Pub Date : 2025-09-01DOI: 10.1016/j.esmogo.2025.100226
S. Kasper , E. Elez , U. Neumann , S. Lang , A.-K. Trampe , F. Salva , C. Dopazo , I. Virchow , S. Hartmann , K. Herrmann , J. Tabernero , A. Westendorf , M. Schuler , A. Schramm
Background
In colorectal cancer (CRC), the liver is the most common site of metastasis, which is the leading cause of CRC-related mortality. Hepatic resection offers long-term survival in some patients with CRC liver metastases (CRLM), but recurrence rates remain high (50%-75% within 2 years). Preoperative immunotherapy may induce tumor regression and improve long-term surgical outcomes. The PURPLE trial evaluates the feasibility, safety, and efficacy of short-term preoperative immunotherapy with the anti-programmed death-ligand 1 (PD-L1) antibody atezolizumab and the anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody tiragolumab in patients with resectable CRLM.
Study design
PURPLE is an international, open-label, multicenter, randomized phase II ‘window of opportunity’ trial. Patients with resectable CRLM are randomized 2 : 1 to receive two cycles of atezolizumab (840 mg) plus tiragolumab (420 mg) before surgery (experimental arm) or immediate surgery (control arm). The primary endpoint is the percentage of patients with complete or major pathological regression of the resected metastases (tumor regression grade 1/2, Rubbia-Brandt criteria). The statistical design follows Simon’s two-stage approach with interim and final analyses comparing pathological response rates using descriptive and exploratory methods. Secondary endpoints include feasibility, safety, post-operative complications, and metabolic response by positron emission tomography. Exploratory studies characterize immune cell infiltration, tumor mutational burden, and circulating tumor DNA dynamics.
{"title":"Preoperative immunotherapy with atezolizumab and tiragolumab in patients with colorectal liver metastases—the PURPLE trial","authors":"S. Kasper , E. Elez , U. Neumann , S. Lang , A.-K. Trampe , F. Salva , C. Dopazo , I. Virchow , S. Hartmann , K. Herrmann , J. Tabernero , A. Westendorf , M. Schuler , A. Schramm","doi":"10.1016/j.esmogo.2025.100226","DOIUrl":"10.1016/j.esmogo.2025.100226","url":null,"abstract":"<div><h3>Background</h3><div>In colorectal cancer (CRC), the liver is the most common site of metastasis, which is the leading cause of CRC-related mortality. Hepatic resection offers long-term survival in some patients with CRC liver metastases (CRLM), but recurrence rates remain high (50%-75% within 2 years). Preoperative immunotherapy may induce tumor regression and improve long-term surgical outcomes. The PURPLE trial evaluates the feasibility, safety, and efficacy of short-term preoperative immunotherapy with the anti-programmed death-ligand 1 (PD-L1) antibody atezolizumab and the anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody tiragolumab in patients with resectable CRLM.</div></div><div><h3>Study design</h3><div>PURPLE is an international, open-label, multicenter, randomized phase II ‘window of opportunity’ trial. Patients with resectable CRLM are randomized 2 : 1 to receive two cycles of atezolizumab (840 mg) plus tiragolumab (420 mg) before surgery (experimental arm) or immediate surgery (control arm). The primary endpoint is the percentage of patients with complete or major pathological regression of the resected metastases (tumor regression grade 1/2, Rubbia-Brandt criteria). The statistical design follows Simon’s two-stage approach with interim and final analyses comparing pathological response rates using descriptive and exploratory methods. Secondary endpoints include feasibility, safety, post-operative complications, and metabolic response by positron emission tomography. Exploratory studies characterize immune cell infiltration, tumor mutational burden, and circulating tumor DNA dynamics.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100226"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-08-07DOI: 10.1016/j.esmogo.2025.100211
K P Ray, W Cruces, Y Mzannar, A Aboukameel, S Motorwala, T Hadid, M N Al-Hallak, G A Ramirez, T T Tesfatsion, M L Docampo-Palacios, A C Collins, P G Jagtap, A S Azmi, H Y Khan
Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal form of cancer with limited treatment options and poor survival rates. Cannabinoids have demonstrated antiproliferative and proapoptotic effects in various cancer types, including PDAC, making them promising therapeutic agents. However, clinical efficacy remains underexplored, particularly for cannabinoids like cannabidiol and tetrahydrocannabinol, which show limited activity against pancreatic cancer.
