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1.
HPB (Oxford) ; 25(3): 301-310, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36529625

RESUMEN

BACKGROUND: Pancreaticoduodenectomy (PD) is complex procedure with high morbidity in the elderly. This retrospective study aimed to compare post-operative outcomes in patients ≥75 years of age who underwent robot-assisted (RA)PD and open PD. METHODS: We analyzed 2502 patients ≥75 years of age who underwent PD from 2015 to 2018 in the National Surgical Quality Improvement Program (NSQIP) database. RAPD and open PD patients were propensity score matched 1:5 to assess the 30-day outcomes of interest: postoperative complications, length of stay, discharge destination, and readmissions. RESULTS: Of 725 matched patients, 110 underwent RAPD, 615 OPD, and 12 were converted to an open operation. Post-operative outcomes were largely similar between cohorts. RAPD was associated a shorter length of stay (median 8 days, interquartile range [IQR] 6 to 11) than OPD (median 8 days, IQR 7 to 13) (p = 0.003). However, RAPD was associated with more readmissions (28.1% vs. 17.7%; p = 0.02). CONCLUSIONS: RAPD in patients ≥75 years of age appears to be safe and has a similar complication profile to open PD. Randomized or well-designed prospective matched studies are needed to confirm these findings.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Anciano , Pancreaticoduodenectomía/efectos adversos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios Retrospectivos , Estudios Prospectivos , Puntaje de Propensión , Técnica del ADN Polimorfo Amplificado Aleatorio , Complicaciones Posoperatorias/etiología , Laparoscopía/efectos adversos , Tiempo de Internación , Neoplasias Pancreáticas/cirugía
2.
HPB (Oxford) ; 20(5): 418-422, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29398424

RESUMEN

BACKGROUND: Pancreatic fistula is a major cause of morbidity after pancreas surgery. In 2014, a single-center, randomized-controlled trial found pasireotide decreased pancreatic fistula rates. However, this finding has not been validated, nor has pasireotide been widely adopted. METHODS: A single-arm study in 111 consecutive patients undergoing pancreatic resection April 2015-October 2016 was conducted. Beginning immediately before surgery, patients received 900 µg subcutaneous pasireotide twice daily for up to seven days. Fistula rates were compared to 168 historical controls from July 2013 to March 2015. The primary outcome was Grade B/C fistula, as defined by the International Study Group on Pancreatic Fistula (ISGPF). RESULTS: There were no significant differences between the pasireotide group and historical controls in demographics, comorbidities, operation type, malignancy, gland texture, or pancreatic duct size. Pasireotide did not reduce fistula rate (15.5% control versus 17.1% pasireotide, p = 0.72). In subgroup analyses of pancreaticoduodenectomy or distal pancreatectomy, or patients with soft gland texture and/or small duct size, there was no decrease in fistulas. Thirty-nine patients (38%) experienced dose-limiting nausea. CONCLUSIONS: In an appropriately-powered, single-institution prospective study, pasireotide was not validated as a preventive measure for pancreatic fistula.


Asunto(s)
Pancreatectomía/efectos adversos , Fístula Pancreática/prevención & control , Pancreaticoduodenectomía/efectos adversos , Somatostatina/análogos & derivados , Anciano , Estudios de Casos y Controles , Esquema de Medicación , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Fístula Pancreática/diagnóstico por imagen , Fístula Pancreática/etiología , Estudios Prospectivos , Factores de Riesgo , Somatostatina/administración & dosificación , Somatostatina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
3.
Br J Cancer ; 114(12): 1367-75, 2016 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-27300108

RESUMEN

BACKGROUND: Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation. METHODS: Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC. RESULTS: We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ⩾3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001). CONCLUSION: CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.


