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.

<p>The treatment of rectal cancer is complex and comprises: diagnostic measures; different preoperative treatments; a multitude of surgical and technical choices; possibilities of postoperative treatments and postoperative care and follow up. In this thesis, some aspects of this complex paradigm have been further investigated. One of the most feared complications after rectal cancer surgery is anastomotic leakage. The risk of anastomotic leakage is affected by non-influenceable factors related to the tumour and the patient. In the first paper, the risk of anastomotic leakage in relation to a surgical instrument, the circular stapler, was investigated. The risk of leakage was 7% or 11%, depending on the choice of instrument. In the second paper, a long-term evaluation of survival and local recurrence rates in the Swedish Rectal Cancer Trial was made. Randomisation was to either preoperative radiotherapy followed by surgery or surgery alone. After 13 years median follow-up, survival was 38% in the radiotherapy group and 30% in the surgery alone group. Differences in local recurrence rates were seen in all stages. Most rectal cancer operations carry a high risk of morbidity and mortality. For early stage cancers, a local procedure may be sufficient and in the third paper, population-based results of local excision of rectal cancer were explored. In stage I, cancer specific survival was the same after local excision as after major resection, but the relative survival was lower. The risk of local recurrence was higher after local excision than after resections. In the fourth paper, differences in survival rates in the Nordic countries and Scotland were investigated. The relative excess risk of death was highest in Denmark, but only in the first 90 postoperative days. </p><p>Through applying already existing knowledge and successively introducing new treatments, the results for rectal cancer treatment will be further improved.</p>

The treatment of rectal cancer is complex and comprises: diagnostic measures; different preoperative treatments; a multitude of surgical and technical choices; possibilities of postoperative treatments and postoperative care and follow up. In this thesis, some aspects of this complex paradigm have been further investigated. One of the most feared complications after rectal cancer surgery is anastomotic leakage. The risk of anastomotic leakage is affected by non-influenceable factors related to the tumour and the patient. In the first paper, the risk of anastomotic leakage in relation to a surgical instrument, the circular stapler, was investigated. The risk of leakage was 7% or 11%, depending on the choice of instrument. In the second paper, a long-term evaluation of survival and local recurrence rates in the Swedish Rectal Cancer Trial was made. Randomisation was to either preoperative radiotherapy followed by surgery or surgery alone. After 13 years median follow-up, survival was 38% in the radiotherapy group and 30% in the surgery alone group. Differences in local recurrence rates were seen in all stages. Most rectal cancer operations carry a high risk of morbidity and mortality. For early stage cancers, a local procedure may be sufficient and in the third paper, population-based results of local excision of rectal cancer were explored. In stage I, cancer specific survival was the same after local excision as after major resection, but the relative survival was lower. The risk of local recurrence was higher after local excision than after resections. In the fourth paper, differences in survival rates in the Nordic countries and Scotland were investigated. The relative excess risk of death was highest in Denmark, but only in the first 90 postoperative days. Through applying already existing knowledge and successively introducing new treatments, the results for rectal cancer treatment will be further improved.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21016号 / 医博第4362号 / 新制||医||1028(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小西 靖彦, 教授 福田 和彦, 教授 松村 由美 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Purpose: One relevant aspect for anastomotic leakage in colorectal surgery is blood perfusion of both ends of the anastomosis. The clinical evaluation of this issue is limited, but new methods like fluorescence angiography with indocyanine green or non-invasive and contactless hyperspectral imaging have evolved as objective parameters for perfusion evaluation. Methods: In this prospective, non-randomized, open-label and two-arm study, fluorescence angiography and hyperspectral imaging were compared in 32 consecutive patients with each other and with the clinical assessment by the surgeon. After preparation of the bowel and determination of the surgical resection line, the tissue was evaluated with hyperspectral imaging for 5 minutes before and after cutting the marginal artery and assessed by 6 hyperspectral pictures followed by fluorescence angiography with indocyanine green. Results: In 30 of 32 patients the image data could be evaluated and compared. Both methods provided a comparable borderline between well perfused and poorly perfused tissue (p = 0.704). In 15 cases, the surgical resection line was shifted to the central position due to the imaging. The border zone was sharper in fluorescence angiography and was best assessed 31sec after injection. With hyperspectral imaging, the border zone was visualized wider and with more