Auswahl der wissenschaftlichen Literatur zum Thema „Anastomotický leak“

Background: Intestinal anastomosis is one of the most commonly performed procedures, especially in the emergency setting and is also in the elective setting when resection is carried out for benign or malignant lesion of the gastrointestinal tract. Anastomotic leakage is a potentially disastrous complication, which can lead to sepsis and abdominal catastrophe. The aim of the study is to determine factors leading to post-operative leaks in gastrointestinal surgeries involving different kinds of anastomosis and to determine the role of parameters such as pre-operative hemoglobin, serum albumin, indication for surgery, degree of contamination, type of anastomosis, technical variations and postoperative management in anastomotic leaks. We also aim to determine the morbidity and mortality variation and to study the various presentations of anastomotic leak in the patient group as well.Methods: A prospective study was conducted from December 2015 till the end of august 2017 at Prathima Institute of Medical Sciences, Karimnagar. All patients undergoing gastrointestinal anastomosis electively and as an emergency procedure were included in this study. The total number of cases studied is 60.Results: Out of the 60 cases in this study, 49 cases were done electively, and 11 cases were done on an emergency basis. Anastomotic leaks occurred most in emergency cases (27.27%). Among 5 patients, (71.42%) leaks were managed conservatively and rest required intervention. There was increased death rate in patients with leak. Leaks occurred maximum in jejunoileal anastomosis. Most common organ involved was esophagus (28.57%).Conclusions: Anastomotic leaks are a common complication following all types of gastrointestinal anastomosis. It is believed, hypoalbuminemia hinders anastomotic healing. Surgeries indicated in emergency situation carried increased risk of operative leaks in post-operative period.

National hospital registries only report colorectal anastomotic leaks (ALs) within 30 days post-operatively. The aim of our study was to determine the incidence and significance of ALs that occur beyond 30 days postoperatively. We performed a retrospective review of our prospective database from June 2008 to August 2012. A total of 504 patients were included. These patients were operated on by two surgeons. Any clinical or radiographic abnormalities were considered to be an anastomotic imperfection. A total of 504 patients were reviewed with a total of 18 (3.6%) anastomotic leaks. Six leaks (31.6% of leaks) were diagnosed more than 30 days postoperatively ( P < 0.001). Of the 18 leaks, interventional radiology drainage was performed for four cases and 14 patients required reoperation. All six delayed leaks required reoperation. There was one leak that occurred under 30 days, which was discovered on autopsy. The median follow-up was 12 months (range, 1 to 4 months). All the delayed leak patients presented with fistulas, whereas 58 per cent of typical leak patients presented with the triad of leukocytosis, fever, and abdominal pain. Colorectal anastomotic leaks can occur after the 30-day postoperative period. In patients with vague and atypical abdominal findings, anastomotic leak must be suspected. More systematic, prospective studies are required to help us further understand the risk factors and natural history of anastomotic failures in elective colorectal surgery.

Abstract Background Anastomotic leak after esophagectomy is associated with high levels of morbidity and may impact negatively on oncological outcomes. The aim of this single centre study was to describe our experience in managing these complications Methods From 2007–2017 data was reviewed retrospectively from our prospectively maintained electronic database. All patients underwent either 2 or 3 phase esophagectomy for cancer of the oesophagus or esophago-gastric junction. All histological sub-types and stage of cancer were included in the analysis. Anastomotic leaks were classified according to the Esophagectomy Complications Consensus Group (ECCG) guidelines; type I—conservative management, type II—non-surgical intervention, type III—surgical intervention. Results 224 esophagectomies were included in our analysis (104 (46%) minimally invasive, 120 (54%) open approach). The incidence of all anastomotic leaks was 10% (23/224). Surgical approach did not influence the incidence of anastomotic leak (minimally invasive 10 (43%), open approach 13(57%), P = 0.76). Five patients (22%) had a type I leak, 9 patients (39%) type II and 9 (39%) had a type III leak. There was an increase in the number of leaks managed non-surgically over the last 5 years compared to those in the first five years of our dataset (2012–2017: 11/23 (48%) vs 2007–2012: 4/23 (17%) P = 0.08). The median time for leak diagnosis was 8 days. Most leaks were diagnosed with oral contrast CT 19 (83%). Median hospital stay after anastomotic leak was 58.5 days. Type III leaks were associated with an increased length of stay (median 84 days) compared to type I&II leaks (median (38.5 days) (P = 0.002 95% CI 18.19- 74.41). There was no significant difference in 30-day mortality between type I&II (0 patients) and type III leaks (1 patient) P = 0.260. Conclusion Low mortality rates with anastomotic leak can be achieved. In centres with experienced radiological and endoscopic skills, most anastomotic leaks can be managed non-surgically. Disclosure All authors have declared no conflicts of interest.

Introduction. Colorectal anastomotic leak or stricture is a dreaded complication leading to significant morbidity and mortality. The novel use of self-expandable metal stents (SEMS) in the management of postoperative colorectal anastomotic leaks or strictures can avoid surgical reintervention. Methods. Retrospective study with particular attention to the indications, operative or postoperative complications, and clinical outcomes of SEMS placement for patients with either a colorectal anastomotic stricture or leak. Results. Eight patients had SEMS (WallFlex stent) for the management of postoperative colorectal anastomotic leak or stricture. Five had a colorectal anastomotic stricture and 3 had a colorectal anastomotic leak. Complete resolution of the anastomotic stricture or leak was achieved in all patients. Three had recurrence of the anastomotic stricture on 3-month flexible sigmoidoscopy follow-up after the initial stent was removed. Two of these patients had a stricture that was technically too difficult to place another stent. Stent migration was noted in 2 patients, one at day 3 and the other at day 14 after stent placement that required a larger 23 mm stent to be placed. Conclusions. The use of SEMS in the management of colorectal anastomotic leaks or strictures is feasible and is associated with high technical and clinical success rate.

Introduction Anastomotic leak is a dreaded complication following esophagectomy. Conventional management for leaks includes invasive reoperation and even gastrointestinal diversion. Objective The aim of this study was to examine our contemporary outcome of using endoscopic esophageal stenting as primary therapy for management of anastomotic leak following minimally invasive esophagectomy (MIE). Methods We reviewed data on 11 patients who developed an esophageal leak following 111 MIE between January 2011 and December 2019. Of the 11 anastomotic leaks, 10 patients had an anastomotic disruption and underwent endoscopic esophageal stenting as primary therapy for management of leaks, while 1 patient had an anastomotic disruption complicated by an associated tracheoesophageal fistula that required surgical reoperation and subsequent colonic interposition. Main outcome measures focused on the 10 patients who were managed with endoscopic stenting, including length of hospital stay following leak management, need for thoracotomy or gastrointestinal diversion for leak, stent complications, and leak-associated mortality. Results Of the 10 patients who underwent endoscopic esophageal stenting as primary therapy for management of leaks, there were 8 males with a median age of 66 years. The median time to diagnosis of anastomotic leak was 10 days postoperatively. One of the ten patients also underwent percutaneous drain placement, while none of the patients required thoracotomy. Median duration of stent placement was 39 (range, 29-105) days. Median length of stay after stent placement was 10 (range, 4-43) days. The median number of stent exchange was 1 (range, 1-3) stent. Gastrointestinal continuity was maintained in all patients. The 90-day leak-associated mortality was 9.1% (1 of 11 patients). Conclusions Endoscopic stenting is an effective primary therapy in the management of postesophagectomy leak and avoids the need for an invasive, reoperative thoracotomy or gastrointestinal diversion procedure.

