Trends in surgical techniques for the treatment of esophageal and gastroesophageal junction cancer: the 2022 update.

The aim of this study was to evaluate the current practice in surgical techniques for esophageal and gastroesophageal junction cancer surgery worldwide and to compare the results to the previous surveys in 2007 and 2014. An online survey was sent out among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association, the Association of Upper Gastrointestinal Surgery of Great Britain and Ireland and Dutch gastroesophageal surgeons via the network of the investigators. In total, 260 surgeons completed the survey representing 52 countries and 6 continents; Europe 56%, Oceania 14%, Asia 14%, South-America 9%, North-America 7%. Of the responding surgeons, 39% worked in a hospital that performed >51 esophagectomies per year. Total minimally invasive esophagectomy was the preferred technique (53%) followed by hybrid esophagectomy (26%) of which 7% consisted of a minimally invasive thoracic phase and 19% of a minimally invasive abdominal phase. Total open esophagectomy was preferred by 21% of the respondents. Total minimally invasive esophagectomy was significantly more often performed in high-volume centers compared with non-high-volume centers (P = 0.002). Robotic assistance was used in 13% during the thoracic phase and 6% during the abdominal phase. Minimally invasive transthoracic esophagectomy has become the preferred approach for esophagectomy. Although 21% of the surgeons prefer an open approach, 26% of the surgeons perform a hybrid procedure which may reflect further transition towards the use of total minimally invasive esophagectomy.

Worldwide trends in surgical techniques in the treatment of esophageal and gastroesophageal junction cancer.

The aim of this study was to evaluate the worldwide trends in surgical techniques for esophageal cancer surgery by comparing it to our survey from 2007. In addition, new questions were added for gastroesophageal junction (GEJ) cancer. An international survey on surgery of esophageal and GEJ cancer was performed among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association. Also, surgeons from personal networks were contacted. The participants filled out a web based questionnaire about surgical strategies for esophageal and gastroesophageal cancer. The overall response rate was 478/1147 (42%). The respondents represented 49 different countries and 6 different continents. The annual cumulative number of esophageal and gastric resections per surgeon was low (≤11) in 11%, medium (11-21) in 17%, and high (≥21) in 72% of respondents. In a subgroup analysis of esophageal surgeons the number of high volume surgeons increased from 45 to 54% over the past 7 years. The preferred lymph node dissection was two-field in 86%. A gastric conduit was the preferred method of reconstruction in 95%. In 2014, the preferred approach to esophagectomy was minimally invasive transthoracic in 43%, compared with 14% in 2007. In minimally invasive transthoracic esophagectomy the cervical anastomosis was favored in 54% of respondents in 2014 compared with 87% in 2007. The preferred technique of construction of the cervical anastomosis was hand-sewn in 64% and stapled in 36%, whereas the thoracic anastomosis was stapled in 77% and hand-sewn in 23%. The preferred surgical approach for Siewert type 1 tumors (5-1 cm proximal of the GEJ) was esophagectomy in 93% of respondents, whereas 6% favored gastrectomy and 3% combined a distal esophagectomy with a proximal gastrectomy. For Siewert type 2 tumors (1-2 cm from the GEJ) an extended gastrectomy was favored by 66% of respondents, followed by esophagectomy in 27% and total gastrectomy in 7%. Siewert type 3 tumors (2-5 cm distal of the GEJ) were preferably treated with gastrectomy in 90% of respondents, esophagectomy in 6%, and extended gastrectomy in 4%. The preferred curative surgical treatment of esophageal cancer is minimally invasive transthoracic esophagectomy with a two-field lymph node dissection and gastric conduit reconstruction. A strong worldwide trend toward minimally invasive surgery is observed. The preferred surgical treatment of GEJ tumors is esophagectomy for Siewert type 1 tumors and gastrectomy for Siewert type 3 tumors. The majority of surgeons favor an extended gastrectomy for Siewert type 2 tumors.

Esophageal and Gastric Cancer Pearl: a nationwide clinical biobanking project in the Netherlands.

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer.

Surgical treatment of adenocarcinomas of the gastro-esophageal junction.

