Immunotherapy combined with apatinib in the treatment of advanced or metastatic gastric/gastroesophageal tumors: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy or apatinib alone has been used as third-line adjuvant therapy for advanced or metastatic gastric/gastroesophageal junction (G/GEJ) tumors, but the efficacy of combining them with each other for the treatment of patients with advanced or metastatic G/GEJ is unknown; therefore, we further evaluated the efficacy and safety of immunotherapy combined with apatinib in patients with advanced or metastatic G/GEJ. METHODS: The main search was conducted on published databases: Embase, Cochrane library, PubMed.The search was conducted from the establishment of the database to December 2023.Clinical trials with patients with advanced or metastatic G/GEJ and immunotherapy combined with apatinib as the study variable were collected. Review Manager 5.4 software as well as stata 15.0 software were used for meta-analysis. RESULTS: A total of 651 patients from 19 articles were included in this meta-analysis. In the included studies, immunotherapy combined with apatinib had a complete response (CR) of 0.03 (95% CI: 0.00 -0.06), partial response (PR) of 0.34 (95% CI: 0.19-0.49), stable disease (SD) of 0.43 (95% CI: 0.32-0.55), objective response rate (ORR) was 0.36 (95% CI: 0.23-0.48), disease control rate (DCR) was 0.80 (95% CI: 0.74-0.86), and median progression-free survival (PFS) was 4.29 (95% CI: 4.05-4.52), median Overall survival (OS) was 8.79 (95% CI: 7.92-9.66), and the incidence of grade ≥ 3 TRAEs was 0.34 (95% CI: 0:19-0.49). PR, ORR, DCR, median PFS and median OS were significantly higher in the immunotherapy and apatinib combination chemotherapy group (IAC) than in the immunotherapy combination apatinib group (IA). And the difference was not significant in the incidence of SD and grade ≥ 3 TRAEs. CONCLUSION: This meta-analysis shows that immunotherapy combined with apatinib is safe and effective in the treatment of advanced or metastatic G/GEJ, where IAC can be a recommended adjuvant treatment option for patients with advanced or metastatic G/GEJ. However, more large multicenter randomized studies are urgently needed to reveal the long-term outcomes of immunotherapy combined with apatinib treatment.

A phase 2 clinical trial of the heat shock protein 90 (HSP 90) inhibitor ganetespib in patients with refractory advanced esophagogastric cancer.

Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2, MET, or FGFR2 or mutations in PIK3CA, EGFR, or BRAF. Ganetespib which is a novel triazolone heterocyclic inhibitor of HSP90, is a potentially biologically rational treatment strategy for advanced EG cancers with these gene amplification. This multicenter, single-arm phase 2 trial enrolled patients with histologically confirmed advanced EG cancer with progression on at least one line of systemic therapy. Patients received Ganetespib 200 mg/m2 IV on Days 1, 8, and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Secondary endpoints included: Progression Free Survival (PFS); to correlate the presence of HSP clients with ORR and PFS; evaluating the safety, tolerability and adverse events profile. In this study 26 eligible patients mainly: male 77%, median age 64 years were enrolled. The most common drug-related adverse events were diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). The ORR of 4% reflects the single patient of 26 who had a complete response and stayed on treatment for more than seventy (70) months. Median PFS and OS was 61 days (2.0 months), 94 days (3.1 months) respectively. Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single-agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug.

Prevention of intra-thoracic recurrent laryngeal nerve injury with robot-assisted esophagectomy.