differences between proximal and distal border. Conclusion: Hyperspectral imaging and fluorencence angiography provide similar results in determining the perfusion border. Both methods allow a good and safe visualization of the blood perfusion at the central resection margin to create a well-perfused anastomosis.:Abbildungsverzeichnis II Abkürzungsverzeichnis III 1. Einleitung 1 1.1 Anastomoseninsuffizienz 1 1.2 Hyperspektralbildgebung 2 Methodik und technische Daten 2 1.3 Fluoreszenzangiographie mit Indocyaningrün 4 Methodik und technische Daten 4 Anwendungsgebiet 6 1.4 Chirurgische Technik 6 1.5 Studiendesign und intraoperative Bildgebung 7 1.6 Bisherige Ergebnisse 10 2. Publikation 12 3. Zusammenfassung der Arbeit 21 4. Literaturverzeichnis IV 5. Darstellung des eigenen Beitrags VIII 6. Erklärung über die eigenständige Abfassung der Arbeit IX 7. Danksagung X

<p>UVOD: Drenaža grudnog ko&scaron;a nakon resekcija pluća je osnovni grudno hirur&scaron;ki postupak, koji omogućuje pro&scaron;irenje (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&nbsp; svakodnevna grudno hirur&scaron;ka 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 fiziolo&scaron;kih podataka, većina hirurga primenjuje aspiraciju od - 10 do - 40 cm H2O. Koncepta pleuralnog deficita - disproporcije volumena preostalog plućnog tkiva i zapremine grudnog ko&scaron;a doveo je do razvoja tehničkih postupaka za postizanje nove fiziolo&scaron;ke ravnoteže u pleuralnom prostoru i razmatranja rutinske primene podvodne (pasivne) drenaže nakon resekcija pluća. Pritisak na zdravstvenu službu za smanjenje tro&scaron;kova i skraćenje postoperativne hospitalizacije uz mogućnost rane mobilizacije pacijenta čine podvodnu drenažu zanimljivom alternativom tradicionalno prihvaćenoj aktivnoj aspiraciji na drenove.&nbsp; 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 hirur&scaron;kih i nehirur&scaron;kih 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 hirur&scaron;ki operativni podaci o postojanju buloznog emfizema, adhezija u pleuralnom prostoru, anatomskoj vrsti lobektomije, dodatnim hirur&scaron;kim 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 ko&scaron;a (broj drenova upotrebljenih za redrenažu), kompletnost reekspanzije pluća pre vađenja drenova, pojavi drugih hirur&scaron;kih komplikacija, pojavi op&scaron;tih medicinskih komplikacija i pojavi kasnih komplikacija &ndash; vi&scaron;e 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),&nbsp; 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 povi&scaron;enje 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&nbsp; 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).&nbsp; 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, &scaron;to može ukazivati na uticaj selekcije pacijenata za operaciju. Između 4 grupe ispitanika nije uočena razlika u potrebi za redrenažom grudnog ko&scaron;a (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.&nbsp; 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 če&scaron;će 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.</p> / <p>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 &ndash; 8cm H2O on average, while the expiratory pressure is &ndash; 4cm H2O. During forced breathing the pressures can reach up to &ndash; 50 cm H2O and + 70 cm H2O. Based on this physiological data, most surgeons apply the aspiration from &ndash; 10 to &ndash; 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 &ndash; 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 &ndash; 20 cm H2O was applied on surgery day and again &ndash; 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 &ndash; 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 &ndash; 20 cm H2O was applied on surgery day, and then daily monitored and modified in such a way that an aspiration of &ndash; 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).&nbsp; Comparison between patients with and without adhesions revealed similar result. Difference exists, but it is not statistically significant (p=0,057).&nbsp; 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.&nbsp; 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.</p>

Background: Novel intraoperative imaging techniques, namely, hyperspectral (HSI) and fluorescence imaging (FI), are promising with respect to reducing severe postoperative complications, thus increasing patient safety. Both tools have already been used to evaluate perfusion of the gastric conduit after esophagectomy and before anastomosis. To our knowledge, this is the first study evaluating both modalities simultaneously during esophagectomy. Methods: In our pilot study, 13 patients, who underwent Ivor Lewis esophagectomy and gastric conduit reconstruction, were analyzed prospectively. HSI and FI were recorded before establishing the anastomosis in order to determine its optimum position. Results: No anastomotic leak occurred during this pilot study. In five patients, the imaging methods resulted in a more peripheral adaptation of the anastomosis. There were no significant differences between the two imaging tools, and no adverse events due to the imaging methods or indocyanine green (ICG) injection occurred. Conclusions: Simultaneous intraoperative application of both modalities was feasible and not time consuming. They are complementary with regard to the ideal anastomotic position and may contribute to better surgical outcomes. The impact of their simultaneous application will be proven in consecutive prospective trials with a large patient cohort.