Materials and methods: We synthesized novel cannabinoid analogues, including CCL-106 and its epimers CCL-114 and CCL-115, which exhibit superior antitumor activity in both two-dimensional and three-dimensional pancreatic cancer models.
Results: These compounds demonstrated substantially lower concentration that causes 50% inhibition of growth (IC50) values in human pancreatic cancer cell lines and enhanced tumor inhibition in pancreatic cancer cell-derived xenograft model without inducing systemic toxicity. Mechanistic studies revealed that the antiproliferative effects of these compounds are primarily mediated through CB2 and GPR55 receptor activation, alongside the generation of reactive oxygen species. Further, CCL-106 has been shown to significantly enhance the efficacy of the standard-of-care chemotherapeutic regimen gemcitabine/nab-paclitaxel in vitro. Moreover, the combination of CCL-106 with gemcitabine/nab-paclitaxel exhibited synergistic effects on growth inhibition of PDAC cells. Additionally, using a patient-derived xenograft model of PDAC, the antitumor efficacy of CCL-115 and CCL-114 in combination with gemcitabine and nab-paclitaxel was demonstrated.
Conclusions: These findings suggest that CCL-106 and its epimers hold potential as effective and less-toxic therapeutic options for PDAC treatment. Further clinical studies are warranted to explore their translational application.
{"title":"Pharmacological advances in cannabinoid-based therapies for pancreatic cancer: preclinical efficacy of CCL-106 and its epimers.","authors":"K P Ray, W Cruces, Y Mzannar, A Aboukameel, S Motorwala, T Hadid, M N Al-Hallak, G A Ramirez, T T Tesfatsion, M L Docampo-Palacios, A C Collins, P G Jagtap, A S Azmi, H Y Khan","doi":"10.1016/j.esmogo.2025.100211","DOIUrl":"10.1016/j.esmogo.2025.100211","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal form of cancer with limited treatment options and poor survival rates. Cannabinoids have demonstrated antiproliferative and proapoptotic effects in various cancer types, including PDAC, making them promising therapeutic agents. However, clinical efficacy remains underexplored, particularly for cannabinoids like cannabidiol and tetrahydrocannabinol, which show limited activity against pancreatic cancer.</p><p><strong>Materials and methods: </strong>We synthesized novel cannabinoid analogues, including CCL-106 and its epimers CCL-114 and CCL-115, which exhibit superior antitumor activity in both two-dimensional and three-dimensional pancreatic cancer models.</p><p><strong>Results: </strong>These compounds demonstrated substantially lower concentration that causes 50% inhibition of growth (IC<sub>50</sub>) values in human pancreatic cancer cell lines and enhanced tumor inhibition in pancreatic cancer cell-derived xenograft model without inducing systemic toxicity. Mechanistic studies revealed that the antiproliferative effects of these compounds are primarily mediated through CB2 and GPR55 receptor activation, alongside the generation of reactive oxygen species. Further, CCL-106 has been shown to significantly enhance the efficacy of the standard-of-care chemotherapeutic regimen gemcitabine/nab-paclitaxel <i>in vitro</i>. Moreover, the combination of CCL-106 with gemcitabine/nab-paclitaxel exhibited synergistic effects on growth inhibition of PDAC cells. Additionally, using a patient-derived xenograft model of PDAC, the antitumor efficacy of CCL-115 and CCL-114 in combination with gemcitabine and nab-paclitaxel was demonstrated.</p><p><strong>Conclusions: </strong>These findings suggest that CCL-106 and its epimers hold potential as effective and less-toxic therapeutic options for PDAC treatment. Further clinical studies are warranted to explore their translational application.</p>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29DOI: 10.1016/j.esmogo.2025.100227
M. Rimini , S. Presi , K. Mohammadi , G.B. Pipitone , A.R. Raucci , F. Ratti , F. Pedica , S. Foti , S. Camera , M. Ferrara , L. Passeri , G. Vanella , F. Rossari , F. Lo Prinzi , M. Persano , F. Vitiello , M.G. Cangi , L. Pecciarini , P.G. Arcidiacono , F. Falcinelli , A. Casadei-Gardini
Background
Recent data reported a significant incidence of germline aberrations in biliary tract cancer (BTC) patients, even if conclusive data on that and on its clinical implication are lacking.
