Diagnosis and Therapeutic Management of Gastrointestinal Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 26220

Special Issue Editors


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Guest Editor
Klinik Floridsdorf Wiener Gesundheitsverbund, Vienna, Austria
Interests: internal medicine; gastroenterology; hepatology; haematology

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Guest Editor
Faculty of Medicine, Sigmund Freud University, Vienna, Austria
Interests: abdominal surgery; gastroenterology; rectal cancer

Special Issue Information

Dear Colleagues,

Gastrointestinal cancers are showing increasing incidence and mortality rates worldwide and are responsible for 4.8 million new cancer cases and 3.4 million cancer related deaths per year (WHO 2018).

Most cases belong to the “big five”, affecting the esophagus, stomach, liver, colon and rectum as well the pancreato-biliary system.

Although some of the mentioned entities still are associated with a poor prognosis, new therapeutic modalities have led to an improvement in the outcome of affected patients.

In addition to advances in combinations of conventional chemotherapy with targeted treatment options and upcoming immunotherapy, novel strategies in tumor treatment, such as neoadjuvant protocols and improved timing (e.g., “liver first”) in the use of these multimodal approaches, have yielded remarkable benefits for the patients.

Translational and clinical research introduction of targeted immune and/or chemotherapy regimens as well as advancements in new surgical technology (minimal invasive surgery, robotic surgery) have led to a significant reduction of morbidity and shown increasingly promising results in the recent past.

Despite these observations of new advancements, challenges still remain, including regarding issues of preventive measures (e.g., screening for chronic hepatitis, preventive endoscopies, etc.) as well as healthcare and/or reimbursement questions.

This upcoming issue of Cancers will cover some of the topics related to the diagnosis and therapeutic management of gastrointestinal cancers by presenting reviews and/or meta-analyses as well as recent results from original research.

Prof. Dr. Christian Sebesta
Prof. Dr. Harald Rainer Rosen
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • esophagus tumor
  • stomach
  • liver
  • colon
  • rectum
  • pancreato-biliary
  • targeted immune and/or chemotherapy
  • surgical technology
  • multimodal approach
  • diagnosis
  • therapeutic management

Published Papers (17 papers)

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Editorial

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3 pages, 183 KiB  
Editorial
Unveiling New Horizons: Progress in the Management of Gastrointestinal and Hepatobiliary Cancer
by Christian Sebesta and Harald Rosen
Cancers 2023, 15(18), 4431; https://doi.org/10.3390/cancers15184431 - 06 Sep 2023
Viewed by 699
Abstract
The field of gastrointestinal cancer research continues to make significant strides in understanding the complexities of these challenging diseases [...] Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)