Introduction: Postoperative anastomotic leak after rectal resection is a life-threatening complication. Late diagnosis and a severe symptomatic leak may cause almost 18 % mortality. Early diagnosis is a challenging issue because of nonspecific clinical signs in the early postoperative period. Minimally invasive rectal surgery and the implementation of ERAS protocol require appropriate markers of inflammatory complications and leak with high sensitivity. Postoperative serum C-reactive protein values seem to be the right answer for this question. Aim: The presented study aimed to determine the importance and cut-off level of serum C-reactive protein as a possible predictive factor for early anastomotic leak diagnosis in rectal surgery. Material and methods: The retrospective observational analysis of patients after resection for rectal cancer in a period of one year. The observation included risk factors (age, sex, BMI, bowel preparation and the acuteness of surgery), recording of complications and serum values of CRP. Results: The study included 178 patients. 63 patients (35,4 %) had non-complicated postoperative course. The complications were present in 115 cases (64,6 %), including surgical site infection (16,3 %) and anastomotic leak (7,3 %). The mortality was 2,2 %. CRP serum value reached the sensitivity 94,7 % and specificity 72,5 % at POD 4 with cut off value of 131,8 mg/l and the sensitivity of 84,2 % and specificity 82,4 % with cut off 175,4 mg/l, respectively. Conclusions: Postoperative serum C-reactive protein may be used as a predictor of anastomotic leakage. The examination of CRP on the 4th postoperative day may lead to early and safe discharge from the hospital after rectal resection. The implementation of the cut off values detects more than 90 % of anastomotic leaks or septic complications.

Introduction Early detection and treatment of anastomotic leak may mitigate its consequences. Within an enhanced recovery setting, the subtle signs of a leak can be more apparent. There are multiple treatment options for anastomotic leak following anterior resection. This study aimed to determine when leaks are diagnosed in enhanced recovery, and whether the choice of intervention affects outcomes. Materials and methods We conducted a retrospective study of a prospectively maintained database of complications of anterior resections for rectal cancer in a district general hospital in the UK. Data were extracted on day of leak diagnosis, length of stay, intensive care admission, mortality and ileostomy reversal rate. Statistical analysis was performed using Student’s t, Mann–Whitney U and chi square tests. Results A total of 323 patients underwent anterior resection for colorectal cancer between 1 January 2007 and 1 October 2015. The leak rate was 10.8% (35/323). Patients were diagnosed in hospital with leaks on median day 4 compared with day 11 for patients diagnosed with leaks after readmission from home (P < 0.001). Defunctioned patients diagnosed with a leak had a longer median length of stay (24 vs 18.0 days, P = 0.31) but were more frequently managed non-operatively (100% vs 19.0%, P < 0.001) and had a lower admission rate to intensive care (9.5% vs 42.9%, P = 0.02) than patients who were not defunctioned at time of resection. Overall mortality from anastomotic leak was 2.9% (1/35). Ileostomies were reversed in 73.5% of patients (25/34). Discussion Enhanced recovery enables early diagnosis of leaks following anterior resection. Defunctioning of patients with anastomotic leak lowers mortality.

Background: Most anastomotic leaks after surgical resection for esophageal or esophagogastric junction malignancies are treated endoscopically with esophageal stents. Internal drainage by double pigtail stents has been used for the endoscopic management of leaks following bariatric surgery, and recently introduced for anastomotic leaks after resections for malignancies. Our aim was to assess the overall efficacy of the endoscopic treatment for anastomotic leaks after esophageal or gastric resection for malignancies. Methods: We conducted a multicenter retrospective study in four digestive endoscopy tertiary referral centers in France. We included consecutive patients managed endoscopically for anastomotic leak following esophagectomy or gastrectomy for malignancies between January 2016 and December 2018. The primary outcome was the efficacy of the endoscopic management on leak closure. Results: Sixty-eight patients were included, among which 46 men and 22 women, with a mean ± SD age of 61 ± 11 years. Forty-four percent had an Ivor Lewis procedure, 16% a tri-incisional esophagectomy, and 40% a total gastrectomy. The median time between surgery and the diagnosis of leak was 9 (6–13) days. Endoscopic treatment was successful in 90% of the patients. The efficacy of internal drainage and esophageal stents was 95% and 77%, respectively ( p = 0.06). The mortality rate was 3%. The only predictive factor of successful endoscopic treatment was the initial use of internal drainage ( p = 0.002). Conclusion: Endoscopic management of early postoperative leak is successful in 90% of patients, preventing highly morbid surgical revisions. Internal endoscopic drainage should be considered as the first-line endoscopic treatment of anastomotic fistulas whenever technically feasible.

