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.

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.

Real-world efficacy and safety of durvalumab-tremelimumab as second-line systemic therapy after atezolizumab-bevacizumab in unresectable hepatocellular carcinoma.

The efficacy and safety of immune-checkpoint inhibitors (ICI) for the treatment of unresectable hepatocellular carcinoma are known. We explored ICI rechallenges with direct switching from 1 ICI regimen to another. This retrospective study included 16 patients who received atezolizumab-bevacizumab (Atezo+Bev) and durvalumab-tremelimumab (Dur+Tre) as the first-line and second-line combination therapy, respectively, at Hiroshima University Hospital. The radiological response and adverse event were evaluated in all patients. Of the 16 patients, 12 were male, and the median age at Atezo+Bev induction was 71 years. The reasons for medication changes were disease progression in 11 patients and adverse events in 5 patients. With Atezo+Bev and Dur+Tre initiation, the Barcelona-Clinic Liver-Cancer stage (A/B/C) progressed in 9/6/3 and 3/4/9 patients and the Child-Pugh classification (A/B/C) progressed in 12/4/0 and 9/6/3 patients, respectively. The disease control rate and overall response rate of Atezo+Bev were 87.5% and 58.3%, respectively, and of Dur+Tre were 62.5% and 0%, respectively. The most common immune-related adverse event in both the Atezo+Bev and Dur+Tre groups was colitis; 3 of the 5 patients with colitis on Atezo+Bev treatment had colitis with Dur+Tre, and 2 had exacerbations. Regarding liver function, ALBI score significantly decreased during Atezo+Bev, but not Dur+Tre, treatment. In patients with colitis following Atezo+Bev, subsequent Dur+Tre treatment may induce colitis recurrence or exacerbation. For immune-related adverse events other than colitis, Dur+Tre could provide relatively safe disease control while maintaining liver function.

Impact of endoscopic ultrasound-guided fine needle aspiration on positive peritoneal lavage cytology in patients with resectable pancreatic body and tail cancer.

BACKGROUND/PURPOSE: A recent study has demonstrated that the timing of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) significantly influences the peritoneal lavage cytology (CY) outcomes in pancreatic body-tail cancer. The aim of this study was to clarify the impact of EUS-FNA on CY positivity in patients with resectable pancreatic body-tail cancer. METHODS: Patients with anatomically resectable pancreatic body-tail cancer surgically resected at Hiroshima University Hospital were enrolled, and elated clinicopathological factors, including EUS-FNA variables and CY positivity rate, were analyzed. RESULTS: Of the 129 eligible patients, 16 (12%) had positive CY. The EUS-FNA rates of the CY-positive and CY-negative groups were not significantly different (63% vs. 52%, p = .440). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for CY positivity (odds ratio: 5.734, p = .031). A total of 10 (14%) of the 69 patients who underwent EUS-FNA had positive CY; however, needle specifications and the interval between EUS-FNA and CY examination did not differ between the CY-positive and CY-negative groups. CY positivity rates were comparable for intervals ≤14 days and ≥15 days (17% vs. 14%, p = 1.000). CONCLUSIONS: EUS-FNA may not affect CY positivity in patients with resectable pancreatic body-tail cancer, regardless of the timing.

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.

Interferon alpha induces a stronger antiviral effect than interferon lambda in HBV/HDV infected humanized mice.

Recent studies indicate that treatment of chronic hepatitis D virus (HDV) with either pegylated interferon (IFN)λ or pegylated IFNα monotherapy leads to a dramatic decline in HDV RNA. Herein, we investigated the innate antiviral efficacy of IFNλ and IFNα in humanized mice that lack an adaptive immune response. Humanized mice were either co-infected with hepatitis B virus (HBV) and HDV simultaneously, or HDV infection was performed subsequent to HBV infection (i.e., superinfected). After steady viral replication was achieved, mice received either IFNλ (n = 6) or IFNα (n = 7) for 12 (or 13) weeks. Pretreatment median levels of serum HBV DNA (8.8 [IQR:0.2] log IU/ml), HDV RNA (9.8 [0.5] log IU/ml), HBsAg (4.0 [0.4] log IU/ml) and human albumin, hAlb (6.9 [0.1] log ng/mL) were similar between mice treated with IFNα or IFNλ and between those coinfected versus superinfected. Compared to mice treated with IFNλ, mice treated with IFNα had a significantly greater decline in HBV, HDV, and HBsAg levels. In conclusion, IFNα induces stronger inhibition of HBV and HDV than IFNλ in humanized mice that lack an adaptive immune response. Further studies are needed to assess the respective role of the combined innate-and adaptive-immune systems in the treatment of HBV and HDV with IFNα and IFNλ.

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.

Significance of changes in tumor markers in patients treated with durvalumab plus tremelimumab combination therapy as a surrogate marker for tumor response to unresectable hepatocellular carcinoma.

