Introduction

Gastric squamous cell carcinoma (GSCC) is an aggressive rare histological subtype accounting for 0.04-0.5% only of all gastric tumors. Due to its scarcity, there are very few case reports in the literature and data are limited to institutional case series with significant variations. Thus, no recommendations for GSCC were published by the European Society of Medical Oncology or the National Comprehensive Cancer Network societies.

Aims & Methods

The aim of this study is to provide the literature with an updated evidence about this rare type for better understanding for its nature and establish a proper management strategy. Data were extracted from the Surveillance, Epidemiology and End Results (SEER) database for 784 patients diagnosed with primary GSCC with sequence 0 or 1 from 2000 to 2020. Patients were selected based on microscopic confirmation for the diagnosis . We used a rate session to calculate the age-adjusted trends as Percent Chance (PC) and Annual Percent Change (APC). We subdivided the patients according to the treatment modality into medical therapy, partial gastrectomy and total gastrectomy group, then followed by smaller subgroups (primary therapy and surgery with systemic therapy) . We used a survival session to calculate the relative survival. SPSS version 23 was used for data analysis, Kaplan-Meier and Log-Rank test for survival analysis. The results were considered significant when P <0.05.

Results

GSCC had 2000-2020 PC of -13.3 [APC= -0.5, 95% CI (-1.6: 0.6), P>0.05]. African-Americans had increased rate compared to Caucasians (RR=2.32, 95%CI: 1.96-2.73, P<0.0001). The overall 3-year and 5-year relative survival of GSCC were 21.7% and 17.4%. Out of 502 patients, 341(68.1%) received medical treatment only, 43(8.6%) had partial gastrectomy and 117(23.3%) had total gastrectomy with 5-year relative survival of 10.4%, 38.1% and 44.6% respectively; P<0.0001. Adjuvant chemoradiotherapy had similar 5-year survival compared to surgery with no systemic therapy while both had improved survival compared to surgical management with systemic chemotherapy only (43.4%, 51.5% and 22.9% respectively; P=0.07). Among the group who received systemic therapy only, primary chemoradiotherapy had improved 5-year relative survival compared to primary chemotherapy and primary radiotherapy (16.3%, 8.1% and 0.0%; P<0.0001).

Conclusion

GSCC is an aggressive malignancy with poor survival outcome. GSCC rates have decreased over the past 20 years. However, the rate in African-Americans is two folds greater to develop GSCC compared to Caucasians. Total gastrectomy had significant improved survival compared to partial gastrectomy and the medical treatment. These results highlights total gastrectomy as the modality of choice for primary GSCC. As adjuvant chemoradiotherapy had no significant benefit over surgery with no systemic therapy, we discourage the use of systemic therapy to avoid serious systemic side effects related to the systemic treatment for better quality of life after the surgical management.

References

1. de Lange G, Bouroumeau A, Coron E, Koessler T. Gastric squamous cell carcinoma: A rare malignancy, literature review and management recommendations (Review). Mol Clin Oncol. 2023;19(4):2–7.
2. Dong C, Jiang M, Tan Y, Kong Y, Yang Z, Zhong C, et al. The clinicopathological features and prognostic factors of gastric squamous cell carcinoma. Med (United States). 2016;95(34):1–7.
3. Akce M, Jiang R, Alese OB, Shaib WL, Wu C, Behera M, et al. Gastric squamous cell carcinoma and gastric adenosquamous carcinoma, clinical features and outcomes of rare clinical entities: A National Cancer Database (NCDB) analysis. J Gastrointest Oncol. 2019;10(1):85–94.

Introduction

Type 1 gastric neuroendocrine tumors (T1-gNETs) are well-differentiated, typically indolent neoplasms associated with chronic atrophic gastritis (CAG) and hypergastrinemia, with nearly 100% long-term survival. However, they have a high recurrence rate of 30-60% within the first year after resection. Tumor size is the most critical prognostic factor, while the role of grading is less definitive compared to other digestive NETs. International guidelines recommend conservative management for tumors <1 cm, advocating for approaches such as endoscopic resection or surveillance, which have shown excellent outcomes. However, the management strategies and outcomes for tumors > 1 cm remain less clearly defined due to the lack of scientific data in this specific patient population.