Anastomotic leak is a catastrophic surgical complication leading to high morbidity, mortality and cancer recurrence. Currently detection is difficult, with a paucity of available diagnostic tests that have variable sensitivity and specificity. The work described in this thesis evaluated the use of local biomarkers within the anastomotic environment coupled with a biosensor application to assess proof-of-concept feasibility as a point-of-care diagnostic tool for anastomotic leak. Using a small animal model of caecal ligation and puncture to replicate abdominal sepsis, local abdominal biomarkers lactate, TNFα, and E. coli were all found to significantly increase compared to sham control models at 24 and 36 hours. Chronoamperometry and electrochemical impedance spectroscopy (EIS) interrogation of biosensors were then used to detect and quantitate levels of these respective biomarkers in real patient samples, and data compared to that obtained by existing commercial assays to evaluate accuracy. Characterisation of each biosensor utilised cyclic voltammetry, SEM, Midland blotting, SDS-PAGE and dot blotting techniques to optimise the fabrication methodology. The lactate biosensor consisted of a pre-impregnated Prussian Blue carbon electrode with lactate oxidase enzyme immobilised onto the surface via polyethyleneimine. Using chronoamperometry, the lactate biosensor gave significantly similar results to a commercial enzyme-based lactate colorimetric assay in ten abdominal fluid patient samples. E. coli immunosensors were constructed using a polytyramine matrix onto which half polyclonal antibody fragments raised against multiple strains of E. coli were immobilised. EIS was used to measure the charge transfer resistance of the biosensors when incubated with a varying concentration of E. coli, with a limit of detection found to be 104 cells ml-1. EIS of E. coli biosensors in the ten patient samples showed statistically significant equivalent results to those from flow cytometry. Immunosensors to TNFα were constructed using a similar methodology to E. coli, with whole antibody to TNFα immobilised onto a polytyramine electrode surface. Initial EIS results in buffered solution showed good biosensor response to varying concentrations of TNFα, but further studies are required for complete biosensor development.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
Esse estudo avaliou as anastomoses colo-cÃlicas sem preparo intestinal comparando com anastomoses realizadas com preparo intestinal prÃvio. Foram utilizados 42 animais (Canis familiares) fÃmeas, pesando entre 8,4 a 16,9 Kg, clinicamente sadios, oriundos do Canil da Prefeitura Municipal de Teresina, PiauÃ. Foram distribuÃdos em 2 grupos de 21 animais: grupo I (controle) â animais submetidos ao preparo intestinal com soluÃÃo glicerinada a 12% via retal 24hs antes do procedimento e grupo II (estudo) â animais submetidos ao procedimento sem preparo intestinal prÃvio. Todos os animais de ambos os grupos foram submetidos à laparotomia com secÃÃo do cÃlon descendente e anastomose primÃria com fio de polipropileno e acompanhados no trans e pÃs-operatÃrio por um mÃdico veterinÃrio, sendo a dieta instituÃda quando ocorreu a primeira evacuaÃÃo. Esses animais foram submetidos à eutanÃsia no 21 dia de pÃs-operatÃrio apÃs anestesia venosa com cloridrato de cetamina e aplicaÃÃo de cloreto de potÃssio a 20% endovenosa; realizou-se nova laparotomia e avaliaÃÃo da anastomose colo-cÃlica. Avaliou-se a evoluÃÃo clÃnica, o grau de aderÃncias intestinais e a pressÃo de ruptura da anastomose. Utilizou-se o teste T para amostras nÃo pareadas para dados paramÃtricos e Mann-Whitney test para dados nÃo paramÃtricos. Ocorreu um (4,5%) Ãbito em cada grupo sendo o do grupo I (controle) no 7 dia pÃs-operatÃrio devido à deiscÃncia da anastomose colo-cÃlica e outro no 10 dia de pÃs-operatÃrio no grupo II(estudo) devido à infecÃÃo de sÃtio cirÃrgico incisional profunda com deiscÃncia total da parede abdominal. NÃo foi observado diferenÃa estatisticamente significante no grau de aderÃncias intestinais entre os grupos. Durante a realizaÃÃo do teste de pressÃo de ruptura ocorreu ruptura da anastomose de um animal em cada grupo e nÃo houve diferenÃa estatisticamente significante entre os grupos (p>0,05). A anastomose colo-cÃlica sem preparo intestinal apresentou a mesma seguranÃa e eficÃcia da anastomose realizada com preparo prÃvio.
Esse estudo avaliou as anastomoses colo-cÃlicas sem preparo intestinal comparando com anastomoses realizadas com preparo intestinal prÃvio. Foram utilizados 42 animais (Canis familiares) fÃmeas, pesando entre 8,4 a 16,9 Kg, clinicamente sadios, oriundos do Canil da Prefeitura Municipal de Teresina, PiauÃ. Foram distribuÃdos em 2 grupos de 21 animais: grupo I (controle) â animais submetidos ao preparo intestinal com soluÃÃo glicerinada a 12% via retal 24hs antes do procedimento e grupo II (estudo) â animais submetidos ao procedimento sem preparo intestinal prÃvio. Todos os animais de ambos os grupos foram submetidos à laparotomia com secÃÃo do cÃlon descendente e anastomose primÃria com fio de polipropileno e acompanhados no trans e pÃs-operatÃrio por um mÃdico veterinÃrio, sendo a dieta instituÃda quando ocorreu a primeira evacuaÃÃo. Esses animais foram submetidos à eutanÃsia no 21 dia de pÃs-operatÃrio apÃs anestesia venosa com cloridrato de cetamina e aplicaÃÃo de cloreto de potÃssio a 20% endovenosa; realizou-se nova laparotomia e avaliaÃÃo da anastomose colo-cÃlica. Avaliou-se a evoluÃÃo clÃnica, o grau de aderÃncias intestinais e a pressÃo de ruptura da anastomose. Utilizou-se o teste T para amostras nÃo pareadas para dados paramÃtricos e Mann-Whitney test para dados nÃo paramÃtricos. Ocorreu um (4,5%) Ãbito em cada grupo sendo o do grupo I (controle) no 7 dia pÃs-operatÃrio devido à deiscÃncia da anastomose colo-cÃlica e outro no 10 dia de pÃs-operatÃrio no grupo II(estudo) devido à infecÃÃo de sÃtio cirÃrgico incisional profunda com deiscÃncia total da parede abdominal. NÃo foi observado diferenÃa estatisticamente significante no grau de aderÃncias intestinais entre os grupos. Durante a realizaÃÃo do teste de pressÃo de ruptura ocorreu ruptura da anastomose de um animal em cada grupo e nÃo houve diferenÃa estatisticamente significante entre os grupos (p>0,05). A anastomose colo-cÃlica sem preparo intestinal apresentou a mesma seguranÃa e eficÃcia da anastomose realizada com preparo prÃvio.
The objective of this study was to evaluate the efficacy of colo-colonic anastomosis in dogs with and without preoperative bowel preparation. The experiment included 42 healthy female mongrel dogs (Canis familiaris) weighing 8.4-16.9 Kg, supplied by the municipal dog pound of Teresina, PiauÃ. The animals were distributed at random in two groups of 21 animals each: Group I (control) = submitted to bowel preparation with rectal administration of 12% glycerin solution one day before the procedure, and Group II (study) = without previous bowel preparation. All animals were submitted to laparotomy with sectioning of the descending colon and primary anastomosis using polypropylene thread under the peri and postoperative supervision of a veterinary physician. The animals were allowed access ad libitum to water and standard feed following the first evacuation. On the 21st postoperative day (POD 21), the dogs were euthanized with ketamine i.v. followed by 20% potassium chloride i.v., and a second laparotomy was performed through the same incision in order to evaluate the anstomosis. In addition, the abdominal cavity was evaluated for adhesions and the burst pressure of the anastomosis was tested. The unpaired samples were compared with Studentʼs t test for parametric data and with the Mann-Whitney test for non-parametric data. One animal in each group (4.5%) died. The death in Group I (control) occurred on POD 7 due to anastomotic dehiscence. The death in Group II (study) occurred on POD 10 due to deep incisional infection at the surgical site and complete dehiscence of the abdominal wall. The groups did not differ significantly with regard to adhesion grade or anastomotic burst pressure (one specimen burst in each group) (p>0.05). In conclusion, the level of safety and efficacy was the same for colo-colonic anastomosis with and without previous bowel preparation.
The objective of this study was to evaluate the efficacy of colo-colonic anastomosis in dogs with and without preoperative bowel preparation. The experiment included 42 healthy female mongrel dogs (Canis familiaris) weighing 8.4-16.9 Kg, supplied by the municipal dog pound of Teresina, PiauÃ. The animals were distributed at random in two groups of 21 animals each: Group I (control) = submitted to bowel preparation with rectal administration of 12% glycerin solution one day before the procedure, and Group II (study) = without previous bowel preparation. All animals were submitted to laparotomy with sectioning of the descending colon and primary anastomosis using polypropylene thread under the peri and postoperative supervision of a veterinary physician. The animals were allowed access ad libitum to water and standard feed following the first evacuation. On the 21st postoperative day (POD 21), the dogs were euthanized with ketamine i.v. followed by 20% potassium chloride i.v., and a second laparotomy was performed through the same incision in order to evaluate the anstomosis. In addition, the abdominal cavity was evaluated for adhesions and the burst pressure of the anastomosis was tested. The unpaired samples were compared with Studentʼs t test for parametric data and with the Mann-Whitney test for non-parametric data. One animal in each group (4.5%) died. The death in Group I (control) occurred on POD 7 due to anastomotic dehiscence. The death in Group II (study) occurred on POD 10 due to deep incisional infection at the surgical site and complete dehiscence of the abdominal wall. The groups did not differ significantly with regard to adhesion grade or anastomotic burst pressure (one specimen burst in each group) (p>0.05). In conclusion, the level of safety and efficacy was the same for colo-colonic anastomosis with and without previous bowel preparation.