Simple Summary Good oxygenation of both bowel ends is an important prerequisite to promote anastomotic healing after colorectal resections. Bowel oxygenation is usually assessed clinically. Hyperspectral imaging is a contactless and contrast-free tool that allows quantifying tissue oxygen intraoperatively. In this study, the results of 105 colorectal resections with hyperspectral imaging are reported. Abstract Background: A perfusion deficit is a well-defined and intraoperatively influenceable cause of anastomotic leak (AL). Current intraoperative perfusion assessment methods do not provide objective and quantitative results. In this study, the ability of hyperspectral imaging (HSI) to quantify tissue oxygenation intraoperatively was assessed. Methods: 115 patients undergoing colorectal resections were included in the final analysis. Before anastomotic formation, the bowel was extracted and the resection line was outlined and imaged using a compact HSI camera, in order to provide instantaneously quantitative perfusion assessment. Results: In 105 patients, a clear demarcation line was visible with HSI one minute after marginal artery transection, reaching a plateau after 3 min. In 58 (55.2%) patients, the clinically determined transection line matched with HSI. In 23 (21.9%) patients, the clinically established resection margin was entirely within the less perfused area. In 24 patients (22.8%), the HSI transection line had an irregular course and crossed the clinically established resection line. In four cases, HSI disclosed a clinically undetected lesion of the marginal artery. Conclusions: Intraoperative HSI is safe, well reproducible, and does not disrupt the surgical workflow. It also quantifies bowel surface perfusion. HSI might become an intraoperative guidance tool, potentially preventing postoperative complications.

Esophagectomy often presents anastomotic leaks (AL), due to tenuous perfusion of gastric conduit fundus (GCF). Hybrid (endovascular/surgical) ischemic gastric preconditioning (IGP), might improve GCF perfusion. Sixteen pigs undergoing IGP were randomized: (1) Max-IGP (n = 6): embolization of left gastric artery (LGA), right gastric artery (RGA), left gastroepiploic artery (LGEA), and laparoscopic division (LapD) of short gastric arteries (SGA); (2) Min-IGP (n = 5): LGA-embolization, SGA-LapD; (3) Sham (n = 5): angiography, laparoscopy. At day 21 gastric tubulation occurred and GCF perfusion was assessed as: (A) Serosal-tissue-oxygenation (StO2) by hyperspectral-imaging; (B) Serosal time-to-peak (TTP) by fluorescence-imaging; (C) Mucosal functional-capillary-density-area (FCD-A) index by confocal-laser-endomicroscopy. Local capillary lactates (LCL) were sampled. Neovascularization was assessed (histology/immunohistochemistry). Sham presented lower StO2 and FCD-A index (41 ± 10.6%; 0.03 ± 0.03 respectively) than min-IGP (66.2 ± 10.2%, p-value = 0.004; 0.22 ± 0.02, p-value < 0.0001 respectively) and max-IGP (63.8 ± 9.4%, p-value = 0.006; 0.2 ± 0.02, p-value < 0.0001 respectively). Sham had higher LCL (9.6 ± 4.8 mL/mol) than min-IGP (4 ± 3.1, p-value = 0.04) and max-IGP (3.4 ± 1.5, p-value = 0.02). For StO2, FCD-A, LCL, max- and min-IGP did not differ. Sham had higher TTP (24.4 ± 4.9 s) than max-IGP (10 ± 1.5 s, p-value = 0.0008) and min-IGP (14 ± 1.7 s, non-significant). Max- and min-IGP did not differ. Neovascularization was confirmed in both IGP groups. Hybrid IGP improves GCF perfusion, potentially reducing post-esophagectomy AL.