Research

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15 pages, 976 KiB  
Article
Patients with Advanced Pancreatic Cancer Treated with Mistletoe and Hyperthermia in Addition to Palliative Chemotherapy: A Retrospective Single-Center Analysis
by Anna Lena Hohneck, Largsi Sadikaj, Lara Heinemann, Maik Schroeder, Hartmut Riess, Annette Gerhards, Iris Burkholder, Stefan Heckel-Reusser, Julia Gottfried and Ralf-Dieter Hofheinz
Cancers 2023, 15(20), 4929; https://doi.org/10.3390/cancers15204929 - 11 Oct 2023
Viewed by 1064
Abstract
This retrospective analysis investigated the influence of integrative therapies in addition to palliative chemotherapy in patients with advanced pancreatic cancer, treated at a single institution specialized in integrative oncology between January 2015 and December 2019. In total, 206 consecutive patients were included in [...] Read more.
This retrospective analysis investigated the influence of integrative therapies in addition to palliative chemotherapy in patients with advanced pancreatic cancer, treated at a single institution specialized in integrative oncology between January 2015 and December 2019. In total, 206 consecutive patients were included in the study, whereof 142 patients (68.9%) received palliative chemotherapy (gemcitabine/nab-paclitaxel 33.8%; FOLFIRINOX 35.9%; gemcitabine 30.3%) while the remainder were treated with best supportive and integrative care. Integrative therapies were used in 117 of 142 patients (82.4%) in addition to conventional chemotherapy, whereby mistletoe was used in 117 patients (82.4%) and hyperthermia in 74 patients (52.1%). A total of 107/142 patients (86.3%) died during the observation period, whereby survival times differed significantly depending on the additional use of integrative mistletoe or hyperthermia: chemotherapy alone 8.6 months (95% CI 4.7–15.4), chemotherapy and only mistletoe therapy 11.2 months (95% CI 7.1–14.2), or a combination of chemotherapy with mistletoe and hyperthermia 18.9 months (95% CI 15.2–24.5). While the survival times observed for patients with advanced pancreatic cancer receiving chemotherapy alone are consistent with pivotal phase-III studies and German registry data, we found significantly improved survival using additional mistletoe and/or hyperthermia. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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15 pages, 2370 KiB  
Article
Synergistic Effects of Metformin and Trastuzumab on HER2 Positive Gastroesophageal Adenocarcinoma Cells In Vitro and In Vivo
by Jin-Soo Kim, Mi Young Kim and Sungyoul Hong
Cancers 2023, 15(19), 4768; https://doi.org/10.3390/cancers15194768 - 28 Sep 2023
Cited by 2 | Viewed by 999
Abstract
The incidence of HER2 amplification in advanced gastroesophageal adenocarcinoma (GC) reportedly ranges between 10% and 20%, depending on the population studied and the geographical region. Trastuzumab (Tmab) is the standard treatment for GCs with HER2 amplification. Metformin, a widely used antidiabetic drug, is [...] Read more.
The incidence of HER2 amplification in advanced gastroesophageal adenocarcinoma (GC) reportedly ranges between 10% and 20%, depending on the population studied and the geographical region. Trastuzumab (Tmab) is the standard treatment for GCs with HER2 amplification. Metformin, a widely used antidiabetic drug, is an activator of AMP kinase that can affect the mTOR signaling pathway. The following GC cells were evaluated: HER2+ NCI-N87, YCC-19, YCC-38, OE19, OE33, and HER2- AGS. The effects of Tmab and metformin on these cell lines were assessed as single agents and in combination using cell viability assays, Western blotting, and xenograft models. Metformin induced phosphorylation of AMP kinase in all tested GC cells and dephosphorylation of mTOR in Tmab-sensitive GC cells. We observed that treatment with Tmab in combination with metformin induced a significant decrease in the number of colonies formed on soft agar by N87, YCC-19, YCC-38, and OE19 cells (88%, 95%, 73%, and 98%, respectively), in comparison to the number formed by control cells or cells in the single-treatment groups. No growth inhibition was detected in OE33 cells treated with Tmab alone. Combination with metformin resulted in decreased phosphorylation of HER2 and its downstream targets, AKT and ERK, in Tmab-sensitive HER2+ cells. Phospho-receptor tyrosine kinase (RTK) arrays were used to profile the phospho-proteome, which demonstrated a synergistic decrease in phosphorylation of EGFR, HER2, and HER3. Furthermore, the combination of Tmab and metformin exhibited enhanced antitumor effects in a xenograft model. Collectively, these data suggest that Tmab and metformin act synergistically in HER2+ GC cells. Since metformin is widely used and relatively non-toxic, its addition to the therapeutic regimen along with Tmab could enhance the clinical efficacy in patients with HER2+ GC. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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12 pages, 605 KiB  