UVOD: Drenaža grudnog koša nakon resekcija pluća je osnovni grudno hirurški postupak, koji omogućuje proširenje (reekspanziju) pluća iz kolabiranog stanja, evakuaciju vazduha, krvi i izliva iz pleuralnog prostora i potpomognuta je primenom aspiracije na drenove (sukciona ili aspiraciona drenaža). Iako je drenaža  svakodnevna grudno hirurška procedura, postupak sa drenovima je zasnovan prvenstveno na iskustvu, a manje na osnovu naučnih studija. Pri mirnom disanju inspiratorni pritisak u pleuralnom prostoru je prosečno - 8 cm H2O, a ekspiratorni - 4 cm H2O. Pri forsiranom disanju pritisci mogu dostići - 50 cm H2O i +70 cm H2O. Na osnovu tih fizioloških podataka, većina hirurga primenjuje aspiraciju od - 10 do - 40 cm H2O. Koncepta pleuralnog deficita - disproporcije volumena preostalog plućnog tkiva i zapremine grudnog koša doveo je do razvoja tehničkih postupaka za postizanje nove fiziološke ravnoteže u pleuralnom prostoru i razmatranja rutinske primene podvodne (pasivne) drenaže nakon resekcija pluća. Pritisak na zdravstvenu službu za smanjenje troškova i skraćenje postoperativne hospitalizacije uz mogućnost rane mobilizacije pacijenta čine podvodnu drenažu zanimljivom alternativom tradicionalno prihvaćenoj aktivnoj aspiraciji na drenove.  CILJ: Da se utvrdi da li aplikacija aktivne aspiracije na drenove nakon lobektomije pluća u poređenju da podvodnom drenažom ima povoljno terapijsko dejstvo na postizanje i održavanje reekspanzije pluća; Da se kvantitativno uporede različiti modovi aktivne aspiracije preko drenova; Da se uporedi dužina hospitalizacije i pojava hirurških i nehirurških komplikacija između grupa ispitanika kod kojih se primenjuje podvodna (pasivna) drenaža i aspiracija preko drenova. METODOLOGIJA: Prospektivna studija bez randomizacije obuhvatila je 301 ispitanika kojima je načinjena lobektomija pluća zbog karcinoma pluća na Klinici za grudnu hirurgiju Instituta za plućne bolesti Vojvodine u Sremskoj Kamenici u periodu od 01.01.2008. - 28.02.2010. godine. Beleženi su i analizirani podaci o preoperativnom stanju: plućnoj funkciji, prethodno primljenoj neoadjuvantnoj hemioterapiji i pridruženim bolestima. Analizirani su hirurški operativni podaci o postojanju buloznog emfizema, adhezija u pleuralnom prostoru, anatomskoj vrsti lobektomije, dodatnim hirurškim procedurama i postojanju gubitka vazduha na kraju operacije. Analizirani su postoperativni podaci o secernaciji na drenove tokom prva 24 h i ukupno, trajanju gubitka vazduha na drenove u danima, ukupnom trajanju drenaže, ukupnom trajanju hospitalizacije, pojavi produženog gubitka vazduha na dren definisanog kao gubitak duže od 7 dana, potrebi za redrenažom grudnog koša (broj drenova upotrebljenih za redrenažu), kompletnost reekspanzije pluća pre vađenja drenova, pojavi drugih hirurških komplikacija, pojavi opštih medicinskih komplikacija i pojavi kasnih komplikacija – više od 30 dana nakon operacije ili nakon otpusta. Prvu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba do klemovanja i vađenja drenova. Drugu grupu ispitanika sačinjavaju pacijenti kojima je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim -10 cm vodenog stuba do klemovanja i vađenja drenova. Treću grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim podvodna drenaža do klemovanja i vađenja drenova. Četvrtu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim dnevna procena i modifikacija na sledeći način: aspiracija od -20 cm vodenog stuba do postizanja reekspanzije pluća, zatim postepeno smanjenje aspiracije po nahođenju operatera do klemovanja i vađenja drenova. REZULTATI: Između grupa ispitanika ne postoji statistički značajna razlika po starosti (p=0,77),  parametrima plućne funkcije: vrednost FEV1 (p=0,6316), vrednost ITGV (p=0,6202), vrednost TLC (p=0,6922) i za vrednost RV ne postoji razlika (p=0,6552). Razlika ne postoji između grupa ni u učestalosti pridruženih bolesti (p=0,4522). Grupe su međusobno homogene po preoperativnim parametrima. Snižen FEV1 u ukupnoj populaciji pacijenata nije uticao na pojavu produženog gubitka vazduha (P=0,571), kao ni povišenje ITGV (P=0,22), RV (p=0,912), niti vrednost TLC (0,521). Upoređene su međusobno osnovne vrste lobektomija: desna gornja, leva gornja, desna donja, leva donja, srednja lobektomija, kao i donja i gornja bilobektomija desno. Kako je učestalost svake pojedinačne lobektomije u 4 grupe ispitanika mali da bi se uporedile iste lobektomije između grupa, poređenje je moguće samo između anatomski različitih lobektomija kumulativno u svim grupama. Razlika u pojavi produženog gubitka vazduha između različitih lobektomija postoji, ali nije dostigla statističku značajnost (p=0,061). Međutim, kada se analizira svaka lobektomija pojedinačno, uočava se da desna donja bilobektomija ima značajno veću učestalost produženog gubitka vazduha u odnosu na sve ostale lobektomije zajedno (P=0,009). Razlika u dužini drenaže kod  različitih lobektomija je dostigla statistički značaj (p=0,0356), kao i u ukupnoj dužini hospitalizacije (p=0,0007). Dodatak resekcije perikarda, grudnog zida ili dijafragme, klinasta resekcija susednog režnja ili sleeve resekcija bronha kao dodatne procedure nisu uticali na pojavu produženog gubitka vazduha (p=0,58). Podaci o učestalosti adhezija u ispitivanoj populaciji pacijenata i njihovom uticaju na pojavu produženog gubitka vazduha daju granične vrednosti. I ovde je broj pacijenata u svakoj pojedinačnoj kategoriji adhezija (postojanje adhezija na skali od 0-3) mali da bi testiranje povezanosti sa produženim gubitkom vazduha moglo dostići statističku značajnost - razlika postoji, ali nije značajna (p=0,065). Radi povećanja statističke snage je izvedeno testiranje za podelu ima ili nema adhezija. Razlika postoji, ali ni ovim testiranjem nije dostignuta statistički značajna razlika (p=0,057). Postojanje buloznog emfizema takođe dovodi do povećanja učestalosti produženog gubitka vazduha, ali ni ovde razlika nije značajna (p=0,063).  Primena hemoterapije pre operacije nije dovela do statistički značajne razlike u pojavi produženog gubitka vazduha (p=0,0623) i ukupnoj stopi komplikacija (p=0,088), kao ni dužine hospitalizacije (p=0,2), iako razlika postoji i paradoksalno rezultat je bolji kod pacijenata koji su primili hemioterapiju, što može ukazivati na uticaj selekcije pacijenata za operaciju. Između 4 grupe ispitanika nije uočena razlika u potrebi za redrenažom grudnog koša (p=0,101), potrebi za povećanjem nivoa aktivne aspiracije (p=0,326), ukupnoj pojavi komplikacija (p=0,087) i pojavi produženog gubitka vazduha (P=0,323). Razlika postoji i visoko je značajna u dužini trajanja drenaže (p=0,001) i dužini hospitalizacije (P=0,000). Broj drenova (1 ili 2 drena postavljena intraoperativno) nije uticao na pojavu produženog gubitka vazduha (p=0,279), ali je značajno kraća hospitalizacija kod pacijenata sa jednim drenom (p=0,0001). Logistička regresiona analiza je pokazala da je samo donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog prostora (space reducing), broja drenova i dodatne operacije (resekcije). ZAKLJUČAK: Sprovedenim istraživanjem utvrđeno je da primena aktivne aspiracije na drenove ne pokazuje razliku u odnosu na podvodnu drenažu u postizanju i održavanju reekspanzije pluća nakon lobektomije. Aktivna aspiracija ne utiče na pojavu produženog gubitka vazduha na drenove definisanog kao gubitak vazduha duže od 7 dana, ali utiče na produženje ukupnog trajanja drenaže i hospitalizacije. Nivo aktivne aspiracije ili primena dnevnih modifikacija nivoa aspiracije ne utiče na rezultate lečenja.  U ovom istraživanju preoperativna plućna funkcija, kao ni preoperativna hemoterapija ne utiču na pojavu produženog gubitka vazduha na drenove. Desna donja bilobektomija u odnosu na sve druge lobektomije dovodi do češće pojave produženog gubitka vazduha, produžene drenaže i hospitalizacije. Dodatne resekcije okolnih tkiva u sklopu lobektomije ili primena redukcije pleuralnog prostora ne utiču na pojavu produženog gubitka vazduha. Intraoperativni nalaz adhezija u pleuri i buloznog emfizema pluća povećavaju rizik produženog gubitka vazduha, ali je taj uticaj na granici statističke značajnosti. Primena jednog drena nakon lobektomije umesto dva ne utiče na pojavu produženog gubitka vazduha, ali utiče na skraćenje drenaže i hospitalizacije. U multivarijatnoj analizi samo je donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog, broja drenova i dodatne resekcije okolnih tkiva.