PURPOSE: Transthoracic esophagectomy for esophageal cancer is one of the most invasive procedures in surgery for gastrointestinal cancer. Serious complications sometimes occur after esophageal cancer surgery, including recurrent laryngeal nerve injury and pneumonia. The purpose of this study was to access the possibility of robot-assisted thoracoscopic esophagectomy for esophageal cancer in terms of preventing recurrent laryngeal nerve injury. METHODS: Operations in thoracic part were performed in prone position with bilateral ventilation. During dissection of the recurrent laryngeal nerve lymph nodes, thin blood vessels were coagulated with Maryland bipolar forceps in the left hand and then dissected with monopolar scissors in the right hand. Especially when dissecting left recurrent laryngeal nerve lymph nodes, the nerve was left unisolated from the vascular sheath that involves the aortic arch. Short-term outcomes including operative time, estimated blood loss, and postoperative complications including recurrent laryngeal nerve injury were accessed. RESULTS: From November 2018 to January 2020, 20 patients underwent robot-assisted thoracoscopic esophagectomy for esophageal cancer. Thoracic operative time was 242 min, estimated blood loss in the thoracic part was minimal, the number of dissected mediastinal lymph nodes was 19 (all median), and the incidence rates of recurrent laryngeal nerve injury and pneumonia were 10% (2 case) and 10% (2 cases), respectively. CONCLUSION: Robot-assisted thoracoscopic esophagectomy for esophageal cancer has the possibility of reducing recurrent laryngeal nerve injury even in the introductory period. Randomized controlled trials are required to confirm this advantage of the robotic surgery.

Treatment strategies for neuroendocrine carcinoma of the upper digestive tract.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy. METHODS: Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12). RESULTS: Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10 months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3 months for the 11 effective and 7 non-effective patients, respectively. CONCLUSIONS: A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.

Emerging Multimodality Approaches to Treat Localized Esophageal Cancer.

Esophageal cancer has a poor prognosis, with 5-year survival rates ranging from 20% to 35% in the nonmetastatic setting. Despite advances in surgical techniques and optimization of chemoradiotherapy regimens, overall survival benefits have been incremental at best. Esophageal cancer requires a concerted multidisciplinary approach, perhaps more so than any other tumor type given the integral role played by the esophagus in maintaining calorific intake and the propensity for early spread through the lymphatics. This review describes the latest in surgical techniques to minimize postoperative complications and examines previous and ongoing systemic therapy approaches. Strategies that harness a patient's own immune system hold great promise, and shifting checkpoint inhibitors from the metastatic setting to the neoadjuvant/adjuvant setting is currently being evaluated in phase II and III clinical trials. In addition, a much better understanding of the interplay between tumors and their immune microenvironment is clearly needed to better judge how best to engage each patient's immune system, and there will be likely demonstrable differences between early-stage tumors and metastatic disease. This review highlights emerging data, which demonstrate that, in addition to The Cancer Genome Atlas classification of esophageal squamous cell carcinoma having a distinct molecular makeup compared with esophageal adenocarcinoma, there are also differing responses to PD-1 inhibitors. Histology and the underlying immune milieu may have important ramifications for the management of localized disease in the future, above and beyond PD-L1 expression, microsatellite instability status, and tumor mutational burden.

Prolonged interval between neoadjuvant chemoradiotherapy and esophagectomy does not benefit the outcome in esophageal cancer: a systematic review and meta-analysis.

Whether a prolonged interval between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy could benefits conditions such as rectal cancer, still remains unknown. We therefore performed the current study to evaluate the influence of the interval between nCRT and esophagectomy on the clinical outcomes in patients with esophageal cancer. PubMed and Embase were searched to identify eligible cohort studies. The primary outcome was five-year overall survival (OS), and secondary outcomes included the incidence of anastomotic complications, perioperative mortality, pathologic complete response (pCR) rate, positive circumferential resection margin (CRM) rate, and R0 resection rate. A random-effects model was used for all meta-analyses irrespective of heterogeneity. Ten cohort studies with 2383 patients were included. Overall, the pooled estimate revealed that the prolonged interval has no impact on five-year OS (odds ratio (OR) 0.87, 95% CI 0.66 to 1.14, P = 0.30), with low heterogeneity (PH = 0.78, I2 = 0%). However, it was associated with an increased risk of anastomotic complication (OR 1.71, 95% CI 1.15 to 2.54, P = 0.008), with no effect on perioperative mortality (OR 1.20, 95% CI 0.79 to 1.83, P = 0.40). Additionally, the prolonged interval failed to increase the pCR rate (OR 1.02, 95% CI 0.78 to 1.33, P = 0.89). Even worse, it was correlated with a decreased R0 resection rate (OR 0.60, 95% CI 0.41 to 0.88, P = 0.009) and increased positive CRM rate (OR 2.20, 95% CI 1.44 to 3.36, P < 0.001). This study suggests that the prolonged interval between nCRT and esophagectomy fails to result in better outcomes, and in fact, could worsen clinical outcomes, with increasing anastomotic complications, and undermine resection completeness. However, this conclusion should be treated with caution because of the limitations of retrospective cohort study and substantial clinical heterogeneity. (The study was registered at PRESPERO as CRD42016048210).