Asunto(s)
Carcinoma Ductal Pancreático/patología , Células Neoplásicas Circulantes/patología , Neoplasias Pancreáticas/patología , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/sangre , Estudios de Cohortes , Humanos , Estadificación de Neoplasias , Neoplasias Pancreáticas/sangre , Proteínas Proto-Oncogénicas p21(ras)/genética
4.
Endoscopy ; 45(5): 397-400, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23616128

RESUMEN

We report a case series of all consecutive patients hospitalized in our two tertiary referral medical centers over the past 17 years for Cameron ulcers causing severe upper gastrointestinal hemorrhage (GIH) or severe obscure GIH. Cameron ulcers were diagnosed in 25 of the 3960 screened patients with severe upper GIH or severe obscure GIH (0.6 %). Of these, 21 patients had a prospective follow-up (median time 20.4 months [interquartile range: 8.5 - 31.8]). Patients were more often elderly women with chronic anemia, always had large hiatal hernias, and were usually referred for obscure GIH. Twelve of the 21 patients (57 %) were referred for surgery while being treated with high-dose proton pump inhibitors (PPIs). The other 9 patients (43 %) continued PPIs without any rebleeding during the follow-up. Cameron ulcers in large hiatal hernias are an uncommon cause of severe upper GIH. The choice of medical vs. surgical therapy should be individualized.


Asunto(s)
Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Hernia Hiatal/complicaciones , Hernia Hiatal/terapia , Úlcera Gástrica/complicaciones , Úlcera Gástrica/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anemia/tratamiento farmacológico , Anemia/etiología , Femenino , Fundoplicación , Gastropexia , Gastroscopía , Humanos , Análisis de Intención de Tratar , Hierro/uso terapéutico , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , Recurrencia
5.
Br J Cancer ; 103(10): 1571-9, 2010 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-20978507

RESUMEN

PURPOSE: Tumour hypoxia activates hypoxia-inducible factor-1 (HIF-1) and indluences angiogenesis, cell survival and invasion. Prolyl hydroxylase-3 (PHD3) regulates degradation of HIF-1α. The effects of PHD3 in tumour growth are largely unknown. EXPERIMENTAL DESIGN: PHD3 expression was analysed in human pancreatic cancer tissues and cancer cell lines by real-time quantitative PCR and immunohistochemistry. PHD3 overexpression was established by stable transfection and downregulation by short interfering RNA technology. VEGF was quantified by enzyme-linked immunosorbent assay. Matrigel invasion assays were performed to examine tumour cell invasion. Apoptosis was measured by annexin-V staining and caspase-3 assays. The effect of PHD3 on tumour growth in vivo was evaluated in an established orthotopic murine model. RESULTS: PHD3 was upregulated in well-differentiated human tumours and cell lines, and regulated hypoxic VEGF secretion. PHD3 overexpression mediated tumour cell growth and invasion by induction of apoptosis in a nerve growth factor-dependent manner by the activation of caspase-3 and phosphorylation of focal adhesion kinase HIF-1 independently. In vivo, PHD3 inhibited tumour growth by abrogation of tumour angiogenesis. CONCLUSION: Our results indicate essential functions of PHD3 in tumour growth, apoptosis and angiogenesis and through HIF-1-dependent and HIF-1-independent pathways.


Asunto(s)
Dioxigenasas/genética , Neovascularización Patológica/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Animales , Anexina A5/análisis , Apoptosis , Carcinoma Ductal Pancreático/enzimología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Caspasa 3/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Dioxigenasas/fisiología , Ensayo de Inmunoadsorción Enzimática , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Prolina Dioxigenasas del Factor Inducible por Hipoxia , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/cirugía , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Neoplásico/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante Heterólogo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/análisis
6.
J Gastrointest Surg ; 12(2): 234-42, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18040749

RESUMEN

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.


Asunto(s)
Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Anciano , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Cistadenoma Seroso/patología , Cistadenoma Seroso/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pancreaticoduodenectomía , Estudios Retrospectivos , Factores de Riesgo
7.
J Clin Endocrinol Metab ; 83(7): 2384-6, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9661614

RESUMEN

The etiology of secondary hyperparathyroidism is multifactorial, and as many as 10% of patients will ultimately require surgical intervention. This condition is most commonly caused by four-gland hyperplasia. We describe a patient who presented with secondary hyperparathyroidism and symptoms of memory loss, pruritus, constipation, and bone and joint pain. These complaints could not be controlled with conventional therapy. Over a three-year period, the patient underwent three neck explorations, with complete and persistent relief of his symptoms following the last parathyroidectomy. A total of eight parathyroid glands were removed during these three procedures. Although recurrence of hyperparathyroidism can be caused by seeding at the time of operation, the glands removed during the second and third procedures were not the typical miliary seeding seen with this complication. These glands were solid and hypertrophied and were found in areas not previously explored. A discussion of the possible causes of this unusual presentation is included.


