Special Issue "Multimodal Therapy of Upper Gastrointestinal Malignancies"

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

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 18031

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Special Issue Editor

Prof. Dr. Ulrich Ronellenfitsch
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Guest Editor
Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Halle (Saale), Germany
Interests: upper gastrointestinal cancer; multimodal treatment; gastrectomy; esophagectomy; sarcoma; quality of care; meta-analysis
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Special Issue Information

Dear Colleagues,

Recent decades have seen remarkable advances in the treatment of upper gastrointestinal malignancies, i.e., adenocarcinoma and squamous cell carcinoma as well as gastrointestinal stromal and other rare tumors of the esophagus and stomach. While, historically, surgical resection has been the sole treatment for these tumors, multimodal therapies have meanwhile proven their efficacy. At present, pre- and postoperative chemotherapy and radiotherapy, targeted drug therapy, and stage-specific surgical approaches are all indispensable cornerstones of an individualized treatment for upper gastrointestinal malignancies. With such multimodal treatment, better outcomes comprising improved quality of life and prolonged survival have been achieved for patients. However, for many tumor entities and stages, the ideal combination and sequence of treatments is still being evaluated in clinical trials. Moreover, the value of novel approaches such as immunotherapy or robotic surgery remains a matter of research.

In this Special Issue of Cancers, up-to-date original research, short communications, and comprehensive review articles on all modalities playing a role in the treatment of upper gastrointestinal malignancies will be published. Moreover, the results of preclinical studies with implications on treatment also qualify for publication.

Prof. Dr. Ulrich Ronellenfitsch
Guest Editor

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Keywords

  • upper gastrointestinal cancer
  • multimodal treatment
  • chemotherapy
  • radiotherapy
  • surgery
  • immunotherapy
  • targeted therapy

Published Papers (17 papers)

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Editorial

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Editorial
Multimodal Therapy of Upper Gastrointestinal Malignancies
Cancers 2021, 13(4), 793; https://doi.org/10.3390/cancers13040793 - 14 Feb 2021
Viewed by 499
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)

