Open left thoracoabdominal esophagectomy a viable option in the era of minimally invasive esophagectomy.

Minimally invasive surgical technique has become standard at many institutions in esophageal cancer surgery. In some situations, however other surgical approaches are required. Left thoracoabdominal esophagectomy (LTE) facilitates complete resection of esophageal cancer particularly for bulky distal esophageal tumors, but there are concerns that this approach is associated with significant morbidity. Prospectively entered esophagectomy databases from three high-volume centers were reviewed for patients undergoing LTE or MIE 2009-2019. Patient demographics, tumor characteristics, operative outcomes, postoperative outcomes, and pathologic surrogates of oncologic efficacy (R0 resection rate, and number of resected lymph nodes) were compared. In total 915 patients were included in the study, LTE was applied in 684 (74.8%) patients, and MIE in 231 (25.2%) patients. LTE patients had more locally advanced tumor stage and received more neoadjuvant treatment. Patients treated with MIE had more comorbidities. The results showed no difference in overall postoperative complications (LTE = 61.7%, MIE = 65.7%, P = 0.289), severe complications (Clavien-Dindo ≥IIIa (LTE = 25.9%, MIE 26.8%, P = 0.806)), pneumonia (LTE = 29.0%, MIE = 24.7%, P = 0.211), anastomotic leak (LTE = 7.8%, MIE = 11.3%, P = 0.101), or in-hospital mortality (LTE = 2.6%, MIE = 3.5%, P = 0.511). Median number of resected lymph nodes was 24 for LTE and 25 for MIE (P = 0.491). LTE was used for more advanced tumors in patients that were more likely to have received neoadjuvant treatment compared with MIE, however postoperative morbidity, mortality, and oncologic outcomes were equivalent to that of MIE in this cohort. In conclusion open resection with left thoracoabdominal approach is a valid option in selected patients when performed at high-volume esophagectomy centers.

Laparoscopic versus open subtotal gastrectomy for gastric adenocarcinoma: cost-effectiveness analysis.

BACKGROUND: Laparoscopic subtotal gastrectomy (LSG) for cancer is associated with good perioperative outcomes and superior quality of life compared with the open approach, albeit at higher cost. An economic evaluation was conducted to compare the two approaches. METHODS: A cost-effectiveness analysis between LSG and open subtotal gastrectomy (OSG) for gastric cancer was performed using a decision-tree cohort model with a healthcare system perspective and a 12-month time horizon. Model inputs were informed by a meta-analysis of relevant literature, with costs represented in 2016 Canadian dollars (CAD) and outcomes measured in quality-adjusted life-years (QALYs). A secondary analysis was conducted using inputs extracted solely from European and North American studies. Deterministic (DSA) and probabilistic (PSA) sensitivity analyses were performed. RESULTS: In the base-case model, costs of LSG were $935 (€565) greater than those of OSG, with an incremental gain of 0·050 QALYs, resulting in an incremental cost-effectiveness ratio of $18 846 (€11 398) per additional QALY gained from LSG. In the DSA, results were most sensitive to changes in postoperative utility, operating theatre and equipment costs, as well as duration of surgery and hospital stay. PSA showed that the likelihood of LSG being cost-effective at willingness-to-pay thresholds of $50 000 (€30 240) per QALY and $100 000 (€60 480) per QALY was 64 and 68 per cent respectively. Secondary analysis using European and North American clinical inputs resulted in LSG being dominant (cheaper and more effective) over OSG, largely due to reduced length of stay after LSG. CONCLUSION: In this decision analysis model, LSG was cost-effective compared with OSG for gastric cancer.

ANTECEDENTES: Pese a su mayor coste, la gastrectomía subtotal laparoscópica se asocia con buenos resultados perioperatorios y una mejor calidad de vida en comparación con la cirugía abierta en el tratamiento del cáncer. Se realizó una evaluación económica comparando los dos abordajes. MÉTODOS: Se efectuó un análisis de coste-efectividad de la gastrectomía subtotal laparoscópica (laparoscopic subtotal gastrectomy, LSG) o de la gastrectomía subtotal abierta (open subtotal gastrectomy, OSG) en el cáncer gástrico utilizando un modelo de cohortes con árbol de decisión desde la perspectiva del sistema de salud y con un horizonte temporal de 12 meses. Los gastos del modelo fueron evaluados tras un metaanálisis de literatura relevante y expresados en dólares canadienses (Canadian dollars, CAD) del 2016. Los resultados se midieron en años de vida ajustados por su calidad (quality-adjusted life years, QALYs). Se realizó un análisis secundario utilizando los datos extraídos únicamente de estudios europeos y norteamericanos. Además, se realizaron análisis de sensibilidad determinístico y probabilístico (deterministic and probabilistic sensitivity analyses, DSA y PSA). RESULTADOS: En el modelo del caso base, los costes de la LSG fueron de 934,78$ (565€) más que en la OSG, con una ganancia incremental de 0,050 QALYs, que supuso una relación coste-efectividad incremental (incremental cost-effectiveness ratio, ICER) de 18.846,12$ (11.398€) por QALY adicional en la LSG. En el DSA, los resultados fueron más sensibles a cambios en el postoperatorio, quirófano y coste de los equipos, así como en la duración de la intervención y la hospitalización. El PSA demostró que la probabilidad de que la LSG fuera rentable en términos de disposición de pago (willingness-to-pay, WTP) para dos umbrales, de 50.000$ (30.240€) y 100.000$ (60.480€) por QALY fue del 64% y del 68%, respectivamente. En el análisis secundario utilizando los datos europeos y norteamericanos se demostró que la LSG era claramente dominante (más barata y más efectiva) que la OSG, en gran parte debido a la reducción de la estancia hospitalaria de la LSG. CONCLUSIÓN: En este modelo de análisis de decisión, la LSG fue coste-efectiva en comparación con la OSG para el cáncer gástrico.

