Treatment burden and cost-effectiveness analysis of the neoadjuvant CROSS regimen in esophageal squamous cell carcinoma: a multicenter retrospective study.

High-quality evidence indicated that both neoadjuvant carboplatin/paclitaxel (CROSS) and cisplatin/5-fluorouracil (PF) regimens in combination with radiotherapy improve survival outcomes compared to surgery alone in patients with esophageal cancer. It is not yet known whether they may differ in terms of treatment burden and healthcare costs. A total of 232 Taiwanese patients with esophageal squamous cell carcinoma who had undergone neoadjuvant chemoradiotherapy (nCRT) with either the CROSS (n = 153) or the PF (n = 79) regimens were included. Hospital encounters and adverse events were assessed for determining treatment burden. Cost-effectiveness analysis was undertaken using the total costs incurred over 3 years in relation to overall survival (OS) and progression-free survival (PFS). Compared with PF, the CROSS regimen was associated with a lower treatment burden: shorter inpatient days on average (4.65 ± 10.05 vs. 15.14 ± 17.63 days; P < 0.001) and fewer admission requirements (70% of the patients were never admitted vs. 20% in the PF group; P < 0.001). Patients in the CROSS group experienced significantly less nausea, vomiting, and diarrhea. While the benefits observed in the CROSS group were associated with additional nCRT-related expenditures (1388 United States dollars [USD] of added cost per patient), this regimen remained cost-effective. At a willingness-to-pay threshold of 50,000 USD per life-year, the probability of the CROSS regimen to be more cost-effective than PF was 94.1% for PFS but decreased to 68.9% for OS. The use of the CROSS regimen for nCRT in patients with ESCC was associated with a lower treatment burden and was more cost-effective than PF.

Safety, efficacy, and cost-effectiveness of minimally invasive esophagectomies versus open esophagectomies: an umbrella review.

Traditionally, esophageal oncological resections have been performed via open approaches with well-documented levels of morbidity and mortality complicating the postoperative course. In contemporary terms, minimally invasive approaches have garnered sustained support in all areas of surgery, and there has been an exponential adaptation of this technology in upper GI surgery with the advent of laparoscopic and robotic techniques. The current literature, while growing, is inconsistent in reporting on the benefits of minimally invasive esophagectomies (MIEs) and this makes it difficult to ascertain best practice. The objective of this review was to critically appraise the current evidence addressing the safety, efficacy, and cost-effectiveness of MIEs versus open esophagectomies. A systematic review of the literature was performed by searching nine electronic databases to identify any systematic reviews published on this topic and recommended Joanna Briggs Institute approach to critical appraisal, study selection, data extraction and data synthesis was used to report the findings. A total of 13 systematic reviews of moderate to good quality encompassing 143 primary trials and 36,763 patients were included in the final synthesis. Eleven reviews examined safety parameters and found a generalized benefit of MIE. Efficacy was evaluated by eight systematic reviews and found each method to be equivalent. There were limited data to judiciously appraise cost-effectiveness as this was only evaluated in one review involving a single trial. There is improved safety and equivalent efficacy associated with MIE when compared with open esophagectomy. Cost-effectiveness of MIE cannot be sufficiently supported at this point in time. Further studies, especially those focused on cost-effectiveness are needed to strengthen the existing evidence to inform policy makers on feasibility of increased assimilation of this technology into clinical practice.

Improved anastomotic leakage rates after the "flap and wrap" reconstruction in Ivor Lewis esophagectomy for cancer.

