Thromboprophylaxis in oesophageal cancer patients-a study protocol for a randomised, controlled trial (TOP-RCT).

BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment. METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery. DISCUSSION: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population. TRIALS REGISTRATION: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.

EndoFLIP evaluation of the pylorus during minimal invasive Ivor-Levis esophagectomy.

BACKGROUND/AIMS: During esophagectomy for malignancy, the anterior and posterior branches of the vagus nerve are transected in order to achieve surgical radicality. This leads to loss of central nervous system-control of the pylorus which may lead to delayed gastric emptying. We aimed to investigate the feasibility of the EndoFLIP technique for assessment of pyloric biomechanical properties in patients undergoing esophagectomy. METHODS: A feasibility study in six patients undergoing surgery was conducted. EndoFLIP measurements were carried out preoperative (Pre-op), after surgical resection (Post-op) and following prophylactic balloon dilatation of the pylorus (Post-dil). By measuring the cross-sectional area and pressure of the pylorus the pyloric compliance and the incremental pressure-strain elastic modulus (Ep) were calculated. RESULTS: Placing the catheter in the pyloric region was successfully achieved in all six patients. No complications were observed. Resection of the esophagus increased the incremental pyloric elastic modulus (Ep) from 0.59 ± 0.18 kPa to 0.99 ± 0.34 kPa (p = 0.03). After dilatation, the Ep was reduced to 0.53 ± 0.23 kPa (p = 0.04), which was close to Pre-op (p = 0.62). The pyloric compliance showed a similar pattern as that found for Ep. CONCLUSION: The EndoFLIP system holds promise for assessment of biomechanics of the pyloric region in patients undergoing esophagectomy for cancer.

Assessing the benefits of repeated esophagogastroduodenoscopy at a specialized center before gastric and esophageal cancer surgery.

BACKGROUND: The surgical treatment of gastric and esophageal cancer in Denmark is centralized in four specialized esophagogastric cancer (EGC) centers. Patients are referred after an esophagogastroduodenoscopy (EGD) at a secondary healthcare facility. The EGD is repeated at the specialized EGC center before determining a surgical treatment strategy. This multicenter retrospective study aimed to investigate the quality of EGDs performed at a secondary healthcare facility and evaluate the clinical value of repeated EGD at a specialized center when determining the surgical treatment strategy. METHODS: Patients from three of the four centers, who underwent esophagectomy or gastrectomy with curative intent from 1 June 2016 to 1 May 2021, were included. EGD reports from the referral facilities and EGC centers were compared based on a predefined checklist. Furthermore, endoscopist experience, the time between examinations, and histology were registered. Finally, it was assessed whether the specialized EGD led to any substantial changes in surgical treatment. Baseline characteristics and differences in EGD reports were described and McNemar's chi-square test was performed. A logistic regression analysis was conducted to identify risk factors for a change in surgical strategy. RESULTS: The study included 953 patients who underwent both an initial EGD and EGD at referral to a specialized center. In 644 cases (68%), the information from the initial EGD was considered insufficient concerning preoperative tumor information. In 113 (12%) cases, the findings in the specialized EGD would lead to a significant alteration in the surgical strategy compared with the primary EGD. CONCLUSION: The findings suggest that repeated EGD at a specialized center is of clinical value and helps ensure proper surgical treatment for patients undergoing curative surgery for gastroesophageal cancer.

Safe and efficient 2-step implementation of totally minimally invasive esophagectomy.

Background: The clinical benefits of totally minimal invasive esophagectomy (TIME) compared to open esophagectomy are documented and include reduced morbidity like pulmonary infections, shorter hospital stay and an increase in short-term quality of life. However, transition to TIME can be associated with a learning curve associated increased morbidity. We report our implementation of TIME using a 2-step approach, where the thoracoscopic part was added to the laparoscopic part in carefully selected patients. The hypothesis was that the 2-step implementation provides a safe and efficient implementation without compromising the outcomes for the patients. The aim of this study was to evaluation the implementation of minimal invasive esophagectomy at Aarhus University Hospital, where a 2-step implementation strategy has been used. Methods: In this retrospective observational cohort study a total of 369 patients with esophagus or gastroesophageal cancers underwent esophagectomy from September 1st, 2016 to July 31st, 2021 in a single high-volume tertiary institution. Totally minimally invasive Ivor Lewis esophagectomy was performed by experienced minimal invasive surgeons in 120 of the cases. The study presents the complication rates of the TIME patients in the implementation phase. Results: Anastomotic leakage occurred in 7.5% of the cases and pneumonia occurred in 5.8% of the cases. The lymph node count reached 16 or more in 94.3% of the cases and R0-resection was performed in 98.3% of the cases. Textbook outcome for esophageal cancer surgery was achieved in 45.8% of the patients. Conclusions: Hybrid minimal invasive esophagectomy can serve as a step towards totally minimally invasive esophagectomy. In our institution, major learning curve associated complications was avoided and a high level of cancer control was achieved by a 2-step implementation strategy in carefully selected patients.