Article
The Effect of Induction Chemotherapy with VEGF Inhibition on Tumor Response in Synchronously Metastasized Potentially Resectable Colorectal Cancer
by Rebecca Thonhauser, Marcus Poglitsch, Jan Philipp Jonas, Yawen Dong, Madita Tschögl, Mariel Gramberger, Mohamed Salem, Jonas Santol, Irmgard Brandl, Martin Klimpfinger, Constantin Vierziger and Thomas Gruenberger
Cancers 2023, 15(11), 2900; https://doi.org/10.3390/cancers15112900 - 24 May 2023
Cited by 2 | Viewed by 1029
Abstract
(1) Background: The pathological tumor response of the primary tumor to induction chemotherapy in synchronously metastasized colorectal cancer (mCRC) patients has not been investigated. The aim of this study was to compare patients treated with induction chemotherapy combined with vascular endothelial growth factor [...] Read more.
(1) Background: The pathological tumor response of the primary tumor to induction chemotherapy in synchronously metastasized colorectal cancer (mCRC) patients has not been investigated. The aim of this study was to compare patients treated with induction chemotherapy combined with vascular endothelial growth factor (VEGF) or with epidermal growth factor receptor (EGFR) antibodies. (2) Methods: We present a retrospective analysis, where we included 60 consecutive patients with potentially resectable synchronous mCRC who received induction chemotherapy combined with either VEGF or EGFR antibodies. The primary endpoint of this study was the regression of the primary tumor, which was assessed by the application of the histological regression score according to Rödel. The secondary endpoints were recurrence-free survival (RFS) and overall survival (OS). (3) Results: A significantly better pathological response and a longer RFS for patients treated with the VEGF antibody therapy compared to those treated with the EGFR antibodies was demonstrated (p = 0.005 for the primary tumor and log-rank = 0.047 for RFS). The overall survival did not differ. The trial was registered with clinicaltrial.gov, number NCT05172635. (4) Conclusion: Induction chemotherapy combined with a VEGF antibody revealed a better pathological response of the primary tumor, leading to a better RFS compared to that with EGFR therapy; this has clinical relevance in patients with potentially resectable synchronously mCRC. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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14 pages, 2533 KiB  
Article
Biosynthetic Mesh Reconstruction after Abdominoperineal Resection for Low Rectal Cancer: Cross Relation of Surgical Healing and Oncological Outcomes: A Multicentric Observational Study
by Claudio Gambardella, Federico Maria Mongardini, Menelaos Karpathiotakis, Francesco Saverio Lucido, Francesco Pizza, Salvatore Tolone, Simona Parisi, Giusiana Nesta, Luigi Brusciano, Antonio Gambardella, Ludovico Docimo and Massimo Mongardini
Cancers 2023, 15(10), 2725; https://doi.org/10.3390/cancers15102725 - 11 May 2023
Cited by 3 | Viewed by 1365
Abstract
Background: Local wound complications are among the most relevant sequelae after an abdominoperineal resection (APR) for low rectal cancer. One of the proposed techniques to improve the postoperative recovery and to accelerate the initiation of adjuvant chemotherapy is the mesh reinforcement of the [...] Read more.
Background: Local wound complications are among the most relevant sequelae after an abdominoperineal resection (APR) for low rectal cancer. One of the proposed techniques to improve the postoperative recovery and to accelerate the initiation of adjuvant chemotherapy is the mesh reinforcement of the perineal wound. The aim of the current study is to compare the surgical and oncological outcomes after APR performed with a biosynthetic mesh reconstruction versus the conventional procedure. Methods: From 2015 to 2020, in two tertiary centres, the surgical outcomes, the wound events (i.e., surgical site infections, wound dehiscence and the complete healing time) and the oncological outcomes (i.e., time length to start adjuvant chemo-radiotherapy, an over 8-week delay in chemotherapy and the recurrence rate) were retrospectively analysed in patients undergoing APR reinforced with biosynthetic mesh (Group A) and conventional APR (Group B). Results Sixty-one patients were treated with APR (25 in Group A and 36 in Group B). Patients in Group A presented lower time for: healing (16 versus 24 days, p = 0.015), inferior perineal wound dehiscence rates (one versus nine cases, p = 0.033), an earlier adjuvant therapy start (26 versus 70 days, p = 0.003) and a lower recurrence rate (16.6% vs. 33.3%, p = 0.152). Conclusions: In our series, the use of a biosynthetic mesh for the neo-perineum reconstruction after a Miles’ procedure has resulted in safe, reproducible results affected by limited complications, guarantying a rapid start of the adjuvant therapy with clear benefits in oncological outcomes. Further randomized clinical trials with long-term follow-up are needed to validate these results. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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13 pages, 816 KiB  
