Randomized controlled trial of nasogastric tube use after esophagectomy: study protocol for the kinetic trial.

Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.

Outcome after stent and endoscopic vacuum therapy-based treatment for postemetic esophageal rupture.

OBJECTIVES: Extent of surgical repair of spontaneous esophageal effort rupture (Boerhaave syndrome) has gradually decreased by the emergence of minimal invasive treatment based on endoscopic stent sealing of the perforation. However, for this diagnosis, use of endoscopic vacuum therapy (EVT) is still in its beginning. We present our results after 7-years with both stent and/or EVT-based treatment. MATERIALS AND METHODS: 17 consecutive patients with Boerhaave syndrome from June 2015 to May 2022 were retrospectively registered in a database. The perforation was sealed by stent and/or EVT, and gastric effluent was drained transthoracically by a chest tube or pigtail catheter. Eight out of 14 patients responded to questions on fatigue and dysphagia (Ogilvie's score). RESULTS: Seventeen patients aged median 67 years (range 34-88), had a primary hospital stay of 38 days (7-68). Ninety-day mortality was 6% (n = 1). Perforations were sealed with stent (n = 10), EVT (n = 3) or stent and EVT (n = 4). One patient (6%) needed laparoscopic lavage and transhiatal drainage. Eight patients (47%) were re-stented due to persistent leakage (n = 4) and stent migration (n = 4). Fifteen patients (88%) had complications, including multi-organ failure (n = 9), pleural empyema (n = 8) and esophageal stricture (n = 3). The perforations healed. After 35.5 months (range 2-62) fourteen patients were alive. Eight that responded had no dysphagia and total fatigue score comparable to an age-matched reference population. CONCLUSION: Mortality rate was low after initial stent and EVT-based treatment of Boerhaave syndrome, combined with adequate transthoracic drainage of gastric effluent. Patients required repeated minimal invasive procedures, but with no apparent negative effect on functional outcome.

Early experience with total robotic D2 gastrectomy in a low incidence region: surgical perspectives.

BACKGROUND: Few European centers have reported on robotic gastrectomy for malignancy. We report our early experience with curative-intent total robotic gastrectomy. MATERIALS AND METHODS: The Intuitive Surgery Da Vinci Surgical System Xi 4 armed robot was used. Routine D2 lymphadenectomy was applied. RESULTS: Some 27 patients with adenocarcinoma (n = 18), hereditary cancer susceptibility (n = 8) and premalignancy (n = 1) were allocated to robotic gastrectomy, three were excluded due to inoperability during surgery. Median (range) age was 66 (18-87) years, 14 (58.3%) were females and body mass index was 25.5 (22.1-33.5) kg/m2. Total gastrectomy was performed in 19 (79.2%) and subtotal in five (20.8%) patients. One (4.2%) procedure was converted to laparotomy. Procedural time was 273 (195-427) minutes. Three (12.5%) patients were reoperated within 30 days, one (4.2%) died. Serious complications (Clavien Dindo IIIb or more) occurred in three (12.5%) patients. Postoperative hospital stay was 10 (6-43) days. Fourteen of 16 (87.5%) patients with adenocarcinoma/premalignancy received radical resections. The median number of harvested lymph nodes was 20 (11-34). Eleven (73.3%) patients with adenocarcinoma had T3/T4 tumors and 6 (40%) had TNM stage III or more. CONCLUSION: Total robotic D2 gastrectomy appears feasible and safe during early introduction in a low incidence region.

Short- and long-term outcomes in patients operated with total minimally invasive esophagectomy for esophageal cancer.

At our hospital, the main treatment for resectable esophageal cancer (EC) has since 2013 been total minimally invasive esophagectomy (TMIE). The aim of this study was to present the short- and long-term results in patients operated with TMIE. This cross-sectional study includes all patients scheduled for TMIE from June 2013 to January 2016 at Oslo University Hospital. Data on morbidity, mortality, and survival were retrospectively collected from the patient administration system and the Norwegian Cause of Death Registry. Long-term postoperative health-related quality of life (HRQL) and level of dysphagia were assessed by patients completing the following questionaries: EORTC QLQ-OG25, QLQ-C30, and the Ogilvie grading scale. A total of 123 patients were included in this study with a median follow-up time of 58 months (1-88 months). 85% had adenocarcinoma, 15% squamous cell carcinoma. Seventeen patients (14%) had T1N0M0, 68 (55%) T2-T3N0M0, or T1-T2N1M0 and 38 (31%) had either T3N1M0 or T4anyNM0. Ninety-eight patients (80%) received neoadjuvant (radio)chemotherapy and 104 (85%) had R0 resection. Anastomotic leak rate and 90-days mortality were 14% and 2%, respectively. The 5-year overall survival was 53%. Patients with tumor free resection margins of >1 mm (R0) had a 5-year survival of 57%. Median 60 months (range 49-80) postoperatively the main symptoms reducing HRQL were anxiety, chough, insomnia, and reflux. Median Ogilvie score was 0 (0-1). In this study, we report relatively low mortality and good overall survival after TMIE for EC. Moreover, key symptoms reducing long-term HRQL were identified.