INTRODUCTION: The drainage of the thorax after pulmonary resection is a basic thoracic surgery procedure which enables reexpansion after lung collapse and the evacuation of air, blood and effusion from the pleural cavity. It is supported by the use of drainage aspiration (suction or aspiration drainage). Although drainage is an everyday procedure in thoracic surgery, the use of drains is based mainly on specialist experience and less on scientific research. During calm breathing the inspiratory pressure in the pleural cavity is – 8cm H2O on average, while the expiratory pressure is – 4cm H2O. During forced breathing the pressures can reach up to – 50 cm H2O and + 70 cm H2O. Based on this physiological data, most surgeons apply the aspiration from – 10 to – 40 cm H2O. The concept of pleural deficit (the disproportion of the volume of the remaining pulmonary tissue and the volume of the thorax) has attributed to development of new technical procedures in order to achieve a new physiological balance in the pleural cavity. It has also brought upon the consideration of routine underwater seal drainage after pulmonary resection. Underwater seal drainage represents an interesting alternative to the traditional active drainage aspiration, especially considering the need to reduce medical expenses and shorten the postoperative hospitalization period. AIM: To determine whether active drainage aspiration after pulmonary lobectomy has a favorable therapeutic effect on achieving and maintaining pulmonary reexpansion in comparison with underwater seal drainage; to quantitatively compare the different modes of active drainage aspiration; to compare hospitalization duration and surgical and non-surgical complication with groups of patients on whom either underwater seal drainage or aspiration drainage was applied. METHODOLOGY: The prospective study without randomization has covered 301 patients on whom pulmonary lobectomy was performed due to lung carcinoma at the Thoracic Surgery Clinic of the Institute of Pulmonary Diseases of Vojvodina from 1st January 2008 to 28th February 2010. The data collected in the pre-operative state included: pulmonary function, previous neoadjuvant chemotherapy and comorbidities. In the research, surgical operative data and postoperative data were analyzed. Surgical operative data included information about the bullous emphysema, adhesion in the pleural cavity, anatomic type of lobectomy, additional surgical procedures and air leak after surgery. Postoperative data involved information about amount of fluid on drainage during the first 24 hours and in total, air leak duration in days, total drainage period, overall hospitalization period, prolonged air leak defined as leak longer than 7 days, the need for redrainage of thorax (number of tubes used for redrainage), completeness of pulmonary reexpansion before the end of drainage, other surgical complications, comorbidities and late complications (after more than 30 days following the surgery or release). The first group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of – 20 cm H2O was applied before clamping and tube extraction. The second group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of – 20 cm H2O was applied on surgery day and again – 10 cm H2O before clamping and tube extraction. The third group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of – 20 cm H2O was applied on surgery day and underwater seal drainage was applied before clamping and tube extraction. The fourth group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of – 20 cm H2O was applied on surgery day, and then daily monitored and modified in such a way that an aspiration of – 20 cm H2O was applied until pulmonary reexpansion and then gradually lowered according to individual surgery experience before clamping and tube extraction. RESULTS: There is no significant statistical difference between groups of patients in: age (p=0.77), FEV1 (p=0.6316), ITGV (p=0.6202), TLC (p=0.6922) and RV (p=0.6552) and comorbidities (p=0.4522). The groups are homogenous in pre-operative parameters. Lowered FEV1 among all patients did not affect prolonged air leak (p=0.571), nor the increase in values of ITGV (p=0.22), RV (p=0.912) and TLC (p=0.5211). The lobectomies that were compared were: upper right, upper left, lower right, lower left, middle, as well as upper and lower right bilobectomy. The comparison was implemented only on anatomically different lobectomies cumulatively among groups, due to the low occurrence of each type of lobectomy in groups. The difference in prolonged air leak does exist, but is not statistically significant (p=0.061). Prolonged air leak has a significantly higher occurrence in lower right bilobectomies (p=0.009). Drainage duration and hospitalization period variations in different kinds of lobectomy are statistically significant (p=0.0356 and p=0.0007, respectively). Additional pericardial, thoracic or diaphragm resection, wedge resection of the neighboring lobe, or sleeve bronchial resection did not affect prolonged air leak (p=0.58). The research has established that the occurrence of adhesion (on a scale 0-3) in patients and bulous emphysema attribute to prolonged air leak (p=0.065 and p=0.063, respectively).  Comparison between patients with and without adhesions revealed similar result. Difference exists, but it is not statistically significant (p=0,057).  Pre-operative chemotherapy had no statistical significance on prolonged air leak (p=0.0623), total rate of complications (p=0.088), nor hospitalization period (p=0.2). Paradoxically, the treatment was in favor of those patients who had taken pre-operative chemotherapy, which could be due to the selection of patients for surgery.  Among the four groups, there was no difference in need for thoracic redrainage (p=0.101), need for increase in level of active aspiration (p=0.326), overall complication occurrence (p=0.087) and prolonged air leak occurrence (p=0.323). There is a statistically significant difference in drainage duration (p=0.001) and hospitalization period (p=0.000). The number of tubes (1 or 2 tubes set intraoperatively) did not affect prolonged air leak occurrence (p=0.279). The hospitalization period in patients with one tube set intraoperatively is significantly shorter (p=0.0001). Logistic regression analysis has shown that only lower bilobectomy had a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bullous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection. CONCLUSION: The research has shown: Active drainage aspiration has no difference in effect in achieving and maintaining pulmonary reexpansion after lobectomy when compared to underwater seal drainage; Active drainage aspiration does not affect prolonged air leak, defined as air leak longer than 7 days; Active drainage aspiration has an impact on the overall drainage duration and hospitalization period; The level of active drainage aspiration and daily modification of the mentioned do not affect treatment results; Preoperative pulmonary function does not affect prolonged air leak occurrence; Preoperative chemotherapy does not affect prolonged air leak occurrence; Prolonged air leak and drainage and hospitalization period occur most often in lower right bilobectomies; Nor additional resections nor pleural cavity reduction affect prolonged air leak occurrence; The presence of pleural adhesions and bullous emphysema rarely attribute to the increase of prolonged air leak occurrence; The number of tubes implemented intraoperatively does not affect prolonged air leak occurrence, but it shortens drainage and hospitalization periods; By multivariate analysis, that only lower bilobectomy has a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bulous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection.