Surgeon Volume and Cancer Esophagectomy, Gastrectomy, and Pancreatectomy: A Population-based Study in England.

OBJECTIVE: The aim of the study was to assess whether there is a proficiency curve-like relationship between surgeon volume and operative mortality and determine the minimum surgeon volume for optimum operative mortality. BACKGROUND: The inverse relationship between hospital volume and operative mortality is well-established for esophageal, gastric, and pancreatic cancer. The recommended minimum surgeon volumes are however uncertain. METHODS: We retrieved data on esophagectomies, gastrectomies, and pancreatectomies for cancer from the NHS Hospital Episodes Statistics database from April 2000 to March 2010. We defined mortality as in-hospital death within 30 days of surgery. We determined whether there was a proficiency curve relationship by inspecting surgeon volume-mortality graphs after adjusting for patient age, sex, socioeconomic, and comorbidity indices. We then statistically determined the minimum surgeon volume that produced a mortality rate insignificantly different from the optimum of the curve. RESULTS: Sixteen thousand five hundred seventy-two esophagectomies, 12,622 gastrectomies, and 9116 pancreatectomies were examined. Surgeon volume ranged from 2 to 29 esophagectomies, from 1 to 14 gastrectomies, and from 2 to 31 pancreatectomies per surgeon per year. We demonstrated a proficiency relationship between surgeon volume and mortality in esophageal, gastric, and pancreatic cancer surgery. Each additional case of esophagectomy, gastrectomy, and pancreatectomy would reduce 30-day mortality odds by 3.4%, 7.2%, and 4.1%, respectively. However, as surgeon volume increased, mortality rate continued to improve. Therefore, we were unable to recommend minimum surgeon volume. CONCLUSIONS: Mortality after resections for esophageal, gastric, and pancreatic cancer falls as surgeon volume rises up to 30 cases. Within this range, we did not demonstrate any statistical threshold that could be recommended as a minimum volume target.

History of lymphadenectomy for esophageal cancer and the future prospects for esophageal cancer surgery.

I would herein like to look back upon surgery for esophageal cancer, particularly on lymphadenectomy, and to speculate a little on the future prospects for esophageal surgery. There are two schools of thought on lymphadenectomy in esophageal cancer: one believes in en bloc esophagectomy, which is commonly performed in Western countries; the other believes in three-field lymphadenectomy, which is commonly performed in Japan. We esophageal surgeons at Kurume University have contributed to some advances in three-field lymphadenectomy. For example, we initiated functional mediastinal dissection to ensure patient safety, and we proposed the lymph node compartment theory to assess the clinical importance of regional nodes. Oncological surgery has progressed in terms of its safety, radicality and functional preservation, leading to improved quality-of-life for patients after surgery. This then evolved to the current development of multimodal and individualized tailor-made treatments. I believe that surgery for esophageal cancer will become bipolarized in the future. One strand will evolve as salvage surgery for residual or recurrent tumors, which non-surgical therapies have failed to cure, and the other strand will evolve as less invasive surgery, adjuvant surgery, for cancers at the relatively early stage, for which micro-metastasis can be cured by non-surgical therapies.

Brain metastasis from gastrointestinal cancers: a systematic review.