Article
Specific Septic Complications after Rectal Cancer Surgery: A Critical Multicentre Study
by Călin Popa, Virgiliu-Mihail Prunoiu, Paul Puia, Diana Schlanger, Mircea-Nicolae Brătucu, Victor Strâmbu, Eugen Brătucu, Hortensia-Alina Moisă, Eduard-Georgian Chiru, Bogdan Vasile Ileanu and Petre Radu
Cancers 2023, 15(8), 2340; https://doi.org/10.3390/cancers15082340 - 17 Apr 2023
Cited by 1 | Viewed by 1442
Abstract
The postoperative septic complications in gastrointestinal surgery impact immediate as well as long-term outcomes, which lead to reinterventions and additional costs. The authors presented the experience of three surgery clinics in Romania regarding the specific septic complications occurring in patients operated on for [...] Read more.
The postoperative septic complications in gastrointestinal surgery impact immediate as well as long-term outcomes, which lead to reinterventions and additional costs. The authors presented the experience of three surgery clinics in Romania regarding the specific septic complications occurring in patients operated on for rectal cancer. The study group comprised 2674 patients who underwent surgery over a 5-year period (2017–2021). Neoplasms of the middle and lower rectum (76%) were the majority. There were 85% rectal resections and 15% abdominoperineal excisions of the rectum. In total, 68.54% of patients were operated on laparoscopically, and 31.46% received open surgery. Without taking wound infections into account, 97 (3.67%) patients had abdominal-pelvic septic complications. The aim was to evaluate the causes of the complications. The percentage of suppurations after surgery of the rectum treated by radiochemotherapy was considerably higher than after surgery of the non-radiated upper rectum. The fatality rate was 5.15%. The risk of fistulas was significantly associated with the preoperative treatment, tumour position and type of intervention. Sex, age, TNM stage or grade were not significant at 0.05 the threshold. The risk of fistulas is reduced with low anterior resection, but the gravity of these complications is higher in the lower rectum compared with the superior rectum. Preoperative radiochemotherapy is a contributing factor to septic complications. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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19 pages, 4099 KiB  
Article
p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins
by Ana Montero-Calle, María Garranzo-Asensio, Rebeca M. Torrente-Rodríguez, Víctor Ruiz-Valdepeñas Montiel, Carmen Poves, Jana Dziaková, Rodrigo Sanz, Cristina Díaz del Arco, José Manuel Pingarrón, María Jesús Fernández-Aceñero, Susana Campuzano and Rodrigo Barderas
Cancers 2023, 15(7), 2102; https://doi.org/10.3390/cancers15072102 - 31 Mar 2023
Cited by 9 | Viewed by 1761
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by [...] Read more.
Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by liquid biopsy. However, new studies related to the humoral immune response in cancer are needed to enable blood-based diagnosis of the disease. Here, our aim was to characterize the humoral immune response associated with the different p53 and p63 proteoforms derived from alternative splicing and previously described as aberrantly expressed in CRC. Thus, here we investigated the diagnostic ability of the twelve p53 proteoforms and the eight p63 proteoforms described to date, and their specific N-terminal and C-terminal end peptides, by means of luminescence HaloTag beads immunoassays. Full-length proteoforms or specific peptides were cloned as HaloTag fusion proteins and their seroreactivity analyzed using plasma from CRC patients at stages I-IV (n = 31), individuals with premalignant lesions (n = 31), and healthy individuals (n = 48). p53γ, Δ40p53β, Δ40p53γ, Δ133p53γ, Δ160p53γ, TAp63α, TAp63δ, ΔNp63α, and ΔNp63δ, together with the specific C-terminal end α and δ p63 peptides, were found to be more seroreactive against plasma from CRC patients and/or individuals with premalignant lesions than from healthy individuals. In addition, ROC (receiver operating characteristic) curves revealed a high diagnostic ability of those p53 and p63 proteoforms to detect CRC and premalignant individuals (AUC higher than 85%). Finally, electrochemical biosensing platforms were employed in POC-like devices to investigate their usefulness for CRC detection using selected p53 and p63 proteoforms. Our results demonstrate not only the potential of these biosensors for the simultaneous analysis of proteoforms’ seroreactivity, but also their convenience and versatility for the clinical detection of CRC by liquid biopsy. In conclusion, we here show that p53 and p63 proteoforms possess differential seroreactivity in CRC patients in comparison to controls, distinctive from canonical proteins, which should improve the diagnostic panels for obtaining a blood-based biomarker signature for CRC detection. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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12 pages, 1242 KiB  
Article
Exploratory Assessment of Nutritional Evaluation Tools as Predictors of Complications and Sarcopenia in Patients with Colorectal Cancer
by Isabel M. Vegas-Aguilar, Patricia Guirado-Peláez, Rocío Fernández-Jiménez, Hatim Boughanem, Francisco J. Tinahones and Jose Manuel Garcia-Almeida
Cancers 2023, 15(3), 847; https://doi.org/10.3390/cancers15030847 - 30 Jan 2023
Cited by 3 | Viewed by 1672
Abstract
Background: Patients with colorectal cancer (CRC) are largely malnourished, which decreases overall survival and treatment efficacy and increases mortality rates. We hypothesize that angle phase might be associated with the risk of sarcopenia as well as cancer complications in patients with CRC. The [...] Read more.
Background: Patients with colorectal cancer (CRC) are largely malnourished, which decreases overall survival and treatment efficacy and increases mortality rates. We hypothesize that angle phase might be associated with the risk of sarcopenia as well as cancer complications in patients with CRC. The inclusion of various nutritional status indicators and clinical cancer outcomes can result in significant variability. Therefore, the objective of this study was to perform an exploratory analysis of nutritional evaluation tools used to assess body composition and muscle quality in patients with CRC, in order to predict cancer complications and survival rate. Methods: A total of 127 patients with CRC were included in this study. Bioelectrical impedance analysis and body composition were performed, which we used to obtain phase angle (PhA) values. Muscle function was assessed by hand-grip strength (HGS) and muscle quality and adipose tissue depot were performed using ultrasound techniques. Results: This study showed that there were significant differences in body composition between females and males, as well as in muscle quantity and quality. PhA was highly correlated with quadriceps rectus femoris of cross-sectional area (RF-CSA), circumference of quadriceps rectus femoris (RF-CIR), superficial subcutaneous abdominal fat (S-SAT), as well as HGS (p < 0.05). PhA was also correlated with water content in females, and with muscle mass and quality in males (p < 0.05). Specifically, we found that PhA was a good predictor for cancer complications in women and the risk of sarcopenia in men. In the linear model controlled for age and body mass index (BMI), high PhA value was associated with a decreased risk of complications in females (Odds Ratio (OR) = 0.15, 95% CI: 0.03–0.81, p < 0.05). High PhA value was associated with a decreased risk of sarcopenia in males (OR = 0.42, 95% CI: 0.19–0.95, p < 0.05). In addition, Receiving Operating Characteristics (ROC) curve analysis showed that PhA had a good diagnostic accuracy for detecting cancer complications in females (Area under curve (AUC) = 0.894, 95% CI: 0.88–0.89, p < 0.05) and the risk of sarcopenia in males (AUC = 0.959, 95% CI: 0.91–0.92, p < 0.05). Conclusions: PhA can accurately predict oncological complications in women and sarcopenia in men. These differences are relevant to understanding the nutritional status of patients with CRC and their personalized nutritional treatment. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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13 pages, 4614 KiB  
Article
Effect of Perioperative Blood Transfusions and Infectious Complications on Inflammatory Activation and Long-Term Survival Following Gastric Cancer Resection
by Noelia Puértolas, Javier Osorio, Carlos Jericó, Coro Miranda, Maite Santamaría, Eva Artigau, Gonzalo Galofré, Elisenda Garsot, Alexis Luna, Aurora Aldeano, Carles Olona, Joan Molinas, Laura Pulido, Marta Gimeno and Manuel Pera
Cancers 2023, 15(1), 144; https://doi.org/10.3390/cancers15010144 - 26 Dec 2022
Cited by 1 | Viewed by 1353
Abstract