Research

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Article
Preservation of Organ Function in Locally Advanced Non-Metastatic Gastrointestinal Stromal Tumors (GIST) of the Stomach by Neoadjuvant Imatinib Therapy
Cancers 2021, 13(4), 586; https://doi.org/10.3390/cancers13040586 - 03 Feb 2021
Cited by 7 | Viewed by 1044
Abstract
Background: Neoadjuvant imatinib mesylate (IM) for advanced, non-metastatic gastrointestinal stromal tumors (GIST) of stomach is recommended to downsize the tumor prompting less-extensive operations and preservation of organ function. Methods: We analyzed the clinical-histopathological profile and oncological outcome of 55 patients (median age 58.2 [...] Read more.
Background: Neoadjuvant imatinib mesylate (IM) for advanced, non-metastatic gastrointestinal stromal tumors (GIST) of stomach is recommended to downsize the tumor prompting less-extensive operations and preservation of organ function. Methods: We analyzed the clinical-histopathological profile and oncological outcome of 55 patients (median age 58.2 years; range, 30–86 years) with biopsy-proven, cM0, gastric GIST who underwent IM therapy followed by surgery with a median follow-up of 82 months. Results: Initial median tumor size was 113 mm (range, 65–330 mm) and 10 patients started with acute upper GI bleeding. After a median 10 months (range, 2–21 months) of treatment, tumor size had shrunk to 62 mm (range, 22–200 mm). According to Response Evaluation Criteria In Solid Tumors version 1.0 and version 1.1 (RECIST 1.1), 39 (75%) patients had partial response and 14 patients had stable disease, with no progressive disease. At plateau response, 50 patients underwent surgery with an R0 resection rate of 94% and pathological complete response in 24%. In 12 cases (24%), downstaging allowed laparoscopic resection. The mean recurrence-free survival (RFS) was 123 months (95%CI; 99–147) and the estimated 5-year RFS was 84%. Conclusions: Neoadjuvant IM allowed stomach preservation in 96% of our patients with excellent long-term RFS, even when starting treatment during an episode of upper GI bleeding. Preservation of the stomach provides the physiological basis for the use of oral IM in the adjuvant or metastatic setting. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
Significance of Lauren Classification in Patients Undergoing Neoadjuvant/Perioperative Chemotherapy for Locally Advanced Gastric or Gastroesophageal Junction Cancers—Analysis from a Large Single Center Cohort in Germany
Cancers 2021, 13(2), 290; https://doi.org/10.3390/cancers13020290 - 14 Jan 2021
Cited by 3 | Viewed by 825
Abstract
Background: the purpose of this analysis was to analyze the outcomes of multimodal treatment that are related to Lauren histotypes in gastro-esophageal cancer (GEC). Methods: patients with GEC between 1986 and 2013 were analyzed. Uni- and multivariate regression analysis were performed to identify [...] Read more.
Background: the purpose of this analysis was to analyze the outcomes of multimodal treatment that are related to Lauren histotypes in gastro-esophageal cancer (GEC). Methods: patients with GEC between 1986 and 2013 were analyzed. Uni- and multivariate regression analysis were performed to identify predictors for overall survival. Lauren histotype stratified overall survival (OS)-rates were analyzed by the Kaplan–Meier method. Further, propensity score matching (PSM) was performed to balance for confounders. Results: 1290 patients were analyzed. After PSM, the median survival was 32 months for patients undergoing primary surgery (PS) and 43 months for patients undergoing neoadjuvant chemotherapy (nCTx) ahead of surgery. For intestinal types, median survival time was 34 months (PS) vs. 52 months (nCTx+surgery) p = 0.07, 36 months (PS) vs. (31) months (nCTx+surgery) in diffuse types (p = 0.44) and 31 months (PS) vs. 62 months (nCTx+surgery) for mixed types (p = 0.28). Five-/Ten-year survival rates for intestinal, diffuse, and mixed types were 44/29%, 36/17%, and 43/33%, respectively. After PSM, Kaplan–Meier showed a survival benefit for patients undergoing nCTx+surgery in intestinal and mixed types. Conclusion: the Lauren histotype might be predictive for survival outcome in GEC-patients after neoadjuvant/perioperative chemotherapy. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
Long-Term Outcomes of Induction Chemotherapy Followed by Chemo-Radiotherapy as Intensive Neoadjuvant Protocol in Patients with Esophageal Cancer
Cancers 2020, 12(12), 3614; https://doi.org/10.3390/cancers12123614 - 03 Dec 2020
Cited by 3 | Viewed by 826
Abstract
Background: A phase II intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for esophageal cancer (EC) was previously tested at our Center with promising results. We here present an observational study to evaluate the efficacy of the protocol also in “real life” patients. Methods: We retrospectively [...] Read more.
Background: A phase II intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for esophageal cancer (EC) was previously tested at our Center with promising results. We here present an observational study to evaluate the efficacy of the protocol also in “real life” patients. Methods: We retrospectively reviewed 122 ECs (45.1% squamous cell (SCC) and 54.9% adenocarcinoma (ADC)) treated with induction docetaxel, cisplatin, and 5-fluorouracil (TCF), followed by concomitant TCF and radiotherapy (50–50.4 Gy/25–28 fractions), between 2008 and 2017. Primary endpoints were overall survival (OS), event-free survival (EFS) and pathological complete response (pCR). Results: With a median follow-up of 62.1 months (95% CI 50–67.6 months), 5-year OS and EFS rates were 54.8% (95% CI 44.7–63.9) and 42.7% (95% CI 33.1–51.9), respectively. A pCR was observed in 71.1% of SCC and 37.1% of ADC patients (p = 0.001). At multivariate analysis, ypN+ was a significant prognostic factor for OS (Hazard Ratios (HR) 4.39 [95% CI 2.36–8.18]; p < 0.0001), while pCR was a strong predictor of EFS (HR 0.38 [95% CI 0.22–0.67]; p < 0.0001). Conclusions: The nCRT protocol achieved considerable long-term survival and pCR rates also in “real life” patients. Further research is necessary to evaluate this protocol in a watch-and-wait approach. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