Asunto(s)
Hiperparatiroidismo Secundario/patología , Glándulas Paratiroides/anomalías , Calcio/sangre , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/cirugía , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/cirugía
8.
Surgery ; 116(6): 1153-7; discussion 1157-8, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7985100

RESUMEN

BACKGROUND: Plasma peptide YY (PYY) levels rise after a meal and have recently been shown to increase small bowel-absorption. The purpose of this study was to determine whether immunoneutralization of PYY would block postprandial absorption in vivo. METHODS: Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm) were created in six mongrel dogs. After a 2-week recovery luminal perfusion with an isotonic buffer, containing [14C]-polyethylene glycol as a volume marker, was used to analyze water and sodium flux after an oral meal. Each meal was accompanied by either intravenous anti-PYY (0.5 mg.kg-1.h-1) or nonspecific immunoglobulin IG (control). PYY antibody binding was determined by radioimmunoassay. RESULTS: Displacement studies showed complete PYY neutralization. In control experiments feeding increased absorption of sodium and water in both segments. PYY immunoneutralization had no effect on jejunal absorption but significantly diminished ileal absorption (p < 0.05). CONCLUSIONS: These results suggest that PYY acts selectively in the ileum to increase postprandial fluid and electrolyte absorption after a meal. Agents directed at PYY-stimulated absorption may prove to be of therapeutic benefit in patients with malabsorptive conditions.


Asunto(s)
Hormonas Gastrointestinales/fisiología , Absorción Intestinal , Péptidos/fisiología , Animales , Perros , Femenino , Alimentos , Inmunoglobulinas Intravenosas/inmunología , Péptido YY , Péptidos/inmunología
9.
Surgery ; 116(2): 401-7; discussion 408, 1994 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8048006

RESUMEN

BACKGROUND: The mechanisms of intestinal adaptation after resection are not completely defined. The purpose of this study was to examine the changes after resection in the enterocyte basolateral Na+,K+ adenosine triphosphatase (ATPase) known to play a critical role in epithelial transport and homeostasis. METHODS: Lewis rats underwent 70% small bowel resection or transection. At 6 hours, 24 hours, 1 week, and 2 weeks, jejunum and ileum were harvested for analysis of Na+,K+ ATPase activity, kinetic analysis, and alpha 1-ATPase messenger RNA and protein levels. RESULTS: Na+,K+ ATPase activity increased (p < 0.05) in both the jejunum and ileum by 2 weeks after resection. This rise in activity correlated with an increase in the maximal activity of ATPase, from 20.8 to 101.01 mumol inorganic phosphate.mg-1.hr-1. ATPase messenger RNA levels increased sixfold in the jejunum and tenfold in the ileum by 2 weeks after resection (p < 0.05). Protein levels rose at 6 hours and remained elevated in both tissues. CONCLUSIONS: After intestinal resection, enterocyte Na+,K+ ATPase activity rises as a result of an increase in the number of transporters per cell. This occurs through both transcriptional and translational mechanisms. It appears that intestinal adaptation after resection involves not only an increase in absorptive surface area but also functional adaptation by the individual enterocyte.


Asunto(s)
Intestinos/enzimología , Intestinos/cirugía , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Adaptación Fisiológica , Animales , Secuencia de Bases , Isoenzimas/metabolismo , Cinética , Datos de Secuencia Molecular , ARN Mensajero/análisis , Ratas , Ratas Endogámicas Lew , ATPasa Intercambiadora de Sodio-Potasio/genética , Regulación hacia Arriba
10.
Arch Surg ; 131(5): 566-8, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8624207

RESUMEN

Intra-abdominal cysts may rise from a variety of organs. However, foreign-body reaction and cyst formation should be considered in the differential diagnosis. In this report, we describe the finding of a preoperatively undetected gossypiboma. A gossypiboma is a mass within the body that is composed of a cotton matrix; in this case, an unmarked laparotomy sponge. The evaluation, findings, and prevention of gossypiboma are discussed.


