Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2006. / Härtill 5 uppsatser.

No description available.

INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a severe complication of ulcerative colitis (UC) that is associated with significant morbidity, treatment refractoriness and need for colectomy. Patients who do not adequately respond to the initial intravenous steroid therapy receive medical rescue therapy with infliximab or cyclosporine or undergo surgery for their refractory disease. However, there is limited guidance on management of steroid responders in this setting. While it is well established that Crohn’s disease (CD) is progressive and benefits from early institution of immunosuppressive therapy, such a paradigm is less well established in UC and thresholds for therapy escalation remain poorly defined. In immunosuppression-naïve patients, whether a single hospitalization for ASUC is a sufficient threshold to escalate to immunomodulator or biologic therapy is unknown. METHODS: From a single tertiary referral center, we identified all patients with ASUC hospitalized for intravenous steroids who were immunosuppression naïve (new UC diagnosis, no therapy, or 5-aminosalicylate (5-ASA) therapy) at their index hospitalization. We excluded patients who were refractory to steroids and initiated medical rescue therapy or required surgery during the index hospitalization. Our primary exposure of interest was initiation of biologic therapy within 1 month of hospital discharge or immunomodulator therapy (thiopurine, methotrexate) within 3 months. Our primary outcomes were need for colectomy within 12 months following hospitalization. Secondary outcomes include re-hospitalization rate within 12 months and late colectomy ( between 91-365 days). RESULTS: Our study included a total of 133 immunosuppressive-naïve ASUC patients among whom 56 (42%) escalated therapy to thiopurine (93%) or biologic (7%) post-hospitalization. The median age of the cohort was 29 years (range 16 – 88 years) and 46% were male. 82 patients (62%) had pancolitis on disease distribution. 38% and 58% were noted to have moderate to severe disease on sigmoidoscopic evaluation. Thirteen patients (10%) underwent surgery by 1 year. At 12 months, there was no difference in the rate of colectomy among those with therapy escalation (13%) compared to those who did not undergo such escalation (8%, unadjusted OR= 1.69 p=0.53). This lack of difference remained robust on multivariable regression analysis and propensity score adjusted models (OR 0.90, 95% confidence interval (CI) 0.18 – 4.45). There was no difference in the rates of hospitalization within 1 year (OR 2.24 95% CI 0.16 – 4.22) or in the time to colectomy between the two groups (log-rank p=0.27). CONCLUSION: Immunosuppression-naïve ASUC patients who respond to intravenous steroids remain at high risk for colectomy with 10% (13/133) receiving such surgery within 1 year. Therapy escalation was not associated with a reduction in this risk. There is an important need for larger prospective studies defining the benefit of early therapy escalation in UC, and appropriate thresholds for the same.

O rearranjo da anatomia gastrointestinal é atualmente o foco de estudos para a remissão e cura do diabetes mellitus tipo 2. Há evidências a favor da melhora desta comorbidade após a gastrectomia em pacientes não obesos, entretanto sem análise de longo prazo. O intestino grosso, como integrante do aparelho digestório e potencialmente produtor de incretinas, ainda não foi estudado em relação à influência de sua retirada (colectomia) no desfecho do diabetes. Nestas circunstâncias, faz-se necessário um estudo em longo prazo destas duas cirurgias na homeostase glicídica. Objetivos: Analisar a resposta em longo prazo do diabetes e pré-diabetes pré-existentes após gastrectomia, bem como, colectomia por câncer. Métodos: Foram analisados pacientes adultos submetidos à gastrectomia subtotal e total (Y de Roux) por câncer gástrico e colectomia (direita ou retossigmoidectomia) por câncer de colo e reto há mais de 3 anos e sem sinais de doença em atividade. Incluíram-se controles nas duas situações de pós-operatório tardio com homeostase glicídica normal, a fim de averiguar também sua evolução em longo prazo. Agregou-se ainda um grupo controle pré-operatório atual constituído de doentes diabéticos com câncer gástrico, candidatos à gastrectomia curativa, pois alguns exames analisados no pós-operatório não haviam sido coletados no período pré-operatório. Os pacientes foram divididos de acordo com a presença e curso clínico