify more low-risk T1 CRC cases. Assessing the curability and the necessity of additional treatment, including SR with lymph node dissection and chemoradiotherapy, according to histopathological findings of the specimens resected using ER, is becoming an acceptable strategy for T1 CRC, particularly for rectal cancer. Therefore, complete resection with negative vertical and horizontal margins is necessary for this strategy. Advanced ER methods for resecting the muscle layer or full thickness, which may guarantee complete resection with negative vertical margins, have been developed. KEY MESSAGE: Although a necessary SR should not be delayed for T1 CRC given its unfavorable prognosis when SR with lymph node dissection is performed, the optimal treatment method should be chosen based on the risk of LNM and the patient's life expectancy, physical condition, social characteristics, and wishes.

Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery.

PURPOSE : A vertical margin (VM) distance of < 500 µm is a risk factor for recurrence in patients with T1 colorectal carcinoma (CRC) resected by endoscopy. We aimed to determine the effects of the VM distance on the recurrence and prognosis of T1 CRC. METHODS: We enrolled 168 patients with T1 CRC who underwent additional surgery after endoscopic submucosal dissection (ESD) at multiple centers between 2008 and 2016. None of the patients were followed up for < 5 years. The enrolled 168 patients were classified into patients with VM distance of < 500 µm including positive VM (n = 72 [43%], VM distance < 500 µm group) and patients with VM distance of ≥ 500 µm (n = 96 [57%], VM distance ≥ 500 µm group). The clinicopathological features, recurrence rates, and prognoses were compared between the groups using propensity-score matching (PSM). RESULTS: Tumors recurred in eight of the 168 patients (5%) with VM distance < 500 µm. After PSM, the rate of overall recurrence and local recurrence in the VM distance < 500 µm group were significantly higher than those in the VM distance ≥ 500 µm group. The 5-year recurrence-free survival rate was significantly higher in the VM distance ≥ 500 µm group than that in VM distance < 500 µm group after PSM (100% vs. 89%, p < 0.012). CONCLUSIONS: Complete en bloc resection of T1 CRC via ESD must include a sufficient amount of SM to reduce the risk of metastasis and recurrence after additional surgery.

Severe Refractory Diarrhea Associated with COVID-19: A Case Report.

Introduction: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is frequently associated with various gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea. Moreover, several cases of refractory diarrhea have been reported after COVID-19 recovery. Herein, we present a case of severe refractory diarrhea associated with COVID-19. Case Presentation: A 50-year-old man with no comorbidities was admitted to our hospital with SARS-CoV-2 pneumonia. His respiratory status deteriorated, and ventilatory management, including extracorporeal membrane oxygenation, was needed. The patient's respiratory condition improved, resulting in a transfer to another hospital for rehabilitation. However, the patient developed diarrhea that worsened to 6,000-7,000 mL/day, and he was transferred to our hospital. We diagnosed the patient with enterocolitis caused by cytomegalovirus infection and treated him with ganciclovir on day 5 after transfer to our hospital. The diarrhea did not improve. We suspected enterocolitis associated with COVID-19 and administered a methylprednisolone pulse (intravenous injection, 1,000 mg/day for 3 days) on day 10 after transfer, resulting in a marked improvement in his symptoms. The prednisolone dose was tapered, and no recurrence of diarrhea was observed thereafter. Conclusion: The prevalence of COVID-19-associated enterocolitis is low, and the pathogenesis of the disease remains unclear. Prednisolone administration should be considered in cases of post-COVID-19 symptoms of severe diarrhea due to a possible abnormal immune response related to COVID-19.

Long-term prognosis after endoscopic submucosal dissection for esophageal cancer in older adult patients.

BACKGROUND: The validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients. METHODS: The clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed. RESULTS: The mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01-1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups. CONCLUSIONS: ESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient's general condition.

Analysis of anti-tumor effect and mechanism of GLS1 inhibitor CB-839 in colorectal cancer using a stroma-abundant tumor model.

BACKGROUND: Glutaminase 1 (GLS1), a key enzyme in glutamine metabolism in cancer cells, acts as a tumor promoter and could be a potential therapeutic target. CB-839, a GLS1-specific inhibitor, was developed recently. Herein, we aimed to elucidate the anti-tumor effects and mechanism of action of CB-839 in colorectal cancer (CRC). METHODS: Using the UCSC Xena public database, we evaluated GLS1 expression in various cancers. Immunostaining for GLS1 was performed on 154 surgically resected human CRC specimens. Subsequently, we examined the GLS1 mRNA expression levels in eight CRC cell lines and evaluated the association between GLS1 expression and CB-839 efficacy. To create a reproducible CRC model with abundant stroma and an allogeneic immune response, we co-transplanted CT26 and stem cells into BALB/c mice and treated them with CB-839. Finally, RNA sequencing of mouse tumors was performed. RESULTS: Database analysis showed higher GLS1 expression in CRC tissues than in normal colon tissues. Clinical samples from 114 of the 154 patients with CRC showed positive GLS1 expression. GLS1 expression in clinical CRC tissues correlated with vascular invasion. CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression in vitro and inhibited tumor growth and metastasis in the CRC mouse model. RNA sequencing revealed that CB-839 treatment inhibited stromal activation, tumor growth, migration, and angiogenesis. These findings were validated through in vitro and in vivo experiments and clinical specimen analysis. CONCLUSIONS: GLS1 expression in CRC plays important roles in tumor progression. CB-839 has inhibitory effects on cancer proliferation and the tumor microenvironment.

Verrucous gastritis-like lesion in intramucosal Helicobacter pylori-uninfected signet ring cell carcinoma with poorly differentiated adenocarcinoma.

In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs.

Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non-drinker and non-smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. METHODS: The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. RESULTS: Multiple logistic regression revealed that older age, fewer multiple Lugol-voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid-thoracic esophagus, posterior wall side, with 0-IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. CONCLUSION: Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0-IIa ESCC with keratinization of the posterior wall of the mid-thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

Culturally adapting relational savoring: A therapeutic approach to improve relationship quality.

Relational savoring (RS) is a brief, strengths-based approach to heightening attentional focus to moments of positive connectedness within relationships. RS can be administered preventatively or within an intervention context when a therapist aspires to foster more optimal relational functioning. Typically administered within a one-on-one therapy setting, RS has demonstrated efficacy in enhancing intra- and interpersonal outcomes. To increase access to mental health services, the developers of RS are committed to engaging in an iterative approach of enhancing the cultural congruence and accessibility of this intervention within various cultural contexts, beginning with Latine groups in Southern California. In this article, we describe relational savoring and its theoretical and empirical support, including the process of culturally adapting the intervention within the context of three major studies, each with a distinct focus on Latine groups, a community that is underserved in mental health care settings. We then provide a vision for future research to improve upon the intervention's compatibility for Latine families and other populations.