Anastomotic leakage after esophagectomy has serious consequences. In Ivor Lewis esophagectomy, a shorter and possibly better vascularized gastric conduit is created than in McKeown esophagectomy. Intrathoracic anastomoses can additionally be wrapped in omentum and concealed behind the pleura ("flap and wrap" reconstruction). Aims of this observational study were to assess the anastomotic leakage incidence after transhiatal esophagectomy (THE), McKeown esophagectomy (McKeown), Ivor Lewis esophagectomy (IL) without "flap and wrap" reconstruction, and IL with "flap and wrap" reconstruction. Consecutive patients undergoing esophagectomy at a tertiary referral center between January 2013 and April 2019 were included. Primary outcome was the anastomotic leakage rate. Secondary outcomes were postoperative outcomes, mortality, and 3-year overall survival. A total of 463 patients were included. The anastomotic leakage incidence after THE (n = 37), McKeown (n = 97), IL without "flap and wrap" reconstruction (n = 39), and IL with "flap and wrap" reconstruction (n = 290) were 24.3, 32.0, 28.2, and 7.2% (P < 0.001). THE and IL with "flap and wrap" reconstruction required fewer reoperations for anastomotic leakage (0 and 1.4%) than McKeown and IL without "flap and wrap" reconstruction (6.2 and 17.9%, P < 0.001). Fewer anastomotic leakages are observed after Ivor Lewis esophagectomy with "flap and wrap" reconstruction compared to transhiatal, McKeown and Ivor Lewis esophagectomy without "flap and wrap" reconstruction. The "flap and wrap" reconstruction seems a promising technique to further reduce anastomotic leakages and its severity in esophageal cancer patients who have an indication for Ivor Lewis esophagectomy.

Surveillance of neo-squamous epithelium after ablation of Barrett's esophagus: is it better to use jumbo over standard biopsy forceps?

BACKGROUND AND AIMS: As obtaining adequate tissue on biopsy is critical for the detection of residual and recurrent intestinal metaplasia/dysplasia in Barrett's esophagus (BE) patients undergone Barrett's endoscopic eradication therapy (BET), we decided to compare the adequacy of biopsy specimens using jumbo versus standard biopsy forceps. METHODS: This is a two-center study of patients' post-radiofrequency ablation of dysplastic BE. After BET, jumbo (Boston Scientific©, Radial Jaw 4, opening diameter 2.8 mm) or standard (Boston Scientific©, Radial Jaw 4, opening diameter 2.2 mm) biopsy forceps were utilized to obtain surveillance biopsies from the neo-squamous epithelium. Presence of lamina propria and proportion of squamous epithelium with partial or full thickness lamina propria was recorded by two experienced gastrointestinal pathologists who were blinded. Squamous epithelial biopsies that contained at least two-thirds of lamina propria were considered 'adequate'. RESULTS: In a total of 211 biopsies from 55 BE patients, 145 biopsies (29 patients, 18 males, mean age 61 years, interquartile range [IQR] 33-83) were obtained using jumbo forceps and 66 biopsies (26 patients, all males, mean age 65 years, IQR 56-76) using standard forceps biopsies. Comparing jumbo versus standard forceps, the proportion of specimens with any subepithelial lamina propria was 51.7% versus 53%, P = 0.860 and the presence of adequate subepithelial lamina propria was 17.9% versus 9.1%, P = 0.096 respectively. CONCLUSIONS: Use of jumbo forceps does not appear to have added advantage over standard forceps to obtain adequate biopsy specimens from the neo-squamous mucosa post-ablation.

ISDE Presidential Biography: David B. Skinner, MD.

Dr. David Skinner, the 4th President of the ISDE, was a world-renowned surgeon, educator, scholar, and leader. He participated in the formation of the ISDE, hosted two international congresses in 1983 and 1989, and made important advances in the ISDE during his presidential tenure 1992-1995.

Impact of supplemental home enteral feeding postesophagectomy on nutrition, body composition, quality of life, and patient satisfaction.

