Pancreatic Cancer Incidence, Mortality, and Survival in Puerto Rico, 2001-2015.

OBJECTIVE: To perform an epidemiologic profile of pancreatic cancer (PC) in Puerto Rico (PR) with data gathered from 2001 to 2015. METHODS: Using data from the PR Central Cancer Registry we estimated incidence and mortality rates and trends of PC in PR, and performed survival analyses. We also compared the age-standardized incidence and mortality rates of PC in people in PR with those of Hispanics, non-Hispanic whites, and non Hispanic blacks in the United States (US). RESULTS: From 2011 to 2015, 7.8 per 100,000 persons were diagnosed with PC in PR; higher rates were observed in men than in women (9.2 vs. 6.7 per 100,000, respectively) and in persons 65 years old and older (42.7 per 100,000 persons). For the same period, 6.7 per 100,000 persons died from PC; men and persons 65 years and older had higher mortality rates. Incidence and mortality trends of PC in PR increased from 2001-2015 (annual percent change [APC] = 3.8% and 1.9%, respectively (p<0.05). Lower risk of being diagnosed with and dying from PC was seen in PR than in members of several racial/ethnic groups in the US. The median survival time for PC cases diagnosed in PR during the period of 2008 to 2012 was 5.3 months. CONCLUSION: We observed increasing mortality rates and low survival in PC patients in PR. Research on access and response to treatment is needed to elucidate the reasons for the observed results and have a positive impact on PC burden and survival.

New simple approach for enhanced rejection of unknown disturbances in LTI systems with input delay.

This work proposes the extension of the simplified filtered Smith predictor (SFSP) for state-space systems to improve rejection of matched and unmatched unknown disturbances in LTI systems with input delay. The proposed structure is simpler than others recently proposed in the literature and can be applied to continuous-time or discrete-time systems. Furthermore, it allows improving rejection of both matched and unmatched disturbances, while also enhancing noise attenuation and robustness characteristics. Finite spectrum assignment (FSA) based implementation is used in order to guarantee the internal stability of the proposed controller. