Long-Term Health-Related Quality of Life (HRQoL) After Redo-Fundoplication.

BACKGROUND: We aim to shed light on long-term subjective outcomes after re-operations for failed fundoplication. METHODS: 1809 patients were operated on for hiatal hernia and/or gastroesophageal reflux disease (GERD) at the Helsinki University Hospital between 2000 and 2017. 111 (6%) of these had undergone a re-operation for a failed antireflux operation. Overall, HRQoL was assessed in 89 patients at the latest follow-up using the generic 15D© instrument. The results were compared to a sample of the general population, weighted to reflect the age and gender distribution of patients. Disease-specific HRQoL was assessed using the GERD-HRQoL questionnaire. We studied variation in the overall HRQoL with respect to disease-specific HRQoL and known patients' parameters using univariate and multivariable linear regression models. RESULTS: The median postoperative follow-up period was 9.3 years. All patients were operated on laparoscopically (6% conversion rate), and 87% were satisfied with the re-operation. Postoperative complications were minimal (5%). Twelve patients (11%) underwent a second re-operation. The median GERD-HRQoL score was nine. In multivariable analysis, four variables were independently associated with the 15D score, suggesting a decrease in the 15D score with increasing GERD-HRQoL score, increasing Charlson Comorbidity Index (CCI) and the presence of chronic pain syndrome (CPS) and depression. CONCLUSION: Re-do LF is a safe procedure in experienced hands and may offer acceptable long-term alleviation in patients with recurring symptoms after antireflux surgery. Decreased HRQoL in the long run is related to recurring GERD and co-morbidities.

Intraoperative colonic pulse oximetry in left-sided colorectal surgery: can it predict anastomotic leak?

BACKGROUND: An anastomotic leak is a fairly common and a potentially lethal complication in colorectal surgery. Objective methods to assess the viability and blood circulation of the anastomosis could help in preventing leaks. Intraoperative pulse oximetry is a cheap, easy to use, fast, and readily available method to assess tissue viability. Our aim was to study whether intraoperative pulse oximetry can predict the development of an anastomotic leak. METHODS: The study was a prospective single-arm study conducted between the years 2005 and 2011 in Helsinki University Hospital. Patient material consisted of 422 patients undergoing elective left-sided colorectal surgery. The patients were operated by one of the three surgeons. All of the operations were partial or total resections of the left side of the colon with a colorectal anastomosis. The intraoperative colonic oxygen saturation was measured with pulse oximetry from the colonic wall, and the values were analyzed with respect to post-operative complications. RESULTS: 2.3 times more operated anastomotic leaks occurred when the colonic StO2 was ≤ 90% (11/129 vs 11/293). The mean colonic StO2 was 91.1 in patients who developed an operated anastomotic leak and 93.0 in patients who did not. With logistic regression analysis, the risk of operated anastomotic leak was 4.2 times higher with StO2 values ≤ 90%. CONCLUSIONS: Low intraoperative colonic StO2 values are associated with the occurrence of anastomotic leak. Despite its handicaps, the method seems to be useful in assessing anastomotic viability.

Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance.

Colorectal cancer (CRC) initiation and growth is often attributed to stem cells, yet little is known about the regulation of these cells. We show here that a subpopulation of Prox1-transcription-factor-expressing cells have stem cell activity in intestinal adenomas, but not in the normal intestine. Using in vivo models and 3D ex vivo organoid cultures of mouse adenomas and human CRC, we found that Prox1 deletion reduced the number of stem cells and cell proliferation and decreased intestinal tumor growth via induction of annexin A1 and reduction of the actin-binding protein filamin A, which has been implicated as a prognostic marker in CRC. Loss of Prox1 also decreased autophagy and the survival of hypoxic tumor cells in tumor transplants. Thus, Prox1 is essential for the expansion of the stem cell pool in intestinal adenomas and CRC without being critical for the normal functions of the gut.

Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-ß.

In the majority of microsatellite-stable colorectal cancers (CRCs), an initiating mutation occurs in the adenomatous polyposis coli (APC) or ß-catenin gene, activating the ß-catenin/TCF pathway. The progression of resulting adenomas is associated with oncogenic activation of KRas and inactivation of the p53 and TGF-ß/Smad functions. Most established CRC cell lines contain mutations in the TGF-ß/Smad pathway, but little is known about the function of TGF-ß in the early phases of intestinal tumorigenesis. We used mouse and human ex vivo 3D intestinal organoid cultures and in vivo mouse models to study the effect of TGF-ß on the Lgr5(+) intestinal stem cells and their progeny in intestinal adenomas. We found that the TGF-ß-induced apoptosis in Apc-mutant organoids, including the Lgr5(+) stem cells, was mediated by up-regulation of the BH3-only proapoptotic protein Bcl-2-like protein 11 (Bim). BH3-mimetic compounds recapitulated the effect of Bim not only in the adenomas but also in human CRC organoids that had lost responsiveness to TGF-ß-induced apoptosis. However, wild-type intestinal crypts were markedly less sensitive to TGF-ß than Apc-mutant adenomas, whereas the KRas oncogene increased resistance to TGF-ß via the activation of the Erk1/2 kinase pathway, leading to Bim down-regulation. Our studies identify Bim as a critical mediator of TGF-ß-induced apoptosis in intestinal adenomas and show that the common progression mutations modify Bim levels and sensitivity to TGF-ß during intestinal adenoma development.

Epidural analgesia diminished pain but did not otherwise improve enhanced recovery after laparoscopic sigmoidectomy: a prospective randomized study.

BACKGROUND: The primary hypothesis for this study was that epidural analgesia reduces the use of opioids and thus advances bowel function and oral intake and shortens hospital stay after laparoscopic sigmoidectomy performed according to principles of enhanced recovery after surgery. METHODS: For this study, 60 patients with complicated diverticular disease were randomized to the epidural anesthesia group or the control group before surgery. Postoperative oxycodone consumption, pain, and recovery parameters were followed for 14 days. RESULTS: The epidural group needed less oxycodone than the control group until 12 h postoperatively. They experienced significantly less pain related to coughing and motion until postoperative day 2. In the epidural group, fewer patients experienced significant pain, and the duration of postoperative pain was shorter. Postoperative oral intake, bowel function, hospital stay, and overall complication rate were similar in the two groups. However, the control group had more postoperative hematomas. CONCLUSIONS: Epidural analgesia significantly alleviates pain, reducing the need for opioids during the first 48 h after laparoscopic sigmoidectomy. However, epidural analgesia does not alter postoperative oral intake, mobilization, or length of hospital stay.

Is the learning curve for laparoscopic fundoplication determined by the teacher or the pupil?

BACKGROUND: For all surgical procedures, a surgeons' learning curve can be anticipated during which complication rates are increased. The aims of this study were to evaluate individual learning curves for a group of surgeons performing laparoscopic fundoplication and to evaluate if the Procedicus MIST-simulator (Mentice Inc., Göteborg, Sweden) accurately predicts surgical performance. METHODS: Twelve Nordic centers participated, each contributing with a "master" and a "pupil" surgeon. The pupils were tested in the simulator and thereafter performed their first 20 supervised operations. All procedures were videotaped and evaluated by 3 independent reviewers. RESULTS: A significant decrease in operative time (P <0.001) and a trend (P = 0.12) toward improved score were seen during the series. The master significantly affected the pupil's score (P =0.0137). The simulator-test showed no correlation with the operative score. CONCLUSIONS: Individual learning curves varied, and the teacher was shown to be the most important factor influencing the pupil's performance score. The correlation between assessed performance and patient outcome will be further investigated.