Does Circular Stapler Size in Surgical Management of Esophageal Cancer Affect Anastomotic Leak Rate? 4-Year Experience of a European High-Volume Center
Cancers 2020, 12(11), 3474; https://doi.org/10.3390/cancers12113474 - 22 Nov 2020
Cited by 7 | Viewed by 755
Abstract
Anastomotic leak is one of the most severe postoperative complications and is therefore considered a benchmark for the quality of surgery for esophageal cancer. There is substantial debate on which anastomotic technique is the best for patients undergoing Ivor Lewis esophagectomy. Our standardized [...] Read more.
Anastomotic leak is one of the most severe postoperative complications and is therefore considered a benchmark for the quality of surgery for esophageal cancer. There is substantial debate on which anastomotic technique is the best for patients undergoing Ivor Lewis esophagectomy. Our standardized technique is a circular stapled anastomosis with either a 25 or 28 mm anvil. The aim of this study was to retrospectively analyze whether the stapler diameter had an impact on postoperative anastomotic leak rates during a 4-year time frame from 2016 to 2020. A total of 632 patients (open, hybrid, and totally minimally invasive esophagectomy) met the inclusion criteria. A total of 214 patients underwent an anastomosis with a 25 mm stapler vs. 418 patients with a 28 mm stapler. Anastomotic leak rates were 15.4% vs. 10.8%, respectively (p = 0.0925). Stapler size should be chosen according to the individual anatomical situation of the patient. Stapler size may be of higher relevance in patients undergoing totally minimally invasive reconstruction. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
The Influence of Pretherapeutic and Preoperative Sarcopenia on Short-Term Outcome after Esophagectomy
Cancers 2020, 12(11), 3409; https://doi.org/10.3390/cancers12113409 - 17 Nov 2020
Cited by 7 | Viewed by 744
Abstract
By introducing minimally invasive surgery the rate of postoperative morbidity in esophageal cancer patients could be reduced. But esophagectomy is still associated with a relevant risk of postoperative morbidity and mortality. Patients often present with nutritional deficiency and sarcopenia even at time of [...] Read more.
By introducing minimally invasive surgery the rate of postoperative morbidity in esophageal cancer patients could be reduced. But esophagectomy is still associated with a relevant risk of postoperative morbidity and mortality. Patients often present with nutritional deficiency and sarcopenia even at time of diagnosis. This study focuses on the influence of skeletal muscle index (SMI) on postoperative morbidity and mortality. Fifty-two patients were included in this study. SMI was measured using computer tomographic images at the time of diagnosis and before surgery. Then, SMI and different clinicopathological and demographic features were correlated with postoperative morbidity. There was no correlation between SMI before neoadjuvant therapy (p = 0.5365) nor before surgery (p = 0.3530) with the short-term postoperative outcome. Regarding cholesterol level before surgery there was a trend for a higher risk of complications with lower cholesterol levels (p = 0.0846). Our findings suggest that a low preoperative SMI does not necessarily predict a poor postoperative outcome in esophageal cancer patients after esophagectomy but that there are many factors that influence the nutritional status of cancer patients. To improve nutritional status, cancer patients at our clinic receive specialized nutritional counselling during neoadjuvant treatment as well as after surgery. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
Article
Histopathologic Response Is a Positive Predictor of Overall Survival in Patients Undergoing Neoadjuvant/Perioperative Chemotherapy for Locally Advanced Gastric or Gastroesophageal Junction Cancers—Analysis from a Large Single Center Cohort in Germany
Cancers 2020, 12(8), 2244; https://doi.org/10.3390/cancers12082244 - 11 Aug 2020
Cited by 6 | Viewed by 797
Abstract
There is conflicting evidence regarding the efficacy of neoadjuvant/perioperative chemotherapy (NCT) for gastro-esophageal cancer (GEC) on overall survival. This study aimed to analyze the outcomes of multimodal treatments in a large single center cohort. We performed a retrospective analysis of patients treated with [...] Read more.
There is conflicting evidence regarding the efficacy of neoadjuvant/perioperative chemotherapy (NCT) for gastro-esophageal cancer (GEC) on overall survival. This study aimed to analyze the outcomes of multimodal treatments in a large single center cohort. We performed a retrospective analysis of patients treated with NCT, followed by intended curative oncological surgery for locally advanced gastric cancer. Uni- and multivariate regression analysis were performed to identify the predictors of overall survival. From over 3000 patients, 702 eligible patients were analyzed. In the univariate analysis clinical stage, application of preoperative PLF, requirement of surgical extension, UICC-stage, grading, R-status, Lauren histotype, and HPR were the prognostic survival factors. In multivariate analysis PLF regimen, UICC-stages, R-status, Lauren histotype, and histopathologic regression (HPR) were significant predictors of overall survival. Overall HPR-rate was 26.9%. HPR was highest in the cT2cN0 stage (55.9%), and lowest in the cT3/4 cN+ stage (21.6%). FLOT demonstrated the highest HPR (37.5%). Independent predictors for HPR were the clinical stage and grading. Kaplan Meier analyses demonstrated significant survival benefits for the responding patients (p < 0.0001). HPR after NCT was an important prognostic factor to predict overall survival for locally advanced GEC. FLOT should be the preferred regimen in patients undergoing NCT ahead of surgery. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