Individualised perioperative blood pressure and fluid therapy in oesophagectomy ­ study protocol for a randomised clinical trial

INTRODUCTION: Oesophagectomy is the mainstay of curative treatment for oesophageal cancer, but it is associated with a high risk of major complications. Goal-directed fluid therapy and individualised blood pressure management may prevent complications after surgery. Extending goal-directed fluid therapy after surgery and applying an individual blood pressure target may have substantial benefit in oesophagectomy. This is a protocol for a clinical trial implementing a novel haemodynamic protocol from the start of anaesthesia to the next day with the patient's own night-time blood pressure as the lower threshold. METHODS: This is a single-centre, single-blind, randomised, clinical trial. Oesophagectomy patients are randomised 1:1 for either perioperative haemodynamic management according to a goal-directed fluid therapy protocol with an individual target blood pressure or for standard care. The primary endpoint is the total burden of morbidity and mortality assessed by the Comprehensive Complication Index 30 days after surgery. Secondary endpoints are complications, reoperations, fluid and vasopressor dosage and quality of life at 90 days after surgery. CONCLUSIONS: The results from this trial provide an objective and easy-to-follow algorithm for fluid administration, which may improve patient-centred outcomes in oesophagectomy patients. FUNDING: The trial is supported by Aarhus University (1,293,400 DKK) and the Novo Nordisk Foundation (625,200 DKK). TRIAL REGISTRATION: EudraCT number: 2021-002816-30.

[The management of gastric polyps].

This review summarizes the work-up and treatment of gastric polyps. Fundic gland polyps can be identified macroscopically, and they generally bear no malignancy potential. Hyperplastic polyps and adenomas require histology to be diagnosed. Adenomas should always be resected, whereas resection of hyperplastic polyps is recommended if they bear atypical features. Eradication of concomitant Helicobacter pylori is recommended as it may causes regression of the polyp(s). Standardized biopsies from the surrounding mucosa should be taken on the smallest indication. The discovery of adenomas or dysplasia calls for a one-year followup.

Localized malignant mesothelioma in the stomach and mediastinum.

Localized malignant mesothelioma is rare. It has a histological pattern identical to diffuse malignant mesothelioma but without diffuse serosal spread. Localized malignant mesothelioma typically originates from the pleura, peritoneum or pericardium, but can occasionally develop from organs. Our cases represent what might be the largest mediastinal localized malignant mesothelioma described and the first presentation of the epithelioid type in the stomach of an adult.

Oncological results and morbidity following intended curative resection and free jejunal graft reconstruction of cervical esophageal cancer: a retrospective Danish consecutive cohort study.

BACKGROUND: The role of surgery in treatment of locally advanced cervical esophageal cancer (CEC) remains debated. In the European and American treatment guidelines, definitive chemoradiotherapy (dCRT) is preferred over surgery, while in the Danish guidelines, the two treatment modalities are equally recommended. Surgical treatment of CEC is centralized at our center in Denmark. We present our outcomes following neoadjuvant chemoradiotherapy (nCRT) when possible and resection as first-line therapy for CEC and compare with recent published dCRT results. METHOD: We retrospectively reviewed the medical charts of patients treated for cervical esophageal cancer at Aarhus University Hospital from 2001-2018 with nCRT when possible and pharyngolaryngectomy followed by reconstruction with a free jejunal graft. RESULTS: Forty consecutive patients were included. About, 45% received nCRT. The median survival was 21 months. The overall, disease-specific and disease-free 5-year survival was 43.6%, 53.2%, and 47.4%, respectively. The rate of microscopically radical resection was 85%. The recurrence rate was 47% and 81% of recurrences were locoregional. The in-hospital and 30-day mortality rate was 0%. Major complications occurred in 27.9%. Anastomotic leakage, graft failure, fistulas and strictures occurred in 10%, 7.5%, 30%, and 30%, respectively. CONCLUSION: Our treatment offers equal oncological results compared to the best internationally published results for dCRT for CEC. Results vary considerably between dCRT studies. Morbidity appears more pronounced following surgery. Future studies are warranted to investigate the Danish national outcomes following dCRT as first-line treatment for curable locally advanced CEC.