Background: The aim of this study was to evaluate the impact of perioperative blood transfusion and infectious complications on postoperative changes of inflammatory markers, as well as on disease-free survival (DFS) in patients undergoing curative gastric cancer resection. Methods: Multicenter cohort study in [...] Read more.
Background: The aim of this study was to evaluate the impact of perioperative blood transfusion and infectious complications on postoperative changes of inflammatory markers, as well as on disease-free survival (DFS) in patients undergoing curative gastric cancer resection. Methods: Multicenter cohort study in all patients undergoing gastric cancer resection with curative intent. Patients were classified into four groups based on their perioperative course: one, no blood transfusion and no infectious complication; two, blood transfusion; three, infectious complication; four, both transfusion and infectious complication. Neutrophil-to-lymphocyte ratio (NLR) was determined at diagnosis, immediately before surgery, and 10 days after surgery. A multivariate Cox regression model was used to analyze the relationship of perioperative group and dynamic changes of NLR with disease-free survival. Results: 282 patients were included, 181 in group one, 23 in group two, 55 in group three, and 23 in group four. Postoperative NLR changes showed progressive increase in the four groups. Univariate analysis showed that NLR change > 2.6 had a significant association with DFS (HR 1.55; 95% CI 1.06–2.26; p = 0.025), which was maintained in multivariate analysis (HR 1.67; 95% CI 1.14–2.46; p = 0.009). Perioperative classification was an independent predictor of DFS, with a progressive difference from group one: group two, HR 0.80 (95% CI: 0.40–1.61; p = 0.540); group three, HR 1.42 (95% CI: 0.88–2.30; p = 0.148), group four, HR 2.85 (95% CI: 1.64–4.95; p = 0.046). Conclusions: Combination of perioperative blood transfusion and infectious complications following gastric cancer surgery was related to greater NLR increase and poorer DFS. These findings suggest that perioperative blood transfusion and infectious complications may have a synergic effect creating a pro-inflammatory activation that favors tumor recurrence. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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12 pages, 1382 KiB  
Article
Clockwise Anterior-to-Posterior—Double Isolation (CAP-DI) Approach for Portal Lymphadenectomy in Biliary Tract Cancer: Technique, Yield, and Outcomes
by Andrew J. Sinnamon, Eric Luo, Aileen Xu, Sarah Zhu, Jason W. Denbo, Jason B. Fleming and Daniel A. Anaya
Cancers 2022, 14(23), 5770; https://doi.org/10.3390/cancers14235770 - 24 Nov 2022
Cited by 3 | Viewed by 1535
Abstract
Background: Portal lymphadenectomy (PLND) is the current standard for oncologic resection of biliary tract cancers (BTCs). However, published data show it is performed infrequently and often yields less than the recommended 6 lymph nodes. We sought to identify yield and outcomes using a [...] Read more.
Background: Portal lymphadenectomy (PLND) is the current standard for oncologic resection of biliary tract cancers (BTCs). However, published data show it is performed infrequently and often yields less than the recommended 6 lymph nodes. We sought to identify yield and outcomes using a Clockwise Anterior-to-Posterior technique with Double Isolation of critical structures (CAP-DI) for PLND. Methods: Consecutive patients undergoing complete PLND for BTCs using CAP-DI technique were identified (2015–2021). Lymph node (LN) yield and predictors of LN count were examined. Secondary outcomes included intraoperative and postoperative outcomes, which were compared to patients having hepatectomy without PLND. Results: In total, 534 patients were included; 71 with complete PLND (36 gallbladder cancers, 24 intrahepatic cholangiocarcinomas, 11 perihilar cholangiocarcinomas) and 463 in the control group. The median PLND yield was 5 (IQR 3–8; range 0–17) and 46% had at least 6 nodes retrieved. Older age was associated with lower likelihood of ≥6 node PLND yield (p = 0.032), which remained significant in bivariate analyses with other covariates (p < 0.05). After adjustment for operative factors, performance of complete PLND was independently associated with longer operative time (+46.4 min, p = 0.001), but no differences were observed in intraoperative or postoperative outcomes compared to the control group (p > 0.05). Conclusions: Yield following PLND frequently falls below the recommended minimum threshold of 6 nodes despite a standardized stepwise approach to complete clearance. Older age may be weakly associated with lower PLND yield. While all efforts should be made for complete node retrieval, failure to obtain 6 nodes may be an unrealistic metric of surgical quality. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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Review