Postoperative Morbidity and Failure to Rescue in Surgery for Gastric Cancer: A Single Center Retrospective Cohort Study of 1107 Patients from 1972 to 2014
Cancers 2020, 12(7), 1953; https://doi.org/10.3390/cancers12071953 - 18 Jul 2020
Cited by 1 | Viewed by 674
Abstract
Background: The aim of this study was to evaluate postoperative morbidity, mortality, and failure to rescue following complications after radical resection for gastric cancer. Methods: A retrospective analysis of the surgical database of patients with gastroesophageal malignancies at our institution was performed. All [...] Read more.
Background: The aim of this study was to evaluate postoperative morbidity, mortality, and failure to rescue following complications after radical resection for gastric cancer. Methods: A retrospective analysis of the surgical database of patients with gastroesophageal malignancies at our institution was performed. All consecutive patients undergoing R0 gastrectomy for pT1–4 M0 gastric adenocarcinoma between October 1972 and February 2014 were eligible for this analysis. Patients were divided into two groups according to the date of surgery: an early cohort operated on from 1972–1992 and a late cohort operated on from 1993–2014. Both groups were compared regarding patient characteristics and surgical outcomes. Results: A total of 1107 patients were included. Postoperative mortality was more than twice as high in patients operated on from 1972–1992 compared to patients operated on from 1993–2014 (6.8% vs. 3.2%, p = 0.017). Between both groups, no significant difference in failure to rescue after major surgical complications was observed (20.8% vs. 20.5%, p = 1.000). Failure to rescue after other surgical and non-surgical complications was 37.8% in the early cohort compared to 3.2% in the late cohort (p < 0.001). Non-surgical complications accounted for 71.2% of lethal complications between 1972 and 1992, but only for 18.2% of lethal complications between 1993 and 2014 (p = 0.002). Conclusion: In the course of four decades, postoperative mortality after radical resection for gastric cancer has more than halved. In this cohort, the reason for this decrease was reduced mortality due to non-surgical complications. Major surgical morbidity after gastrectomy remains challenging. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
Article
Outcomes of Radiotherapy for Mesenchymal and Non-Mesenchymal Subtypes of Gastric Cancer
Cancers 2020, 12(4), 943; https://doi.org/10.3390/cancers12040943 - 10 Apr 2020
Cited by 2 | Viewed by 1326
Abstract
Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. [...] Read more.
Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. Methods: Of the 458 patients enrolled in the ARTIST trial, formalin-fixed, paraffin-embedded (FFPE) specimens were available from 106 (23.1%) patients for RNA analysis. The mesenchymal subtype was classified according to a previously reported 71-gene MSS/EMT signature using the NanoString assay. Results: Of the 106 patients analyzed (50 in XP arm, 56 in XP-RT arm), 36 (34.0%) patients were categorized as mesenchymal subtype by NanoString assay. Recurrence-free survival (RFS, p = 0.009, hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.21–3.70) and overall survival (OS, p = 0.003, HR = 2.28, 95% CI: 1.31–3.96) were significantly lower in the mesenchymal subtype than in the non-mesenchymal subtype. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort. However, there was a trend in the adjuvant XP arm, which showed higher OS than the XP-RT arm for the mesenchymal subtype and lower OS than the XP-RT arm for the non-mesenchymal subtype. Conclusions: We could not determine any significant differences between the mesenchymal and non-mesenchymal subtypes with respect to the effects of adjuvant XP with or without RT in gastric cancer following curative surgery. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
Clinical Pathways for Oncological Gastrectomy: Are They a Suitable Instrument for Process Standardization to Improve Process and Outcome Quality for Patients Undergoing Gastrectomy? A Retrospective Cohort Study
Cancers 2020, 12(2), 434; https://doi.org/10.3390/cancers12020434 - 13 Feb 2020
Cited by 3 | Viewed by 1047
Abstract
(1) Background: Oncological gastrectomy requires complex multidisciplinary management. Clinical pathways (CPs) can potentially facilitate this task, but evidence related to their use in managing oncological gastrectomy is limited. This study evaluated the effect of a CP for oncological gastrectomy on process and [...] Read more.
(1) Background: Oncological gastrectomy requires complex multidisciplinary management. Clinical pathways (CPs) can potentially facilitate this task, but evidence related to their use in managing oncological gastrectomy is limited. This study evaluated the effect of a CP for oncological gastrectomy on process and outcome quality. (2) Methods: Consecutive patients undergoing oncological gastrectomy before (n = 64) or after (n = 62) the introduction of a CP were evaluated. Assessed parameters included catheter and drain management, postoperative mobilization, resumption of diet and length of stay. Morbidity, mortality, reoperation and readmission rates were used as indicators of outcome quality. (3) Results: Enteral nutrition was initiated significantly earlier after CP implementation (5.0 vs. 7.0 days, p < 0.0001). Readmission was more frequent before CP implementation (7.8% vs. 0.0%, p = 0.05). Incentive spirometer usage increased following CP implementation (100% vs. 90.6%, p = 0.11). Mortality, morbidity and reoperation rates remained unchanged. (4) Conclusions: After implementation of an oncological gastrectomy CP, process quality improved, while indicators of outcome quality such as mortality and reoperation rates remained unchanged. CPs are a promising tool to standardize perioperative care for oncological gastrectomy. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
Article
Conversion Surgery in Metastatic Gastric Cancer and Cancer Dormancy as a Prognostic Biomarker