AIM: When evaluating response to immune checkpoint inhibitor therapy, the tumor sometimes initially swells before shrinking and ultimately responding, also called pseudo-progression. In this study, we analyzed whether tumor markers were useful for reflecting the treatment response. METHODS: Thirty-three patients who were treated with durvalumab plus tremelimumab combination therapy (Dur + Tre) were enrolled. Their functional reserve was Child-Pugh grade A. Their tumor markers α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), or AFP-Lectin 3 fraction (AFP-L3) were positive. Tumor markers were evaluated before treatment and at 1, 4, and 8 weeks after the start of treatment. The first radiological evaluation was carried out at 4 weeks and the second evaluation at 8-12 weeks. The responders included those with complete response and partial response and the nonresponders included those with stable disease (SD) and progression disease at best response evaluated by Response Evaluation Criteria in Solid Tumors. RESULTS: In the responder group, the change ratio of AFP, DCP, and AFP-L3 specifically decreased at 8 weeks. In the nonresponder group, the change ratio of DCP specifically increased at 4 weeks. The optimal cut-off value to divide responders and nonresponders at 4 weeks was approximately -40%. The ratio of responders was 72.7% in the patients whose AFP or DCP decreased over 40% at 4 weeks. CONCLUSIONS: The change in tumor markers is a more useful predicter of tumor response to Dur + Tre than imaging evaluation alone.

Endoscopic Retrograde Cholangiopancreatography-Related Procedures for the Differential Diagnosis of Isolated Immunoglobin G4-Related Sclerosing Cholangitis and Perihilar Cholangiocarcinoma.

BACKGROUND/PURPOSE: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). METHODS: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. RESULTS: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. CONCLUSIONS: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended.

Integrator complex subunit 6 promotes hepatocellular steatosis via ß-catenin-PPARγ axis.

Hepatic adipogenesis has common mechanisms with adipocyte differentiation such as PPARγ involvement and the induction of adipose tissue-specific molecules. A previous report demonstrated that integrator complex subunit 6 (INTS6) is required for adipocyte differentiation. This study aimed to investigate INTS6 expression and its role in hepatic steatosis progression. The expression of INTS6 and PPARγ was examined in the liver of a mouse model of steatohepatitis and in paired liver biopsy samples from 11 patients with severe obesity and histologically proven metabolic dysfunction associated steatohepatitis (MASH) before and one year after bariatric surgery. To induce hepatocellular steatosis in vitro, an immortalized human hepatocyte cell line Hc3716 was treated with free fatty acids. In the steatohepatitis mouse model, we observed hepatic induction of INTS6, PPARγ, and adipocyte-specific genes. In contrast, ß-catenin which negatively regulates PPARγ was reduced. Biopsied human livers demonstrated a strong positive correlation (r2 = 0.8755) between INTS6 and PPARγ mRNA levels. After bariatric surgery, gene expressions of PPARγ, FABP4, and CD36 were mostly downregulated. In our in vitro experiments, we observed a concentration-dependent increase in Oil Red O staining in Hc3716 cells after treatment with the free fatty acids. Alongside this change, the expression of INTS6, PPARγ, and adipocyte-specific genes was induced. INTS6 knockdown using siRNA significantly suppressed cellular lipid accumulation together with induction of ß-catenin and PPARγ downregulation. Collectively, INTS6 expression closely correlates with PPARγ. INTS6 suppression significantly reduced hepatocyte steatosis via ß-catenin-PPARγ axis, indicating that INTS6 could be a novel therapeutic target for treating MASH.

The Spatial Extracellular Proteomic Tumor Microenvironment Distinguishes Molecular Subtypes of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) mortality rates continue to increase faster than those of other cancer types due to high heterogeneity, which limits diagnosis and treatment. Pathological and molecular subtyping have identified that HCC tumors with poor outcomes are characterized by intratumoral collagenous accumulation. However, the translational and post-translational regulation of tumor collagen, which is critical to the outcome, remains largely unknown. Here, we investigate the spatial extracellular proteome to understand the differences associated with HCC tumors defined by Hoshida transcriptomic subtypes of poor outcome (Subtype 1; S1; n = 12) and better outcome (Subtype 3; S3; n = 24) that show differential stroma-regulated pathways. Collagen-targeted mass spectrometry imaging (MSI) with the same-tissue reference libraries, built from untargeted and targeted LC-MS/MS was used to spatially define the extracellular microenvironment from clinically-characterized, formalin-fixed, paraffin-embedded tissue sections. Collagen α-1(I) chain domains for discoidin-domain receptor and integrin binding showed distinctive spatial distribution within the tumor microenvironment. Hydroxylated proline (HYP)-containing peptides from the triple helical regions of fibrillar collagens distinguished S1 from S3 tumors. Exploratory machine learning on multiple peptides extracted from the tumor regions could distinguish S1 and S3 tumors (with an area under the receiver operating curve of ≥0.98; 95% confidence intervals between 0.976 and 1.00; and accuracies above 94%). An overall finding was that the extracellular microenvironment has a high potential to predict clinically relevant outcomes in HCC.