do diabetes. O grupo diabético foi subdividido em Refratários (permaneceram diabéticos) e Responsivos (remissão parcial ou completa). O grupo controle foi dividido em Estáveis (permaneceram sem diabetes) e Neodiabetes (ficaram diabéticos ou pré-diabéticos). Também foram avaliados de acordo com o tipo de cirurgia. Foram coletados exames de albumina, transferrina, ferritina, ferro sérico, hemoglobina, leucócitos, colesterol total, LDL, VLDL e HDL, triglicérides, insulina, hemoglobina A1C, Peptídeo C, IGF-1, Leptina, proteína C reativa, fibrinogênio, tempo de protrombina, dímero D, complemento C3 e C4, ácido fólico e vitamina B12. Peso, altura e perímetro abdominal e do quadril também foram analisados. Resultados: Os seguimentos atingiram 86,8 ± 25,1 meses nos gastrectomizados e 79,2 ±27,4 nos colectomizados. Os pacientes gastrectomizados beneficiaram-se com remissão do diabetes em 41,2% dos casos e os colectomizados em 32,4%. No grupo controle de gastrectomizados surgiram em longo prazo 63,2% de neodiabéticos e no de colectomizados 30,8%. Nos pacientes diabéticos responsivos com câncer gástrico houve paralelismo entre queda da glicemia e do IMC, algo que não se sucedeu nos acometidos de câncer colorretal. Em nenhuma das duas populações refratárias pode-se atribuir um papel para a variação do IMC no desfecho do diabetes. Nos pacientes neodiabéticos nenhuma contribuição do IMC foi despistada em quaisquer dos grupos estudados. Os pacientes diabéticos gastrectomizados e colectomizados não revelaram diferenças significativas nos valores de glicemia e prevalência de diabetes quando separados por tipo de cirurgia. Conclusão: Nos pacientes gastrectomizados, comprovou-se remissão do diabetes a longo prazo ainda que em proporções menores que as documentadas usualmente, com obesos tratados por cirurgia bariátrica. A perda de peso demonstrou influência positiva na resposta do diabetes. A exclusão duodenal pode ser outro fator envolvido na melhora do diabetes ao lado deste moderado emagrecimento. Já a remoção do fundo gástrico não demonstrou influência na evolução destes pacientes. Não há indícios de que a gastrectomia protegeu contra o aparecimento de novos casos de diabetes e pré-diabetes, pois estes se manifestaram em elevadas proporções. Os pacientes colectomizados diabéticos apresentaram taxa ligeiramente menor de responsivos quando comparados com o grupo bariátrico, sem diferenças significativas. A variação do peso e o local de ressecção não se relacionaram com o desfecho do diabetes. As conversões de pacientes normoglicêmicos para diabetes, ao final do tempo de seguimento, foram mais baixas que nos gastrectomizados. São necessários mais estudos para elucidar os mecanismos envolvidos na história natural da homeostase glicídica, tanto após gastrectomia quanto cirurgia colorretal / The rearrangement of gastrointestinal anatomy is currently the focus of research for the cure and remission of type 2 diabetes mellitus. There is evidence suggesting that this comorbidity improves after cancer gastrectomy in non-obese patients, however no long-term analysis is available. The large intestine, as part of the digestive system and potentially producing incretins, has not been studied with regard to the influence of surgical removal (colectomy) on the outcome of diabetes. In these circumstances, a study focusing the long-term outcome of glucose homeostasis after these two surgeries was deemed appropriate. Objectives: Analysis of the long-term response of preexisting diabetes and pre-diabetes after gastrectomy and colectomy for cancer. Population: Adult patients who underwent subtotal and total (Roux-en Y) gastrectomy for gastric cancer, as well as colorectal operation (right hemicolectomy or anterior resection) for colon and rectum cancer, with at least 3 years of follow up and no signs of active disease. Controls with normal glucose homeostasis were included in both contexts, in order to investigate long term evolution also in euglycemic subjects. A current preoperative control group was added consisting of diabetic patients with gastric cancer, aiming to provide information not available in the retrospective analysis of the preoperative period. Patients were divided according to the presence and clinical course of diabetes. The diabetes group was divided into Refractory (remained diabetic) and Responsive cases (partial or complete remission). The control group was similarly divided into Stable (remained without diabetes) and New onset diabetes/NOD (became diabetic or pre-diabetic). Surgical modality was also considered in the stratification (subtotal versus total gastrectomy and right colectomy versus anterior resection). Biochemical tests included albumin, transferrin, ferritin, serum iron, hemoglobin, white blood cell count, total cholesterol, LDL, VLDL, and HDL, triglycerides, insulin, hemoglobin A1C, C-peptide, IGF-1, leptin, C-reactive protein, fibrinogen, prothrombin time, D-dimer, complement C3 and C4, folic acid and vitamin B12. Weight, height and waist/hip ratio were also documented. Results: The follow-up reached 86.8 ± 25.1 months in patients submitted to gastrectomy and 79.2 ± 27.4 in colorectal surgery. Gastrectomized patients benefited from diabetes remission in 41.2% of cases and 32.4% after large bowel operation. NOD was detected in 63.2% and 30.8% of nondiabetic subjects, respectively. Among responsive diabetic patients with gastric cancer direct relation between fall in blood glucose and BMI was demonstrated, but not with colorectal cancer. In both refractory populations BMI failed to correlated with outcome of diabetes. In NOD patients no contribution of BMI was shown in any group either. Prevalence of diabetes was not different when stratified according to type of surgery. Conclusion: In gastrectomized patients, long term remission of diabetes was confirmed, even though is smaller proportions than those reported after bariatric surgery. Weight loss showed a positive influence in the responsive diabetes population submitted to gastrectomy. There are reasons to believe that duodenal exclusion was involved as well in diabetes amelioration, besides moderate weight loss. The removal of the gastric fundus was not relevant for the evolution of these patients. No evidence in favor of gastrectomy protection against the onset of new diabetes and pre-diabetes was detected. On the contrary, these were registered in high proportions. Colorectal diabetic patients had slightly lower rate of response when compared to the gastrectomy group, without significance. Weight shift and location of the resection were unrelated to the outcome of diabetes. NOD cases at the end of follow-up period were less frequent than after gastric surgery. Further studies are needed to elucidate the mechanisms involved in the natural history of glucose homeostasis, after both gastric and colorectal surgery

The overall aims of this thesis were to investigate the incidence of inflammatory bowel disease in the Uppsala Region of Sweden, to study the clinical course and the impact of the disease with regards to complications. Patients in Uppsala County were included in the study from the 1st of January 2005 and patients in Falun, Eskilstuna and Åland counties from the 1st of January 2007. The study was closed for all centres on the 31st of December 2009. Mean population in the study region was 305,381 in 2005–2006 and 642,117 in 2007–2009. The mean incidence for ulcerative colitis (UC) during the time period 2005-2009 was 20.0 /100,000/year (95% CI: 16.1-23.9) and for Crohn’s disease (CD) it was 9.9/100,000/year (95% CI: 7.1-12.6). The combined incidence for UC or CD in the area was thus 29.9/100,000/year (95% CI: 25.1-34.7). Half of the UC patients relapsed during the first year. Risk factors for relapse were female gender and young age. Colectomy during the first year was uncommon (2.5%). CD patients with complicated disease had longer symptom duration before diagnosis and less often diarrhoea and blood in stools compared to patients with non-complicated disease. The risk for surgery during the first year was 12%. The prevalence of anaemia at the time of diagnosis was 30% and after one year 18%. Anaemia was more common among newly diagnosed patients with CD compared with UC. 13% of the UC patients developed an acute severe episode. During the first 90 days 22% of these patients were subjected to colectomy. There was a significant difference between University and County hospitals in colectomy frequency (7.5% vs. 41%). The cumulative prevalence of treatment complications was 12% at the hospital with low colectomy rate versus 41% at the hospitals with high colectomy rate. In conclusion, the incidence of UC and CD in Sweden was high compared to international studies. Colectomy frequency for UC during the first year was low. Patients with complicated CD at the time of diagnosis had longer symptom duration and less alarming symptoms compared to uncomplicated disease. Anaemia was a common trait among patients with newly diagnosed IBD and more effort is needed to treat anaemia in these patients. Severe UC can be treated safely with prolonged medical therapy instead of colectomy.