Local Pressure Drives Low-Density Lipoprotein Accumulation and Coronary Atherosclerosis in Hypertensive Minipigs.

BACKGROUND: The mechanisms by which hypertension accelerates coronary artery disease are poorly understood. Patients with hypertension often have confounding humoral changes, and to date, no experimental models have allowed analysis of the isolated effect of pressure on atherosclerosis in a setting that recapitulates the dimensions and biomechanics of human coronary arteries. OBJECTIVES: This study sought to analyze the effect of pressure on coronary atherosclerosis and explore the underlying mechanisms. METHODS: Using inflatable suprarenal aortic cuffs, we increased mean arterial pressure by >30 mm Hg in the cephalad body part of wild-type and hypercholesterolemic proprotein convertase subtilisin kexin type 9 (PCSK9)D374Y Yucatan minipigs for >1 year. Caudal pressures remained normal. RESULTS: Under hypercholesterolemic conditions in PCSK9D374Y transgenic minipigs, cephalad hypertension accelerated coronary atherosclerosis to almost 5-fold with consistent development of fibroatheromas that were sufficiently large to cause stenosis on computed tomography angiography. This was caused by local pressure forces, because vascular beds shielded from hypertension, but exposed to the same humoral factors, showed no changes in lesion formation. The same experiment was conducted under normocholesterolemic conditions in wild-type minipigs to examine the underlying mechanisms. Hypertension produced clear changes in the arterial proteome with increased abundance of mechanical strength proteins and reduced levels of infiltrating plasma macromolecules. This was paralleled by increased smooth muscle cells and increased intimal accumulation of low-density lipoproteins in the coronary arteries. CONCLUSIONS: Increased pressure per se facilitates coronary atherosclerosis. Our data indicate that restructuring of the artery to match increased tensile forces in hypertension alters the passage of macromolecules and leads to increased intimal accumulation of low-density lipoproteins.

Long-term outcome of peroral endoscopic myotomy for esophageal achalasia in patients with previous Heller myotomy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging procedure in the treatment of esophageal achalasia, a primary motility disorder. However, the long-term outcome of POEM in patients, who have previously undergone a Heller myotomy, is unknown. METHODS: Using a local database, we identified patients with esophageal achalasia, who underwent POEM. We compared patients with a previous Heller myotomy to those, who had received none or only non-surgical therapy prior to the POEM procedure. We conducted follow-up examinations at 3, 12, and 24 months following the procedure. RESULTS: We included 66 consecutive patients undergoing POEM for achalasia, of which 14 (21.2 %) had undergone a prior Heller myotomy. In both groups, the preoperative Eckardt score was 7. Postoperatively, the non-Heller group experienced a more pronounced symptom relief at both 3-, 12-, and 24-month follow-up compared with the Heller group, and there was a tendency for the effect of POEM to reduce over time. We suggest that there is a correlation between preoperative measurements of gastroesophageal sphincter pressures and the chance of a successful POEM. CONCLUSIONS: POEM has a place in the treatment of esophageal achalasia in patients with a prior Heller myotomy and persistent symptoms as it is a safe procedure with acceptable long-term results.

More patients should undergo surgery after sigmoid volvulus.

AIM: To assess the outcome of patients treated conservatively vs surgically during their first admission for sigmoid volvulus. METHODS: We conducted a retrospective study of 61 patients admitted to Aarhus University Hospital in Denmark between 1996 and 2011 for their first incidence of sigmoid volvulus. The condition was diagnosed by radiography, sigmoidoscopy or surgery. Patients treated with surgery underwent either a sigmoid resection or a percutaneous endoscopic colostomy (PEC). Conservatively treated patients were managed without surgery. Data was recorded into a Microsoft Access database and calculations were performed with Microsoft Excel. Kaplan-Meier plotting and Mantel-Cox (log-rank) testing were performed using GraphPad Prism software. Mortality was defined as death within 30 d after intervention or surgery. RESULTS: Among the total 61 patients, 4 underwent emergency surgery, 55 underwent endoscopy, 1 experienced resolution of the volvulus after contrast enema, and 1 died without treatment because of large bowel perforation. Following emergency treatment, 28 patients underwent sigmoid resection (semi-elective n = 18; elective n = 10). Two patients who were unfit for surgery underwent PEC and both died, 1 after 36 d and the other after 9 mo, respectively. The remaining 26 patients were managed conservatively without sigmoid resection. Patients treated conservatively on their first admission had a poorer survival rate than patients treated surgically on their first admission (95%CI: 3.67-14.37, P = 0.036). Sixty-three percent of the 26 conservatively treated patients had not experienced a recurrence 3 mo after treatment, but that number dropped to 24% 2 years after treatment. Eight of the 14 patients with recurrence after conservative treatment had surgery with no 30-d mortality. CONCLUSION: Surgically-treated sigmoid volvulus patients had a higher long-term survival rate than conservatively managed patients, indicating a benefit of surgical resection or PEC insertion if feasible.