BACKGROUND: Patients with adenocarcinoma of the gastro-esophageal junction (GEJ) may undergo either esophagectomy or gastrectomy. The aim of this study was to evaluate the outcome of surgical therapy with regard to postoperative outcome and survival in patients with Siewert type II tumors. METHODS: A prospective database of 266 consecutive patients with surgically resectable GEJ adenocarcinomas from 2003 to 2013 was analyzed. The surgical approach was based on preoperative imaging and intraoperative findings. RESULTS: According to the histopathological analysis, 67 patients (25 %) had type I tumor, 176 patients (66 %) had type II tumor, and 16 patients (6 %) had type III tumor. In total, 86 % were treated with esophagectomy and 14 % with gastrectomy. Overall 5-year survival was 38 %. In type II patients, the type of operation did not significantly influence overall survival on multivariate analysis (p = 0.606). A positive circumferential resection margin (CRM) at the site of the esophagus was more common with gastrectomy (29 vs. 11 %; p = 0.025). No significant differences in mortality, morbidity, or disease recurrence were found. In patients with type II tumors, upper mediastinal nodal involvement (subcarinal, paratracheal, and aortapulmonary window) was found in 11 % of the patients. In 34 % of patients treated with esophagectomy, paraesophageal lymph nodes metastases were harvested compared with 5 % of patients treated with gastrectomy. CONCLUSIONS: In patients with a type II GEJ adenocarcinoma, a positive CRM was more common with gastrectomy. Esophagectomy provides for a more complete para-esophageal lymphadenectomy. Furthermore, the high prevalence of mediastinal nodal involvement indicates that a full lymphadenectomy of these stations should be considered.

Oncologic Long-Term Results of Robot-Assisted Minimally Invasive Thoraco-Laparoscopic Esophagectomy with Two-Field Lymphadenectomy for Esophageal Cancer.

BACKGROUND: Open transthoracic esophagectomy is the worldwide gold standard in the treatment of resectable esophageal cancer. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RAMIE) for esophageal cancer may be associated with reduced blood loss, shorter intensive care unit (ICU) stay, and less cardiopulmonary morbidity; however, long-term oncologic results have not been reported to date. METHODS: Between June 2007 and September 2011, a total of 108 patients with potentially resectable esophageal cancer underwent RAMIE at the University Medical Centre Utrecht, with curative intent. All data were recorded prospectively. RESULTS: Median duration of the surgical procedure was 381 min (range 264-636). Pulmonary complications were most common and were observed in 36 patients (33 %). Median ICU stay was 1 day, and median overall postoperative hospital stay was 16 days. In-hospital mortality was 5 %. The majority of patients (78 %) presented with T3 and T4 disease, and 68 % of patients had nodal-positive disease (cN1-3). In 65 % of patients, neoadjuvant treatment (chemotherapy 57 %, chemoradiotherapy 7 %, radiotherapy 1 %) was administered, and in 103 (95 %) patients, a radical resection (R0) was achieved. The median number of lymph nodes was 26, median follow-up was 58 months, 5-year overall survival was 42 %, median disease-free survival was 21 months, and median overall survival was 29 months. Tumor recurrence occurred in 51 patients and was locoregional only in 6 (6 %) patients, systemic only in 31 (30 %) patients, and combined in 14 (14 %) patients. CONCLUSION: RAMIE was shown to be oncologically effective, with a high percentage of R0 radical resections and adequate lymphadenectomy. RAMIE provided good local control with a low percentage of local recurrence at long-term follow up.

Reduction of naturally occurring motoneuron death in vivo by a target-derived neurotrophic factor.

Treatment of chick embryos in ovo with crude and partially purified extracts from embryonic hindlimbs (days 8 to 9) during the normal cell death period (days 5 to 10) rescues a significant number of motoneurons from degeneration. The survival activity of partially purified extract was dose-dependent and developmentally regulated. The survival of sensory, sympathetic, parasympathetic, and a population of cholinergic sympathetic preganglionic neurons was unaffected by treatment with hindlimb extract. The massive motoneuron death that occurs after early target (hindlimb) removal was partially ameliorated by daily treatment with the hindlimb extract. These results indicate that a target-derived neurotrophic factor is involved in the regulation of motoneuron survival in vivo.

Laparoscopic gastrectomy in Western European patients with advanced gastric cancer.

BACKGROUND: The advantage of laparoscopic gastrectomy compared to open gastrectomy has been established in Asian patient series with early gastric cancer. However, its feasibility in Western European patients with locally advanced gastric cancer is unknown. METHODS: Between 2006 and 2014 70 consecutive patients with advanced gastric cancer underwent laparoscopic gastrectomy with D2 lymph node dissection. A Billroth II reconstruction was performed after distal gastrectomy. In case of total gastrectomy a jejunal J-pouch reconstruction was performed. RESULTS: Total gastrectomy was performed in 56 patients and distal gastrectomy in 14 patients. Perioperative chemotherapy was administered in 45/70 (64%) patients. A radical resection was achieved in 63/70 (90%). The median number of dissected lymph nodes was 17 (2-62). The median intraoperative blood loss was 305 (30-2700) milliliters. The median postoperative hospital stay was 11 (5-91) days. The 30-day mortality was 4.3%. CONCLUSIONS: Laparoscopic gastrectomy can be performed in Western European patients with advanced gastric cancer and meets the oncologic standard with low intraoperative blood loss and short hospital stay.