Methods
We selected patients for genetic counselling basing on four criteria: personal history of oncologic disease other than BTC; familial history of oncologic disease (considering relatives of first and second grade); patients ≤50 years old; patients presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair.
Results
A total of 22/150 patients met at least one criterion and were directed to genetic counselling. Of these, 17 received the germline test. Four patients carried a pathogenic variant. Some 18/22 patients received the somatic test on tissue samples. Patients who carried a germline pathogenic variant had the same variant also at a somatic level. No statistically significant differences were found in terms of incidence of germline pathogenic variants between patients diagnosed with BTC before the age of 50 years versus after the age of 50 years and in patients with intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma.
Conclusion
The present study is one of the first prospective experiences investigating the role of genetic counselling and germline testing in a BTC setting, thus suggesting several improvements in the selection criteria of patients directed to genetic counselling.
{"title":"Comprehensive genetic analysis in biliary tract cancer: a prospective single-center experience","authors":"M. Rimini , S. Presi , K. Mohammadi , G.B. Pipitone , A.R. Raucci , F. Ratti , F. Pedica , S. Foti , S. Camera , M. Ferrara , L. Passeri , G. Vanella , F. Rossari , F. Lo Prinzi , M. Persano , F. Vitiello , M.G. Cangi , L. Pecciarini , P.G. Arcidiacono , F. Falcinelli , A. Casadei-Gardini","doi":"10.1016/j.esmogo.2025.100227","DOIUrl":"10.1016/j.esmogo.2025.100227","url":null,"abstract":"<div><h3>Background</h3><div>Recent data reported a significant incidence of germline aberrations in biliary tract cancer (BTC) patients, even if conclusive data on that and on its clinical implication are lacking.</div></div><div><h3>Methods</h3><div>We selected patients for genetic counselling basing on four criteria: personal history of oncologic disease other than BTC; familial history of oncologic disease (considering relatives of first and second grade); patients ≤50 years old; patients presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair.</div></div><div><h3>Results</h3><div>A total of 22/150 patients met at least one criterion and were directed to genetic counselling. Of these, 17 received the germline test. Four patients carried a pathogenic variant. Some 18/22 patients received the somatic test on tissue samples. Patients who carried a germline pathogenic variant had the same variant also at a somatic level. No statistically significant differences were found in terms of incidence of germline pathogenic variants between patients diagnosed with BTC before the age of 50 years versus after the age of 50 years and in patients with intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma.</div></div><div><h3>Conclusion</h3><div>The present study is one of the first prospective experiences investigating the role of genetic counselling and germline testing in a BTC setting, thus suggesting several improvements in the selection criteria of patients directed to genetic counselling.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100227"},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29DOI: 10.1016/j.esmogo.2025.100204
A. Boilève , M. Brugel , M. Rémond , M. Valéry , M. Ducreux , A. Turpin , C. Smolenschi
The rising incidence of early-onset pancreatic and biliary tract cancers (PBTCs) challenges conventional assumptions that these malignancies primarily affect older populations. Although early-onset PBTCs have a similarly poor prognosis to later-onset cases, emerging evidence suggests that unique or mixed genetic, environmental, and lifestyle factors contribute to their distinct etiologies. This review synthesizes current data on the epidemiology, risk factors, and molecular features of early-onset (in individuals <50 years of age) pancreatic ductal adenocarcinoma and biliary tract cancers. Recent studies indicate a significant increase in early-onset PBTC incidence, with variations by sex, geographic region, and genetic predisposition. Hereditary factors, including BRCA1/2, CDKN2A, and mismatch repair gene mutations, contribute to familial clustering, while other nonhereditary risk factors such as obesity, smoking, pancreatitis, and diabetes seem to disproportionately impact younger patients.
