Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

The ISCON-trial protocol: laparoscopic ischemic conditioning prior to esophagectomy in patients with esophageal cancer and arterial calcifications.

BACKGROUND: Anastomotic leakage is the most important surgical complication following esophagectomy. A major cause of leakage is ischemia of the gastric tube that is used for reconstruction of the gastrointestinal tract. Generalized cardiovascular disease, expressed by calcifications of the aorta and celiac axis stenosis on a pre-operative CT scan, is associated with an increased risk of anastomotic leakage. Laparoscopic ischemic conditioning (ISCON) aims to redistribute blood flow and increase perfusion at the anastomotic site by occluding the left gastric, left gastroepiploic and short gastric arteries prior to esophagectomy. This study aims to assess the safety and feasibility of laparoscopic ISCON in selected patients with esophageal cancer and concomitant arterial calcifications. METHODS: In this prospective single-arm safety and feasibility trial based upon the IDEAL recommendations for surgical innovation, a total of 20 patients will be included recruited in 2 European high-volume centers for esophageal cancer surgery. Patients with resectable esophageal carcinoma (cT1-4a, N0-3, M0) with "major calcifications" of the thoracic aorta accordingly to the Uniform Calcification Score (UCS) or a stenosis of the celiac axis accordingly to the modified North American Symptomatic Carotid Endarterectomy Trial (NASCET) score on preoperative CT scan, who are planned to undergo esophagectomy are eligible for inclusion. The primary outcome variables are complications grade 2 and higher (Clavien-Dindo classification) occurring during or after laparoscopic ISCON and before esophagectomy. Secondary outcomes include intra- and postoperative complications of esophagectomy and the induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow by measurement of indocyanine green (ICG) fluorescence angiography. DISCUSSION: We hypothesize that in selected patients with impaired vascularization of the gastric tube, laparoscopic ISCON is feasible and can be safely performed 12-18 days prior to esophagectomy. Depending on the results, a randomized controlled trial will be needed to investigate whether ISCON leads to a lower percentage and less severe course of anastomotic leakage in selected patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03896399 . Registered 4 January 2019.

Two-stage hybrid Ivor-Lewis esophagectomy as surgical strategy to reduce postoperative morbidity for high-risk patients.

BACKGROUND: Ivor-Lewis esophagectomy (ILE) is the standard surgical care for esophageal cancer patients but postoperative morbidity impairs quality of life and reduces long-term oncological outcome. Two-stage ILE separating the abdominal and thoracic phase into two distinct surgical procedures has proven to enhance microcirculation of the gastric conduit and therefore most likely reduces complications. However, two-stage ILE has not been evaluated systematically in selected groups of patients scheduled for this procedure. This investigation aims to demonstrate the feasibility of two-stage ILE in high-risk patients. PATIENTS AND METHODS: In this retrospective analysis of data obtained from a prospective database, a consecutive series of 275 hybrid ILE (hILE) were included. Patients were divided into two groups based on one- or two-stage hILE. Postoperative complications were assessed according to ECCG (Esophageal Complication Consensus Group) criteria and compared using the Clavien-Dindo score. Indication for two-stage esophagectomy was classified as pre- or intraoperative decision. RESULTS: 34 out of 275 patients (12.7%) underwent two-stage hILE. Patients of the two-stage group were significantly older. In 21 of 34 patients (61.8%) the decision for a two-stage procedure was made prior to esophagectomy, in 13 (38.2%) patients intraoperatively after completion of the laparoscopic gastric mobilization. The most frequent preoperative reason to select the two-stage procedure was a stenosis of the coeliac trunc and superior mesenteric artery (n = 10). The predominant cause for an intraoperative change of strategy was a laparoscopically diagnosed hepatic fibrosis/cirrhosis (n = 5).Overall morbidity and major' complications (CD > IIIa) were comparable for both groups (11.7% in both groups). The overall anastomotic leak rate was 12.4% and was non-significant lower for the two-stage procedure. CONCLUSION: Two-stage hILE is a feasible concept to individualize the surgical treatment of patients with well-defined clinical risk factors for postoperative morbidity. It can also be applied after completion of the abdominal phase of IL esophagectomy without compromising the patient safety.

Incidental diagnosis of the tall-cell variant of the papillary microcarcinoma of the thyroid gland requires completion lymphadenectomy: case report.

Papillary thyroid carcinoma is the most common neoplasm of the thyroid gland which is usually associated with a very good prognosis. The aim of this case report is to present the disease course of a rare tumor of the thyroid gland, which is worthwhile due to its extraordinary appearance and specific management. A 46-year-old patient presented with a pronounced right-sided, but bilateral, multinodular goiter, with a volume of approximately 80 mL, as assessed on ultrasonography. Surgical removal was indicated as scintigraphy showed a 4-cm cold nodule that almost completely took up the right thyroid lobe. Because of the micronodular texture of the left thyroid lobe, complete thyroidectomy was performed according to well-established guidelines. Histopathological investigation of the specimen revealed a follicular adenoma without any malignancy in the right thyroid lobe and the tall-cell variant of the papillary thyroid microcarcinoma in the left lobe, with a capsular invasion and diameter of 0.6 cm. Because this rare tumor subtype is known for its aggressive behavior, and there was capsular invasion, low-grade differentiation, and an increased risk for lymphatic metastases, completion lymphadenectomy of the central compartments was performed after an interdisciplinary board decision. On histopathology, there were 30 tumor-free lymph nodes; final TNM classification was as follows: pT3 pN0 [0/30] L0 V0 Pn0 R0). The postoperative course was uneventful, and surgery was followed by radioiodine therapy. Six months after the surgery, clinical follow-up did revealed any sign of recurrence. The tall-cell variant is a rare and aggressive subtype of the papillary thyroid carcinoma, and it is characterized by poor 5-year survival and high recurrence rate. According to our understanding and based on current literature, this disease requires an aggressive surgical treatment and a close follow-up, as recommended by the current guidelines.