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12 pages, 649 KiB

Open AccessArticle

Should We Offer Universal Germline Genetic Testing to All Patients with Pancreatic Cancer? A Multicenter Study

by Joan Llach, Irina Luzko, Julie Earl, Emma Barreto, Mercedes Rodríguez-Garrote, Marc Lleixà, Cristina Herrera-Pariente, Guerau Fernández, Jenifer Munoz, Laia Bonjoch, Tamara Saurí, Fabio Ausania, Teresa Ocaña, Lorena Moreno, Elia Grau, Josep Oriola, Maria Isabel Alvarez-Mora, Marta Herreros-Villanueva, Sergi Castellví-Bel, Francesc Balaguer, Luis Bujanda and Leticia Moreira Show full author list Hide full author list

Cancers 2024, 16(22), 3779; https://doi.org/10.3390/cancers16223779 - 9 Nov 2024

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Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a significant percentage of germline pathogenic variants (GPVs). Unlike in the United States, routine universal genetic testing is not performed in Europe. The aim of the study is to evaluate the diagnostic yield of germline [...] Read more.

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a significant percentage of germline pathogenic variants (GPVs). Unlike in the United States, routine universal genetic testing is not performed in Europe. The aim of the study is to evaluate the diagnostic yield of germline genetic testing in all patients with PDAC. Methods: Individuals with newly diagnosed PDAC from three Spanish hospitals were enrolled, regardless of family history. Thirteen known susceptibility genes for PDAC were studied using a multigene panel or whole-exome sequencing. Results: One hundred seventy-nine PDAC patients underwent genetic testing. Fourteen (7.8%) had a GPV or likely pathogenic variant In the genes studied: six in ATM, six in BRCA2, one in PALB2, and one in TP53. Of these, seven (50%) did not meet the clinical criteria for genetic study and would have been classified as sporadic PDAC. Presenting with a personal history of any other neoplasm was associated with some GPV, with an odds ratio (OR) of 3.5 (1.1–11.5). A family history of PDAC and breast cancer was also associated with some GPV, with oRs of 3.7 (1.08–13.6) and 8.5 (2.6–26.6), respectively. None of the patients over 60 years without a relevant family history of malignancies presented a GPV associated with PDAC. Conclusions: In our PDAC cohort, a noteworthy number of GPVs were identified, and half of these patients would have been classified as sporadic based solely on clinical criteria. Genetic testing should always be considered, particularly in patients under 60 years or those with a history of other malignancies, especially where economic resources need optimization. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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11 pages, 1619 KiB

Open AccessArticle

High Rates of Organ Preservation in Rectal Cancer with Papillon Contact X-ray Radiotherapy: Results from a Swiss Cohort

by Cristina Picardi, Francesca Caparrotti, Michael Montemurro, Daniel Christen, Nora-Brunner Schaub, Marie Fargier-Voiron, Laetitia Lestrade, Jeremy Meyer, Guillaume Meurette, Emilie Liot, Daniel Helbling, Jan Schmidt, Jean-Pierre Gutzwiller, Marco Bernardi, Oscar Matzinger and Frederic Ris

Cancers 2024, 16(13), 2318; https://doi.org/10.3390/cancers16132318 - 25 Jun 2024

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Abstract

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external [...] Read more.

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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13 pages, 1708 KiB

Open AccessArticle

A Comparative Study of Postoperative Complications Associated with Distal Gastrectomy and Pylorus-Preserving Gastrectomy among Gastric Cancer Patients Based on Nationwide Survey Data and Propensity Score Weighting

by Sang-Ho Jeong, Miyeong Park, Kyung Won Seo, Rock Bum Kim, Jae-Seok Min and Information Committee of the Korean Gastric Cancer Association

Cancers 2024, 16(12), 2203; https://doi.org/10.3390/cancers16122203 - 12 Jun 2024

Cited by 1 | Viewed by 840 | Correction

Abstract

Background/Objective. This study aimed to compare complication rates between pylorus-preserving gastrectomy (PPG) and distal gastrectomy (DG) using Korean nationwide survey data and propensity score weighting (PSW). PPG preserves gastric function but may lead to more postoperative complications than DG. Methods and Results. We [...] Read more.