Additionally, environmental exposures, including air pollution, pesticides, and endocrine-disrupting chemicals, are suggested to contribute to carcinogenesis, while changes in microbiota may cause inflammation, immune modulation, and treatment resistance. As the burden of early-onset PBTCs grows, refining screening strategies and integrating microbiome-based risk assessment into biobanking strategies will be critical. Future research should focus on age-stratified genetic risk profiling, microbiota-driven interventions, and personalized therapeutic approaches to improve early detection and patient outcomes.
{"title":"The increasing burden of early-onset pancreatic and biliary tract cancers: a review of risk factors","authors":"A. Boilève , M. Brugel , M. Rémond , M. Valéry , M. Ducreux , A. Turpin , C. Smolenschi","doi":"10.1016/j.esmogo.2025.100204","DOIUrl":"10.1016/j.esmogo.2025.100204","url":null,"abstract":"<div><div>The rising incidence of early-onset pancreatic and biliary tract cancers (PBTCs) challenges conventional assumptions that these malignancies primarily affect older populations. Although early-onset PBTCs have a similarly poor prognosis to later-onset cases, emerging evidence suggests that unique or mixed genetic, environmental, and lifestyle factors contribute to their distinct etiologies. This review synthesizes current data on the epidemiology, risk factors, and molecular features of early-onset (in individuals <50 years of age) pancreatic ductal adenocarcinoma and biliary tract cancers. Recent studies indicate a significant increase in early-onset PBTC incidence, with variations by sex, geographic region, and genetic predisposition. Hereditary factors, including <em>BRCA1/2</em>, <em>CDKN2A</em>, and mismatch repair gene mutations, contribute to familial clustering, while other nonhereditary risk factors such as obesity, smoking, pancreatitis, and diabetes seem to disproportionately impact younger patients.</div><div>Additionally, environmental exposures, including air pollution, pesticides, and endocrine-disrupting chemicals, are suggested to contribute to carcinogenesis, while changes in microbiota may cause inflammation, immune modulation, and treatment resistance. As the burden of early-onset PBTCs grows, refining screening strategies and integrating microbiome-based risk assessment into biobanking strategies will be critical. Future research should focus on age-stratified genetic risk profiling, microbiota-driven interventions, and personalized therapeutic approaches to improve early detection and patient outcomes.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-28DOI: 10.1016/j.esmogo.2025.100232
J. Dekervel , N. Sanford , B. Groot Koerkamp
{"title":"Controversies in upper gastrointestinal cancers—the role of radiotherapy in borderline resectable pancreatic cancer","authors":"J. Dekervel , N. Sanford , B. Groot Koerkamp","doi":"10.1016/j.esmogo.2025.100232","DOIUrl":"10.1016/j.esmogo.2025.100232","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100232"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-28DOI: 10.1016/j.esmogo.2025.100222
K. Yoshino, M. Tamba, H. Osumi, S. Fukuoka, M. Ogura, S. Udagawa, K. Shimozaki, T. Wakatsuki, E. Shinozaki, K. Yamaguchi, K. Chin, A. Ooki
Background
The prognostic nutritional index (PNI) is an inflammation- and nutrition-based indicator that serves as a prognostic factor for various cancer types. This study aimed to evaluate the association between PNI and survival in patients with esophageal squamous-cell carcinoma (ESCC) receiving immune checkpoint inhibitor (ICI)-based therapies.