Dynamic Alteration of Neutrophil-to-Lymphocyte Ratio over Treatment Trajectory is Associated with Survival in Esophageal Adenocarcinoma.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been identified as a biomarker for multiple malignancies. There is emerging evidence that implicates neutrophils in cancer progression. Alterations of neutrophil counts and NLR during treatment may reflect a change in oncologic outcome that is more important than baseline values. The aim of this study is to investigate the prognostic role of NLR changes during the treatment trajectory of patients with esophageal adenocarcinoma. PATIENTS AND METHODS: NLR values of patients with esophageal adenocarcinoma who underwent surgery between 2005 and 2016 were measured at baseline and in the late postoperative period. Primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcome was pathological response to neoadjuvant chemotherapy. RESULTS: 330 patients were included; mean age was 65.6 years, and 82% were male. Most patients had cT3 (74.8%), cN-positive (59.7%) disease. Two-thirds (65.2%) received neoadjuvant chemotherapy. The independent predictors of OS were pathological N-stage, size of primary tumor, and delta NLR (late - baseline NLR). Patients with persistently elevated NLR did worse than those with decreasing NLR trends between baseline and postoperative time points (3-year OS 43.4% versus 71.3%, p < 0.0001, 3-year DFS 29.7% versus 61.9%, p < 0.0001). High baseline and postoperative NLR were associated with significantly worse OS and DFS. Patients with complete pathological response had lower mean baseline NLR. CONCLUSION: Dynamic changes in NLR during treatment are associated with survival and may be more informative than static baseline values.

Management of Dysphagia in Esophageal Adenocarcinoma Patients Undergoing Neoadjuvant Chemotherapy: Can Invasive Tube Feeding be Avoided?

BACKGROUND: Neoadjuvant chemotherapy is an accepted standard for locally advanced esophagogastric junction adenocarcinoma. However, the dysphagia frequently associated with this condition may interfere with patient tolerance of this treatment. In many centers, invasive tube feeding, placed either endoscopically, radiographically, or surgically, is used to address this issue, but it can cause significant morbidity. We sought to determine if an approach of goal-directed dietary counseling and appropriately timed neoadjuvant chemotherapy could obviate the need for invasive tube feeding. METHODS: Patients with locally advanced (cT3 or N+) esophageal and esophagogastric junction adenocarcinoma undergoing neoadjuvant TCF [Taxotere, cisplatin 5-fluorouracil (5-FU)], ECF (epirubicin, cisplatin, 5-FU), or FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) at the McGill University Health Center from March 2007 to September 2012 were identified from a prospective database. All received individualized goal-directed dietary counseling, were monitored for signs/symptoms of malnutrition with serial (baseline/presurgery) body mass index, albumin, and completed serial symptom scores (dysphagia), and quality-of-life questionnaires (Functional Assessment in Cancer Therapy with the esophageal subset, FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant chemotherapy and the need for invasive tube feeding. RESULTS: Of 130 patients undergoing neoadjuvant chemotherapy, 78 had severe dysphagia (defined as dysphagia score ≥2 on a 5-point Likert scale), most of whom received TCF (91 %). Overall dysphagia scores improved in 75 (96 %) of 78 patients from a dysphagia score of 3-0, most of which improved after the first cycle of therapy. This was associated with an increase in quality of life (FACT-E scores 117 ± 23 to 140 ± 20). With maintenance of weight (70 ± 22 to 69 ± 24 kg), body mass index (24.5 ± 8 to 23.9 ± 7 kg/m(2)), and serum albumin (40 ± 5 to 37 ± 4 g/L). Only one patient required a stent, and none required jejunostomy or gastrostomy. CONCLUSIONS: Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.

Pattern of esophageal eosinophilic infiltration in patients with achalasia and response to Heller myotomy and Dor fundoplication.