BACKGROUND: Brain metastases (BM) from the gastrointestinal tract (GIT) cancers are relatively rare. Despite those advances in diagnostic and treatment options, life expectancy and quality of life in these patients are still poor. In this review, we present an overview of the studies which have been previously performed as well as a comprehensive strategy for the assessment and treatment of BM from the GIT cancers. METHOD: To obtain information on brain metastases from GIT, we performed a systematic review of Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The collected data included patient characteristics, primary tumor data and brain metastases data. RESULT: In our search of the literature, we found 74 studies between 1980 and 2011, which included 2538 patients with brain metastases originated from gastrointestinal cancer. Analysis of available data showed that among 2538 patients who had brain metastases from GIT, a total of 116 patients (4.57%) had esophageal cancer, 148 patients (5.83%) had gastric cancer, 233 patients (9.18%) had liver cancer, 13 patients had pancreas cancer (0.52%) and 2028 patients (79.90%) had colorectal cancer. The total median age of the patients was 58.9 years. CONCLUSION: Brain metastases have been considered the most common structural neurological complication of systemic cancer. Due to poor prognosis they influence the survival rate as well as the quality of life of the patients. The treatment of cerebral metastasis depends on the patients' situation and the decisions of the treating physicians. The early awareness of a probable metastasis from GI to the brain will have a great influence on treatment outcomes as well as the survival rate and the quality-of-life of the patients.

Surgical quality of care in esophageal malignancies.

AIM: Esophagectomy is the primary surgical treatment for localized malignant neoplasms of the esophagus, and while outcomes have shown that substantial improvement has been made, the ceiling for improvement is still high. METHODS: A total of 2506 publications published from January 2002 to March 2012 were identified from PubMed, MEDLINE and the Cochrane Library using the keywords: 'esophagectomy', 'esophagus', 'neoplasm' and 'cancer' to identify quality key surgical articles in esophagectomy that were broken down into three groups: preoperative, intraoperative and postoperative care. DISCUSSION: There have been limited preoperative surgical trials, mostly in preoperative antibiotic use, which have led to changes in surgical management. Key and substantial changes have occurred in the intraoperative management for esophageal malignancies around surgical anastomosis technique and anesthesia. Nutritional outcomes still remain a key challenge, and currently there is no established standard of care in the postoperative management of esophagectomy patients. CONCLUSION: We established quality parameters for leak rates, overall morbidity and mortality, and these form the foundation from which all esophageal surgeons should rank their results. We then utilized the techniques described above to maintain those rates or, better yet, to significantly improve those rates in each surgeons' practice.

Thoracoscopic esophagectomy while in a prone position for esophageal cancer: a preceding anterior approach method.

BACKGROUND: In 2009, the rate of thoracoscopic esophagectomy for esophageal cancer was about 20% in Japan. This low rate may be due to the difficulty in maintaining a good surgical field and the meticulous procedures that are required. The purpose of this study was to establish and evaluate a new procedure for performing a thoracoscopic esophagectomy while the patient is in a prone position using a preceding anterior approach to make the esophagectomy easier to perform. METHODS: We have performed thoracoscopic esophagectomy using our new procedure in 60 patients with esophageal cancer. Each patient was placed in a prone position and five trocars were inserted; only the left lung was ventilated and a pneumothorax was maintained. The esophagus was mobilized from the anterior structure during the first step and from the posterior structure during the second step. The lymph nodes around the esophagus were also dissected anteriorly and posteriorly. The patients were sequentially divided into two groups and their clinical outcomes were evaluated. RESULTS: The mean operative time for the thoracoscopic procedure for the latter 30 cases (203 min) was shorter than that for the former 30 cases (260 min) (P = 0.001). Among the 52 cases without pleural adhesion, the mean blood loss in the latter 26 cases (18 mL) was also less than that in the former 26 cases (40 mL) (P = 0.027). There were no conversions to a thoracotomy and no operative deaths in this series. Postoperative complications related to the thoracoscopic procedure occurred in 8 cases (27%) in the former group and in 4 cases (13%) in the latter group. CONCLUSIONS: Thoracoscopic esophagectomy with the patient in the prone position using a preceding anterior approach is a safe and feasible procedure. As experience performing the procedure increases, the performance of the procedure stabilizes. This method seems to make the esophagectomy easier to perform.