Materials and methods
This single-center retrospective study included two cohorts: 109 patients treated with nivolumab monotherapy as second-line or later therapy and 92 patients receiving first-line ICI-based treatments (ICI plus chemotherapy or nivolumab plus ipilimumab).
Results
In the nivolumab monotherapy cohort, higher PNI (PNI ≥ 40.5) was linked to longer overall survival (OS) compared with lower PNI (16.2 versus 5.5 months, P = 0.001). In the first-line cohort, 92 patients received ICI plus chemotherapy (n = 60) or nivolumab plus ipilimumab (n = 32). Higher PNI was linked to better OS in both the ICI plus chemotherapy (21.2 versus 7.7 months, P = 0.0008) and the nivolumab plus ipilimumab (not reached versus 10.2 months, P = 0.02) cohorts. Multivariate analysis identified PNI status as an independent prognostic factor in both cohorts. Dynamic changes in PNI (delta PNI ≥ 1.25) 1 month after treatment were linked to better progression-free survival in patients with lower PNI receiving nivolumab monotherapy or nivolumab plus ipilimumab but not in those receiving first-line ICI plus chemotherapy.
Conclusions
PNI and its dynamic changes may serve as useful indicators of prognosis in patients with ESCC receiving ICI-based therapies.
{"title":"Prognostic nutritional index as a prognostic marker in metastatic esophageal squamous-cell carcinoma treated with immune checkpoint inhibitor","authors":"K. Yoshino, M. Tamba, H. Osumi, S. Fukuoka, M. Ogura, S. Udagawa, K. Shimozaki, T. Wakatsuki, E. Shinozaki, K. Yamaguchi, K. Chin, A. Ooki","doi":"10.1016/j.esmogo.2025.100222","DOIUrl":"10.1016/j.esmogo.2025.100222","url":null,"abstract":"<div><h3>Background</h3><div>The prognostic nutritional index (PNI) is an inflammation- and nutrition-based indicator that serves as a prognostic factor for various cancer types. This study aimed to evaluate the association between PNI and survival in patients with esophageal squamous-cell carcinoma (ESCC) receiving immune checkpoint inhibitor (ICI)-based therapies.</div></div><div><h3>Materials and methods</h3><div>This single-center retrospective study included two cohorts: 109 patients treated with nivolumab monotherapy as second-line or later therapy and 92 patients receiving first-line ICI-based treatments (ICI plus chemotherapy or nivolumab plus ipilimumab).</div></div><div><h3>Results</h3><div>In the nivolumab monotherapy cohort, higher PNI (PNI ≥ 40.5) was linked to longer overall survival (OS) compared with lower PNI (16.2 versus 5.5 months, <em>P</em> = 0.001). In the first-line cohort, 92 patients received ICI plus chemotherapy (<em>n</em> = 60) or nivolumab plus ipilimumab (<em>n</em> = 32). Higher PNI was linked to better OS in both the ICI plus chemotherapy (21.2 versus 7.7 months, <em>P</em> = 0.0008) and the nivolumab plus ipilimumab (not reached versus 10.2 months, <em>P</em> = 0.02) cohorts. Multivariate analysis identified PNI status as an independent prognostic factor in both cohorts. Dynamic changes in PNI (delta PNI ≥ 1.25) 1 month after treatment were linked to better progression-free survival in patients with lower PNI receiving nivolumab monotherapy or nivolumab plus ipilimumab but not in those receiving first-line ICI plus chemotherapy.</div></div><div><h3>Conclusions</h3><div>PNI and its dynamic changes may serve as useful indicators of prognosis in patients with ESCC receiving ICI-based therapies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100222"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-27DOI: 10.1016/j.esmogo.2025.100231
H. Ueno , N.K. Kim , J.C. Kim , P. Tsarkov , W. Hohenberger , R. Grützmann , N.E Samalavičius , A. Dulskas , J.-T. Liang , P. Quirke , N. West , A. Shiomi , M. Ito , M. Shiozawa , K. Komori , K. Matsuda , Y. Kinugasa , T. Sato , K. Yamada , Y. Hashiguchi , K. Sugihara
Background
Substantial variations in the extent of lymphadenectomy are acknowledged internationally in colon cancer surgery because essential data for standardization, including the anatomical distribution of metastatic lymph nodes (LN), are lacking.