Staging of adenocarcinoma of the gastroesophageal junction.

BACKGROUND: Clinical staging of adenocarcinoma of the gastroesophageal junction (GEJ) determines the curative treatment regimen containing either neoadjuvant chemotherapy or chemoradiotherapy followed by either gastrectomy or esophagectomy. The value of current diagnostic tools is a matter of debate. METHODS: A prospective database (2003-2013) was used to identify 266 consecutive patients with adenocarcinoma of the GEJ in order to evaluate the accuracy of endoscopic ultrasound (EUS) and computed tomography (CT) regarding tumor localization according to Siewert, nodal status and its consequences on treatment strategy. RESULTS: Overall accuracy in determining tumor localization was 73% for endoscopy/EUS and 61% for CT (p = 0.018). With endoscopy/EUS, the accuracy was 97%, 66% and 75% respectively for type I, II and III. With CT this was respectively 69%, 57% and 80%. The overall accuracy for determining N-status (N0/N+) per patient was 75% for EUS and 71% for CT. Accuracy for determining a positive nodal station in patients without neoadjuvant therapy was 77% for EUS and 71% for CT (p = 0.001). Accuracy for detecting positive upper mediastinal nodes was 80-92%, whereas for peritumoral and abdominal nodes this was 50-80% in both EUS and CT. In 8/266 patients (3%) the type of surgery changed due to intraoperative findings. A radical resection was performed in 233 patients (88%). CONCLUSIONS: Despite the suboptimal accuracy of determining tumor localization with EUS and CT, in only a small number of patients an intraoperative change of surgical treatment was needed. EUS is superior to CT in determining nodal status and tumor localization in GEJ tumors.

Long-term quality of life after oesophagectomy with gastric conduit interposition for cancer.

BACKGROUND: Gaining insight in long-term health-related quality of life more than 1year after oesophagectomy will assist clinical decision-making and inform patients about the long-term consequences of surgery. METHODS: In this cross-sectional study, all consecutive patients who underwent oesophageal resection with gastric interposition for cancer at a tertiary referral centre between January 2007 and July 2012 were included. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and QLQ-OES18 were sent to all patients alive without recurrence more than 1year after surgery. RESULTS: The questionnaires were completed by 92 of 100 patients. Median duration of follow-up after surgery at completing the questionnaire was 36months (range: 12-75). Global quality of life scores were similar to a general population reference group (76±19 versus 78±17; p=0.26). However, patients scored significantly worse compared to the general population reference group on physical-, role-, cognitive- and social functioning (p<0.001). Neoadjuvant therapy and minimally invasive oesophagectomy were associated with significantly better health-related quality of life (HRQL) and symptom scores (p<0.05). CONCLUSION: Global HRQL more than 1year after oesophagectomy with gastric tube reconstruction is comparable to the general Dutch background population, while specific functional and symptom scores are significantly worse. Neoadjuvant therapy and minimally invasive surgery are associated with quality of life benefits in long-term survivors.

Prophylactic Laparoscopic Total Gastrectomy with Jejunal Pouch Reconstruction in Patients Carrying a CDH1 Germline Mutation.

BACKGROUND: For patients with an identified germline E-cadherin-1 (CDH1) mutation, prophylactic gastrectomy is the treatment of choice to eliminate the high risk of developing diffuse gastric cancer. Laparoscopic total gastrectomy with jejunal pouch reconstruction is a novel approach that may be especially suitable in these patients. METHODS: Patients with a germline CDH1 mutation who underwent prophylactic laparoscopic total gastrectomy with jejunal pouch were included in our prospective database. RESULTS: A total of 11 patients with a median age of 40 (22-61) years were included. The average operative time was 4:26 ± 0:49 h and the average blood loss was 219 ± 155 ml. Median length of hospital stay was 10 (7-27) days. In two patients, an esophagojejunal anastomotic leakage occurred (grade 4). The leakages were seen in patient numbers 2 and 3, which may be a result of a learning curve. The latter eight patients did not develop anastomotic leakage. Pulmonary complications occurred in one patient with atelectasis and in one patient with pneumonia (grade 2). The 60-day mortality rate was 0 %. Multiple foci of intramucosal diffuse gastric signet ring cell carcinoma were found in the resection specimen of 9/11 (82 %) patients. All 11/11 (100 %) resections were microscopically radical. CONCLUSIONS: Prophylactic laparoscopic total gastrectomy with jejunal pouch reconstruction in patients with a CDH1 germline mutation is feasible and safe. In 82 % of patients, foci of intramucosal diffuse gastric signet ring cell carcinoma in the resection specimen were found.

A functional framework for neurotrophic activities.

In attempts to understand the diverse roles which trophic activities exert in neuronal development and maintenance, it is useful to define some framework from within which to view their function. An example of such an outline is presented, sufficiently broad to avoid excluding by definition agents with clearly neurotrophic effect.

Senile plaques stimulate microglia to release a neurotoxin found in Alzheimer brain.

Senile plaques found in the brains of patients with Alzheimer's disease (AD) are surrounded by clusters of reactive microglia. Isolated human microglia placed in contact with plaques in vitro are activated to release a factor which is toxic to neurons. This same neurotoxin is found in AD brain tissue and causes damage to pyramidal neurons in vivo when infused into rat hippocampus. Highest concentrations of the neurotoxin are in those brain structures most burdened by reactive microglia, suggesting that plaque-activated cells contribute to the neuronal damage and impaired cognition seen in patients with Alzheimer's dementia.

Skeletal muscle proteins rescue motor neurons from cell death in vivo.

Because embryonic neurons are more sensitive to the effects of target derived factors than adult neurons, the developing nervous system provides a sensitive model for investigating the in vivo actions of target-derived growth factors. We have used the developing chick embryo to document that skeletal muscle contains substances that selectively enhance the in vivo survival of motor neurons. We have also shown that a single purified skeletal muscle protein (CDF) is capable of rescuing motor neurons during the period of naturally occurring cell death. The rescue of motor neurons in vivo by CDF is consistent with the hypothesis that distinct neurotrophic factors exist which regulate the timing and extent of the naturally occurring death of specific populations of neurons. The effects of CDF appear to be specific for cholinergic somatic motor neurons, since the survival of other types of spinal cord neurons, which also exhibit cell loss during the treatment period, was not affected by CDF treatment. In contrast, treatment of the embryos with extracts of tissues not innervated by motor neurons, or with NGF or bFGF, does not affect motor neuron survival. Thus the ability to rescue motor neurons during the period of cell death appears to be a distinct property of CDF and provides indirect evidence that this molecule may play a role in the survival and development of motor neurons. The role of neurotrophic factor involvement in the pathophysiology of degenerative diseases such as ALS remains entirely speculative. However, the demonstration that such factors affect the neuronal subtypes at risk in these diseases provides experimental support for this possibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Systematic review of the surgical strategies of adenocarcinomas of the gastroesophageal junction.

INTRODUCTION: The optimal surgical treatment of patients with adenocarcinoma of the gastroesophageal junction has not been established yet. OBJECTIVE: To evaluate the surgical strategies to treat adenocarcinoma of the gastroesophageal junction. METHODS: Databases Pubmed, Cochrane, and Embase were searched for "adenocarcinoma of the gastroesophageal junction" AND ("surgery" OR "esophagectomy" OR "gastrectomy") or its synonyms or abbreviations. Only comparative studies that evaluated gastrectomy versus esophagectomy were included. RESULTS: In total 10 cohort studies comparing esophagectomy versus gastrectomy fulfilled the quality criteria. The R0 resection rates varied between 72-93% for esophagectomy and 62%-93% for gastrectomy. Morbidity was 33-39% after esophagectomy versus 11-54% after gastrectomy. The 30-day mortality ranged between 1.0-2.3 after esophagectomy and 1.8-2.7% after gastrectomy. At 6 months after surgery, health-related quality of life was higher after total gastrectomy than after esophagectomy. The 5-year survival rates varied between 30-42% for esophagectomy and 18-38% for gastrectomy, but were not significantly different. CONCLUSION: No clear oncologic benefit of either esophagectomy or gastrectomy in patients with adenomacarcinoma of gastroesophageal junction could be observed. However, gastrectomy seems to be accompanied with better quality of life. Future research should preferably consist of a multicenter RCT comparing esophagectomy and gastrectomy for adenocarcinomas of the gastroesophageal junction.

The value of database controls in pilot or futility studies in ALS.