Cancers 2020, 12(1), 86; https://doi.org/10.3390/cancers12010086 - 30 Dec 2019
Cited by 7 | Viewed by 1379
Abstract
The role of conversion surgery in metastatic gastric cancer remains unclear. Cancer dormancy markers might have a role in predicting the survival in patients with conversion surgery. We identified 26 patients who went through conversion surgery, i.e., a curative-intent gastrectomy with metastasectomy after [...] Read more.
The role of conversion surgery in metastatic gastric cancer remains unclear. Cancer dormancy markers might have a role in predicting the survival in patients with conversion surgery. We identified 26 patients who went through conversion surgery, i.e., a curative-intent gastrectomy with metastasectomy after chemotherapy in initially metastatic gastric cancer. As controls, 114 potential candidates for conversion surgery who only received chemotherapy were included for the propensity score matching. Conversion surgery showed a significantly longer overall survival (OS) compared with only palliative chemotherapy (median—43.6 vs. 14.0 months, respectively, p < 0.001). This better survival in the conversion surgery group persisted even after propensity matching (p < 0.001), and also when compared to patients with tumor response over 5.1 months in the chemotherapy only group (p = 0.005). In the conversion surgery group, OS was longer in patients with R0 resection (22/26, 84.6%) than without R0 resection (4/26, 15.4%) (median—not reached vs 22.1 months, respectively, p = 0.005). Although it should be interpreted with caution due to the primitive analysis in a small population, the positive expression of NR2F1 showed a longer duration of disease-free survival (DFS) after conversion surgery (p = 0.016). In conclusion, conversion surgery showed a durable OS even in patients with initially metastatic gastric cancer when R0 resection was achieved after chemotherapy. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
The Role of the Lymph Node Ratio in Advanced Gastric Cancer After Neoadjuvant Chemotherapy
Cancers 2019, 11(12), 1914; https://doi.org/10.3390/cancers11121914 - 01 Dec 2019
Cited by 12 | Viewed by 1470
Abstract
The ratio of positive lymph nodes (LNs) to the total LN harvest is called the LN ratio (LNR). It is an independent prognostic factor in gastric cancer (GC). The aim of the current study was to evaluate the impact of neoadjuvant chemotherapy (NAC) [...] Read more.
The ratio of positive lymph nodes (LNs) to the total LN harvest is called the LN ratio (LNR). It is an independent prognostic factor in gastric cancer (GC). The aim of the current study was to evaluate the impact of neoadjuvant chemotherapy (NAC) on the LNR (ypLNR) in patients with advanced GC. We retrospectively analyzed the data of patients with advanced GC, who underwent gastrectomy with N1 and N2 (D2) lymphadenectomy between August 2011 and January 2019 in the Department of Surgical Oncology at the Medical University of Lublin. The exclusion criteria were a lack of preoperative NAC administration, suboptimal lymphadenectomy (<D2 and/or removal of less than 15 lymph nodes), and a lack of data on tumor regression grading (TRG) in the final pathological report. A total of 95 patients were eligible for the analysis. A positive correlation was found between the ypLNR and tumor diameter (p < 0.001), post treatment pathological Tumour (ypT) stage (p < 0.001), Laurén histological subtype (p = 0.0001), and the response to NAC (p < 0.0001). A multivariate analysis demonstrated that the ypLNR was an independent prognostic factor in patients with intestinal type GC (p = 0.0465) and in patients with no response to NAC (p = 0.0483). In the resection specimen, tumor diameter and depth of infiltration, Laurén histological subtype, and TRG may reflect the impact of NAC on LN status, as quantified by ypLNR in advanced GC. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Article
Role of Postoperative Complications in Overall Survival after Radical Resection for Gastric Cancer: A Retrospective Single-Center Analysis of 1107 Patients
Cancers 2019, 11(12), 1890; https://doi.org/10.3390/cancers11121890 - 27 Nov 2019
Cited by 10 | Viewed by 1179
Abstract
Background: The aim of this study was to investigate the impact of postoperative complications on overall survival (OS) after radical resection for gastric cancer. Methods: A retrospective analysis of our institutional database for surgical patients with gastroesophageal malignancies was performed. All consecutive patients [...] Read more.
Background: The aim of this study was to investigate the impact of postoperative complications on overall survival (OS) after radical resection for gastric cancer. Methods: A retrospective analysis of our institutional database for surgical patients with gastroesophageal malignancies was performed. All consecutive patients who underwent R0 resection for M0 gastric cancer between October 1972 and February 2014 were included. The impact of postoperative complications on OS was evaluated in the entire cohort and in a subgroup after exclusion of 30 day and in-hospital mortality. Results: A total of 1107 patients were included. In the entire cohort, both overall complications (p < 0.001) and major surgical complications (p = 0.003) were significant risk factors for decreased OS in univariable analysis. In multivariable analysis, overall complications were an independent risk factor for decreased OS (p < 0.001). After exclusion of patients with complication-related 30 day and in-hospital mortality, neither major surgical (p = 0.832) nor overall complications (p = 0.198) were significantly associated with decreased OS. Conclusion: In this study, postoperative complications influenced OS due to complication-related early postoperative deaths. In patients successfully rescued from early postoperative complications, neither overall complications nor major surgical complications were risk factors for decreased survival. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Review