Materials and methods
Pre-specified LN mappings based on in vivo bowel measurements were conducted for stages I-III colon cancer patients treated at 31 leading hospitals in six countries. The extent of lymphadenectomy was classified from levels A (pericolic) to C (central LNs) according to the pre-specified anatomical landmarks. The primary outcome was the extent of pericolic lymphatic spread and the incidence of metastasis in central LNs, and secondary ones included the real-world status of central radicality and its association with short-term outcomes.
Results
Among 3647 patients, pericolic spread beyond 10 cm (0.2%) and absence of feeding arteries supplying the bowel within 10 cm from the primary tumor (0.3%) were rare, irrespective of nationality. The incidence of metastasis in central LNs was ∼3% (range: 0.2% in T1 to 7% in T4 tumors) and was lower in tumors located at the splenic flexure (0.5%). The proportion of patients with level C radicality was ∼76%, which was statistically significantly associated with T stage only in one country. A higher radicality level conferred no adverse impact on either the incidence of Clavien–Dindo grade ≥III or 30-day mortality.
Conclusions
The ‘10-cm rule’ could be an international criterion for determining the bowel-resection margin. Central lymphadenectomy is feasible internationally, though the indication should be selective, not routine, depending on the stage and location of the primary tumor.
{"title":"Lymph node mapping-based optimal bowel-resection margin and central radicality in colon cancer surgery: an international, prospective, observational cohort study","authors":"H. Ueno , N.K. Kim , J.C. Kim , P. Tsarkov , W. Hohenberger , R. Grützmann , N.E Samalavičius , A. Dulskas , J.-T. Liang , P. Quirke , N. West , A. Shiomi , M. Ito , M. Shiozawa , K. Komori , K. Matsuda , Y. Kinugasa , T. Sato , K. Yamada , Y. Hashiguchi , K. Sugihara","doi":"10.1016/j.esmogo.2025.100231","DOIUrl":"10.1016/j.esmogo.2025.100231","url":null,"abstract":"<div><h3>Background</h3><div>Substantial variations in the extent of lymphadenectomy are acknowledged internationally in colon cancer surgery because essential data for standardization, including the anatomical distribution of metastatic lymph nodes (LN), are lacking.</div></div><div><h3>Materials and methods</h3><div>Pre-specified LN mappings based on <em>in vivo</em> bowel measurements were conducted for stages I-III colon cancer patients treated at 31 leading hospitals in six countries. The extent of lymphadenectomy was classified from levels A (pericolic) to C (central LNs) according to the pre-specified anatomical landmarks. The primary outcome was the extent of pericolic lymphatic spread and the incidence of metastasis in central LNs, and secondary ones included the real-world status of central radicality and its association with short-term outcomes.</div></div><div><h3>Results</h3><div>Among 3647 patients, pericolic spread beyond 10 cm (0.2%) and absence of feeding arteries supplying the bowel within 10 cm from the primary tumor (0.3%) were rare, irrespective of nationality. The incidence of metastasis in central LNs was ∼3% (range: 0.2% in T1 to 7% in T4 tumors) and was lower in tumors located at the splenic flexure (0.5%). The proportion of patients with level C radicality was ∼76%, which was statistically significantly associated with T stage only in one country. A higher radicality level conferred no adverse impact on either the incidence of Clavien–Dindo grade ≥III or 30-day mortality.</div></div><div><h3>Conclusions</h3><div>The ‘10-cm rule’ could be an international criterion for determining the bowel-resection margin. Central lymphadenectomy is feasible internationally, though the indication should be selective, not routine, depending on the stage and location of the primary tumor.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100231"},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-26DOI: 10.1016/j.esmogo.2025.100224
A. Sartore-Bianchi , F. Toscano , D.P. Bernasconi , A. Curaba , P. Colombo , C. Mazzali , A. Piantelli , A. Dotti , D. Tedesco , K. Bencardino , A. Amatu , F. Tosi , E. Bonazzina , F. Villa , V. Gori , D. Piscazzi , A.G. Agostara , G. Calvanese , G. Saporetti , S. Siena
Background
Patient-reported experience measures (PREMs) offer an objective measure of the patient experience by investigating various fields of the care pathway. We analyzed PREMs in patients with metastatic colorectal cancer (mCRC) undergoing anticancer therapy integrating an auditing process to allow corrective actions.