Background/Objective. This study aimed to compare complication rates between pylorus-preserving gastrectomy (PPG) and distal gastrectomy (DG) using Korean nationwide survey data and propensity score weighting (PSW). PPG preserves gastric function but may lead to more postoperative complications than DG. Methods and Results. We analyzed 9424 gastric cancer patients who underwent either DG (n = 9183) or PPG (n = 241). PSW balanced variables such as age, sex, TNM stage, comorbidities, ASA score, and surgical approach. Before PSW, 87.8% of DG patients and 87.1% of PPG patients had no complications (p = 0.053). Severe complications (Clavien–Dindo IIIa or higher) were more frequent in PPG (6.6%) than in DG (3.8%) (p = 0.039). After PSW, overall complication rates (p = 0.960) and severe complication rates (p = 0.574) were similar between groups. Incidence rates of anastomotic stricture and leakage were higher in PPG (2.9% and 1.7%) compared to DG (0.6% and 0.5%) (p = 0.001 and 0.036) before PSW, but these differences were not significant after PSW (p = 0.999 and 0.123). Conclusion. The PSW-adjusted analysis indicates no significant difference in overall and severe complication rates between PPG and DG in gastric cancer patients. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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14 pages, 5892 KiB

Open AccessArticle

Prospective, Observational Study of Aflibercept Use in Combination with FOLFIRI in Patients with Metastatic Colorectal Cancer: A Real-World Effectiveness Study

by Agnieszka Durbajło, Marcin Świeżyński, Beata Ziemba, Danuta Starzyczny-Słota, Marzena Samborska-Plewicka, Anna Cencelewicz-Lesikow, Agata Chrzanowska-Kapica, Aneta Dobrzyńska-Rutkowska, Iwona Drab-Mazur, Monika Kulma-Kreft, Magdalena Sikora-Skrabaka, Elwira Matuszewska, Małgorzata Foszczyńska-Kłoda, Tomasz Lewandowski, Grzegorz Słomian, Krystyna Ostrowska-Cichocka, Ewa Chmielowska, Rafał Wiśniowski, Anna Twardosz, Katarzyna Wierzbicka, Leszek Rumianowski and Lucjan Wyrwicz Show full author list Hide full author list

Cancers 2024, 16(11), 1992; https://doi.org/10.3390/cancers16111992 - 24 May 2024

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Abstract

Background: This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland. Methods: Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every [...] Read more.

Background: This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland. Methods: Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every 2 weeks until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); overall survival (OS) and safety were the secondary endpoints. Results: A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9–9.9] and 27.0 months [95% CI, 23.9–30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS. Main grade ≥ 3 adverse events were neutropenia (16%), hypertension (8%), diarrhea (4%), and stomatitis (4%). Conclusions: The benefits/risks of Aflibercept plus FOLFIRI administered per the Polish reimbursement criteria in second-line treatment of mCRC after failure of a prior oxaliplatin-based regimen is confirmed. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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14 pages, 2546 KiB

Open AccessArticle

Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center

by Elliott J. Yee, Danielle Gilbert, Jeffrey Kaplan, Sachin Wani, Sunnie S. Kim, Martin D. McCarter and Camille L. Stewart

Cancers 2024, 16(7), 1428; https://doi.org/10.3390/cancers16071428 - 7 Apr 2024

Viewed by 1940

Abstract

Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the [...] Read more.

Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles, as evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, as well as total TILs (CD4+, CD8+, T_reg, B cells), within chemotherapy-treated tumors compared with chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic responses with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherapy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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17 pages, 2987 KiB

Open AccessArticle

HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches

by Marta Baptista Freitas, Irene Gullo, Dina Leitão, Lúcia Águas, Carla Oliveira, António Polónia, Joana Gomes, Fátima Carneiro, Celso Albuquerque Reis and Henrique Oliveira Duarte

Cancers 2024, 16(6), 1227; https://doi.org/10.3390/cancers16061227 - 20 Mar 2024

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Abstract

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and [...] Read more.