Asunto(s)
Abdomen , Quistes/etiología , Reacción a Cuerpo Extraño/complicaciones , Tapones Quirúrgicos de Gaza , Abdomen/cirugía , Quistes/diagnóstico por imagen , Quistes/cirugía , Humanos , Radiografía Abdominal , Tomografía Computarizada por Rayos X
11.
Arch Surg ; 135(9): 1070-4; discussion 1074-5, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10982512

RESUMEN

HYPOTHESIS: In patients with duodenal adenocarcinoma, certain pathologic features of the tumor will have prognostic significance. DESIGN: Retrospective case series. PATIENTS: Forty-nine patients diagnosed with duodenal adenocarcinoma between 1957 and 1998. RESULTS: The tumors of 31 (63%) of the 49 patients underwent resection, 18 (37%) had surgical palliation or underwent biopsy. Mean (+/- SEM) survival for all patients was 49 +/- 9 months. The patients whose tumors were resected had longer survival than those who underwent palliation (mean +/- SEM, 66 +/- 13 months vs 18 +/- 6 months, P =.02). Multivariate analysis revealed large tumor size (P =.01), transmural invasion (P =.004), and moderate to poor tumor grade (P =.03) were negatively correlated with survival. Lymph node status did not influence survival. CONCLUSIONS: Our 40-year experience with duodenal adenocarcinoma demonstrates that large tumor size, advanced histological grade, and transmural invasion are associated with decreased survival. These results underscore the importance of early diagnosis, and suggest the presence of nodal spread is not a contraindication to resection.


Asunto(s)
Adenocarcinoma/mortalidad , Neoplasias Duodenales/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreaticoduodenectomía , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Análisis de Supervivencia
12.
Pancreas ; 22(2): 113-21, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11249064

RESUMEN

The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant animal models. The aims of this study were to establish an orthotopic model of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distant metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of the resulting s.c. tumors were microsurgically implanted into the pancreas of recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal tumors, surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group occurred simultaneous with primary tumor growth, indicating PaCa cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of ductal pancreatic adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.


Asunto(s)
Adenocarcinoma/patología , Modelos Animales de Enfermedad , Neoplasias Pancreáticas/patología , Animales , Trasplante de Neoplasias , Ratas , Ratas Endogámicas Lew , Células Tumorales Cultivadas
13.
Pancreas ; 21(4): 414-20, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11075997

RESUMEN

Severe acute pancreatitis (AP) is associated with both the local (pancreatic) release of cytokines and an elevation in their systemic plasma concentrations. This may lead to organ dysfunction and death of the patient. The aims of this study were to investigate the source(s) of systemic cytokine production during experimental AP. Forty-two rats were allocated to five groups (control, sham operation and saline injection, sham operation and gadolinium chloride injection, intraductal sodium-taurocholate infusion and saline injection, or intraductal sodium-taurocholate infusion and gadolinium chloride injection). Blood from the iliac artery, portal vein, and hepatic vein, along with tissue from the pancreas, liver, and lung, were collected. Serum levels of TNFalpha, IL-1beta, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay. Tissue mRNA for IL-1beta and IL-10 was assessed by reverse-transcription polymerase chain reaction. In untreated animals with AP, the lowest serum cytokine levels were found in the portal vein. In the hepatic vein, the levels of TNFalpha, IL-1beta, and IL-6 were higher. The highest serum levels were detected in the systemic circulation. In the gadolinium chloride-treated group, there was no increase in hepatic or systemic cytokine levels and less lung injury was observed. Extrapancreatic cytokine production from both the liver and the lung contributed significantly to systemic levels of TNFalpha, IL-1beta, IL-6, and IL-10 in this experimental model of AP.


