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Int J Surg Case Rep ; 93: 106994, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35367952


INTRODUCTION AND IMPORTANCE: Endometriosis is a gynecological condition referring to the presence of endometrial tissue outside the endometrium with the potential of progressing to malignancy. It mostly affects pelvic organs; however, it has been described beyond the pelvis. In 10% of cases it occurs in the bowel, mostly rectum and sigmoid. Involvement of the small bowel is rare. Here we report endometriosis of the terminal ileum and appendix in a patient with no previous diagnosis of endometriosis. CASE PRESENTATION: We describe a case of a 39-year-old-female who presented with abdominal pain, nausea and vomiting to the emergency department. This was on background history of intermittent abdominal pain every 2 weeks for the previous 5 months. Further investigation with computed tomography (CT) of the abdomen and pelvis showed small bowel dilatation with a polypoidal lesion obstructing the terminal ileum. On colonoscopy, no intraluminal lesions were identified in the terminal ileum. The patient underwent right hemicoloectomy. Histopathological results revealed endometriosis. The patient had uneventful recovery post-operatively and at her follow-up review at 4 weeks and 2 months from surgery. DISCUSSION: The presentation of endometriosis of the bowel is highly variable and difficult to diagnose pre-operatively. Due to lack of specific diagnostic measures, surgical resection and histology can be the only reliable way for first-time endometriosis diagnosis presenting as small bowel obstruction. CONCLUSION: Extra-pelvic endometriosis should be considered as the cause of small bowel obstruction in the absence of other causes of bowel obstruction in young female patients.

Transl Oncol ; 14(12): 101229, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592589


Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions. The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model. Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR. Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

Diab Vasc Dis Res ; 17(1): 1479164119879039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31726864


BACKGROUND: Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported. METHODS: We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease. RESULTS: At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin-creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology. CONCLUSION: Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.

Albuminúria/etiologia , Diferenciação Celular , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Derivação Gástrica , Obesidade/cirurgia , Podócitos/patologia , Idoso , Albuminúria/sangue , Albuminúria/patologia , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Obesidade/complicações , Obesidade/diagnóstico , Estudos Prospectivos , Ratos Zucker , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Perda de Peso
Curr Diab Rep ; 15(8): 55, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26122095


Progressive renal impairment (diabetic kidney disease (DKD)) occurs in upwards of 40 % of patients with obesity and type 2 diabetes mellitus (T2DM) and is a cause of significant morbidity and mortality. Means of attenuating the progression of DKD focus on amelioration of risk factors. Visceral obesity is implicated as a causative agent in impaired metabolic and cardiovascular control in T2DM, and various approaches primarily targeting weight have been examined for their impact on markers of renal injury and dysfunction in DKD. The current report summarises the evidence base for the impact of surgical, lifestyle and pharmacological approaches to weight loss on renal end points in DKD. The potential for a threshold of weight loss more readily achievable by surgical intervention to be a prerequisite for renal improvement is highlighted. Comparing efficacious non-surgical weight loss strategies with surgical strategies in appropriately powered and controlled prospective studies is a priority for the field.

Nefropatias Diabéticas/diagnóstico , Perda de Peso , Animais , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Comportamento Alimentar , Humanos , Estilo de Vida , Obesidade/complicações , Fatores de Risco
Histopathology ; 61(3): 488-96, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22463746


AIMS: Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding. METHOD AND RESULTS: Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over-represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2-6.4; P = 0.02). CONCLUSION: Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.

Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Peritônio/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
PLoS One ; 6(10): e26125, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22022533


Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.

Degranulação Celular , Neovascularização Patológica/patologia , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologia , Adesividade Plaquetária , Transdução de Sinais , Difosfato de Adenosina/análogos & derivados , Difosfato de Adenosina/farmacologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Trifosfato de Adenosina/farmacologia , Apirase/farmacologia , Ácido Araquidônico/farmacologia , Degranulação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/genética , Fragmentos de Peptídeos/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Receptores Purinérgicos P2Y1/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Receptores de Trombina/antagonistas & inibidores , Receptores de Trombina/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos