The coexpression of fibroblast activation protein (FAP) and basal-type markers (CK 5/6 and CD44) predicts prognosis in high-grade invasive urothelial carcinoma of the bladder.

High-grade urothelial carcinoma (UC) of the bladder is a heterogeneous disease with dismal prognosis. Bladder tumors with basal phenotype are intrinsically aggressive, and morphological parameters that define disease staging remain main prognosticators. We intend to evaluate the role of cancer-associated fibroblasts (CAFs) in the prognosis of bladder cancer and its association with basal and luminal phenotypes. Clinical and pathological parameters, including the immunohistochemical expression of fibroblast activation protein (FAP) and markers of basal (CK5/6, CD44) and luminal (CK20, GATA3) phenotypes, have been investigated in a series of 121 patients with UC of the bladder treated by radical cystectomy with lymph node dissection, and their implication in long-term cancer-specific survival has been evaluated. A cytoplasmic immunostaining of FAP in CAFs implies worse disease-specific survival (hazard ratio [HR] = 1.68; P = .048). FAP expression is associated with tumor staging (P < .0001), with best discrimination at T2a/T2b level, and with negative expression of markers of luminal phenotype, such as CK20 (P < .0001) and GATA3 (P = .005). In the multivariate analysis, simultaneous expression of FAP, CK5/6, and CD44 is a strong prognosticator of disease-specific survival (HR = 2.3; P = .001), together with nodal invasion (HR = 3.47; P < .0001) and bladder infiltration up to deep muscle or beyond (HR = 2.47; P = .02). There is no association between positive FAP expression in primary tumor and nodal disease (P = .22). FAP expression in CAFs favors tumor invasion in high-grade invasive UC of the bladder with basal phenotype. This new immunohistochemical marker could be added to the routine immunohistochemical protocol to predict clinical behavior in these patients.

Surgical versus nonsurgical treatment of infected pancreatic necrosis: more arguments to change the paradigm.

OBJECTIVES: This study aimed to compare primary surgical versus nonsurgical treatment in a series of patients with infected pancreatic necrosis (IPN) and to investigate whether the success of nonsurgical approach is related to a less severe disease. METHODS: Thirty-nine consecutive patients with IPN have been included and further subdivided into two groups: primary surgical (n = 21) versus nonsurgical (n = 18). Outcome measures were the differences in mortality, morbidity, and pancreatic function. Comorbidity, organ failure, and other severity indexes were compared between the two groups. RESULTS: Mortality occurred in 16.7% of cases in the nonsurgical group versus 42.9% in the surgical group. In the primary nonsurgical group, seven were operated on due to failure of initial conservative treatment. In this latter group, mortality was 28.6% and was performed significantly later than in the primary surgical group. The group of primary surgical treatment was associated with a significant higher rate of multiple organ failure (MOF) at IPN diagnosis, new onset or worsening of organ failure, and MOF and nosocomial infection after surgery. CONCLUSIONS: Initial nonsurgical approach in IPN is associated with better results both in cases which respond to this treatment as well as in those who, failing this conservative approach, have to be operated on after a delayed period. Primary surgically treated patients had a more severe disease at the time of IPN.

[Pancreatic and periampullary tumors: morbidity, mortality, functional results and long-term survival]. / Neoplasias de páncreas y periampulares: morbimortalidad, resultados funcionales y supervivencia a largo plazo.

AIMS: To evaluate postoperative morbidity and mortality, pancreatic function and long-term survival in patients with surgically treated pancreatic or periampullar tumours. PATIENTS AND METHODS: Cohort study including 160 patients consecutively operated on: 80 pancreaticoduodenectomies (PD), 30 distal pancreatectomies (DP), 7 total pancreatectomies, 4 central pancreatic resections and 3 ampullectomies. The tumour was not resected in 36 patients. Pancreatic function was evaluated by oral glucose tolerance test, faecal fat excretion and elastase. RESULTS: Resectability rate was 77.5%. In resected patients (n = 124), 38.7% had complications with a pancreatic fistula rate of 6.4% and a mortality rate of 4%. In PD, endocrine function worsened in 41% and 58.6% had steatorrhoea; these figures in DP were 53.6% and 21.7% respectively. In the 36 non-resected patients, postoperative morbidity was 27.7% and mortality 8.3%. Two and five-year survival rates in resected patients with pancreatic cancer were 42% and 9% respectively; in malignant ampulloma 71% and 53%; in mucinous adenocarcinomas 83% and 33%; in duodenal adenocarcinoma 100% and 75%; and in distal cholangiocarcinoma 50% and 50%. CONCLUSIONS: Morbidity associated with resective pancreatic surgery is still high, but perioperative mortality is low. Endocrine and exocrine disturbances are very common depending on the type of resection. Despite the associated morbidity and functional disorders, surgery provides long-term survival in selected cases.

[Effect of neoadjuvant chemotherapy on the results of resection of colorectal liver metastases]. / Efecto de la quimioterapia neoadyuvante en los resultados de la cirugía de resección de las metástasis hepáticas de origen colorrectal.