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Review
Epidemiology, Diagnosis, Staging and Multimodal Therapy of Esophageal and Gastric Tumors
Cancers 2021, 13(3), 582; https://doi.org/10.3390/cancers13030582 - 02 Feb 2021
Cited by 9 | Viewed by 1739
Abstract
Gastric and esophageal tumors are diverse neoplasms that involve mucosal and submucosal tissue layers and include squamous cell carcinomas, adenocarcinomas, spindle cell neoplasms, neuroendocrine tumors, marginal B cell lymphomas, along with less common tumors. The worldwide burden of esophageal and gastric malignancies is [...] Read more.
Gastric and esophageal tumors are diverse neoplasms that involve mucosal and submucosal tissue layers and include squamous cell carcinomas, adenocarcinomas, spindle cell neoplasms, neuroendocrine tumors, marginal B cell lymphomas, along with less common tumors. The worldwide burden of esophageal and gastric malignancies is significant, with esophageal and gastric cancer representing the ninth and fifth most common cancers, respectively. The approach to diagnosis and staging of these lesions is multimodal and includes a combination of gastrointestinal endoscopy, endoscopic ultrasound, and cross-sectional imaging. Likewise, therapy is multidisciplinary and combines therapeutic endoscopy, surgery, radiotherapy, and systemic chemotherapeutic tools. Future directions for diagnosis of esophageal and gastric malignancies are evolving rapidly and will involve advances in endoscopic and endosonographic techniques including tethered capsules, optical coherence tomography, along with targeted cytologic and serological analyses. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Review
Progress in Multimodal Treatment for Advanced Esophageal Squamous Cell Carcinoma: Results of Multi-Institutional Trials Conducted in Japan
Cancers 2021, 13(1), 51; https://doi.org/10.3390/cancers13010051 - 27 Dec 2020
Cited by 6 | Viewed by 1086
Abstract
In Japan, the therapeutic strategies adopted for esophageal carcinoma are based on the results of multi-institutional trials conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Owing to the differences in the proportion of patients [...] Read more.
In Japan, the therapeutic strategies adopted for esophageal carcinoma are based on the results of multi-institutional trials conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Owing to the differences in the proportion of patients with squamous cell carcinoma among all patients with esophageal carcinoma, chemotherapeutic drugs available, and surgical procedures employed, the therapeutic strategies adopted in Asian countries, especially Japan, are often different from those in Western countries. The emphasis in respect of postoperative adjuvant therapy for patients with advanced esophageal squamous cell carcinoma (ESCC) shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy in the 1990s. In the 2000s, the optimal timing of administration of perioperative adjuvant chemotherapy returned from the postoperative adjuvant setting to the preoperative neoadjuvant setting. Recently, the JEOG commenced a three-arm randomized controlled trial of neoadjuvant therapies (cisplatin + 5-fluorouracil (CF) vs. CF + docetaxel (DCF) vs. CF + radiation therapy (41.4 Gy) (CRT)) for localized advanced ESCC, and patient recruitment has been completed. Salvage and conversion surgeries for ESCC have been developed in Japan, and the JEOG has conducted phase I/II trials to confirm the feasibility and safety of such aggressive surgeries. At present, the JEOG is conducting several trials for patients with resectable and unresectable ESCC, according to the tumor stage. Herein, we present a review of the JEOG trials conducted for advanced ESCC. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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Review
From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective
Cancers 2020, 12(8), 2105; https://doi.org/10.3390/cancers12082105 - 29 Jul 2020
Cited by 3 | Viewed by 958
Abstract
Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing [...] Read more.
Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing a tailored treatment. Data from large studies investigating the role of immunotherapy in gastrointestinal cancers are promising but further investigations are necessary to better select those patients who can mostly benefit from these novel therapies. This review will focus on the treatment of metastatic esophageal and gastric cancer. We will review the standard of care and the role of novel therapies such as immunotherapies and CAR-T. Moreover, we will focus on the analysis of potential predictive biomarkers such as Modify as: Microsatellite Instability (MSI) and PD-L1, which may lead to treatment personalization and improved treatment outcomes. A multidisciplinary point of view is mandatory to generate an integrated approach to properly exploit these novel antiproliferative agents. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)