Jump to: Editorial, Research, Other

12 pages, 1142 KiB  
Review
Targeting Myeloid-Derived Suppressor Cell Trafficking as a Novel Immunotherapeutic Approach in Microsatellite Stable Colorectal Cancer
by Benny Johnson
Cancers 2023, 15(22), 5484; https://doi.org/10.3390/cancers15225484 - 20 Nov 2023
Viewed by 873
Abstract
Myeloid-derived suppressor cells (MDSCs) are a unique subset of immune cells that promote an immunosuppressive phenotype due to their impacts on CD8 and regulatory T cell function. The inhibition of MDSC trafficking to the tumor microenvironment (TME) may represent a novel target in [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are a unique subset of immune cells that promote an immunosuppressive phenotype due to their impacts on CD8 and regulatory T cell function. The inhibition of MDSC trafficking to the tumor microenvironment (TME) may represent a novel target in microsatellite stable (MSS) colorectal cancer with the potential to reprogram the immune system. Here, we review the rationale of inhibiting myeloid suppressor cell trafficking in treatment-refractory MSS colorectal cancer and circulating tumor DNA (ctDNA) positive settings to determine whether this approach can serve as a backbone for promoting immunotherapy response in this difficult-to-treat disease. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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25 pages, 2384 KiB  
Review
Contrast-Enhanced Imaging in the Management of Intrahepatic Cholangiocarcinoma: State of Art and Future Perspectives
by Lucia Cerrito, Maria Elena Ainora, Raffaele Borriello, Giulia Piccirilli, Matteo Garcovich, Laura Riccardi, Maurizio Pompili, Antonio Gasbarrini and Maria Assunta Zocco
Cancers 2023, 15(13), 3393; https://doi.org/10.3390/cancers15133393 - 28 Jun 2023
Cited by 3 | Viewed by 2278
Abstract
Intrahepatic cholangiocarcinoma (iCCA) represents the second most common liver cancer after hepatocellular carcinoma, accounting for 15% of primary liver neoplasms. Its incidence and mortality rate have been rising during the last years, and total new cases are expected to increase up to 10-fold [...] Read more.
Intrahepatic cholangiocarcinoma (iCCA) represents the second most common liver cancer after hepatocellular carcinoma, accounting for 15% of primary liver neoplasms. Its incidence and mortality rate have been rising during the last years, and total new cases are expected to increase up to 10-fold during the next two or three decades. Considering iCCA’s poor prognosis and rapid spread, early diagnosis is still a crucial issue and can be very challenging due to the heterogeneity of tumor presentation at imaging exams and the need to assess a correct differential diagnosis with other liver lesions. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) plays an irreplaceable role in the evaluation of liver masses. iCCA’s most typical imaging patterns are well-described, but atypical features are not uncommon at both CT and MRI; on the other hand, contrast-enhanced ultrasound (CEUS) has shown a great diagnostic value, with the interesting advantage of lower costs and no renal toxicity, but there is still no agreement regarding the most accurate contrastographic patterns for iCCA detection. Besides diagnostic accuracy, all these imaging techniques play a pivotal role in the choice of the therapeutic approach and eligibility for surgery, and there is an increasing interest in the specific imaging features which can predict tumor behavior or histologic subtypes. Further prognostic information may also be provided by the extraction of quantitative data through radiomic analysis, creating prognostic multi-parametric models, including clinical and serological parameters. In this review, we aim to summarize the role of contrast-enhanced imaging in the diagnosis and management of iCCA, from the actual issues in the differential diagnosis of liver masses to the newest prognostic implications. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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11 pages, 546 KiB  
Review
Management of Low Anterior Resection Syndrome (LARS) Following Resection for Rectal Cancer
by Harald Rosen, Christian G. Sebesta and Christian Sebesta
Cancers 2023, 15(3), 778; https://doi.org/10.3390/cancers15030778 - 27 Jan 2023
Cited by 4 | Viewed by 3446
Abstract
Introduction: A total of 60–80% of patients undergoing rectal resection (mostly as a treatment for rectal cancer) suffer from a variety of partly severe functional problems despite preservation of the anal sphincter. These patients are summarized under the term low anterior resection syndrome [...] Read more.
Introduction: A total of 60–80% of patients undergoing rectal resection (mostly as a treatment for rectal cancer) suffer from a variety of partly severe functional problems despite preservation of the anal sphincter. These patients are summarized under the term low anterior resection syndrome (LARS). Preoperative radiotherapy, vascular dissection and surgical excision of the low rectum and mesorectum lead, alone or all together, to a significant impairment of colonic and (neo-) rectal motility. This results in a variety of symptoms (multiple defecation episodes, recurrent episodes of urge, clustering, incontinence, etc.) which are associated with severe impairment of quality of life (QOL). Methods: This narrative review summarizes the present state of knowledge regarding the pathophysiology of LARS as well as the evidence for the available treatment options to control the symptoms resulting from this condition. Results: A review of the literature (Medline, Pubmed) reveals a variety of treatment options available to control symptoms of LARS. Medical therapy, with or without dietary modification, shows only a modest effect. Pelvic floor rehabilitation consisting of muscle exercise techniques as well as biofeedback training has been associated with improvement in LARS scores and incontinence, albeit with limited scientific evidence. Transanal irrigation (TAI) has gained interest as a treatment modality for patients with LARS due to an increasing number of promising data from recently published studies. Despite this promising observation, open questions about still-unclear issues of TAI remain under debate. Neuromodulation has been applied in LARS only in a few studies with small numbers of patients and partly conflicting results. Conclusion: LARS is a frequent problem after sphincter-preserving rectal surgery and leads to a marked impairment of QOL. Due to the large number of patients suffering from this condition, mandatory identification, as well as treatment of affected patients, must be considered during surgical as well as oncological follow-up. The use of a standardized treatment algorithm will lead to sufficient control of symptoms and a high probability of a marked improvement in QOL. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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24 pages, 1530 KiB  
Review
Isolated Pancreatic Metastases of Renal Cell Carcinoma—Clinical Particularities and Seed and Soil Hypothesis
by Franz Sellner, Sabine Thalhammer and Martin Klimpfinger
Cancers 2023, 15(2), 339; https://doi.org/10.3390/cancers15020339 - 04 Jan 2023