Open or minimally invasive resection for oesophageal cancer?

Oesophagectomy is one of the most challenging surgical operations. Potential for morbidity and mortality is high. Minimally invasive techniques have been introduced in an attempt to reduce postoperative complications and recovery times. Debate continues over whether these techniques decrease morbidity and whether the quality of the oncological resection is compromised. Globally, minimally invasive oesophagectomy (MIO) has been shown to be feasible and safe, with outcomes similar to open oesophagectomy. There are no controlled trials comparing the outcomes of MIO with open techniques, just a few comparative studies and many single institution series from which assessments of the current role of MIO have been made. The reported improvements of MIO include reduced blood loss, shortened time in high dependency care and decreased length of hospital stay. In comparative studies there is no clear reduction in respiratory complications, although larger series suggest that MIO may have a benefit. Although MIO approaches report less lymph node retrieval compared with open extended lymphadenectomy, MIO cancer outcomes are comparable. MIO will be a major component of the future oesophageal surgeons' armamentarium, but should continue to be carefully assessed. Randomized trials comparing MIO versus open resection in oesophageal cancer are urgently needed: two phase III trials are recruiting, the TIME and the MIRO trials.

Does obesity affect outcomes in patients undergoing esophagectomy for cancer? A meta-analysis.

BACKGROUND: The incidence of esophageal carcinoma and the global prevalence of obesity are both increasing. As a result, there is an increased number of esophagectomies being performed on obese patients. The identification of specific complications in obese patients undergoing esophagectomy may allow improved risk assessment and postoperative management to reduce morbidity and mortality. This meta-analysis aimed to determine whether obese patients are at increased risk of postoperative complications, mortality, and compromised survival compared to non-obese patients following esophageal resection. METHODS: A Medline, Embase, Ovid, and Cochrane database search was performed on all articles between January 1980 and January 2012 comparing post-esophagectomy outcomes between obese and non-obese patients. This study was conducted in accordance with the recommendations of the Cochrane Collaboration and the Quality of Reporting of Meta-Analyses guidelines. RESULTS: There was no significant difference between obese and non-obese patients with respect to extent of tumor resection, cardiorespiratory complications, anastomotic leakage, reoperation rates, wound infection, or postoperative mortality. Meta-regression analysis showed that diabetes in obese patients was associated with a significant impact on the risk of anastomotic leakage (coefficient = -7.94 [-15.24-0.65, P = 0.03) and atrial fibrillation (coefficient = -6.94 [-12.79-1.10], P = 0.02). Overall, obese patients had significantly better long-term survival than non-obese patients (Hazard Ratio = 0.78 [0.64-0.96], P = 0.02). CONCLUSIONS: In patients who are eligible for surgery, obesity alone does not increase risk of postoperative complications or mortality and should not be an independent contraindication for esophagectomy. However, the presence of diabetes mellitus in conjunction with obesity may be associated with increased risk of anastomotic leakage and atrial fibrillation. Because of the adverse physiological remodeling in obesity, surgeons should maintain a low threshold for the investigation and management of complications and ensure meticulous management of co-morbidities. Obesity may also improve long-term postoperative survival after esophageal surgery, although further studies with higher levels of evidence are necessary to fully determine any advantageous effects of obesity following oncological esophageal surgery.

Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy.