Materials and methods
This is a prospective, observational, monocentric study with a four-phase sequential design: phase I validation of the PREMs questionnaires in five-level Likert item format in Italian; phase II administration of questionnaires at T0 (0-30 days since the start of oncology care), T1 (30 days-6 months), T2 (6-12 months), T3 (>12 months); phase III analysis of results during quality audits and implementation of strategies to improve care pathways; phase IV re-administration and results compared with phase II.
Results
PREMs were tested for validity in 47 patients (phase I of the EPIC study). In phase II, 102 patients were enrolled, 150 questionnaires were administered and 142 returned (94.6%). Sixteen questions grouped in four areas (information about care path, contacts and accessibility, patient needs, health care awareness monitoring) were analyzed. A high proportion of patients were concerned about their future/possibility of relapse at T1 (61.6%/58.3%) and T2 (62.5%/63.7%). After the implementation of a checklist for clinicians (phase III), in phase IV, 74 patients were enrolled and the proportion of patients concerned about their future/possibility of a relapse decreased at T1 (35.7%/25%) and T2 (31.3%/43.4%).
Conclusions
PREMs evaluation is feasible in the setting of mCRC. A checklist for clinicians tailored after an ad hoc audit improved results about patients’ concerns about their future and possibility of relapse.
{"title":"Patient-Reported Experience Measures (PREMs) in patients with metastatic colorectal cancer undergoing treatment supported by feedback auditing: the EPIC study","authors":"A. Sartore-Bianchi , F. Toscano , D.P. Bernasconi , A. Curaba , P. Colombo , C. Mazzali , A. Piantelli , A. Dotti , D. Tedesco , K. Bencardino , A. Amatu , F. Tosi , E. Bonazzina , F. Villa , V. Gori , D. Piscazzi , A.G. Agostara , G. Calvanese , G. Saporetti , S. Siena","doi":"10.1016/j.esmogo.2025.100224","DOIUrl":"10.1016/j.esmogo.2025.100224","url":null,"abstract":"<div><h3>Background</h3><div>Patient-reported experience measures (PREMs) offer an objective measure of the patient experience by investigating various fields of the care pathway. We analyzed PREMs in patients with metastatic colorectal cancer (mCRC) undergoing anticancer therapy integrating an auditing process to allow corrective actions.</div></div><div><h3>Materials and methods</h3><div>This is a prospective, observational, monocentric study with a four-phase sequential design: phase I validation of the PREMs questionnaires in five-level Likert item format in Italian; phase II administration of questionnaires at T0 (0-30 days since the start of oncology care), T1 (30 days-6 months), T2 (6-12 months), T3 (>12 months); phase III analysis of results during quality audits and implementation of strategies to improve care pathways; phase IV re-administration and results compared with phase II.</div></div><div><h3>Results</h3><div>PREMs were tested for validity in 47 patients (phase I of the EPIC study). In phase II, 102 patients were enrolled, 150 questionnaires were administered and 142 returned (94.6%). Sixteen questions grouped in four areas (information about care path, contacts and accessibility, patient needs, health care awareness monitoring) were analyzed. A high proportion of patients were concerned about their future/possibility of relapse at T1 (61.6%/58.3%) and T2 (62.5%/63.7%). After the implementation of a checklist for clinicians (phase III), in phase IV, 74 patients were enrolled and the proportion of patients concerned about their future/possibility of a relapse decreased at T1 (35.7%/25%) and T2 (31.3%/43.4%).</div></div><div><h3>Conclusions</h3><div>PREMs evaluation is feasible in the setting of mCRC. A checklist for clinicians tailored after an <em>ad hoc</em> audit improved results about patients’ concerns about their future and possibility of relapse.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100224"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-26DOI: 10.1016/j.esmogo.2025.100229
I.T. Lee , A. Dohlman , T. Gao , Z. Zhang , Y. Kasai , G.E. Kim , C. Thirlwell , E. Nakakura , M. Meyerson , N. Mäkinen
Background
Small intestinal neuroendocrine tumors (SI-NETs) are among the most common neoplasms of the small bowel; however, the molecular mechanisms underlying their pathogenesis are largely unknown. The multifocal nature of SI-NETs, their putative distinct genomic origins, and their enrichment in the distal ileum led us to hypothesize that environmental factors, such as pathogenic organisms, might play a role in the development of these lesions.