Aims & Methods

This study aimed to investigate management strategies and clinical outcomes in a homogeneous population of patients with T1-gNETs > 1 cm. The findings are expected to provide valuable insights and guide the development of more effective management strategies.
The present study was designed as an international multicentric retrospective analysis, conducted in 7 Western centers. It included consecutive patients diagnosed with T1-gNETs >1 cm in diameter, collected between 2004 and 2023, with at least 12 months of follow-up. The primary endpoints were disease progression (DP) (tumor recurrence or metastasis development) and the Progression-Free Survival. The Cox regression method was used to identify factors associated with progression.

Results

The study included 104 patients (61 females, 43 males) with a median age of 61 years and a median tumor size of 15 mm (range 11–60 mm). 61.5% of tumors were classified as G1, 37.5% as G2, and 1% as G3. 75 patients (72.1 %) underwent endoscopic resection (27 EMR, 5 m-EMR, 14 ESD, 7 snare polypectomy, and 22 unspecified techniques). Surgical procedures were performed in 33 patients (31.7%), 13 of whom had previously undergone endoscopic resection. One patient (1%) received treatment with somatostatin analogues, while 8 patients (7.7%) received no treatment.
The R0 resection rate was 51.9%. During follow-up, 26 patients (25%) experienced recurrence, 7 (6.7%) developed metastases, and 12 (11.5%) died, with 2 deaths (1.9%) due to tumor-related causes. The median overall survival and progression-free survival were 59.5 months (range 13–215) and 51.5 months (range 4–215), respectively.
Univariate analysis showed that R0 resection (HR 0.32, p=0.02) and advanced endoscopic techniques (m-EMR/ESD) (HR 0.09, p=0.02) were associated with better outcomes. In contrast, other resection methods (standard EMR, snare polypectomy, or unspecified techniques) and tumor size were associated with a higher risk of disease progression (HR 10.13, p=0.02; HR 1.03, p=0.003, respectively).

Conclusion

T1-gNETs >1 cm often recur and can progress, exhibiting potentially aggressive behavior, especially in larger lesions. Endoscopic resection should employ advanced techniques to prevent incomplete removal, which is associated with poor outcomes.

Introduction

Gastric cancer (GC) remains a challenging disease mainly due to its heterogeneity and complex tumour microenvironment[1]. GC has a 5-year survival rate of less than 40%, however, advanced GC has a much lower survival rate of around 5%. Standard treatment for resectable gastric cancer consists of surgical resection in combination with perioperative chemotherapy. Based on the FLOT4 trial, perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy improved overall survival in locally advanced, resectable esophagogastric adenocarcinoma compared to perioperative ECF/ECX[2]. Despite advances, around 50% of patients do not respond to any of these treatments, and the majority will have recurrence and treatment resistance. By suppressing the immune system and remodelling the extracellular matrix, cancer-associated fibroblasts (CAFs) have been found to promote drug resistance in several tumor types, including GC[3]. Given their high plasticity, the exact role of CAFs in tumor development and treatment resistance in GC remains unknown.

Aims & Methods

This project aims to establish mini-tumour (MT) models that accurately reflect the characteristics of gastric tumours, facilitating the evaluation of the role of stroma upon gastric cancer therapy. The study focuses on two key objectives: (1) evaluating whether CAF subsets in gastric MTs resemble those in parental tumour tissues, ensuring a reflective model for personalized treatment strategies, and (2) assess drug responses in MTs, identifying the most effective therapies, and evaluating CAF-tumor interactions in treatment resistance.
First, we isolate and culture patient-derived tumor organoids and CAFs from gastric cancer resected material, which forms our patient GC biobank. Then, we establish MTs consisting of co-cultured matched patient-derived organoids and CAFs. MT establishment includes mimicking parental tumor tissue tumour-stroma ratio, hotspot mutation data, and specific culture conditions. Once established, treatment assays are designed to study chemotherapy responses (single-drug and combination drugs), as well as CAF subset changes. Untreated and treated MTs are subsequently fixed and stained with cell proliferation, death, and tumor/stroma markers.

Results

Up to date, a total of n=3 MT models have been established, which recapitulate the primary tumour, based on mutation status (e.g. HER2, KRAS, CTNNB1, TP53) , tumor/stroma structures and CAF enrichment. Upon treatment, majority of chemotherapeutics used as single drug showed to be non-effective, and only a few combinations seemed to be clinically relevant (≤ 50% cell viability). Preliminary data shows that CAF sensitivity to chemotherapy differs between patients, particularly between treatment naïve and FLOT-treated, and seems to resemble patient responses.

Conclusion

Overall, MT models display patient-specific features, showcasing interpatient heterogeneity, and highlighting the need for tailored models to optimally evaluate therapy responses. Future experiments will evaluate intrinsic resistance mechanisms potentially associated with specific CAF subsets. To further look into these, spatial profiling of gastric MTs and primary tumours will be evaluated using a stromal 42-marker panel by Imaging Mass Cytometry. To evaluate the immune cell compartment in these MTs, incorporating cytomegalovirus (CMV)-stimulated T cells or patient-derived tumor infiltrating lymphocytes is planned.

References

1. Lei ZN, Teng QX, Tian Q, Chen W, Xie Y, Wu K, Zeng Q, Zeng L, Pan Y, Chen ZS, He Y. Signaling pathways and therapeutic interventions in gastric cancer. Signal Transduct Target Ther. 2022 Oct 8;7(1):358. doi: 10.1038/s41392-022-01190-w.
2. Möhring C, Mańczak A, Timotheou A, et al. Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real-world cohort. Int J Cancer. 2023; 153(3): 609-622. doi:10.1002/ijc.34511
3. Ozmen, E., Demir, T. D., & Ozcan, G. (2024). Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer. Frontiers in Molecular Biosciences, 11. https://doi.org/10.3389/fmolb.2024.1340124

Disclosure

No conflict of interest.

Introduction

Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (SESCC) involving the entire circumference carries the extremely high risk of stricture and also raises concerns about curative resection. Therefore, the current Japanese guidelines weakly recommend ESD only for circumferential SESCCs diagnosed as cEP/LPM and sized ≤ 50 mm, while surgery or chemoradiotherapy (CRT) is recommended for circumferential SESCCs other than the above. ¹ However, in clinical practice, ESD is implemented on a case-by-case basis through the discussion in a multi-disciplinary cancer board at each institution because the outcomes of each treatment for circumferential SESCCs remain unclear.²

Aims & Methods

This multicenter prospective observational study aimed to reveal the outcomes of each treatment for circumferential SESCCs. Patients with cT1a-EP/LPM or cT1a-MM/T1b-SM1 N0M0 SESCCs involving the entire circumference were enrolled in this study. At this stage, short-term outcomes, such as the proportion of curative resection after ESD, complete response (CR) after CRT/radiotherapy (RT), and adverse events including esophageal stricture, were evaluated. Curative resection in ESD was defined as pT1a without lymphovascular invasion (LVI). Esophageal stricture was defined as inability to pass the ordinary-sized endoscope thorough the treated site, and refractory stricture was defined as stricture requiring ≥ 6 endoscopic balloon dilation procedures.

Results

A total of 126 patients with circumferential SESCCs were enrolled from 16 Japanese tertiary institutions between May 2021 and November 2024. ESD was performed for 90 (71.4%) patients including 6 undergoing stepwise ESD, surgery for 18 (14.3%), CRT for 16 (12.7%), and RT alone for 2 (1.6%). Median longitudinal length of tumor was 55 (range: 30–140) mm in the ESD group, 80 (50–150) mm in the surgery group, and 70 (30–100) mm in the CRT/RT group. Tumor depth was diagnosed as cEP/LPM in 65.4% (55/84) of the ESD group, 38.9% (7/18) of the surgery group, and 50.0% (9/18) of the CRT/RT group, and the others were diagnosed as cMM/SM1. As stricture prevention method after ESD, local injection or filling of triamcinolone (TA) alone was used in 9 patients (10.7%), and both local injection of TA and oral steroid of prednisolone were used in 75 (89.3%). Among the 63 patients who did not receive additional treatment after ESD, the proportion of stricture and refractory stricture were 46.0% (29/63) and 27.0% (17/63), respectively. Curative resection after ESD was achieved in 58 patients (69.0%), including 46 (83.6%) with cEP/LPM and 12 (41.4%) with cMM/SM1. Of 26 patients with non-curative resection after ESD, 20 (76.9%) received additional treatment of either surgery, CRT, or RT, while the remaining 6 opted for follow-up. Of 18 patients in the surgery group, 7 with cEP/LPM and 4 with cMM/SM1 were diagnosed as pT1aN0 without LVI, while the remaining 7 with cMM/SM1 were diagnosed as pT1b, 3 of whom had lymph node metastasis. Anastomotic stricture was observed in 11.1% (2/18) of patients treated with surgery. Of 18 patients in the CRT/RT group, CR was confirmed in all patients without forming stricture.