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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12 pages, 447 KiB

Open AccessArticle

Preoperative Chronic Inflammation Is a Risk Factor for Postoperative Complications Independent of Body Composition in Gastric Cancer Patients Undergoing Radical Gastrectomy

by Ryota Matsui, Noriyuki Inaki, Toshikatsu Tsuji and Tetsu Fukunaga

Cancers 2024, 16(4), 833; https://doi.org/10.3390/cancers16040833 - 19 Feb 2024

Cited by 1 | Viewed by 1134

Abstract

The purpose of this study was to investigate the association between preoperative inflammation and postoperative complications in gastric cancer patients having elective gastrectomy. Participants in this study were those who underwent radical gastrectomy between April 2008 and June 2018 and were diagnosed with [...] Read more.

The purpose of this study was to investigate the association between preoperative inflammation and postoperative complications in gastric cancer patients having elective gastrectomy. Participants in this study were those who underwent radical gastrectomy between April 2008 and June 2018 and were diagnosed with stage I–III primary gastric cancer. Preoperative CRP values were used to divide the patients into two groups: the inflammation group comprised individuals having a CRP level of ≥0.5 mg/dL; the other was the non-inflammation group. The primary outcome was overall complications of Clavien–Dindo grade II or higher after surgery. Using propensity score matching to adjust for background, we compared the postoperative outcomes of the groups and conducted a multivariate analysis to identify risk variables for complications. Of 951 patients, 852 (89.6%) were in the non-inflammation group and 99 (10.4%) were in the inflammation group. After matching, both groups included 99 patients, and no significant differences in patient characteristics were observed between both groups. The inflammation group had a significantly greater total number of postoperative complications (p = 0.019). The multivariate analysis revealed that a preoperative CRP level of ≥0.5 mg/dL was an independent risk factor for total postoperative complications in all patients (odds ratio: 2.310, 95% confidence interval: 1.430–3.730, p < 0.001). In conclusion, in patients undergoing curative resection for gastric cancer, preoperative inflammation has been found to be an independent risk factor for overall complications after surgery. Patients with chronic inflammation require preoperative treatment to reduce inflammation because chronic inflammation is the greatest risk factor for postoperative complications. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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Review

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25 pages, 1498 KiB

Open AccessReview

Current Applications and Future Directions of Circulating Tumor Cells in Colorectal Cancer Recurrence

by Kun-Yu Tsai, Po-Shuan Huang, Po-Yu Chu, Thi Ngoc Anh Nguyen, Hsin-Yuan Hung, Chia-Hsun Hsieh and Min-Hsien Wu

Cancers 2024, 16(13), 2316; https://doi.org/10.3390/cancers16132316 - 24 Jun 2024

Cited by 3 | Viewed by 1761

Abstract

The ability to predict or detect colorectal cancer (CRC) recurrence early after surgery enables physicians to apply appropriate treatment plans and different follow-up strategies to improve patient survival. Overall, 30–50% of CRC patients experience cancer recurrence after radical surgery, but current surveillance tools [...] Read more.

The ability to predict or detect colorectal cancer (CRC) recurrence early after surgery enables physicians to apply appropriate treatment plans and different follow-up strategies to improve patient survival. Overall, 30–50% of CRC patients experience cancer recurrence after radical surgery, but current surveillance tools have limitations in the precise and early detection of cancer recurrence. Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream. These can provide real-time information on disease status. CTCs might become novel markers for predicting CRC recurrence and, more importantly, for making decisions about additional adjuvant chemotherapy. In this review, the clinical application of CTCs as a therapeutic marker for stage II CRC is described. It then discusses the utility of CTCs for monitoring cancer recurrence in advanced rectal cancer patients who undergo neoadjuvant chemoradiotherapy. Finally, it discusses the roles of CTC subtypes and CTCs combined with clinicopathological factors in establishing a multimarker model for predicting CRC recurrence. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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13 pages, 1286 KiB