Τα επίπεδα της γκρελίνης και του PYY μετά από χειρουργείο χολοπαγκρεατικής εκτροπής και Roux-en-Y γαστρικού bypass και μετά από χειρουργείο κολεκτομής: προοπτική συγκριτική μελέτη Οι ορμόνες του γαστρεντερικού γκρελίνη και PYY έχει αποδειχθεί ότι παίζουν κάποιο ρόλο στη ρύθμιση του μεταβολισμού και της όρεξης. Μελετάμε την επίδραση του χειρουργείου της χολοπαγκρεατικής εκτροπής και RYGBP (BPD-RYGBP) στα κυκλοφορούντα επίπεδα της γκρελίνης και του PYY άμεσα μετεγχειρητικά και τα συγκρίνουμε με την αντίστοιχη επίδραση μιας άλλης χειρουργικής επέμβασης της ίδιας βαρύτητας, την κολεκτομή. Μέθοδος. Μελετάμε τα επίπεδα νηστείας της γκρελίνης και του PYY σε 20 παχύσαρκους ασθενείς (super-obese) που υποβλήθηκαν σε BPDRYGBP και σε 13 ασθενείς που υποβλήθηκαν σε κολεκτομή για καρκίνο παχέος εντέρου. Οι μετρήσεις έγιναν προεγχειρητικά, και τις μετεγχειρητικές ημέρες 1,3,7,30 και 90 και στις δύο ομάδες, καθώς και στον 1 χρόνο στην ομάδα των παχυσάρκων. Αποτελέσματα. Προεγχειρητικά, τα επίπεδα και της γκρελίνης και του PYY ήταν χαμηλότερα στην ομάδα των παχυσάρκων. Μια προσωρινή μείωση των τιμών της γκρελίνης παρατηρήθηκε και στις δύο ομάδες άμεσα μετεγχειρητικά με σταδιακή επάνοδο στα προεγχειρητικά επίπεδα έως τον 3ο μήνα. Επιπλέον τα επίπεδα της γκρελίνης αυξήθηκαν 40%, σε σύγκριση με τα προεγχειρητικά, στην ομάδα των παχυσάρκων στον 1ο χρόνο παρακολούθησης. Τα επίπεδα του PYY στην ομάδα των κολεκτομών μειώθηκαν τις πρώτες 3 μετεγχειρητικές ημέρες και έπειτα επέστρεψαν στα προεγχειρητικά. Σε αντίθεση, τα επίπεδα του PYY στην ομάδα των παχυσάρκων δεν άλλαξαν άμεσα μετεγχειρητικά αλλά αυξήθηκαν σε επίπεδα 50% υψηλότερα στον 3ο μήνα και 170% υψηλότερα στον 1ο χρόνο, σε σύγκριση με τα προεγχειρητικά. Συμπεράσματα. Η μεγάλη μετεγχειρητική αύξηση των επιπέδων της ανορεξιογόνου ορμόνης PYY μετά από BPD-RYGBP μπορεί να παίζει ρόλο στην μειωμένη όρεξη που παρατηρείται μετά από αυτό τον τύπο βαριατρικής επέμβασης. Οι αλλαγές της γκρελίνης μετεγχειρητικά κάνουν τη συμμετοχή της ορμόνης αυτής στη μείωση της όρεξης λιγότερο πιθανή. / Ghrelin and Peptide YY levels anfter a variant of biliopancreatic diversion with Roux-en-Y gastric bypass versus after colectomy: A prospective comparative study Background. The gastrointestinal peptide hormones ghrelin and PYY, have been shown to play a role in the regulation of metabolism and apetite. We investigate the effect of the biliopancreatic diversion with Roux-en-Y gastric bypass (BPD-RYGBP) procedure on the circulating levels of ghrelin and PYY during the first 3 months postoperatively as compared to the effects of colectomy, an abdominal operation of similar severity. Methods. We determined the fasting plasma levels of ghrelin and PYY in 20 morbidly super obese patients that underwent BPD-RYGBP and in 13 subjects that underwent a colectomy because of large bowel cancer. Fasting plasma ghrelin and PYY levels were measured preoperatively and during the postoperative period on days 1,3,7,30 and 90 in all patients of both groups and at the 1 year for the patients who had attained 1-year follow up. Results. Preoperatively, both plasma ghrelin and PYY levels were lower in the BPD-RYGBP group of patients. A temporary decrease in plasma ghrelin levels was observed in both groups of patients during the immediate postoperative period with a gradual return to preoperative levels by the third month. In addition, ghrelin concentrations increased at one year to levels 40% higher than those in baseline, in ten of the BPD-RYGBP patients who had completed the one-year follow up (p=0.004). Plasma PYY levels in the colectomy group decreased the first three postoperative days and then returned to baseline. In contrast, PYY levels in the BPD-RYGBP group did not change during the early postopera¬tive period but increased to levels 50% higher at 3 months (p<0.001) and 170% higher at one year (p<0.001) than the baseline. Conclusions. The great postoperative increase of the levels of the anorexigenic peptide PYY following BPD-RYGBP may contribute to the reduced appetite observed after this type of bariatric surgery. The changes in ghrelin levels postoperatively make its contribution to the appetite suppression less likely.

