Gastro-esophageal junction cancers: what is the best minimally invasive approach?
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ABSTRACT:
SUBMITTER: Jezerskyte E
PROVIDER: S-EPMC5538974 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:The high morbidity and mortality of patients with esophageal (E) and gastro-esophageal junction (GEJ) cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs) as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR), and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55) in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32). Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04) and older patients (p=0.01). Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers.
| S-EPMC4380353 | biostudies-literature
Project description:Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.
| S-EPMC10869364 | biostudies-literature
Project description: Not available
| S-EPMC3693147 | biostudies-literature
Project description:ObjectiveNewer minimally invasive approaches to esophagectomy have brought substantial benefits to esophageal-cancer patients and continue to improve. We report here our experience with a streamlined procedure as part of a comprehensive perioperative-care program that provides additional advances in the continued evolution of this procedure.MethodsAll patients with primary esophageal cancer referred for resection to the Oakland Medical Center of the Kaiser-Permanente Northern California health plan who underwent this approach between January 2013 and August 2018 were included. Operative and clinical outcome variables were extracted from the electronic medical record, operating-room files, and manual chart review.Results142 patients underwent the new procedure and care program; 121 (85.2%) were men with mean age of 64.5 years. 127 (89.4%) were adenocarcinoma; 117 (82.4%) were clinical stage III or IVA. 115 (81.0%) required no jejunostomy. Median hospital length-of-stay was 3 days and 8 (5.6%) patients required admission to the intensive care unit. Postoperative complications occurred in 22 (15.5%) patients within 30 days of the procedure. There were no inpatient deaths; one patient (0.7%) died within 30 days following discharge and three additional deaths (2.1%) occurred through 90 days of follow-up.ConclusionsThis approach resulted in excellent clinical outcomes, including short hospital stays with limited need for the intensive care unit, few perioperative complications, and relatively few patients requiring feeding tubes on discharge. This comprehensive approach to esophagectomy is feasible and provides another clinically meaningful advance in the progress of minimally invasive esophagectomy. Further development and dissemination of this method is warranted.
| S-EPMC8895824 | biostudies-literature
Project description:BackgroundOur objective was to develop a new, minimally invasive surgical technique for the resolution of craniovertebral junction pathologies, which can eliminate the complications of the previous methods, like liquor-leakage, velopharyngeal insufficiency and wound-dehiscence associated with the transoral or lateral approaches.MethodsDuring the first stage of the operation, three patients underwent occipito-cervical dorsal fusion, while the fourth patient received C1-C2 fusion according to Harms. C1-C2 decompressive laminectomy was performed in all four cases. Ventral C1-C2 decompression with microscope assisted minimally invasive anterior submandibular retropharyngeal key-hole approach (MIS ASR) method was performed in the second stage. The MIS ASR-similarly to the traditional anterior retropharyngeal surgery-preserves the hard and soft palates, yet can be performed through a 25 mm wide incision with the use of only one retractor.ResultsThe MIS ASR approach was a success in all four cases, there were no intra- and postoperative complications. This method, compared to the transoral approach, provided on average 23% (4.56 cm2/6.05 cm2) smaller dural decompression area; nonetheless, the entire pathology could be removed in all cases. After the surgery, all patients have shown significant neurological improvement.ConclusionBased on the outcome of these four cases we think that the MIS ASR approach is a safe alternative to the traditional methods while improving patient safety by reducing the risk of complications.
| S-EPMC8054389 | biostudies-literature
Project description:The robotic platform has permeated esophageal surgery both in the abdominal and thoracic approaches. The most widely studied entities include achalasia, gastroesophageal reflux disease, hiatal hernia and esophageal cancer. A literature review of robotic surgeries for the management of the above mentioned disorders is presented. Data is limited to meta-analyses, case series, or small prospective trials in the different indications. One exception is a randomized controlled trial looking at outcomes in esophageal cancer being managed with a hybrid robotic versus open approach. Overall differences when comparing laparoscopic or thoracoscopic surgery to robotic are few. These differences are best highlighted in the achalasia and esophageal cancer literature. There are less intraoperative mucosal injuries in robotic Heller myotomy. A large meta analysis found a rate of 1% versus 24.5% mucosal injury rate favoring the robotic versus laparoscopic Heller myotomy methods. With respect to esophagectomy data, there is slightly less vocal cord paralysis in the robotic versus MIE data, with a P value of 0.044. However, length of stay, intraoperative bleeding and major morbidity are similar across the various indications. Robotic esophageal surgery is a safe alternative to laparoscopic/thoracoscopic techniques. Further large-scale randomized trials are needed to fully ascertain if it yields superior outcomes.