Materials and methods
To study the tumor-associated microbiome of multifocal SI-NETs and its potential role in pathogenesis, we used matched whole genome and transcriptome sequencing data from a cohort of 10 multifocal SI-NET patients, including 70 primary ileal NETs and their matched normal ileal mucosa and/or whole blood specimens.
Results
Microbial communities in the ileal tissue samples were primarily composed of bacteria. The most abundant genera included well-known gastrointestinal, oral, and mucosal bacteria. Ileal tissue samples from individual patients contained distinct patient-specific microbial communities. Although the microbiota composition did not show significant differences between ileal NET and normal ileal tissues, genus Propionibacterium was found to be enriched in the normal tissue specimens.
Conclusions
This study comprehensively characterizes the tissue-resident ileal microbiome of multifocal SI-NET patients. We provide clear evidence that the microbial communities in the ileum are largely patient specific, whereas our genus-level analyses suggest that SI-NET pathogenesis is unlikely driven by individual microorganisms present in the tumors at the time of surgical resection.
{"title":"Characterization of tumor-associated microbiome in multifocal small intestinal neuroendocrine tumors (SI-NETs)","authors":"I.T. Lee , A. Dohlman , T. Gao , Z. Zhang , Y. Kasai , G.E. Kim , C. Thirlwell , E. Nakakura , M. Meyerson , N. Mäkinen","doi":"10.1016/j.esmogo.2025.100229","DOIUrl":"10.1016/j.esmogo.2025.100229","url":null,"abstract":"<div><h3>Background</h3><div>Small intestinal neuroendocrine tumors (SI-NETs) are among the most common neoplasms of the small bowel; however, the molecular mechanisms underlying their pathogenesis are largely unknown. The multifocal nature of SI-NETs, their putative distinct genomic origins, and their enrichment in the distal ileum led us to hypothesize that environmental factors, such as pathogenic organisms, might play a role in the development of these lesions.</div></div><div><h3>Materials and methods</h3><div>To study the tumor-associated microbiome of multifocal SI-NETs and its potential role in pathogenesis, we used matched whole genome and transcriptome sequencing data from a cohort of 10 multifocal SI-NET patients, including 70 primary ileal NETs and their matched normal ileal mucosa and/or whole blood specimens.</div></div><div><h3>Results</h3><div>Microbial communities in the ileal tissue samples were primarily composed of bacteria. The most abundant genera included well-known gastrointestinal, oral, and mucosal bacteria. Ileal tissue samples from individual patients contained distinct patient-specific microbial communities. Although the microbiota composition did not show significant differences between ileal NET and normal ileal tissues, genus <em>Propionibacterium</em> was found to be enriched in the normal tissue specimens.</div></div><div><h3>Conclusions</h3><div>This study comprehensively characterizes the tissue-resident ileal microbiome of multifocal SI-NET patients. We provide clear evidence that the microbial communities in the ileum are largely patient specific, whereas our genus-level analyses suggest that SI-NET pathogenesis is unlikely driven by individual microorganisms present in the tumors at the time of surgical resection.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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