Le cancer colorectal (CCR) est le 3ème plus diagnostiqué au Canada. Son traitement implique une résection chirurgicale du côlon ou du rectum, et une reconnexion des deux bouts intestinaux pour rétablir la continuité gastrointestinale. Cette reconnexion, appelée « anastomose », peut ne pas bien guérir chez jusqu’à 30% des patients, ce qui mène à une complication morbide et mortelle appelée « fuite anastomotique ». En plus de diminuer la survie et la qualité de vie, la fuite est possiblement associée à une récidive accrue du cancer pour des raisons qui demeurent obscures. Malgré des progrès techniques importants dans les dernières décennies, les taux de fuite n’ont pas significativement diminué, et sa survenue demeure hautement imprévisible. Des données récentes ont suggéré que le microbiote intestinal, ou la collection de microorganismes dans l’intestin, peut influencer le processus de guérison après la chirurgie, mais l’évidence sur cette relation reste faible. Les études suivantes visaient donc à évaluer le lien causal entre le microbiote, la fuite anastomotique le CCR. En utilisant des échantillons de selles collectés avant la chirurgie de 18 patients avec CCR (9 avec fuite et 9 sans fuite), on a évalué le rôle causal du microbiote humain chez des souris assujetties à une greffe de microbiote fécal (GMF) puis une chirurgie colique. On a trouvé que la GMF avec des échantillons de patients avec fuite a entrainé chez la souris une mauvaise guérison anastomotique, un affaiblissement de la matrice extracellulaire dans la plaie colique, et une inflammation accrue localement. On a identifié 2 souches bactériennes, Parabacteroides goldsteinii kh35 et Alistipes onderdonkii kh33, qui influençaient la guérison anastomotique, la 1ère positivement et la 2ème négativement. Ces souches modulaient l’inflammation dans la muqueuse colique, avec P. goldsteinii exerçant un effet anti-inflammatoire et A. onderdonkii un effet pro-inflammatoire. En utilisant des échantillons de muqueuses collectés de patients avant la complétion de l’anastomose, on a trouvé avec une analyse multiplex que les patients présentant une fuite avaient des niveaux basaux plus élevés des macrophage inflammatory protein-1 alpha, monocyte chemoattractant protein-1, macrophage inflammatory protein 2 et interleukin-17A/F, et que le microbiote de ces patients entraine une augmentation similaire de ces cytokines pro-inflammatoires dans l’intestin des souris. Pour corroborer l’hypothèse que les patients présentant une fuite après la chirurgie avaient des niveaux basaux plus élevés d’inflammation intestinale de bas-grade induite par le microbiote, on a quantifié 9 cytokines dans la muqueuse colorectale de 77 patients avec CCR, pami lesquels 13 ont présenté une fuite après la chirurgie. Les 9 cytokines étaient plus élevées chez les patients ayant développé une fuite. On a exploré des marqueurs inflammatoires potentiels dans les selles, et qui peuvent être utilisés comme des biomarqueurs de dépistage avant la chirurgie, et avons identifié la calprotectine et la lipocaline-2 comme étant significativement différentes entre les patients présentant, ou pas, une fuite anastomotique. Ensuite, on a exploré si des métabolites bactériens peuvent être utilisés pour améliorer la guérison anastomotique. Les acides-gras à courte chaine (AGCCs) sont produits dans le côlon après la fermentation bactérienne de fibres alimentaires. On a ainsi testé si une supplémentation chez la souris avec de l’inuline ou des galacto-oligosaccharides (GOS), deux oligosaccharides fermentables, peut améliorer la guérison. On a trouvé que l’inuline et le GOS ont augmenté les niveaux du bénéfique AGCC butyrate, amélioré la guérison anastomotique, favorisé la réparation épithéliale, la déposition du collagène et la barrière intestinale. Enfin, puisque le butyrate est connu pour son effet anticancérigène via une activation peroxysome proliferator-activated receptor gamma (PPAR-γ), on a investigué la relation entre l’amélioration de la guérison intestinale postopératoire avec l’inuline et le 5-aminosalicylate (5-ASA), un activateur de PPAR-γ, et la récidive du CCR. Une revue de la survie postopératoire de patients avec CCR ayant, ou pas, présenté une fuite a été effectuée. L’effet d’une supplémentation alimentaire avec de l’inuline ou du 5-ASA sur les tumeurs anastomotiques a été évalué chez des souris subissant une chirurgie colique. L’inuline et le 5-ASA ont été aussi évalués dans un modèle murin de métastases hépatiques où les cellules de CCR étaient inoculées chirurgicalement dans la rate. Les patients présentant une fuite présentaient une survie globale et oncologique moindre que les patients sans fuite. Une mauvaise guérison anastomotique chez la souris a entrainé des tumeurs anastomotiques et péritonéales plus volumineuses. L’inuline et le 5-ASA ont renforcé la barrière intestinale et prévenu les tumeurs anastomotiques et dissémination métastatique chez la souris. Ces trouvailles renforcent l’hypothèse que prévenir la fuite améliore les issues oncologiques des patients avec CCR, et ouvre la voie à des essais cliniques où des interventions modifiant le microbiote seraient utilisées pour favoriser la guérison et diminuer la récidive du cancer. En résumé, on a démontré pour la première fois le lien causal entre le microbiote intestinal préopératoire et la guérison anastomotique