The number of patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), continues to increase in many countries and regions. With recent rapid advances in medical therapies targeting intestinal inflammation, the number of patients with long-term disease duration is also increasing. It is well-recognized that longstanding IBD carries an increased risk of developing gastrointestinal (GI) neoplasia, particularly colorectal cancer. However, compared to sporadic GI tumors, IBD-associated GI tumors are relatively rare, and even among specialists in GI diseases, opportunities to encounter such cases remain limited. In light of this situation, the Japanese Society for Cancer of the Colon and Rectum (JSCCR), in collaboration with the Japanese Inflammatory Bowel Disease Research Group (funded by the Japan Sciences Research Grant for Research on Intractable Diseases affiliated with the Ministry of Health, Labour, and Welfare) launched the Guideline Development Committee for IBD-associated Gastrointestinal Tumors in 2021, with the aim of establishing clinical practice guidelines to support the diagnosis and management of these tumors. The committee-comprising experts in gastroenterology, surgery, pathology, guideline development, and literature review-conducted extensive discussions and successfully published the first Japanese edition of the guidelines in July 2024. We believe that the current edition provides the best possible guidance based on presently available knowledge. Furthermore, the guideline development process highlighted several key issues to be addressed in future research and clinical practice. We are pleased to present here the English version of the JSCCR Guidelines 2024 for the Clinical Practice of IBD-associated Intestinal Neoplasia.
INTRODUCTION: Acute lower gastrointestinal bleeding is common in clinical practice. However, it is rarely caused by the appendix, and cases caused by a Dieulafoy's lesion are even more uncommon. CASE PRESENTATION: A 39-year-old man presented to a previous hospital with sudden onset of hematochezia. He underwent emergency lower gastrointestinal endoscopy, which revealed bleeding from the appendiceal orifice. Appendiceal bleeding was suspected, and the patient was referred to our department for surgical management. Contrast-enhanced CT performed at our hospital showed an enlarged appendix and a high-density area in the lumen. In conjunction with the colonoscopy findings, he was diagnosed with appendiceal bleeding and underwent an emergency appendectomy. Histopathological examination revealed a shallow ulcer with a torn mucosal fascia; however, most of the submucosal layer remained intact. Capillaries were observed near the disrupted mucosal fascia. The pathological diagnosis was appendiceal bleeding due to Dieulafoy's lesion. The postoperative course was uneventful, and the patient was discharged on POD 4. CONCLUSIONS: Symptomatic appendiceal hemorrhage with massive bleeding should be considered for emergency surgical intervention, given the possibility of bleeding due to a Dieulafoy's lesion.
8081 Background: Concurrent chemoradiotherapy (CCRT) followed by prophylactic cranial irradiation (PCI) is potentially curative for limited-stage small-cell lung cancer (LS-SCLC), yet reliable markers for identifying long-term survivors remain undefined. The Enhanced Assessment for SCLC Treatment (EAST) score was originally derived from a retrospective, single-center training cohort for prognostic stratification of LS-SCLC patients receiving CCRT. This score integrates N3 status, serum lactate dehydrogenase (LDH), pro-gastrin-releasing peptide (ProGRP), and cytokeratin 19 fragment (CYFRA 21-1) levels measured at diagnosis. This study (JCOG2401A) validated its prognostic utility using data from two randomized controlled trials (RCTs) of LS-SCLC. Methods: The validation cohort comprised patients enrolled in JCOG0202 and JCOG1011: randomized phase 3 and 2 studies, respectively, that compared multiple consolidation chemotherapy regimens following CCRT. External validation of the dichotomized EAST score (low: score 0–1, high: 2–5) was performed by assessing discrimination and calibration for progression-free survival (PFS) and overall survival (OS). Exploratory subgroup analyses were conducted in an integrated cohort of the training cohort (N = 224; median follow-up, 64.5 months) and the validation cohort. Hazard ratios (HRs) for PCI were estimated using propensity score-weighted Cox models. Results: Out of 309 patients in these trials, 205 with complete data for EAST score components were included in the validation cohort. Median age was 62 years. Low- vs. high-risk groups showed stage (I-II/III) distributions of 28/72% vs. 11/89%, and tumor response (CR-PR/SD) distributions of 89/3% vs. 91/2%, respectively. The low-risk group (N = 114) showed better outcomes than the high-risk group (N = 91) for both PFS and OS (Table). Integrated