Background: The main focus of the dissertation is the use of nanofibrous biodegradable materials for the healing support of intestinal anastomoses in colorectal surgery. The altered healing process of intestinal anastomosis leads to several types of local complications. Anastomotic leakage is one of the most feared ones. Severe anastomotic leakage causes peritonitis, sepsis and is a life-threatening condition. Reoperation is necessary in many cases, bringing the need for intensive care, and hospital stays prolongation. Extensive peritoneal adhesions are another source of postoperative complications. These adhesions are a frequent cause of bowel obstruction and abdominal discomfort and are the most common reason for readmission after colorectal procedures. Nanofibrous biodegradable materials showed positive effects on the healing process in various locations. We aimed to develop and perfect a biodegradable patch for both prevention of anastomotic leakage and the formation of extensive peritoneal adhesions. Methods: We conducted 3 subsequential experiments on porcine models. In Experiment A, we managed to develop polycaprolactone and polylactic acid- polycaprolactone copolymer nanofibrous patches and applied them on anastomoses on the small porcine intestine. The animals were observed for 3 weeks....

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017
INTRODUÇÃO: Apesar da extensa investigação sobre deiscência da anastomose após cirurgia colorectal, o conhecimento científico ainda é insuficiente e mesmo o cirurgião mais experiente não consegue evitar esta complicação. Através desta revisão analítica pretende-se identificar áreas de conhecimento ainda não totalmente esclarecidas sobre deiscência de anastomose e que merecem ser estudadas em futuros trabalhos de investigação. MÉTODOS: Foi realizada uma revisão analítica de artigos pesquisados na base de dados PUBMED e Cochrane Library, em língua inglesa, de 2006 até Outubro de 2016, utilizando-se as palavras chave “colorectal surgery AND anastomotic leakage” com o objectivo de identificar áreas de conhecimento por esclarecer no que concerne à definição, epidemiologia, fisiopatologia, factores de risco, abordagem terapêutica, prevenção e gestão da deiscência de anastomose após cirurgia colorectal. Artigos relevantes pesquisados manualmente na bibliografia dos artigos inicialmente selecionados também foram incluídos, sendo esta revisão referente aos 139 artigos selecionados e analisados. CONCLUSÃO: A investigação sobre deiscência da anastomose em cirurgia colorectal tem-se concentrado nas consequências clínicas da mesma, havendo poucos estudos acerca da fisiopatologia da deiscência e dos processos de cicatrização normal da anastomose. É necessário compreender na totalidade estes mecanismos básicos associados à cicatrização normal e patológica das anastomoses e estabelecer de forma definitiva e universal vários conceitos e definições antes de se conseguirem desenvolver intervenções eficazes que permitam reduzir a prevalência e as consequências nefastas desta tão temida complicação.
INTRODUCTION: Despite extensive research on anastomotic leakage after colorectal surgery, scientific knowledge is still insufficient and even the most experienced surgeon cannot avoid this complication. Through this analytical review we intend to identify areas of knowledge where the anastomotic leakage has not yet been fully clarified and that deserve to be studied in future research. METHODS: An analytical review of articles, in English, searched in the PUBMED and Cochrane Library, from 2006 to October 2016, was performed, using the keywords "colorectal surgery AND anastomotic leakage" with the objective of identifying areas of knowledge where clarification regarding definition, epidemiology, pathophysiology, risk factors, therapeutic approach, prevention and management of anastomotic leakage after colorectal surgery is needed. Relevant articles researched manually in the bibliography of the articles initially selected were also included and this review pertains to the 139 articles selected and analyzed. CONCLUSION: Research on anastomotic leakage in colorectal surgery has focused on its clinical consequences, with few studies on the physiopathology of leakage and normal anastomoses healing processes. It is necessary to fully understand these basic mechanisms associated with the normal and pathological healing of the anastomoses and to definitively and universally establish various concepts and definitions before effective actions can be taken to reduce the prevalence and the harmful consequences of this much-feared complication.

Key words: adenocarcinoma of the esophagus and esophagogastric junction, neoadjuvant chemotherapy, PET/CT, histopathological response, technique of esophagogastric anastomosis, anastomotic leak, anastomotic stricture Previous studies have shown that preoperative chemotherapy of locally advanced AEG is beneficial only for patients with a good histopathological response, the so-called responders. The aim of the first part of the thesis was to prospectively verify whether positron emission tomography (PET/CT) could be used for early identification of histopathological non- responders, who could be spared ineffective neoadjuvant treatment. Our study did not prove that the early metabolic response, expressed as the percentage change of the consumption of glucosis on PET/CT performed before (PET1) and 12 to 22 days after the start of the first cycle of preoperative chemotherapy (PET2) correlated with the histopathological response in the resection specimen in the entire population of 90 patients. In a post hoc explorative analysis we found the correlation between metabolic and histopathological response in a subgroup of patients with PET2 performed ≤16 days after the start of the therapy, but this hypothesis needs to be prospectively validated. Our study suggests that PET/CT performed after the first...