The survey and subsequent knowledge of the records of patients who underwent surgical treatment due to the colon and rectum tumor are fundamental to the knowledge of the epidemiological profile of this prevalent malignancy today. Thus, knowledge of such data are relevant for developing strategies for prevention and treatment of this disease in the population. Thus, the objective of the study was to evaluate the data of patients undergoing colectomy and rectosigmoidectomy by colorectal tumor at the University Hospital of Santa Maria (HUSM) in the period 2010 to 2014. This is a cross-sectional, descriptive study with data obtained from medical records on the demographic profile, length of stay, number and type of surgical procedure, stage, location and histological-pathological type of colon tumor among others. During the study period were performed 224 surgeries colectomy and rectosigmoidectomy in patients with colorectal cancer in HUSM. Most (52.7%) patients were female. The merits, 30.8% were from Santa Maria, 11.2% of São Sepe and 58.0% from another location of the Rio Grande do Sul state. The average age of patients was 63.2 years, and 97.7% were between 40 and 89 years and the most frequent age group 60-69 years (28.1%). Regarding the onset of symptoms time, time of diagnosis to surgical treatment, hospital stay and time to diagnosis of treatment related to staging there was no improvement in service levels over the years analyzed. Furthermore, in relation to Dukes classification there was no difference in clinical evolution during the study period. This study reveals the need for reevaluation of continuously service, so that we can develop alternatives in order to optimize the service to patient with the colon and rectum cancer, and mainly seek strategies for early diagnosis. / O levantamento e conhecimento dos registros dos pacientes submetidos ao tratamento cirúrgico para tumor maligno de cólon e reto são fundamentais para determinar o perfil epidemiológico dessa neoplasia maligna tão prevalente nos dias atuais. Conhecer esses dados é relevante para a estruturação de estratégias de prevenção e tratamento desta moléstia na população. Portanto, o objetivo deste estudo foi avaliar as informações sobre os pacientes submetidos a colectomia e retossigmoidectomia por câncer colorretal no Hospital Universitário de Santa Maria (HUSM) no período de 2010 a 2014. Trata-se de um estudo transversal, descritivo com dados obtidos de prontuários sobre o perfil demográfico, tempo de internação, quantidade e tipo de procedimento cirúrgico, estadiamento, localização e tipo histológico-patológico do tumor de cólon e reto entre outros. Foram realizadas 224 cirurgias de colectomia e retossigmoidectomia em pacientes portadores de neoplasia colorretal. A maioria (52,7%) dos pacientes era do sexo feminino. Quanto à procedência, 30,8% eram de Santa Maria, 11,2% do município de São Sepé e 58,0% de outra localidade do estado do Rio Grande do Sul. A média de idade dos pacientes foi de 63,2 anos, sendo que 97,7% tinham entre 40 e 89 anos, e a faixa etária mais frequente a de 60 a 69 anos (28,1%). Com relação ao tempo do inicio dos sintomas, tempo do diagnóstico ao tratamento cirúrgico, tempo de internação hospitalar e tempo do diagnóstico ao tratamento relacionado ao estadiamento não houve melhora nos índices do Serviço no decorrer dos anos analisados, pelo contrário, o tempo do diagnóstico até a cirurgia e o tempo de internação antes da cirurgia aumentaram, significativamente, de 2010 para 2012. Em relação a classificação de Dukes não houve diferença na evolução clínica no período estudado. Os resultados obtidos nesse estudo revelam a necessidade de reavaliação do Serviço de forma continuada, afim de que se possam desenvolver alternativas no sentido de melhorar o atendimento ao paciente portador de neoplasia do cólon e reto, além de, principalmente, buscar estratégias para o diagnóstico precoce.