cohort analysis revealed a numerical survival benefit from PCI in low-risk patients (N = 214), whereas the benefit was highly limited in the high-risk group (N = 202) (Table). Conclusions: The prognostic value of the EAST score was validated even in external RCT datasets. High-risk patients, characterized by early recurrence and inferior OS, derive minimal benefit from PCI. These findings provide a rationale for a planned risk-adapted RCT utilizing the EAST score. Median PFS, months PFS, HR (95% CI) Median OS, months OS, HR (95% CI) Low- vs. high-risk Training cohort (N=107/117) 20.6/9.4 0.48 (0.34-0.67) 53.0/34.2 0.67 (0.46-0.98) Validation cohort (N=114/91) 25.0/10.7 0.55 (0.40-0.77) 63.2/29.6 0.51 (0.36-0.73) PCI vs. no-PCI All (N=287/129) 14.5/12.9 0.91 (0.65-1.28) 50.0/35.5 0.78 (0.56-1.10) Low risk (N=152/62) 31.3/14.6 0.86 (0.49-1.48) 67.9/40.1 0.75 (0.43-1.31) High risk (N=135/67) 10.2/10.6 0.99 (0.71-1.39) 34.2/30.9 0.86 (0.59-1.28)
Background Cardiac metastasis from colorectal cancer is rare and has a poor prognosis. However, the optimal management remains uncertain. Case Summary A 50-year-old woman underwent colectomy with lymph node dissection for descending colon cancer, followed by chemotherapy. Six months later, computed tomography revealed a right ventricular mass that was initially suspected to be a thrombus. Despite anticoagulation, the mass enlarged, causing progressive right ventricular outflow tract stenosis, and was considered a cardiac metastasis from colon cancer. To prevent sudden death, complete resection with pulmonary valve replacement and right ventricular outflow tract reconstruction was performed. Seventeen months after surgery, no intracardiac recurrence or systemic progression was observed with continued chemotherapy. Discussion This case suggests that surgical resection of a cardiac mass followed by early chemotherapy may reduce life-threatening events and improve prognosis. Take-Home Messages Systemic therapy is central to managing colorectal cancer with cardiac metastasis. Surgery may be warranted to prevent catastrophic cardiac events and facilitate safe chemotherapy.
8573 Background: Pembrolizumab is a standard 1st line treatment for advanced non–small cell lung cancer (NSCLC) with high PD-L1 expression (tumor proportion score [TPS] ≥50%); however, durable benefit is achieved in only a subset of patients. Prior pembrolizumab-based combination strategies (e.g., anti-TIGIT) have inconsistently improved outcomes over pembrolizumab monotherapy in this setting. Epidermal growth factor receptor (EGFR) signaling may promote immune evasion by stabilizing PD-L1 expression and shaping an immunosuppressive tumor microenvironment, providing a rationale for combining the anti-EGFR antibody necitumumab with pembrolizumab. We therefore evaluated the efficacy and safety of necitumumab plus pembrolizumab in treatment-naive patients with PD-L1–high advanced NSCLC. Methods: K-TAIL-202 (jRCT2031200248) was an open-label, multicenter, single-arm phase II study conducted in Japan. Eligible patients were aged ≥20 years with unresectable stage III/IV or recurrent NSCLC, PD-L1 TPS ≥50% (22C3), ECOG PS 0–1, and ≥1 measurable lesion. Patients received necitumumab 800 mg IV on days 1 and 8 plus pembrolizumab 200 mg IV on day 1 every 3 weeks for up to 35 cycles or until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1; secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The study assumed an expected ORR of 54.8% and a threshold ORR of 39.0% (one-sided α = 0.10; 80% power), requiring enrollment of 50 patients. Results: Between December 2020 and March 2023, 50 patients were enrolled (median age, 72 years). The ORR was 68.0% (95% CI, 53.3–80.5) and the disease control rate was 78.0% (95% CI, 64.0–88.5). Complete response, partial response, stable disease, progressive disease, and not evaluable status were observed in 2.0%, 66.0%, 10.0%, 12.0%, and 10.0% of patients, respectively, meeting the primary endpoint. Median PFS was 16.0 months (95% CI, 9.0–24.0), with a 24-month PFS rate of 35.9%. Median OS was not attained (95% CI, 38.0 months–not estimable), and the 24-month OS rate was 71.3%. The most treatment-emergent adverse events included acneiform dermatitis (66.0%), hypomagnesemia (60.0%), and pneumonitis (12.0%). One grade 5 cardiac arrest occurred in 1 patient (2.0%), for which a causal relationship to study treatment could not be ruled out. Conclusions: At final analysis, first-line necitumumab plus pembrolizumab demonstrated durable antitumor activity and encouraging long-term survival as a chemotherapy-free regimen in patients with PD-L1–high advanced NSCLC. Toxicities were consistent with the known profiles of EGFR-targeted antibodies and PD-1 inhibitor therapy, underscoring the need for careful monitoring. These findings warrant further confirmation in a randomized phase III clinical trial. Clinical trial information: jRCT2031200248.