Asunto(s)
Citocinas/análisis , Macrófagos del Hígado/fisiología , Hígado/química , Pulmón/patología , Pancreatitis/etiología , Enfermedad Aguda , Animales , Citocinas/genética , Femenino , Pancreatitis/patología , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley
14.
J Am Coll Surg ; 180(4): 417-26, 1995 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7719545

RESUMEN

BACKGROUND: Previous studies suggest that peptide YY (PYY) and enteroglucagon have an important role in intestinal adaptation after massive small bowel resection. This study was done to define the mechanisms, timing, and anatomic distribution of the PYY and enteroglucagon response. STUDY DESIGN: Lewis rats underwent resection of 70 percent of the small bowel (leaving equal segments of jejunum and ileum), transection, or laparotomy alone. Jejunum, ileum, and colon were compared in resected, transected, and control bowel six hours, 24 hours, one week, and two weeks postoperatively. RESULTS: Analysis of DNA, RNA, and protein per cm of bowel demonstrated hyperplastic changes. Radioimmunoassay revealed plasma PYY and enteroglucagon to be significantly elevated 24 hours after resection and they remained so through week two. In contrast, tissue PYY and enteroglucagon content decreased significantly in all tissues (p < 0.05) after resection. Reverse transcriptase polymerase chain reaction and Southern blot analysis demonstrated an immediate and sustained increase in PYY messenger RNA (mRNA) in both the ileum (fourfold) and in the colon (2.5-fold) at six hours (p < 0.05). A gradual increase in PYY mRNA was also demonstrated in the jejunum with significance at two weeks (p < 0.05). Proglucagon mRNA was significantly higher in the jejunum, compared with the ileum and colon, at 24 hours, one week, and two weeks postresection. CONCLUSIONS: Alterations in PYY and enteroglucagon synthesis occur early in the ileum and colon after massive small bowel resection. The residual jejunum, however, is primarily responsible for the adaptive hyperenteroglucagonemia. These findings suggest that although PYY and enteroglucagon are colocalized to the same cell type, there is a gene-specific response for these two peptides after resection.


Asunto(s)
Péptidos Similares al Glucagón/biosíntesis , Intestino Delgado/cirugía , Biosíntesis de Péptidos , Adaptación Fisiológica , Animales , Southern Blotting , Colon/metabolismo , Hormonas Gastrointestinales/biosíntesis , Hormonas Gastrointestinales/genética , Péptidos Similares al Glucagón/genética , Péptidos Similares al Glucagón/metabolismo , Íleon/metabolismo , Intestino Delgado/metabolismo , Yeyuno/metabolismo , Péptido YY , Péptidos/genética , Péptidos/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Ratas , Ratas Endogámicas Lew
15.
J Gastrointest Surg ; 5(2): 131-8, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11331474

RESUMEN

In this study we investigated the effects of the angiogenesis inhibitor TNP-470 on human pancreatic cancer cells in vitro and in vivo. The action of TNP-470 on vascular endothelial growth factor (VEGF) was also assessed. In vitro human pancreatic cancer cells (MIAPaCa-2, AsPC-1, and Capan-1), and human umbilical vein endothelial cells (HUVEC) were exposed to increasing concentrations (1 pg/ml to 100 microg/ml) of TNP-470. Cell proliferation was assessed after 3 days by cell count and MTT assay. In vivo, 5 x 10(6) pancreatic cancer cells were injected subcutaneously into nude mice. Four weeks later, 1 mm3 fragments of the resulting tumors were implanted into the pancreas of other mice. Animals received either TNP-470 (30 mg/kg every other day) or vehicle subcutaneously for 14 weeks. The volume of the primary tumor and metastatic spread were determined at autopsy. Concentrations of VEGF were determined in serum (VEGF(S)) and ascites (VEGF(A)) by enzyme-linked immunosorbent assay. Microvessel density was analyzed by immunohistochemistry in CD31-stained tumor sections. In vitro, proliferation and viability of the human pancreatic cancer cell lines were significantly inhibited at high concentrations of TNP-470 (> 1 microg/ml). In contrast, TNP-470 effectively decreased the growth of HUVEC at 100 pg/ml. In vivo, tumor volume and dissemination scores were significantly lower in all three pancreatic cancer cell lines. VEGF(S) and VEGF(A) were not different between treated groups. Treatment with TNP-470 significantly reduced neoangiogenesis in tumors of all three human pancreatic cancer cell lines: MIAPaCa-2 = 74.8 +/- 7.8/0.74 mm2 vs. 24.8 +/- 3.7/0.74 mm2; AsPC-1 = 65.3 +/- 5.0/0.74 mm2 vs. 26.0 +/- 3.4/0.74 mm2; and Capan-1 = 82.2 +/- 5.8/0.74 mm2 vs. 26.9 +/- 2.5/0.74 mm2 (P < 0.001). However, survival was not statistically different between groups. TNP-470 reduced tumor growth and metastatic spread of pancreatic cancer in vivo. This was probably due to the antiproliferative effect of the agent on endothelial cells rather than to the direct inhibition of pancreatic cancer cell growth. TNP-470 activity was not associated with alteration of VEGF secretion.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Sesquiterpenos/uso terapéutico , Adenocarcinoma/irrigación sanguínea , Animales , División Celular , Ciclohexanos , Modelos Animales de Enfermedad , Factores de Crecimiento Endotelial/metabolismo , Endotelio Vascular/citología , Inmunohistoquímica , Linfocinas/metabolismo , Masculino , Ratones , Ratones Desnudos , Neovascularización Fisiológica/efectos de los fármacos , O-(Cloroacetilcarbamoil) Fumagilol , Neoplasias Pancreáticas/irrigación sanguínea , Distribución Aleatoria , Células Tumorales Cultivadas , Venas Umbilicales/citología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Ensayos Antitumor por Modelo de Xenoinjerto
16.
J Gastrointest Surg ; 5(2): 139-46, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11331475