The aim of this prospective cohort study is to analyze the impact of supplemental home enteral nutrition (HEN) post-esophageal cancer surgery on nutritional parameters, quality of life (QL), and patient satisfaction. A systematic review reported that over 60% of patients lose >10% of both body weight and BMI by 6 months after esophagectomy. Enteral feeding (EF) is increasingly a modern standard postoperatively; however, the impact of extended HEN postdischarge has not been systematically studied. One hundred forty-nine consecutive patients [mean age 62 ± 9, 80% male,76% adenocarcinoma, 66% on multimodal protocols, and 69% with BMI ≥ 25 kg/m2] were studied. Jejunal EF commenced day 1 postoperatively, and supplemental overnight HEN (764 kcal; 32g protein) continued on discharge for a planned further 4 weeks. Weight, BMI, and body composition analysis (bioimpedance analysis) were measured at baseline, preoperatively and at 1, 3, and 6 months, along with the EORTC QLQ-C30/OES18 QL measures. A patient satisfaction questionnaire addressed eight key items in relation to HEN (max score 100/item). Median (range) total duration of EF was 49 days (28-96). Overall compliance was 96%. At 6 months, compared with preoperatively, 58 (39%) patients lost >10% weight, with median (IQR) loss of 6.8 (4-9) kg, and 62 (41%) patients lost >10% BMI. Lean body mass and body fat were significantly (p < 0.001) decreased. Mean global QL decreased (p < 0.01) from 82 to 72. A high mean satisfaction score (>70 ± 11/100) was reported, >80 for practical training, activities of daily living, pain, anxiety, recovery and impact on caregivers, with lower scores for appetite (33 ± 24) and sleep (63 ± 30). Supplemental HEN for a minimum of one month postdischarge is associated with high compliance and patient satisfaction. Weight and BMI loss may still be substantial, however this may be less than published literature, in addition the impact on HR-QL may be attenuated. HEN has both subjective and objective rationale and merits further validation toward optimizing nutritional recovery and overall wellbeing.

Comparison of curative surgery and definitive chemoradiotherapy as initial treatment for patients with cervical esophageal cancer.

Esophagectomy and definitive chemoradiotherapy are recognized standard initial treatment modalities for cervical esophageal cancer. The goal of this study was to compare the treatment outcomes of curative surgery with those of chemoradiotherapy in patients who had potentially resectable tumor and who were candidates for surgery. We evaluated the data from 49 consecutive patients who were diagnosed with potentially resectable cervical esophageal cancer and who were deemed candidates for surgery. Thirteen patients were included in the surgery group, and 36 patients were included in chemoradiotherapy group. Baseline characteristics were balanced between the two groups. In the chemoradiotherapy group, the complete response rate was 58.3%. There was no significant difference in 5-year overall survival when comparing the surgery group and the chemoradiotherapy group (surgery, 60.6%; chemoradiotherapy, 51.4%; P = 0.89). In the chemoradiotherapy group, of the 15 patients who failed to respond to initial treatment, 11 patients subsequently underwent salvage surgery. In conclusion, curative surgery and chemoradiotherapy as initial treatment for cervical esophageal cancer have comparable survival outcomes. Chemoradiotherapy should be selected as the initial larynx-preserving treatment for patients with cervical esophageal cancer although chemoradiotherapy non-responders require additional treatment, including salvage surgery.

A bridging stent to surgery in patients with esophageal and gastroesophageal junction cancer has a dramatic negative impact on patient survival: A retrospective cohort study through data acquired from a prospectively maintained national database.

This study aimed to assess the impact of esophageal stenting on postoperative complications and survival in patients with obstructing esophageal and gastroesophageal junction (GEJ) cancer. All patients treated without neoadjuvant therapy that had an R0-resection performed for esophageal and GEJ cancer between January 2003 and December 2010 were identified from a prospectively maintained database. Data on stenting, postoperative mortality, morbidity, recurrence-free survival, complications, and length of hospital stay were collected. Kaplan-Meier plots for survival and recurrence-free survival curves were constructed for R0 resected patients. Data were compared between the stent and no-stent group by nonparametric tests. Two hundred seventy three consecutive R0 resected patients with esophageal or GEJ cancer were identified. Of these patients, 63 had a stent as a bridge to surgery. The male/female ratio was 2.64 (198/75) with a median age in the stent group (SG) of 65.1 versus 64.3 in the no stent group (NSG). Patients were comparable with respect to gender, age, smoking, TNM-classification, oncological treatment, hospital stay, tumor location, and histology. The median survival in the SG was 11.6 months compared with 21.3 months for patients treated without a bridging stent (P < 0.001). There were no statistically significant differences in 30-day mortality between the two groups, but NSG patients exhibited a significantly better two-year survival (P = 0.017). The median recurrence-free survival was 9.1 months for the SG compared with 15.2 months for the NSG. The use of a stent as a bridging procedure to surgery in patients treated without neaoadjuvant therapy for an esophageal or GEJ cancer that later underwent R0 resection decreased the two year survival and the recurrence-free survival.