BACKGROUND: Metabolic imaging is of interest in esophageal cancer; however, the usefulness of initial standardized uptake value (SUV) in positron emission tomography (PET) is unknown in patients with esophageal or gastroesophageal carcinoma treated with definitive chemoradiotherapy. The authors hypothesized that initial SUV would correlate with patient outcome. METHODS: The authors retrospectively analyzed esophageal or gastroesophageal carcinoma patients who had baseline PET and endoscopic ultrasonography in addition to other routine staging. All patients received definitive chemoradiotherapy. Multiple statistical methods were used. RESULTS: The authors analyzed 209 consecutive esophageal or gastroesophageal carcinoma patients treated with definitive chemoradiation for outcome; of these, 180 had baseline PET for additional analyses. The median overall survival (OS) for all patients was 20.7 months (95% confidence interval, 18.8-26.3). Patients with clinical complete response (CR) lived longer than those with less than clinical CR (P < .0001). The median initial SUV was 12.7 (range, 0-51). Higher initial SUV was associated with longer tumors (P = .0001), higher T-stage status (P < .0001), positive N-stage status (P = .0001), higher overall stage (P < .0001), lack of clinical CR (P = .0002), and squamous cell histology (P < .0001). In the univariate analysis, initial SUV was associated with OS (Cox model, P = .016; log-rank test, P = .002). In the multivariate analysis, initial SUV dichotomized by the median value (P = .024) and tumor grade (P = .016) proved to be independent OS prognosticators. Median initial SUV for clinical CR patients was 10.2, compared with 15.3 for less than clinical CR patients (P = .0058). CONCLUSIONS: The data indicate that a higher initial SUV is associated with poorer OS in patients with esophageal or gastroesophageal carcinoma receiving definitive chemoradiation. Upon validation, baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy.

Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer: A Randomized Clinical Trial.

Background: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE. Objective: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. Design, Setting, and Participants: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. Intervention: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. Main Outcomes and Measures: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. Results: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7]). Conclusions and Relevance: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer. Trial Registration: Trialregister.nl Identifier: NL4183 (NTR4333).

Outcome of Locally Advanced Esophageal Cancer Patients Treated With Perioperative Chemotherapy and Chemoradiotherapy Followed by Surgery.

OBJECTIVES: Perioperative chemotherapy (P-CT) or neoadjuvant chemoradiation (C-RT) followed by surgical resection is the standard of care for locally advanced esophageal cancer (LAEC). We present an institutional review and outcome of patients with LAEC treated with neoadjuvant C-RT or P-CT followed by surgery. METHODS: Patients were identified through the Manitoba Cancer Registry. Overall survival (OS), recurrence-free survival (RFS), and time to recurrence (TTR) were compared using proportion hazard regression analysis. Metabolic and pathologic response rates were compared by the Fisher exact test. RESULTS: Sixty-seven patients were treated with C-RT and 32 with P-CT. Fifty-two percent of the patients had pretreatment and posttreatment positron emission tomography scans before surgery. Ninety-five percent of the patients in C-RT and 91% in P-CT had a partial metabolic response or stable disease. Sixty-one percent of C-RT and 34% of P-CT patients had tumor regression grade (TRG) 0 to 1; 39% of C-RT and 66% of P-CT had TRG 2 to 3 (P=0.018). Median OS was 37 and 18 months for patients with TRG 0 to 1 and 2 to 3, respectively (P=0.013, hazard ratio [HR]=1.96). Three-year OS was 43% versus 37% (P=0.37, HR=1.30), RFS was 34% versus 26% (P=0.87, HR=0.96), and median TTR was 30 versus 13 months (P=0.07, HR=0.59) for C-RT and P-CT, respectively. CONCLUSIONS: C-RT was associated with a higher degree of pathologically tumor regression. Patients with major tumor regression had a better outcome than those with minimal to poor response. There was a trend toward improved TTR with C-RT but no difference in OS or RFS.

The Short- and Long-term Outcomes of Esophagectomy for Esophageal Cancer in Patients Older than 75 Years.