INTRODUCTION: Surgery is the treatment of choice in patients with colorectal liver metastases. However, only 10% to 20% of these cases are resectable. The use of neoadjuvant chemotherapy may allow surgery in patients with tumors initially considered unresectable. The aim of this study was to compare the results of liver resection due to colorectal liver metastases in patients with and without neoadjuvant chemotherapy. PATIENTS AND METHOD: We studied 105 patients who underwent surgery for liver metastases from colorectal cancer. The patients were divided into two groups according to treatment: surgery in patients with initially resectable tumors (group 1) and neoadjuvant chemotherapy plus surgery (group 2) in patients with initially irresectable tumors, who were considered for surgery after response to chemotherapy. Age, sex, origin of primary tumor, time of presentation, number, maximum size and location of metastases, CEA, resection margin, postoperative morbidity and mortality, length of hospital stay, recurrence rate, survival and disease-free survival were compared between the 2 groups of patients. RESULTS: When group 1 was compared with group 2, statistically significant differences were observed in synchronicity (30.8% vs 77.4%), bilobarity (13.5% vs 58.5%), number and size of metastases (1 vs 3 nodules and 4 cm vs 2 cm), resectability rate (96.1% vs 81.1%), disease-free interval (25 vs 11 months) and long-term survival at 1, 3 and 5 years (93%, 67% and 36% vs 78%, 26% and 12%). However, no statistically significant differences were found in postoperative morbidity and mortality (28.8% and 0% in group 1 and 22.6% and 1.8% in group 2, respectively). CONCLUSIONS: Neoadjuvant chemotherapy was not associated with greater postoperative morbidity and mortality after resection of colorectal liver metastases, but long-term survival was lower in the group of patients receiving this treatment modality than in those with tumors initially considered resectable.

Multiple intrahepatic pseudocysts in acute pancreatitis.

Liver pseudocysts are a very rare complication in acute pancreatitis with only a few cases previously described. The lack of experience and literature on this condition leads to difficulties in the differential diagnosis and management. We report herein a case of acute pancreatitis who developed multiple intrahepatic pseudocysts. After complete imaging evaluation, the diagnosis was still unclear and the patient was operated on. The presence of liver lesions in patients with acute pancreatitis should raise the possibility of intrahepatic pseudocysts.

Effect of simultaneous inhibition of TNF-alpha production and xanthine oxidase in experimental acute pancreatitis: the role of mitogen activated protein kinases.

OBJECTIVE: To assess the effects of inhibiting both tumor necrosis factor (TNF)-alpha production and xanthine oxidase activity on the inflammatory response, mitogen-activated protein kinase (MAPK) activation and mortality in necrotizing acute pancreatitis in rats. SUMMARY BACKGROUND DATA: Pancreatic injury triggers 2 major pathways involved in the systemic effects of severe acute pancreatitis: pro-inflammatory cytokines and oxidative stress. METHODS: Pancreatitis was induced by intraductal infusion of 3.5% sodium taurocholate. We examined whether treatment with oxypurinol, a specific inhibitor of xanthine oxidase, and/or pentoxifylline, an inhibitor of TNF-alpha production, affects pancreatic damage, ascites, lung inflammation, and MAPK phosphorylation. RESULTS: Oxypurinol prevented p38 phosphorylation in the pancreas and partially avoided the rise in lung myeloperoxidase activity. Pentoxifylline prevented erk 1/2 and JNK phosphorylation in the pancreas, and it partially reduced ascites and the rise in lung myeloperoxidase activity. Combined treatment with oxypurinol and pentoxifylline almost completely abolished ascites, MAPK phosphorylation in the pancreas, and the increase in lung myeloperoxidase activity. Histology revealed a reduction in pancreatic and lung damage. These changes were associated with a significant improvement of survival. CONCLUSIONS: : Simultaneous inhibition of TNF-alpha production and xanthine oxidase activity greatly reduced local and systemic inflammatory response in acute pancreatitis and decreased mortality rate. These effects were associated with blockade of the 3 major MAPKs.

Effects of PEEP on residual vascularization in oesophageal substitution gastroplasty by surface oximetry-capnometry and photoplethysmography: an experimental study.

OBJECTIVE: To evaluate the effects of positive end-expiratory pressure (PEEP) on residual vascularization in gastric tubes for oesophageal replacement. DESIGN: Experimental open study. MATERIALS: Eleven mongrel dogs. METHODS: Intestinal parietal blood flow was evaluated by photoplethysmography (PPG) and measurement of surface oxygen (PsO(2)) and carbon dioxide (PsCO(2)) tensions under basal conditions. After Akiyama's tubular gastroplasty, three levels of PEEP were administered. At each level, fluids were infused to counter the drop in cardiac output. PPG, surface gas tensions, arterial pressure, cardiac output and arterial blood gas tensions were monitored. Control sections of the bowel were also monitored by PPG. RESULTS: Cardiac output dropped for each level of PEEP and returned to basal levels on volume restabilization and on removal of PEEP. Central venous pressure and pulmonary arterial and capillary pressures increased for each level of PEEP and only returned to basal levels on removal of PEEP. PsO(2) values dropped for each level of PEEP and returned to basal levels on volume restabilization and on removal of PEEP. PsCO(2) levels rose, and PPG wave amplitude dropped, for each level of PEEP; these two variables only returned to basal levels on removal of PEEP. PPG values for the control sections reflected those of the anastomotic area. CONCLUSIONS: PEEP affects surface oxygen values at the level of the gastroplasty by means of its effect on cardiac output. PEEP also creates a venous return compromise and PPG wave amplitude and surface carbon dioxide values are related to this compromise. All three variables could be significant in anastomotic wound healing.