Definitive radiation therapy with dose escalation is beneficial for patients with squamous cell cancer of the esophagus.

Objective: We report the long term follow-up, toxicity, and outcomes of patients with localized squamous cell carcinoma of the esophagus(ESCC) who underwent definitive chemo-radiotherapy(dCRT) at our institute. Materials and Methods: Patients diagnosed with carcinoma post cricoid, upper cervical and thoracic oesophagus and treated with dCRT between January 2000 and March 2012 were retrospectively analyzed. Radiotherapy was delivered in two phases to a maximum dose of 63Gy in daily fractions of 1.8Gy using conventional or conformal techniques. OS and PFS were defined from date of registration and were calculated by Kaplan-Meier method with comparisons between different subgroups performed using log-rank test. All data were analysed using SPSS Version 22. Results: Three hundred and fourteen patients with ESCC treated with dCRT were included in this analysis. Median age at presentation was 56 years and median KPS at presentation was 70. Two-third of patients were treated with conformal technique. Median dose of radiation delivered was 60Gy(range 30.6Gy-70Gy). Neoadjuvant chemotherapy was administered in about 35% patients and 57% patients received concurrent chemotherapy. About 10% patients required hospitalization during treatment due to complications and 7 patients did not complete treatment. Grade 1/2 dermatitis and mucositis was seen in 77% and 71% patients respectively. Complete response at first follow up was observed in 56% of patients. At a median follow up of 56 months, 77 patients were alive with controlled disease. The 1- and 3-yr OS were 80% and 62% respectively. Median PFS was 28 months; 1- and 3-yr PFS were 66% and 46% respectively. A higher RT dose was found to be a significant predictor for OS and PFS on both uni- and multivariate analysis. Conclusion: Our study highlights that the delivery of higher RT doses (≥63Gy) is feasible in this patient group and that a higher RT dose was associated with significantly better PFS and OS.

A study of serum zinc, selenium and copper levels in carcinoma of esophagus patients.

The association of serum trace elements like selenium, zinc and copper has been found in different types of cancer. This study was conducted to see the serum level of these three trace elements in cancer esophagus patients. Biopsy confirmed cancer esophagus, 24 patients (12 males, 12 females, mean age 54.5±11.65 year with 23 healthy subjects (16 males, 7 females, mean age 44 ±13.82 years) were included in this study. Both control and study group patients were of same socio-economic status and dietary habits. Serum zinc and copper level were estimated using standard absorption spectrometer technique and serum selenium by Hydride generation method.We observed significant low serum levels of zinc and selenium while high level of serum copper in carcinoma esophagus patients, as compared with normal healthy controls. This shows an association of serum selenium zinc and copper with cancer esophagus.

Long Term Outcome in Patients with Esophageal Stenting for Cancer Esophagus - Our Experience at a Rural Hospital of Punjab, India.