Eosinophilic esophagitis (EoE) is now recognized as a common cause of dysphagia. Eosinophilic infiltration of the esophagus has also been associated with other conditions, such as gastroesophageal reflux disease (GERD); however, the incidence, pattern, and clinical significance of eosinophilic infiltration in achalasia are poorly documented. We sought to characterize this histological finding in patients undergoing Heller myotomy (HM) for achalasia. Ninety-six patients undergoing laparoscopic HM for primary achalasia between 1999 and 2008 were identified from a prospective database. Serial mid and distal per-endoscopic esophageal biopsies taken from patients before and after surgery were assessed for the presence of elevated intraepithelial eosinophils (EIEs). Slides from patients with reports suggestive of EIE were reviewed independently by two pathologists, and the highest eosinophil count/high-power field (eos/hpf) was recorded. Dysphagia scores (0 = none to 5 = severe dysphagia), GERD health-related quality of life scores (0 = best to 45 = worst), and 24-hour pH results were compared before and 3 months after surgery. We related the highest eos to the symptoms and response to HM. Data are presented as median (range). Paired t-test and Wilcoxon signed-rank test determined significance, *P < 0.05. Of 96 patients with achalasia, 50 had undergone pre-HM biopsies revealing EIE in 17/50 (34%), with a median of 3 eos/hpf (1-21). Two patients were found to have superimposed esophageal candidiasis. One patient met the pathologic criteria for EoE. Twenty-five of 50 (50%) postoperative biopsies demonstrated a median of 5 eos/hpf (1-62) for a total of 28/50 patients (56%) with EIE in either the preoperative or postoperative period. Four patients (8%) met the pathologic criteria for EoE, and two demonstrated persistent esophageal candidiasis. A decrease in eosinophils was found in 6/28 patients (21%) from 3/hpf (1-21) to 0.5/hpf (0-4). Increase in eosinophils was found in 22/28 patients (79%) from 0.5/hpf (0-8) to 5/hpf (1-62). Preoperative and postoperative dysphagia scores were available in 23 patients. Dysphagia scores improved in 22/23 patients. (3 [0-5] to 0 [0-2])*. Preoperative and postoperative GERD scores were available in 21 patients. GERD scores improved in 20/21 patients (10 [3-38] to 2 [2-14])*. Four of 13 patients (30.7%) demonstrated significant reflux in the postoperative period. No difference in clinical response to HM was detected between patients with preoperative EIE compared with patients with no EIE. No correlation between postoperative esophageal pH and eos was observed. A significant number of patients with achalasia demonstrate esophageal eosinophilic infiltration even at numbers demonstrable in patients with EoE (8% 4/50). While the interaction between achalasia and esophageal eosinophilic infiltration needs further investigation, this does not represent a distinct clinical entity. Thus, the presence of esophageal eosinophils in patients presenting with dysphagia should not preclude further work-up for other etiologies, including achalasia.

Clinical predictors of achalasia.

Limited access to esophageal manometry (EM) may delay identification and treatment of patients with achalasia. In order to assess predictors to fast-track patients for manometric confirmation of achalasia, we compared the clinical, radiographic, and endoscopic characteristics of achalasia patients to patients with functional dysphagia without manometric features of achalasia (controls). Patients referred for esophageal manometry to assess functional dysphagia prospectively identified over a 12-month period were asked to participate in this study. The Achalasia Symptom Questionnaire (ASQ), a structured 11-question survey (score: 0-best, 67-worst), was completed by all consenting patients. ASQ scores, esophago-gastro-duodenoscopy and upper gastro-intestinal (UGI) contrast study findings were compared between patents with subsequently confirmed achalasia and those in whom achalasia was excluded by EM. Univariate logistic regression identified predictors that were tested by multivariate logistic regression to generate the model. Of the 803 EM performed over this 12-month period, 95 patients were referred specifically to assess functional dysphagia. Of these, 50 were confirmed to have achalasia, and 45 had dysphagia without manometric evidence for achalasia and hence comprised the control group. ASQ scores were higher in achalasia patients (37+/-13 versus 23+/-10). Endoscopy and/or contrast esophagogram reports were available in 92% achalasia patients and 80% controls. Significant predictors for achalasia identified on univariate logistic regression included ASQ score, abnormal findings on endoscopy, and contrast UGI study. Using multivariate logistic regression, we were able to accurately predict the probability of achalasia to be P where P=ey/(1+ey) and y=5.6+(0.089xASQ)+(2.088xEGD)+(3.083xUGI), e=exponential constant 2.7182, esophagogastroduodenoscopy (EGD) and UGI=0 if normal and 1 if abnormal. Dropping the predictor ASQ, the formula changes to y=-2.7+(1.987xEGD)+(2.861xUGI). Using only noninvasive investigations (i.e. eliminating EGD), the formula changes to y=-4.9653+(0.0951xASQ)+(3.4312xUGI). The probability of achalasia can be calculated in patients with functional dysphagia based on clinical, endoscopic, and radiographic findings allowing for a prioritization of EM studies.