Tese de doutoramento em Ciências da Saúde, no ramo de Medicina, na especialidade de Cirurgia, apresentada à Faculdade de Medicina da Universidade de Coimbra
Despite recent progresses in surgical technique and perioperative care, failure of intestinal anastomotic healing remains one of the most feared complications in digestive surgery, exerting a profound adverse impact on the operative morbidity and mortality rates, oncologic, and functional outcomes and socioeconomic costs. Teduglutide is an enterotrophic analogue of glucagon-like peptide 2 (GLP-2) approved for the pharmacological rehabilitation of short-bowel syndrome. Present study aims to clarify the potential of teduglutide as a promoting strategy for the improvement of intestinal anastomotic healing, on an animal model, through the influence on the cellular, humoral and molecular mediators of repair. An experimental rat model of standard small-bowel anastomosis was used with evaluation at the third and seventh postoperative days. Structural assessment of the anastomosis included the macroscopic integrity and the histological and immunohistochemical examination of healing parameters, comprising reepithelialization, neoangiogenesis and fibroplasia. Cellular and molecular mediators of anastomotic healing were analyzed, including: putative epithelial stem cells response (using Lgr5, Bmi1 and the panel CD24/CD44/CD166/Grp78 surface markers by flow cytometry); cellular viability and death (with double staining with annexin-V/propidium iodide by flow cytometry); oxidative stress [quantification of cytosolic peroxides with 2’,7’-dichlorodihydrofluorescein diacetate (DCFH2) probe, mitochondrial reactive species with dihydrorhodamine 123 (DHR 123) probe, total intracellular reduced glutathione with mercury orange staining and mitochondrial membrane potential with 5,5',6,6'-tethrachloro-1,1',3,3'-tethraethylbenzimidazolcarbocyanine iodide (JC-1) probe, by flow cytometry]; local and systemic inflammatory response (tissue and plasma concentrations of interleukine-1α, macrophage chemo-attractant protein-1, tumor necrosis factor-α, interferon-γ and interleukine-4 by flow cytometric multiplexed bead assay); gene expression of main extracellular matrix components (Collagen, type I, alpha 1: Col1a1; Collagen, type III, alpha 1: Col3a1; Collagen, type IV, alpha 1: Col4a1; Collagen, type V, alpha 1: Col5a1) and remodeling factors, matrix metalloproteinases (Mmp; Mmp1 and Mmp13, Mmp2 and Mmp9, Mmp3, Mmp12 and Mmp14) and tissue inhibitors of metalloproteinases 1 and 2 (Timp; Timp1 and Timp2); gene expression of growth factors and receptor potentially implicated on anastomotic repair (Insulin-like growth factor 1, transcript variant: Igf1; Vascular endothelial growth factor A, transcript variant 2: Vegfa; Transforming growth factor, beta 1: Tgfb1; Connective tissue growth factor: Ctgf; Fibroblast growth factor 2: Fgf2; Fibroblast growth factor 7: Fgf7; Epidermal growth factor: Egf; Heparin-binding epidermal-like growth factor: Hbegf; Platelet-derived growth factor beta polypeptide: Pdgfb; Glucagon-like peptide 2 receptor: Glp2r) by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR); and Glp-2 plasma levels (by competitive enzyme immunoassay). Teduglutide had no apparent relevant impact on the rate or severity of intestinal anastomotic leakage. A favorable influence of teduglutide on the reepithelialization and neoangiogenesis events of the proliferative phase of anastomotic repair was documented. Teduglutide was associated with an increase of subepithelial myofibroblasts density score, but no significant effect on the goblet, Paneth and glial cellular indexes was observed. This growth factor was associated with an enhancement of type III collagen deposition on the submucosa at the seventh postoperative day, although with simultaneous reduction of type I collagen level in that layer, and a non-significant reduction of global anastomotic collagen content. Teduglutide inhibited the gene modulation of fibrolysis in the predominantly inflammatory phase of anastomotic repair, while stimulated the fibrolysis in the proliferative stage. Teduglutide induced the upregulation of gene expression of Timp1, Timp2 and Col4a1, and the downregulation of Mmp3 and Mmp12, at the third postoperative day; and the repression of gene expression of Timp1, Col3a1, Col4a1 and Col5a1, at the seventh day. Teduglutide contributed to the expansion of the putative crypt base columnar stem cells pool at the seventh day and to the concomitant depletion of the putative “position +4” stem cells fraction. An increase (non-significant) of the overall putative intestinal epithelial stem cells was also observed in teduglutide-treated animals. Teduglutide was associated with a non-significant prooxidative effect, with an increase of the cytosolic peroxides level and mitochondrial reactive species levels and a reduction of the cellular reduced glutathione content. Those effects were coincident with an increase of cellular viability indexes and a non-significant decrease of early apoptotic events. No relevant influence on mitochondrial membrane potential was verified. A non-significant increase of tissue levels of the anti-inflammatory interleukin-4 at the seventh day, and a significant reduction of plasma levels of interferon-γ at the third day were observed in teduglutide-treated animals. Teduglutide induced the upregulation of the gene expression of Igf1, Vegfa and Ctgf and the downmodulation of Fgf2, Fgf7, Tgfb1 and Glp2r. To conclude, the present study reflects the complexity of the intestinal anastomotic repair and points to a favorable influence of teduglutide on this process that deserves additional investigation.
Apesar dos recentes progressos da técnica cirúrgica e suporte peri-operatório, a falência da cicatrização anastomótica intestinal constitui, ainda, uma das mais temíveis complicações da cirurgia digestiva, com um importante impacto adverso na mortalidade e morbilidade operatórias, resultados oncológicos e funcionais e custos económico-sociais. O teduglutide é um análogo enterotrófico do glucagon-like peptide 2 (GLP-2) aprovado para a reabilitação farmacológica da síndroma do intestino curto. Este estudo procurou analisar as potencialidades do teduglutide como estratégia adjuvante da cicatrização anastomótica intestinal, num modelo animal, através da sua influência nos mediadores celulares, humorais e moleculares do processo reparativo. Foi utilizado um modelo experimental de anastomose intestinal estandardizada, em rato, com avaliação ao terceiro e ao sétimo dias pós-operatórios. A avaliação estrutural da anastomose incluiu a integridade macroscópica e os exames histológico e imunohistoquímico dos parâmetros de cicatrização, tais como reepitelização, neoangiogénese e fibroplasia. Foram analisados os seguintes mediadores celulares e moleculares da cicatrização anastomótica: resposta das putativas células estaminais epiteliais (usando os marcadores de superfície Lgr5, Bmi1 e o painel CD24/CD44/CD166/GrpP78 por citometria de fluxo); viabilidade e morte celular (com marcação dupla com anexina V/iodeto de propídeo, por citometria de fluxo); stresse oxidativo [quantificação de peróxidos citoplasmáticos com sonda de diacetato de 2’,7’-diclorodihidrofluoresceína (DCFH2), espécies reactivas mitocondriais com sonda de dihidrorodamina 123 (DHR 123), glutatião reduzido intracelular com marcação com alaranjado de mercúrio e potencial de membrana mitocondrial com sonda de iodeto de 5,5',6,6'-tetracloro-1,1',3,3'-tetraetilbenzimidazolcarbocianina (JC-1), por citometria de fluxo]; resposta inflamatória local e sistémica (concentrações tecidulares e plasmáticas de interleucina-1α, macrophage chemo-attractant protein-1, factor de necrose tumoral-α, interferon-γ e interleucina-4 por citometria de fluxo; expressão génica de componentes da matriz extracelular (Collagen, type I, alpha 1: Col1a1; Collagen, type III, alpha 1: Col3a1; Collagen, type IV, alpha 1: Col4a1; Collagen, type V, alpha 1: Col5a1) e respectivos factores de remodelação, metaloproteinases (Mmp) da matriz 1, 13, 2, 9, 3, 12 e 14 (Mmp1 e Mmp13, Mmp2 e Mmp9, Mmp3, Mmp12 e Mmp14) e inibidores tecidulares das Mmp 1 e 2 (Timp1 and Timp2); assim como dos factores de crescimento potencialmente implicados na reparação anastomótica (Insulin-like growth factor 1, transcript variant: Igf1; Vascular endothelial growth factor A, transcript variant 2: Vegfa; Transforming growth factor, beta 1: Tgfb1; Connective tissue growth factor: Ctgf; Fibroblast growth factor 2: Fgf2; Fibroblast growth factor 7: Fgf7; Epidermal growth factor: Egf; Heparin-binding EGF-like growth factor: Hbegf; Platelet-derived growth factor beta polypeptide: Pdgfb; Glucagon-like peptide 2 receptor: Glp2r) por transcrição reversa quantitativa da reacção em cadeia da polimerase em tempo real; e da concentração plasmática do Glp-2 (por imunoensaio enzimático competitivo). O teduglutide não teve impacto relevante aparente na incidência e gravidade da deiscência anastomótica mas exerceu uma influência favorável nos processos de reepitelização e de neoangiogénese da fase proliferativa da cicatrização. Associou-se, ainda, a um aumento da densidade de miofibroblastos subepiteliais, sem modificação significativa dos índices de células caliciformes, de Paneth e gliais. Este factor de crescimento associou-se ao aumento da deposição de colagéneo III na submucosa ao sétimo dia pós-operatório, embora com redução concomitante do colagéneo I na mesma camada, e à redução não significativa do teor global de colagéneo na anastomose. O teduglutide inibiu a modulação génica da fibrólise na fase predominantemente inflamatória da reparação enquanto, pelo contrário, reprimiu a fibrogénese na fase proliferativa. O teduglutide aumentou a expressão génica de Timp1, Timp2 e Col4a1 e, reduziu a de Mmp3 e Mmp12, ao terceiro dia pós-operatório; e diminuiu a expressão génica do Timp1, Col3a1, Col4a1 e Col5a1, ao sétimo dia. O teduglutide induziu a expansão das putativas células estaminais colunares basais das criptas e, concomitantemente, a depleção das células da “posição +4”. Nos animais tratados com teduglutide, observou-se, ainda, um aumento global não significativo das putativas células epiteliais intestinais. O teduglutide associou-se a um efeito pro-oxidativo não significativo, com aumento dos níveis de peróxidos citoplasmáticos e das espécies reactivas mitocondriais e redução do glutatião reduzido celular. Estes efeitos foram acompanhados por um aumento do índice de viabilidade celular e uma redução não significativa dos eventos apoptóticos precoces. Não se verificou influência significativa no potencial de membrana mitocondrial. Nos animais tratados com teduglutide, observou-se um aumento não significativo dos níveis tecidulares da citocina anti-inflamatória interleucina-4 ao sétimo dia, assim como uma redução significativa da concentração plasmática de interferon-γ ao terceiro dia. O teduglutide promoveu o aumento da expressão génica do Igf1, Vegfa e Ctgf e a repressão do Fgf2, Fgf7, Tgfb1 e Glp2r. Em conclusão, o presente estudo reflecte a complexidade da cicatrização anastomótica intestinal e sugere uma influência favorável do teduglutide neste processo que justifica uma investigação adicional.