Open AccessReview

Autoimmune Atrophic Gastritis: A Clinical Review

by Chiara Castellana, Leonardo Henry Eusebi, Elton Dajti, Veronica Iascone, Amanda Vestito, Pietro Fusaroli, Lorenzo Fuccio, Antonietta D’Errico and Rocco Maurizio Zagari

Cancers 2024, 16(7), 1310; https://doi.org/10.3390/cancers16071310 - 28 Mar 2024

Cited by 6 | Viewed by 8699

Abstract

Autoimmune atrophic gastritis (AAG) is a chronic condition characterized by the presence of atrophy in the oxyntic mucosa due to anti-parietal cell antibodies. This review provides a comprehensive and up-to-date overview of autoimmune atrophic gastritis, reporting recent evidence on epidemiology, pathogenesis, diagnosis, clinical [...] Read more.

Autoimmune atrophic gastritis (AAG) is a chronic condition characterized by the presence of atrophy in the oxyntic mucosa due to anti-parietal cell antibodies. This review provides a comprehensive and up-to-date overview of autoimmune atrophic gastritis, reporting recent evidence on epidemiology, pathogenesis, diagnosis, clinical presentation, risk of malignancies, and management. The prevalence of AAG has been estimated at between 0.3% and 2.7% in the general population. The diagnosis of AAG is based on a combination of the serologic profile and the histological examination of gastric biopsies. Patients with AAG are often asymptomatic but can also have dyspeptic or reflux symptoms. The atrophy of the oxyntic mucosa leads to iron and vitamin B12 malabsorption, which may result in anemia and neurological affections. Autoimmune atrophic gastritis is associated with an increased risk of type I neuroendocrine tumors (NETs) and gastric cancer, with an incidence rate of 2.8% and 0.5% per person/year, respectively. Management is directed to reinstate vitamins and iron and to prevent malignancies with endoscopic surveillance. In conclusion, atrophic autoimmune gastritis is an infrequent condition, often asymptomatic and misdiagnosed, that requires an early diagnosis for appropriate vitamin supplementation and endoscopic follow-up for the early diagnosis of NETs and gastric cancer. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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Other

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1 pages, 146 KiB

Open AccessCorrection

Correction: Jeong et al. A Comparative Study of Postoperative Complications Associated with Distal Gastrectomy and Pylorus-Preserving Gastrectomy among Gastric Cancer Patients Based on Nationwide Survey Data and Propensity Score Weighting. Cancers 2024, 16, 2203

by Sang-Ho Jeong, Miyeong Park, Kyung Won Seo, Rock Bum Kim, Jae-Seok Min and Information Committee of the Korean Gastric Cancer Association

Cancers 2024, 16(22), 3745; https://doi.org/10.3390/cancers16223745 - 6 Nov 2024

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Text Correction [...] Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

11 pages, 682 KiB

Open AccessSystematic Review

Robotic versus Laparoscopic Liver Resections for Colorectal Metastases: A Systematic Review and Meta-Analysis

by Kamil Safiejko, Michal Pedziwiatr, Michal Pruc, Radoslaw Tarkowski, Marcin Juchimiuk, Marian Domurat, Jacek Smereka, Khikmat Anvarov, Przemyslaw Sielicki, Krzysztof Kurek and Lukasz Szarpak

Cancers 2024, 16(8), 1596; https://doi.org/10.3390/cancers16081596 - 22 Apr 2024

Cited by 4 | Viewed by 1804

Abstract

Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach [...] Read more.

Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach (LRL). We performed a systematic review and meta-analysis of operative and short-term oncologic outcomes of the laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. An online search of PubMed, Embase, Scopus, and the Cochrane databases was performed. Eight studies involving 3210 patients were considered eligible for the meta-analysis. In the LRL group, a higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; p = <0.001). 30-day mortality was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76). Mortality in longer periods among LLR and RLR amounted to 18.2% vs. 8.0% for 1-year mortality (p = 0.07), 34.1% vs. 26.7% for 2-year mortality (p = 0.13), and 52.3% vs. 48.3% for 3-year mortality (p = 0.46). The length of hospital stay was 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (p = 0.47). There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p = 0.78). Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small. Full article

(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)

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