Other

Commentary
Current Trends in Endoscopic Diagnosis and Treatment of Early Esophageal Cancer
Cancers 2021, 13(4), 752; https://doi.org/10.3390/cancers13040752 - 11 Feb 2021
Cited by 3 | Viewed by 1064
Abstract
Diagnosis of esophageal adenocarcinoma mostly occurs in the context of reflux disease or surveillance of Barrett’s metaplasia. Optimal detection rates are obtained with high definition and virtual or dye chromoendoscopy. Smaller lesions can be treated with endoscopic mucosal resection. Endoscopic submucosal dissection (ESD) [...] Read more.
Diagnosis of esophageal adenocarcinoma mostly occurs in the context of reflux disease or surveillance of Barrett’s metaplasia. Optimal detection rates are obtained with high definition and virtual or dye chromoendoscopy. Smaller lesions can be treated with endoscopic mucosal resection. Endoscopic submucosal dissection (ESD) is an option for larger lesions. Endoscopic resection is considered curative (i.e., without significant risk of lymph node metastasis) if histopathology confirms en bloc and R0 resection of a well-differentiated (G1/2) tumor without infiltration of lymphatic or blood vessels and the maximal submucosal infiltration depth is 500µm. Ablation of remaining Barrett’s metaplasia is important, to reduce the risk of metachronous cancer. Esophageal squamous cell cancer is associated with different risk factors, and most of the detected lesions are diagnosed during upper gastrointestinal endoscopy for other indications. Virtual high definition and dye chromoendoscopy with Lugol’s solution are used for screening and evaluation. ESD is the preferred resection technique. The criteria for curative resection are similar to Barrett’s cancer, but the maximum infiltration depth must not exceed lamina propria mucosae. Although a submucosal infiltration depth of up to 200 µm carries a substantial risk of lymph node metastasis, ESD combined with adjuvant chemo-radiotherapy gives excellent results. The complication rates of endoscopic resection are low, and the functional outcomes are favorable compared to surgery. Full article
(This article belongs to the Special Issue Multimodal Therapy of Upper Gastrointestinal Malignancies)
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