This chapter discusses the main issues with a selected group of surgical complications after Roux-en-Y gastric bypass. The main focus is on diagnosis and management of anastomotic leak and stricture, marginal ulcers, and gastrogastric fistulas. Anastomotic leak is one of the most feared and potentially catastrophic complications. The most common site is at gastrojejunostomy. Avoiding devascularization of the gastric pouch, creating a tension-free anastomosis, and performing an intraoperative anastomotic leak test are crucial technical points in preventing leaks. Once the leak is highly suspected or diagnosed, it needs to be managed swiftly. Different surgical techniques have different anastomotic stricture rates, with circular staplers being associated with the highest frequency of strictures at the gastrojejunostomy. Endoscopic dilatations are the mainstay of treatment.

Dietary intolerance and poor oral intake account for a disproportionate number of emergency department visits and readmissions after bariatric surgery. Micronutrient, vitamin, and protein deficiencies can occur after both malabsorptive and restrictive weight-loss operations, and they are best mitigated against by conscientious preoperative counseling and vigilance in follow-up. Routine vitamin supplementation can prevent the need for unnecessary laboratory testing, while symptoms of dumping syndrome can frequently be managed with dietary and behavioral modification alone. Alternative enteral feeding access for alimentary supplementation can be safely performed surgically or with assistance by interventional radiology, and should be considered in the management of perforation, early anastomotic leak, surgical revision, or patients with refractory malnourishment.

Readmission after bariatric surgery occurs in about 5% of cases and increases the average costs up to 2.5-fold. Risk factors for readmission are dependent functional status, diabetes mellitus, steroid or immunosuppressant use, cardiac disease with intervention, bleeding disorders, longer operative time, concurrent splenectomy, high preoperative creatinine, low serum albumin, and occurrence of postoperative complications during index admission. The most common reasons for readmissions are procedure-related complications, including dehydration, abdominal pain, bleeding, anastomotic leak, gastrointestinal obstruction, and thromboembolic events. Measures that decrease readmissions after bariatric surgery include: effective preoperative education, thorough evaluation before discharge, appropriate discharge instruction with required medications, reasonable discharge disposition, 24-hour phone support, active follow-up of high-risk patients, walk-in clinic, hydration clinic, and training of other hospital teams to manage common complaints after bariatric surgery.

Abdominal injuries are common following blunt and penetrating trauma. They can result in a spectrum of severity from benign to potentially life-threatening conditions. Soon after injury, haemorrhage is the predominant concern, and leading cause of morbidity and mortality. Active haemorrhage resulting in shock requires emergent operative intervention and aggressive haemostatic resuscitation. However haemodynamically-stable patients benefit from non-operative management of solid organ injuries with or without angiographic embolization. Sepsis usually occurs as a result of intra-abdominal infections from missed bowel perforations or anastomotic leaks. Sterile systemic hyperinflammatory conditions can result from major hepatic necrosis or pancreatic injuries, and closely mimic infectious conditions. Damage control surgery is a valuable adjunct to the operative management of major abdominal trauma. This concept recognizes that the time and procedures required to perform definitive operative repair may be detrimental when physiological derangements are excessive. By limiting operations to controlling haemorrhage and enteric contamination, further deterioration, and the ‘vicious bloody cycle of trauma’ can be avoided. The operative and critical care management of patients with abdominal trauma should be closely integrated to correct physiological derangements with rapid stabilization and reversal of hypoperfusion. Abdominal compartment syndrome, characterized by intra-abdominal hypertension and resultant remote organ dysfunction, is a risk in patients undergoing high-volume fluid resuscitation. Emergent decompressive laparotomy is indicated in patients with abdominal compartment syndrome and results in rapid reversal of physiological compromise. Paramount to optimal management of abdominal injuries is the close integration of operative and critical care approaches.