BACKGROUND: The short- and long-term outcomes of esophagectomy for esophageal cancer were fully evaluated in patients older than 75 years of age. PATIENTS AND METHODS: The present study selected patients who received esophagectomy for esophageal cancer. Patients were divided into non-elderly patients [age <75 years (non-elderly group)] and elderly patients [age ≥75 years (elderly group)]. The postoperative surgical morbidity, postoperative 30-days mortality, recurrence-free survival (RFS), and overall survival (OS) rates were evaluated between the non-elderly group and elderly group. RESULTS: One hundred twenty-two patients were evaluated in this study. Ninety-eight patients and 24 patients were classified into the non-elderly group and elderly group, respectively. The postoperative surgical complication rates in the non-elderly and elderly groups were 71.4% and 75.0%. There was not a statistically significant difference between the two groups (p=0.710). Mortality was observed in 1 patient in the elderly group (4.2%) due to cardiovascular disease. Significant differences were observed in the five-year OS and RFS rates of the elderly and non-elderly groups (55.4% vs. 29.7%, p=0.0017 and 42.2% vs. 21.2%, p=0.0334, respectively). CONCLUSION: Although the rate of postoperative surgical complications after esophagectomy for esophageal cancer was almost equal in the elderly and the non-elderly patients, significant differences were observed in the mortality and long-term outcomes of the two groups. Thus, the surgical strategy and perioperative care must be carefully planned for esophageal cancer patients older than 75 years of age.

Neoadjuvant therapy or upfront surgery? A systematic review and meta-analysis of T2N0 esophageal cancer treatment options.

BACKGROUND: Esophageal carcinoma usually shows poor long-term survival rates, even when esophagectomy, the standard curative treatment is performed. As a result, there has been increasing interest in the neoadjuvant therapy, which could potentially downstage cancer, eliminate micrometastasis and ergo increase resectability and curative (R0) resection. Currently, for the earliest stage esophageal cancers, most guidelines point out to the role of endoscopic treatment, and for T1bN0 upfront surgery. For locally advanced cases, several studies have demonstrated the benefits of neoadjuvant therapy to increase resectability. For clinical stage T2N0 esophageal cancer, there is no consensus as to the optimal treatment strategy. METHODS: A systematic review and meta-analysis was performed to compare neoadjuvant therapy with surgery alone on clinical stage T2N0 esophageal cancer patients, concerning overall survival, recurrence, post-operative mortality, anastomotic leak, and R0 resection rate. RESULTS: For overall survival at the mean follow-up point, the neoadjuvant therapy was not associated to a higher probability of survival than upfront surgery in cT2N0 patients (risk difference: 0.00; 95% CI: -0.09, 0.09). There was no difference between neoadjuvant therapy and primary surgery concerning recurrence (risk difference: 0.21; 95% CI: -0.03, 0.45); perioperative mortality (risk difference: 0.00; 95% CI: -0.02, 0.01); and risk for anastomotic leak (risk difference: -0.08; 95% CI: -0.21, 0.05). Pooled data showed that neoadjuvant therapy was associated to a higher risk for positive margins after resection (risk difference: 0.04; 95% CI: 0.02, 0.06). CONCLUSIONS: This review showed that neoadjuvant therapy is not associated to better results than surgery alone, for the management of clinical stage T2N0 esophageal cancer patients, concerning overall survival, recurrence rate, perioperative mortality, anastomotic leak, and seems to be associated to a higher risk for resection with positive margins.

Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?

Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

Systematic review of minimally invasive resection for gastro-oesophageal cancer.

BACKGROUND: This article reviews the evidence on the safety and efficacy of minimally invasive surgery for gastric and oesophageal cancer. METHODS: An electronic search of the literature between 1997 and 2007 was undertaken to identify primary studies and systematic reviews; studies were retrieved and analysed using predetermined criteria. Information on the safety and efficacy of minimally invasive surgery for gastric and oesophageal cancer was recorded and analysed. RESULTS: From 188 abstracts reviewed, 46 eligible studies were identified, 23 on oesophagectomy and 23 on gastrectomy. There were 35 case series, eight case-matched studies and three randomized controlled trials. Compared with the contemporary results of open surgery, reports on minimally invasive surgery indicate potentially favourable outcomes in terms of operative blood loss, recovery of gastrointestinal function and hospital stay. However, the quality of the data was generally poor, with many potential sources of bias. CONCLUSION: Minimally invasive surgery is feasible but evidence of benefit is currently weak.