Discovering cancer stem-like molecule, nuclear factor I X, using spatial transcriptome in gastric cancer.

Gastric cancer (GC) is characterized by significant intratumoral heterogeneity, and stem cells are promising therapeutic targets. Despite advancements in spatial transcriptome analyses, unexplored targets for addressing cancer stemness remain unknown. This study aimed to identify Nuclear Factor IX (NFIX) as a critical regulator of cancer stemness in GC and evaluate its clinicopathological significance and function. Spatial transcriptome analysis of GC was conducted. The correlation between NFIX expression, clinicopathological factors, and prognosis was assessed using immunostaining in 127 GC cases. Functional analyses of cancer cell lines validated these findings. Spatial transcriptome analysis stratified GC tissues based on genetic profiles, identified CSC-like cells, and further refined the classification to identify and highlight the significance of NFIX, as validated by Monocle 3 and CytoTRACE analyses. Knockdown experiments in cancer cell lines have demonstrated the involvement of NFIX in cancer cell proliferation and kinase activity. This study underscores the role of spatial transcriptome analysis in refining GC tissue classification and identifying therapeutic targets, highlighting NFIX as a pivotal factor. NFIX expression is correlated with poor prognosis and drives GC progression, suggesting its potential as a novel therapeutic target for personalized GC therapies.

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.

Two Cases of Increased Gastrointestinal Polyps in Familial Adenomatous Polyposis following Antiacid Agent Intake.

Introduction: Familial adenomatous polyposis (FAP), a hereditary disorder of the gastrointestinal tract, is an autosomal dominant inherited condition caused by germline mutations in the adenomatous polyposis coli (APC) gene. It is characterized by the development of hundreds to thousands of colorectal adenomatous polyps, which, if left untreated, can eventually develop into colorectal carcinomas. Representative extracolonic tumors in FAP include multiple duodenal adenomas and desmoid tumors. Moreover, multiple fundic gland polyps are frequently identified in the stomachs of patients with FAP. Case Presentation: Herein, we report the two cases. A 52-year-old woman who underwent total colectomy for FAP, and pancreatoduodenectomy was initiated on esomeprazole for the treatment of anastomotic erosion. Esophagogastroduodenoscopy performed 42 months later showed an increased number and size of gastric fundic gland polyps, which subsequently decreased after replacing esomeprazole with ranitidine. Similarly, a 39-year-old woman with FAP was initiated on vonoprazan for the treatment of reflux symptoms. Esophagogastroduodenoscopy and colonoscopy performed 14 months later indicated an increase in the number of gastric fundic gland polyps and colorectal polyps, which subsequently decreased after vonoprazan discontinuation. In these two cases, the increase and decrease in the number and size of fundic gland polyps and colon adenoma were associated with serum gastrin levels. Conclusion: Gastric fundic gland polyps and colon polyps may rapidly increase in number and size due to increased gastrin levels induced by proton pump inhibitor/potassium-competitive acid blocker use. Hence, these drugs should be prescribed with caution.

Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts.

Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.

Long-Term Outcomes of Additional Surgery After Endoscopic Resection Versus Primary Surgery for T1 Colorectal Cancer.

INTRODUCTION: There is considerable concern about whether endoscopic resection (ER) before additional surgery (AS) for T1 colorectal cancer (CRC) has oncologically potential adverse effects. Therefore, the aim of this study was to compare the long-term outcomes, including overall survival (OS), of patients treated with AS after ER vs primary surgery (PS) for T1 CRC using a propensity score-matched analysis from a large observational study. METHODS: This study investigated 6,105 patients with T1 CRC treated with either ER or surgical resection between 2009 and 2016 at 27 high-volume Japanese institutions, with those undergoing surgery alone included in the PS group and those undergoing AS after ER included in the AS group. Propensity score matching was used for long-term outcomes of mortality and recurrence analysis. RESULTS: After propensity score matching, 1,219 of 2,438 patients were identified in each group. The 5-year OS rates in the AS and PS groups were 97.1% and 96.0%, respectively (hazard ratio: 0.72, 95% confidence interval: 0.49-1.08), indicating the noninferiority of the AS group. Moreover, 32 patients (2.6%) in the AS group and 24 (2.0%) in the PS group had recurrences, with no significant difference between the 2 groups (odds ratio: 1.34, 95% confidence interval: 0.76-2.40, P = 0.344). DISCUSSION: ER before AS for T1 CRC had no adverse effect on patients' long-term outcomes, including the 5-year OS rate. ER is a viable first-line treatment option for endoscopically resectable T1 CRC.

Ramucirumab for advanced hepatocellular carcinoma in the current real world: a Japanese single-arm study post-REACH-2 (The R-evolution study).

This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.