RESUMEN

The HER2/neu oncogene is overexpressed in human pancreatic cancer, but the clinical significance of that overexpression is uncertain. In the present study we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene. That antibody may retard tumor growth in certain patients with those diseases. We quantified HER2 expression in various human pancreatic cancer cell lines and studied the bioactivity of this antibody both in vitro and in vivo. Growth inhibition by Herceptin was observed in vitro in cell lines with high levels of HER2/neu expression. Cell lines with low levels of this protein did not respond significantly to the antibody. In vivo we studied two different pancreatic cancer cell lines in an orthotopic mouse model of the disease. Herceptin treatment suppressed tumor growth in the MIA PaCa-2 tumor cell line, which expressed high levels of HER2/neu. These data suggest that Herceptin treatment of patients with pancreatic cancer who express high levels of the HER2/neu oncogene may be reasonable.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/metabolismo , Animales , Anticuerpos Monoclonales Humanizados , Western Blotting , Modelos Animales de Enfermedad , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/metabolismo , Receptor ErbB-2/metabolismo , Trastuzumab , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Am J Surg ; 167(6): 570-4, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8209930

RESUMEN

Since feeding increases intestinal fluid and electrolyte losses in short bowel syndrome, an agent increasing postprandial small bowel absorption might have a therapeutic role. Peptide YY (PYY) has recently been shown to increase net small bowel absorption under basal conditions. The aim of this study was to determine whether PYY can also augment postprandial absorption. Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm Thiry-Vella loops) were created in dogs (n = 6) and gastrointestinal continuity was restored. Luminal perfusion with [14C]polyethylene glycol was used to calculate the change in water (H2O) and sodium (Na+) and chlorine (Cl-) ion fluxes after an oral meal. Changes in fluxes were also determined after a 2-hour infusion of a physiological dose of PYY (100 pmol/kg per hour). In a third series of experiments, fluxes were measured after a meal, during PYY infusion. Feeding increased small bowel absorption of fluid and electrolytes independent of the luminal content. This effect persisted for 2 hours after the meal. PYY infusion significantly augmented this proabsorptive response in both jejunum and ileum. These results suggest that PYY-agonists may have a therapeutic role in conditions such as short bowel syndrome where postprandial absorption is reduced.