Cited by 6 | Viewed by 2553
Abstract
A meta-analysis of 1470 isolated pancreatic metastases of renal cell carcinoma revealed, that, in addition to the unusual exclusive occurrence of pancreatic metastases and the favourable treatment results, the isPMRCC is characterised by further peculiarities of the clinical course: The lack of prognostic [...] Read more.
A meta-analysis of 1470 isolated pancreatic metastases of renal cell carcinoma revealed, that, in addition to the unusual exclusive occurrence of pancreatic metastases and the favourable treatment results, the isPMRCC is characterised by further peculiarities of the clinical course: The lack of prognostic significance of volume and growth rate dependent risk factors and the independence of treatment results from standard or local resections. As an explanation for all these peculiarities, according to today’s knowledge, a strong acting seed and soil mechanism can serve, which allows embolized tumour cells to grow to metastases only in the pancreas, and prevents them definitively or for years in all other organs. The good prognosis affects not only isolated PM, but also multi-organ metastases of the RCC, in which the additional occurrence of PM is also associated with a better prognosis. Genetic studies revealed specific changes in cases of PM of RCC: Lack of loss of 9p21.3 and 14q31.2, which are otherwise specific gene mutations at the onset of generalization, a low weight genome instability index, i.e., high genetic stability, and a low rate of PAB1 and a high rate of BPRM1 alterations, which signal a more favourable course. The cause of pancreatic organotropism in isPMRCC is still unclear, so only those factors that have been identified as promoting organotropism in other, more frequent tumour entities can be presented: Formation of the pre-metastatic niche, chemokine receptor–ligand mechanism, ability to metabolic adaptation, and immune surveillance. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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13 pages, 3682 KiB  
Opinion
The Added Value of Transcatheter CT Hepatic Angiography (CTHA) Image Guidance in Percutaneous Thermal Liver Ablation: An Experts’ Opinion Pictorial Essay
by Robbert S. Puijk, Madelon Dijkstra, Susan van der Lei, Hannah H. Schulz, Danielle J. W. Vos, Florentine E. F. Timmer, Bart Geboers, Hester J. Scheffer, Jan J. J. de Vries, Maarten L. J. Smits, Rutger C. G. Bruijnen, Frédéric Deschamps, Thierry de Baère, Bruno C. Odisio and Martijn R. Meijerink
Cancers 2024, 16(6), 1193; https://doi.org/10.3390/cancers16061193 - 18 Mar 2024
Viewed by 757
Abstract
With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, [...] Read more.
With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect ‘vanished’ and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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18 pages, 2007 KiB  
Systematic Review
Influence of Laparoscopic Surgery on Cellular Immunity in Colorectal Cancer: A Systematic Review and Meta-Analysis
by Annika Bohne, Elena Grundler, Helge Knüttel, Alois Fürst and Vinzenz Völkel
Cancers 2023, 15(13), 3381; https://doi.org/10.3390/cancers15133381 - 28 Jun 2023
Cited by 1 | Viewed by 1146
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. The main treatment options are laparoscopic (LS) and open surgery (OS), which might differ in their impact on the cellular immunity so indispensable for anti-infectious and antitumor defense. MEDLINE, Embase, Web of Science [...] Read more.
Colorectal cancer (CRC) is the third most common cancer worldwide. The main treatment options are laparoscopic (LS) and open surgery (OS), which might differ in their impact on the cellular immunity so indispensable for anti-infectious and antitumor defense. MEDLINE, Embase, Web of Science (SCI-EXPANDED), the Cochrane Library, Google Scholar, ClinicalTrials.gov, and ICTRP (WHO) were systematically searched for randomized controlled trials (RCTs) comparing cellular immunity in CRC patients of any stage between minimally invasive and open surgical resections. A random effects-weighted inverse variance meta-analysis was performed for cell counts of natural killer (NK) cells, white blood cells (WBCs), lymphocytes, CD4+ T cells, and the CD4+/CD8+ ratio. The RoB2 tool was used to assess the risk of bias. The meta-analysis was prospectively registered in PROSPERO (CRD42021264324). A total of 14 trials including 974 participants were assessed. The LS groups showed more favorable outcomes in eight trials, with lower inflammation and less immunosuppression as indicated by higher innate and adaptive cell counts, higher NK cell activity, and higher HLA-DR expression rates compared to OS, with only one study reporting lower WBCs after OS. The meta-analysis yielded significantly higher NK cell counts at postoperative day (POD)4 (weighted mean difference (WMD) 30.80 cells/µL [19.68; 41.92], p < 0.00001) and POD6–8 (WMD 45.08 cells/µL [35.95; 54.21], p < 0.00001). Although further research is required, LS is possibly associated with less suppression of cellular immunity and lower inflammation, indicating better preservation of cellular immunity. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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12 pages, 1130 KiB  
Systematic Review
Systematic Review of Single-Agent vs. Multi-Agent Chemotherapy for Advanced Pancreatic Adenocarcinoma in Elderly vs. Younger Patients
by Alison Lewis and Adnan Nagrial
Cancers 2023, 15(8), 2289; https://doi.org/10.3390/cancers15082289 - 13 Apr 2023
Cited by 2 | Viewed by 1294
Abstract
Purpose: To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma, so as to compare the outcomes of young and elderly patients. Methods: This review searched three databases for relevant studies. The inclusion [...] Read more.
Purpose: To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma, so as to compare the outcomes of young and elderly patients. Methods: This review searched three databases for relevant studies. The inclusion criteria were diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, comparison of an elderly versus young population, comparison of single-agent versus multi-agent chemotherapy, data on survival outcomes, and randomised controlled trials. The exclusion criteria were phase I trials, incomplete studies, retrospective analyses, systematic reviews, and case reports. A meta-analysis was performed on second-line chemotherapy in elderly patients. Results: Six articles were included in this systematic review. Three of these studies explored first-line treatment and three explored second-line treatment. In the subgroup analysis, the meta-analysis showed statistically improved overall survival for elderly patients receiving single-agent second-line treatment. Conclusions: This systematic review confirmed that combination chemotherapy improved survival in the first-line treatment of advanced pancreatic adenocarcinoma, regardless of age. The benefit of combination chemotherapy in second-line studies for elderly patients with advanced pancreas cancer was less clear. Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
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