Internal gallbladder drainage prevents development of acute cholecystitis in a pig model: a randomized study.

BACKGROUND: Acute cholecystitis can be the result of retention of bile in the gallbladder with possible secondary infection and ischaemia. The aim of the present study was to investigate whether internal drainage of the gallbladder could protect against the development of acute cholecystitis in a pig model. MATERIALS AND METHODS: Twenty pigs were randomized to either internal drainage (drained) or not (undrained). Day 0 acute cholecystitis was induced by ligation of the cystic artery and duct together with inoculation of bacteria. Four days later the pigs were killed and the gallbladders were removed and histologically scored for the presence of cholecystitis. Bile and blood samples were collected for bacterial culturing and biochemical analyses. RESULTS: The histological examination demonstrated statistical significant differences in acute cholecystitis development between groups, the degree of inflammation being highest in undrained pigs. There were no differences in bacterial cultures between the two groups. CONCLUSION: Internal drainage of the gallbladder protected against the development of acute cholecystitis in the present pig model. These findings support the theory that gallstone impaction of the cystic duct plays a crucial role as a pathogenetic mechanism in the development of acute cholecystitis and suggest that internal drainage may be a way to prevent and treat acute cholecystitis.

Accurate microfour-point probe sheet resistance measurements on small samples.

We show that accurate sheet resistance measurements on small samples may be performed using microfour-point probes without applying correction factors. Using dual configuration measurements, the sheet resistance may be extracted with high accuracy when the microfour-point probes are in proximity of a mirror plane on small samples with dimensions of a few times the probe pitch. We calculate theoretically the size of the "sweet spot," where sufficiently accurate sheet resistances result and show that even for very small samples it is feasible to do correction free extraction of the sheet resistance with sufficient accuracy. As an example, the sheet resistance of a 40 microm (50 microm) square sample may be characterized with an accuracy of 0.3% (0.1%) using a 10 microm pitch microfour-point probe and assuming a probe alignment accuracy of +/-2.5 microm.

Outcome of site-specific fascia repair for rectocele.

BACKGROUND: This article presents the anatomic and functional outcome of site-specific fascia repair for rectocele performed under local anesthesia. Methods. In this case series, 51 consecutive patients underwent site-specific rectocele repair under local anesthesia. Patients were subsequently reviewed in the outpatient clinic. RESULTS: The mean follow-up period was 26.7 months. Pelvic examination revealed recurrence of posterior vaginal wall prolapse in 31% (16/51). Improvement in emptying the rectum was achieved in 23% (7/30), and 23% (7/30) were relieved from constipation. One patient developed de novo dyspareunia. Some 92% of the patients (47/51) would recommend local anesthesia. CONCLUSIONS: Anatomic correction of posterior vaginal wall prolapse does not guarantee alleviation of all symptoms, especially those regarding defecation; however, postoperative dyspareunia levels are low. The use of local anesthesia is associated with high patient satisfaction. Patients should be informed that total recovery from accompanying subjective symptoms cannot be guaranteed.

Reversibility of central neuronal changes in patients recovering from gallbladder stones or acute cholecystitis.

AIM: To investigate the referred pain area in patients 2-7 years after cholecystectomy in order to test the hypothesis that neuroplastic changes could give rise to post cholecystectomy pain. METHODS: Forty patients were tested. Twenty five were cholecystectomized due to uncomplicated gallbladder stones and 15 because of acute cholecystitis. Sensitivity to pinprick, heat, cold, pressure and single and repeated electrical stimulation was studied both in the referred pain area and in the control area on the contra lateral side of the abdomen. RESULTS: Five patients still intermittently suffered from pain. But in the objective test of the 40 patients, no statistical significant difference was found between the referred pain area and the control area. CONCLUSION: This study does not support the hypothesis that de novo neuroplastic changes could develop several years after cholecys-tectomy.