Conclusion

Considering the high curative resection rate, ESD could be indicated for circumferential SESCCs diagnosed as cEP/LPM. In contrast, the careful consideration may be required in indicating ESD for circumferential SESCCs diagnosed as cMM/SM1 due to its low curative resection rate. Long-term outcome needs to be confirmed for further treatment comparisons.

References

1. Ishihara R, Arima M, Iizuka T, et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020; 32: 452–93.
2. Kadota T, Ishihara R, Hatta W, et al. Multi-institutional questionnaire on treatment strategies for superficial entire circumferential esophageal squamous cell carcinoma. DEN Open. 2023; 3: e206.

Introduction

Primary gastric neoplasms (PGNs) in children and young adults are exceedingly rare, and as a result, their clinicopathological features, biological behavior, and long-term outcomes remain poorly characterized.

Aims & Methods

The aim of this study was to comprehensively evaluate the clinical and pathological features of PGNs in this young population and to assess their prognosis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database. A retrospective cohort study was conducted using SEER data spanning a 13-year period (2004–2016). Patients under 24 years of age with PGNs were identified using SEERStat. Demographic and clinical characteristics, tumor features, treatment modalities, and survival outcomes were analyzed. Overall survival (OS) was estimated, and multivariable Cox regression analysis was performed to identify factors independently associated with OS. All statistical analyses were conducted using R version 4.4.2.

Results

A total of 324 patients under the age of 24 with PGNs were included (mean age 20.1 years); 13.3% were <15 years, 25.3% were 16–20 years, and 61.4% were 20–24 years. The cohort was evenly distributed by sex (50% female), with 70.4% identifying as white race. The most common histologic types was adenocarcinoma and signet ring cell carcinoma (59.0%), followed by lymphomas (17.0%), and complex mixed or stromal neoplasms (16.4%). Among cases with available data, 48.2% were diagnosed at stage IV according to American Joint Committee on Cancer (AJCC). Surgical resection was performed in 39.5% of patients, radiotherapy in 14.0% and chemotherapy in 57.3%. Median follow-up was 65 months and median OS was 36 months (range 0–154). The 1- and 5-year OS rates were 66.7% (95% confidence interval [95% CI]: 61.6%–71.2%) and 49.0% (95% CI: 43.4%–55.2%), respectively. In multivariate analysis, histologic type, AJCC stage, and surgery were independently associated with OS, when adjusting for sex, age, year of diagnosis, race, radiation and chemotherapy. Compared to signet ring cell carcinoma, adenocarcinomas (hazard ratio [HR] = 0.65, 95% CI: 0.44–0.97) and lymphomas (HR = 0.16, 95% CI: 0.07–0.37) were associated with superior OS, while undifferentiated carcinomas were associated with inferior OS (HR = 2.50, 95% CI: 1.10–5.69). Advanced AJCC stages were associated with increased risk of mortality (stage II: HR = 3.80; stage III: HR = 8.81; stage IV: HR = 8.39). Surgery was associated with improved OS (HR = 0.34, 95% CI: 0.20–0.57).

Conclusion

PGNs in children and young adults are rare, often diagnosed at advanced stages, and associated with poor prognosis. In our cohort, histologic type, AJCC stage, and surgery were independently associated with OS. These findings highlight the impact of tumor biology in young patients with PGNs and underscore the need to include pediatric and young adult patients in prospective clinical trials and to discuss such rare cases in multidisciplinary tumor boards to inform treatment decisions and improve outcomes in this vulnerable population.

Disclosure

Nothing to disclosure.