Asunto(s)
Hormonas Gastrointestinales/fisiología , Absorción Intestinal/fisiología , Intestino Delgado/fisiología , Péptidos/fisiología , Análisis de Varianza , Animales , Perros , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/fisiología , Electrólitos/metabolismo , Hormonas Gastrointestinales/farmacología , Absorción Intestinal/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Péptido YY , Péptidos/farmacología , Radioinmunoensayo , Factores de Tiempo , Agua/metabolismo
18.
Am Surg ; 67(12): 1195-9, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11768829

RESUMEN

Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women. We retrospectively reviewed our experience with pancreatic neoplasms from 1986 to the present and identified nine patients with SPENP. All nine patients were female with a mean age of 32 years (range 16-66). All patients presented with gastrointestinal complaints including pain, mass, dyspepsia, or bloating and were subsequently diagnosed with a tumor of the pancreas by CT scan. All patients underwent surgical resection. Two patients had tumors located in the head of the pancreas and underwent a pancreaticoduodenectomy. The remainder had tumors located in the tail of the pancreas and underwent distal pancreatectomy. Pathology demonstrated solid and papillary or solid and cystic pseudopapillary neoplasm of the pancreas. Three tumors were positive for both vimentin and alpha-1 antitrypsin on immunohistochemical studies, and three were positive for neuron-specific enolase. All nine patients underwent curative resection and are alive without any evidence of recurrence with a mean follow-up of 5.4 years. SPENP is considered to be a low-grade malignancy with an excellent prognosis. Prompt diagnosis and surgical resection can result in cure.


Asunto(s)
Cistoadenoma Papilar/cirugía , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Adolescente , Adulto , Anciano , Cistoadenoma Papilar/patología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía
19.
Am Surg ; 67(12): 1185-9, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11768827

RESUMEN

Acute diverticulitis requiring surgical intervention has conventionally been treated by resection with colostomy or delayed resection with primary anastomosis at a second admission. Our objective was to determine the outcome for treatment of diverticulitis with resection and primary anastomosis during the same hospitalization. We conducted a retrospective review of patients (n = 74) undergoing surgery for diverticulitis. Groups included: 1) resection with primary anastomosis (n = 33), 2) resection with colostomy followed by a takedown colostomy (n = 32), and 3) delayed resection with primary anastomosis at a second admission (n = 9). Despite local perforation primary anastomosis was often performed unless patients were clinically unstable or had fecal contamination. The operation was urgent in five (15%) patients in Group 1 as compared with 26 patients (88%) in Group 2. Serious intra-abdominal complications occurred in two patients (6%) in Group 1 as compared with nine patients (28%) in Group 2 and one patient (11%) in Group 3. Postoperative abscesses occurred in two patients in Group 1, five patients in Group 2, and one patient in Group 3. We have shown that resection with primary anastomosis for acute diverticulitis--even in selected patients requiring urgent operation--can be safely performed during the same hospital admission with a low complication rate.


Asunto(s)
Colectomía , Diverticulitis del Colon/cirugía , Absceso Abdominal/etiología , Enfermedad Aguda , Adulto , Anastomosis Quirúrgica , Diverticulitis del Colon/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
20.
Am Surg ; 65(10): 927-30, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10515536

RESUMEN

Current standard of care for complicated diverticulitis includes urgent resection with colostomy versus antibiotic treatment, followed by delayed resection with primary anastomosis at a second admission. In certain circumstances, it is possible to perform resection and anastomosis on the same admission for acute diverticulitis. A retrospective review was completed for patients undergoing surgery for diverticulitis from 1991 to 1998. Groups included: 1) sigmoid resection with primary anastomosis on same admission (n = 18); 2) resection with protective end colostomy (n = 16); and 3) in-patient antibiotic treatment alone, followed by a second admission for resection with primary anastomosis (n = 5). Four patients initially treated with antibiotics worsened symptomatically or developed radiographic evidence of perforation and required resection with colostomy. Five patients in Group 1 had abscesses or contained perforations based on radiographic studies. Findings on CT scans did not predict treatment. Group 1 patients had uneventful recoveries and few minor complications (wound infections and an incisional hernia). One anastomotic leak occurred in Group 2 after colostomy closure. Although there will continue to be a role for emergent operation for diverticulitis, same admission sigmoid resection with primary anastomosis after antibiotic treatment is safe, uses a shorter course of antibiotics, and has a low complication rate.


Asunto(s)
Colon Sigmoide/cirugía , Diverticulitis del Colon/cirugía , Hospitalización , Enfermedad Aguda , Adulto , Anastomosis Quirúrgica , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos
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