OBJECTIVE: To evaluate the use and reliability of database controls in place of a placebo group in pilot or "futility" ALS trials. METHODS: We compared the rates of disease progression in the placebo arm of the clinical phase III US Insulin-like Growth Factor-I Trial (n = 90) with the rates of disease progression of 207 patients with ALS selected from 1,600 ALS database patients using the same inclusion criteria. RESULTS: The mean rates of change in the Appel ALS (AALS) score were nearly identical in the placebo group (4.70 points/month) and in the database group (4.79 points/month). In addition, there was no significant difference in the median time to achieving a 20-point progression in AALS score: 143 days for database match vs 146 days for the placebo group (log rank p = 0.88). Furthermore, in the multivariate Cox analysis, both the rate at which the disease had progressed prior to first exam (preslope) (p < 0.001) and first exam AALS total score (p = 0.01) were shown to be covariates of subsequent rate of disease progression. CONCLUSION: The similarity in disease progression between placebo arm of clinical phase III trial and matched database group suggests the value of historical databases in futility trials. However, the proposed study design requires appropriate matching of study patients with database controls. Based on our results, we suggest matching by stage of the disease and rate of clinical decline in a contemporaneous ALS population.

Anatomical and physiological development of the Xenopus embryonic motor system in the absence of neural activity.

Embryos of Xenopus laevis were continually immobilized by immersion in solutions of either chloretone or lidocaine, from the late neural-fold stage to the approximate time of hatching. Such treatment has been shown to result in only transient quantitative effects on swimming behavior. Chronic immobilization was without either immediate or long-term effect on the ventral root output exhibited during "fictive" swimming episodes. Development under these conditions of diminished or absent neural activity similarly had no effects on a number of measures of the size and complexity of motoneuron dendritic arborizations. These results support the premise that the early development of specific neuronal morphology and connectivity may be largely independent of functional activity.

Behavioral development in the absence of neural activity: effects of chronic immobilization on amphibian embryos.

Embryos of Xenopus laevis and Ambystoma mexicanum were continually immobilized from premotile stages of development to stages at which normally reared embryos were swimming well. Immobilization was achieved through exposure to solutions of chloretone, lidocaine, or alpha-bungarotoxin. At a number of stages after recovery from the drugs, spontaneous and stimulated behaviors were extensively quantified. Immobilization of Ambystoma embryos resulted in temporary defects in musculoskeletal development. In contrast, treated Xenopus embryos could not be distinguished from controls by simple visual observation within minutes to hours after removal from the drug solutions. Quantifications of behavior revealed, however, a transient period of 24-48 hr during which treated embryos exhibited consistently reduced measures of stimulated swimming, while showing an increase in frequency of spontaneous movements. Detailed behavioral testing could detect no permanent effects of chronic immobilization in either species after this initial period of recovery. The results are discussed in reference to the classic works of Harrison (1904), Carmichael (1926, 1927), and Matthews and Detwiler (1926).

Neurotrophic interactions in the development of spinal cord motoneurons.

The final number of spinal cord motoneurons is attained by a two-step process involving the proliferation of precursor cells and the loss by cell death of a proportion (approximately 50%) of the post-mitotic neurons. Although the mechanisms responsible for the proliferation of stereotyped numbers of motoneurons are not understood, considerable evidence from in vitro as well as in vivo studies indicates that the second step in attaining population size (cell death) is controlled by the interaction of motoneurons with both their efferent targets and their afferent inputs. Target influences on motoneuron survival are thought to be regulated by muscular activity and by competition for limited amounts of neurotrophic factors derived from striated skeletal muscles. However, evidence that such putative neurotrophic factors actually modulate motoneuron survival in vivo has been lacking. Using crude and partially purified extracts from embryonic hindlimbs (Days 8-9) we have found that the treatment of chick embryos in ovo with these agents during the normal cell death period (Days 5-10) rescues a significant number of motoneurons from degeneration. Kidney or lung extracts and heat-inactivated hindlimb extracts were ineffective. The survival-inducing activity of partially purified extract was dose dependent and developmentally regulated. The survival of sensory, sympathetic and a population of cholinergic sympathetic preganglionic neurons was unaffected by treatment with hindlimb extract. The massive motoneuron death that occurs after early target (hindlimb) removal was partially ameliorated by daily treatment with the hindlimb extract. Survival-inducing activity of the extract is lost after trypsin treatment. Taken collectively these results indicate that a target-derived protein or polypeptide neurotrophic factor is involved in the regulation of motoneuron survival in vivo.