Gastric adenocarcinoma and proximal polyposis of the stomach ­ a rare form of hereditary gastric cancer. / Gastrisk adenokarsinom og proksimal ventrikkelpolypose ­ en sjelden form for arvelig magesekkreft.

Hereditary ventricular polyposis in the form of gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare condition characterised by a typical distribution of polyps in the stomach and risk of gastric cancer at a young age. Prophylactic gastrectomy may be indicated. The condition is not thought to be associated with increased risk of colon cancer, but the evidence base is limited.

Laparascopic resection for gastric cancer at Oslo University Hospital, Ullevål 2015­18. / Laparoskopisk reseksjon av ventrikkelcancer ved Oslo universitetssykehus, Ullevål 2015­18.

BACKGROUND: We wished to assess our experiences with laparoscopy used in curative resection for gastric cancer. MATERIAL AND METHOD: All patients with gastric cancer who underwent curative-intent surgery, irrespective of access, in the period 1 May 2015-28 February 2018 at Oslo University Hospital Ullevål were included. The patient care pathway and oncological results were registered continuously and analysed retrospectively. RESULTS: A total of 93 patients underwent surgery, 48 of whom were women. Median age was 73 (32-89) years, and 16 patients were 80 years of age or above. The duration of the procedure was 265 (125-644) minutes. Altogether seven patients underwent laparotomy, one was planned and six were converted to open surgery. Standardised lymph node dissection was performed in 88 patients. Complications were recorded in 48 patients, of which 11 were serious. A total of six patients had anastomotic leakage. Three died within 30 days/during hospitalisation. Postoperative hospitalisation was 12 (5-78) days. A total of 86 patients underwent radical surgery, five had tumour infiltration in the resection margins, and two had indeterminate resection status. The median number of lymph nodes identified was 18 (0-53). Tumours were locally advanced in 56 patients. INTERPRETATION: Laparoscopic gastric resection with standardised lymph node dissection can be performed in most patients with gastric cancer who undergo curative-intent surgery. The method has become standard in our department.

Human monocyte responses to lipopolysaccharide and 9-cis retinoic acid after laparoscopic surgery for colon cancer.

Surgery, even modern minimal invasive laparoscopic surgery, induces an initial inflammatory and acute phase response which is followed by a period of immunosuppression rendering surgical patients more susceptible to infection. Here, we aimed to study changes in monocyte inflammatory responses and inflammatory modulation mechanisms following laparoscopic colorectal surgery for colon cancer. Blood samples were collected from 19 colon cancer patients before, directly after and daily for 3 days following surgery. Blood cells were exposed ex vivo to bacterial lipopolysaccharide (LPS) or the inflammatory modulator 9-cis retinoic acid (9cisRA). In blood samples taken prior to surgery, we found significant pro-inflammatory responses to LPS, indicating classical monocyte activation. Directly after surgery, LPS induced significantly less early pro-inflammatory cytokines and monocyte/granulocyte-attracting chemokines. The LPS-mediated release of interleukin (IL)-1ß was still significantly attenuated 3 days after surgery. In patient monocytes collected after surgery, we found increased levels of suppressors of cytokine signaling (SOCS)1 and SOCS3 mRNA, reported to be associated with polarization towards resolving macrophages. The retinoic acid isomer 9cisRA, reported to attenuate LPS-mediated inflammatory responses and alter chemokine responses in cultured monocytes, had a similar effect in patient blood. Three days after surgery, 9cisRA still attenuated pro-inflammatory responses, but the induction of monocyte chemoattractive protein (MCP)-1/CCL2 mRNA in monocytes was reduced. This study indicates changes in monocyte responses that last for at least 3 days after laparoscopic surgery.

Effect of AndoSan™ on expression of adhesion molecules and production of reactive oxygen species in human monocytes and granulocytes in vivo.

BACKGROUND: Oral intake (60 ml daily) over 12 days in eight healthy volunteers of an immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM (AndoSan™)), reduced the monocyte and granulocyte release of mainly proinflammatory cytokines in vivo, suggesting an anti-inflammatory effect. In this foremost in vivo study, the aim was to examine the effect of such AndoSan™ consumption on the expression of adhesion molecules CD11b, CD11c and CD62L and production of reactive oxygen species (ROS) in leukocytes. METHODOLOGY/PRINCIPAL FINDINGS: As shown by flow cytometry, there was a significant increase of CD62L expression on monocytes and granulocytes from before (day 0) compared with 12 days after daily AndoSan™ consumption. However, only minor alterations and no clear trend in the expression of CD11b and CD11c were detected. Intracellular ROS (mainly superoxide ion) were significantly reduced in these cells from days 0 to 12. CONCLUSIONS/SIGNIFICANCE: These results support that oral intake of AndoSan™ exhibits an anti-inflammatory effect in humans in vivo.