| S-EPMC8184479 | biostudies-literature
Project description:RationaleMinimally invasive esophagectomy (MIE) have been increasingly used and are regarded as suitable alternatives to open esophagectomy. However, few previous reports described minimally invasive esophagectomy using a left-sided approach.Patient concerns and diagnosesA 71-year-old man was admitted to our hospital because of progressive dysphagia. Synchronous double primary thoracic esophageal and left lung cancers were considered before the operation.Interventions and outcomesA lobectomy and MIE, via a left video-assisted thoracoscopic approach, was performed. Preparation of a gastric conduit and an intra-abdominal lymphadenectomy were completed by laparoscopy and a cervical anastomosis was made. In addition, a cervical mediastinoscopy was performed to dissect the lymph nodes along the bilateral recurrent laryngeal nerves. No postoperative complications were observed. The patient achieved a favorable short-term outcome.LessonsThis is the first report of a patient with synchronous esophageal and left lung cancers treated with minimally invasive resection via left thoracoscopy, laparoscopy, and cervical mediastinoscopy. Our results showed that the left MIE approach in combination with cervical mediastinoscopy is potentially most appropriate for some esophageal cancer patients, when the right MIE approach is not applicable in certain conditions.
| S-EPMC5943863 | biostudies-literature
Project description:Gastroesophageal (GE) cancers continue to be a significant cause of mortality globally. Despite therapeutic advances in oncology, the prognosis of advanced GE cancer remains exceedingly poor. Immunotherapy has caused a major paradigm shift in the field of oncology. Not all patients benefit from these agents and several studies are trying to identify predictive and prognostic biomarkers to better inform and guide treatment decisions. The potential role of immunotherapy in GE cancers is emerging. These cancer types are molecularly and immunologically heterogeneous, and this heterogeneity influences the tumor microenvironment posing a significant challenge to studying biomarkers of response to immunotherapy. Here in this article, we discuss the need for new therapeutic approaches in GE cancers, review the emerging data on the activity of checkpoint inhibitors and the role of biomarkers in this setting.
| S-EPMC5848035 | biostudies-literature
Project description:Gastric and gastro-esophageal junction adenocarcinoma (GEA) remains a considerable major public health problem worldwide, being the fifth most common cancer with a fatality-to-case ratio that stands still at 70%. Angiogenesis, which is a well-established cancer hallmark, exerts a fundamental role in cancer initiation and progression and its targeting has been actively pursued as a promising therapeutic strategy in GEA. A wealth of clinical trials has been conducted, investigating anti-angiogenic agents including VEGF-directed monoclonal antibodies, small molecules tyrosine kinase inhibitors and VEGF-Trap agents both in the resectable and advanced setting, reporting controversial results. While phase III randomized trials testing the anti-VEGFR-2 antibody Ramucirumab and the selective VEGFR-2 tyrosine kinase inhibitor Apatinib demonstrated a significant survival benefit in later lines, the shift of angiogenesis inhibitors in the perioperative and first-line setting failed to improve patients' outcome in GEAs. The molecular landscape of disease, together with novel combinatorial strategies and biomarker-selected approaches are under investigation as key elements to the success of angiogenesis blockade in GEA. In this article, we critically review the existing literature on the biological rationale and clinical development of antiangiogenic agents in GEA, discussing major achievements, limitations and future developments, aiming at fully realizing the potential of this therapeutic approach.
| S-EPMC9540203 | biostudies-literature
Project description:BackgroundThe current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts but is technically demanding owing to its complexity. Moreover, the actual advantages of MIPG over minimally invasive TG (MITG) with regards to postoperative QoL are unknown. Our overall objective of this study is to determine the short-term QoL benefits of MIPG. Our central hypotheses are that MIPG is safe and that patients have improved appetite after MIPG with effective antireflux techniques, which leads to an overall QoL improvement when compared with MITG.MethodsEnrollment of a total of 60 patients in this prospective survey-collection study is expected. Procedures (MITG versus MIPG, antireflux techniques for MIPG [double-tract reconstruction versus the double-flap technique]) will be chosen based on surgeon and/or patient preference. Randomization is not considered feasible because patients often have strong preferences regarding MITG and MIPG. The primary outcome is appetite level (reported on a 0-10 scale) at 3 months after surgery. With an expected 30 patients per cohort (MITG versus MIPG), this study will have 80% power to detect a one-point difference in appetite level. Patient-reported outcomes will be longitudinally collected (including questions about appetite and reflux), and specific QoL items, body weight, body mass index and ghrelin, albumin, and hemoglobin levels will be compared.DiscussionSurgeons from the US, Japan, and South Korea formed this collaboration with the agreement that the surgical approach to P/GEJ cancers is an internationally important but controversial topic that requires immediate action. At the completion of the proposed research, our expected outcome is the establishment of the benefit and safety of MIPG.Trial registrationThis trial was registered with Clinical Trials Reporting Program Registration under the registration number NCI-2022-00267 on January 11, 2022, as well as with ClinicalTrials.gov under the registration number NCT05205343 on January 11, 2022.
| S-EPMC10472658 | biostudies-literature