Clinical Case Summary

Case: We present a case of parietal cell carcinoma presenting with melena and pain abdomen. A 57-year-old Indian male, known diabetic and reformed smoker/alcoholic presented with upper abdominal pain and generalised weakness for three months. He also reported passage of black tarry stools for 3–4 days, about 15 days back, following which he started having general weakness and easy fatigability. Physical examination showed pallor with normal abdominal examination. Investigations revealed haemoglobin to be 10 g/dl and peripheral blood film showed microcytic hypochromic anaemia. Liver and renal function test were normal. Contrast enhanced CT scan of abdomen revealed arterial phase enhancing polypoidal lesion on greater curvature of the stomach. Esophagogastroduodenoscopy showed a six cm size ulcerated, friable mass in proximal body of stomach. Biopsies showed evidence of parietal cell carcinoma. The cells showed glandular arrangement, abundant granular eosinophilic cytoplasm, along with positive immunohistochemistry for Pan-Cytokeratin. Patient underwent exploratory laparotomy with total gastrectomy, distal pancreatectomy, splenectomy, roux-en-y esophagojejunostomy. He received adjuvant chemoradiotherapy. Patient recovered well and became asymptomatic.
Discussion: Parietal Cell Carcinoma is a rare malignant tumor of stomach with a strikingly male (9:1) preponderance. It generally occurs in older males and runs a relatively indolent course. These well to moderately differentiated tumors are usually diagnosed by pathology. Lymph node and distant metastasis occur rarely, hence prognosis is generally favourable.
Conclusion: Parietal cell carcinoma is rare cause of gastric mass and upper gastrointestinal bleeding. It is rarely considered in differential diagnosis clinically and diagnosis invariable emerges on histopathology.

References

Motta, M., Athanazio, D., Motta, A., Studart, E. and Athanazio, P., 2008. Parietal Cell (Oncocytic) Adenocarcinoma of the Stomach in a Female Patient: Superficial Spreading and Extensive Nodal Involvement. International Journal of Surgical Pathology, 16(4), pp.447-449.
Byrne, D., Holley, M. and Cuschieri, A., 1988. Parietal cell carcinoma of the stomach: association with long-term survival after curative resection. British Journal of Cancer, 58(1), pp.85-87.
Takubo, K., Honma, N., Sawabe, M., Arai, T., Izumiyama-Shimomura, N., Kammori, M., Sasajima, K. and Esaki, Y., 2002.

Clinical Case Summary

This case presents a 64-year old man with verrucous carcinoma of the esophagus (VCE), a rare variant of squamous cell carcinoma. The patient has a history of type 2 diabetes and tobacco abuse, and presented in September 2019 with complaints of dysphagia. Upper endoscopy revealed reflux-, and candida esophagitis, and a proximal stenosis. Treatment was initiated with proton pump inhibitors, antifungal therapy, and dilatations. Over three years, multiple endoscopies were conducted, almost all revealing extensive white hyperkeratotic and exophytic lesions. Histopathology reports described fungal threads and no dysplasia, leading to a diagnosis of therapy-resistant candida esophagitis due to poorly regulated diabetes. After two times failure of intravenous antifungal therapy, in February 2023, the patient was referred to our center, a tertiary hospital. Targeted bite on bite biopsies revealed candida aggregates, parakeratosis, and squamous cell proliferation, highly suggestive of well-differentiated VCE. A PET-CT showed no signs of metastatic disease; therefore, considering the early stage and endoscopic extent of the lesion, a laparoscopic esophagostomy was performed.

The prolonged interval from clinical presentation to VCE diagnosis is thought to result from the hyperkeratotic growth pattern, which causes inadequate material for histologic confirmation of underlying neoplastic tissue. Additionally, the presence of fungal threads and white lesions results in diagnosis of candida esophagitis, misleading physicians and causing diagnostic delay. In patients with therapy-resistant candida esophagitis and atypical hyperkeratotic esophageal lesions VCE should be considered, enabling early diagnosis and treatment.

References

Figures that will be presented when accepted:
Figure 1: upper GI endoscopy during initial presentation showing white/yellow keratotic plaques and a proximal stenosis.
Figure 2: upper GI endoscopy at time of VCE diagnosis at our center 4-years after the initial presentation, showing a circumferentially narrowed esophagus, with white, granular and keratotic plaques and lesions at white light endoscopy
Figure 3: upper GI endoscopy at time of VCE diagnosis at our center 4-years after the initial presentation, with NBI showing a circumferentially narrowed esophagus, and diffusely irregular mucosa with white plaques and keratotic lesions.

References:
1. Sweetser S, Jacobs NL, Wong Kee Song LM. Endoscopic diagnosis and treatment of esophageal verrucous squamous cell cancer. Dis Esophagus. 2014;27(5):452-6.
2. Egeland C, Achiam MP, Federspiel B, Svendsen LB. Verrucous Squamous Cell Cancer in the Esophagus: An Obscure Diagnosis. Case Rep Gastroenterol. 2016;10(2):466-71.
3. Tabuchi S, Koyanagi K, Nagata K, Ozawa S, Kawachi S. Verrucous carcinoma of the esophagus: a case report and literature review. Surg Case Rep. 2020;6(1):35.