chez les patients avec CCR. On a aussi identifié des biomarqueurs potentiels qui peuvent être utilisés en pratique pour détecter l’inflammation subclinique de bas-grade induite par le microbiote pour prédire la guérison avant la chirurgie. On a aussi démontré que le microbiote et PPAR-γ peuvent être modulés avec des oligosaccharides fermentables pour améliorer la guérison, renforcer la barrière intestinale et prévenir la récidive du cancer. / Colorectal cancer (CRC) is the third most diagnosed cancer in Canada. Its treatment involves a surgical resection of the colon or rectum, and a reconnection of the remaining bowel segments to re-establish gastrointestinal continuity. This reconnection, termed “anastomosis”, may fail to heal and leak in up to 30% of patients, which leads to a morbid and mortal complication called “anastomotic leak” (AL). In addition to decreasing survival and quality of life, AL may be linked to higher cancer recurrence for reasons that remain unclear. Despite significant technical progress over the last decades, the rates of AL have not significantly decreased, and its occurrence remains highly unpredictable. Recent data have suggested that the gut microbiota, or the collection of microorganisms in the gut, may influence the healing process after surgery, but evidence on this relation remains weak. The following studies aimed therefore at assessing the causal link between the gut microbiota, AL, and CRC in patients undergoing surgery. Using fecal samples collected before surgery from 18 patients with CRC (9 with AL and 9 without AL), we assessed the causal role of the human microbiota in mice subjected to fecal microbiota transplantation (FMT) then colonic surgery. We found that FMT from AL patients led to poor anastomotic healing, a weakened extracellular matrix in the colonic wound, and heightened inflammation locally. We identified 2 bacterial strains, Parabacteroides goldsteinii kh35 and Alistipes onderdonkii kh33, that were found to influence anastomotic healing, the first one positively and the second one negatively. These strains were found to modulate inflammation in the colonic mucosa, with P. goldsteinii exerting an anti-inflammatory effect and A. onderdonkii a pro-inflammatory effect. Using mucosal samples collected from patients before the completion of the anastomosis, we found with a multiplex assay that patients experiencing AL harbor higher basal levels of macrophage inflammatory protein- 1 alpha, monocyte chemoattractant protein-1, macrophage Inflammatory Protein 2 and interleukin-17A/F, and that the microbiota of these patients lead to the same increase in pro-inflammatory cytokines in mice. To corroborate the hypothesis that patients experiencing AL after surgery harbor higher basal levels of microbiota-driven low-grade inflammation in the gut, we quantified 9 cytokines in the colorectal mucosa of 77 patients with CRC, among whom 13 experienced AL after surgery. All 9 cytokines were found to be increased in patients developing AL. We explored potential fecal inflammatory markers that could be used as screening biomarkers before surgery, and identified calprotectin and lipocalin-2 as being significantly different between patients that subsequently developed, or not, AL. 4 Next we explored whether bacterial metabolites may be used to improve anastomotic healing. Short-chain fatty acids are produced in the gut upon bacterial fermentation of dietary fibers. We therefore tested in mice whether dietary supplementation with inulin or galacto-oligosaccharides (GOS), two fermentable oligosaccharides, could improve healing. We found that inulin and GOS increased the levels of the beneficial SCFA butyrate, improved anastomotic healing, promoted epithelial repair, collagen deposition and the gut barrier function. Finally, as butyrate is known to exert anticarcinogenic effect by stimulating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ), we further investigated the relationship between promotion of postoperative intestinal healing using inulin and 5-aminosalicylate (5-ASA), a PPAR-γ activator, and CRC recurrence. A review of postoperative survival of CRC patients with and without AL was performed. The effect of dietary supplementation with inulin and 5-ASA on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5- ASA were also assessed in a mouse model of liver metastasis where CRC cells are surgically inoculated into the spleen. Patients experiencing AL displayed significantly lower overall and oncological survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. Inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. These findings reinforce the hypothesis that preventing AL improves oncological outcomes in patients with CRC, and pave the way towards clinical trials in which microbiotatargeted interventions may be used to enhance healing and diminish cancer recurrence. In summary, we demonstrated for the first time the causal link between the preoperative gut microbiota and anastomotic healing in patients with CRC. We also identified potential biomarkers that could be used in practice to detect microbiota-driven subclinical inflammation and predict healing before surgery. We also showed that the gut microbiota and PPAR-g could be modulated using fermentable oligosaccharides to improve healing, reinforce the gut barrier and prevent cancer recurrence.