INTRODUCTION: Cancer of the esophagus is among the leading cause of cancer deaths in Punjab, India. Patients generally present with dysphagia as their first symptom and more often they have advanced disease at the time of presentation to a tertiary care centre. Palliative procedures have important roles in this setting. Stenting is the best option to palliate the symptoms of dysphagia, from which patient is suffering the most. AIM: To know the success rate, early and long term complications and mortality in esophageal stenting, when it was done in malignant esophageal stricture patients. MATERIALS AND METHODS: One hundred patients, who had undergone esophageal stenting from January 2012 to January 2015, were included in the study. We retrospectively analysed the data for patient characteristics, causes of non-operability, early and long term complications, re-interventions, efficacy and mortality. RESULTS: Out of 100 patients, indications for stenting were locally advanced disease not amenable to surgery (52%), metastatic disease (35%), CVA (1%), cardiac and respiratory problem (8%), un-willing for surgery in 5% of patients. Majority of patients (94%) had squamous cell carcinoma, while only 6% had adenocarcinoma. 84% of patients presented with dysphagia with or without chest pain and recurrent cough while 16% had recurrent vomiting. 58% had dysphagia to liquids and solids and 17% had complete dysphagia. After stenting 93% had significant improvement in dysphagia score from median of 3 to 1. Post procedure stay was 3.61±1.0 days. One patient had procedure related major complication in the form of post procedural bleed (after 16 days of stenting) leading to death of that patient. Minor complications were present in 52 patients treated conservatively not affecting the efficacy of procedure. These include pain after stenting (38%), stent obstruction (23%) and stent migration (6%). All the minor complications were treated conservatively except in six patients in whom re-stenting was done. CONCLUSION: Esophageal stenting is relatively safe procedure with short stay of the patient in the hospital. Although, it helps in alleviating patients' morbidity very effectively and reliably, there are many technical glitches, which needs to be kept into account and patient should be properly counseled before the procedure to prevent and manage post procedure complications and medico legal aspects.

Total oesophagectomy for squamous cell carcinoma with or without standard two field node dissection - a prospective study.

Cancer of the esophagus and gastroesophageal junction (GEJ) is notorious for its advanced stage at the time of diagnosis with transmural invasion and early lymphatic spread in the majority of the patients. R0 resection is the aim of surgery with curative intent. Regarding the role of lymphadenectomy, as in any other solid organ cancer, there are opposing views. Some surgeons argue that the presence of lymph node involvement equals systemic disease and that survival remains unchanged despite removal of these lymph nodes. For others the presence of lymph node involvement, even at a distance from the primary tumor, justifies an aggressive approach with radical esophagectomy combined with lymphadenectomy. The purpose of this article is to compare standard two field lymph node dissection versus non formal lymph node dissection in carcinoma esophagus. The conclusions are based on the experience with 60 cases of carcinoma esophagus over 2 years. In our opinion total esophagectomy with 2-field lymphadenectomy is the standard surgery for resectable squamous cell carcinoma of esophagus. It improves the lymphnode yield thereby ensuring adequate staging of the disease. It can be performed with acceptable morbidity and mortality as the nonformal lymphadenectomy procedure. Locoregional recurrence following 2 field lymphadenectomy is significantly low as compared to nonformal lymphadenectomy procedure though the distant recurrence rate is same. 2 year disease free survival in this study shows advantage of 2 field lymphadenectomy compared to non formal lymphadenectomy procedure.

A Case of Aortoesophageal Fistula due to Esophageal Cancer Treated with Endovascular Stent Grafting / 대한내과학회지

Hemorrhage into the esophagus due to aortoesophageal communication is very rare but life-threatening with high morbidity and mortality. Because of this, most cases of aortoesophageal fistula are confirmed by autopsy. However, we report herein a case of a 62-year-old male with an aortoesophageal fistula who was successfully treated with endovascular stent-grafting. The patient had undergone esophageal stent insertion due to esophageal cancer and experienced hematemesis and hemodynamic shock due to an aortoesophageal fistula. Emergency endoscopy was unable to identify the source of the hemorrhage due to massive bleeding. Computed tomography of the chest revealed a focal pseudoaneurysm at the descending aorta and diffuse thinning of the esophageal wall, which were treated with endovascular stent-grafting. Although aortoesophageal fistulas are usually fatal, implantation of a covered stent into the esophagus may help prevent massive bleeding, providing valuable time to treat the patient.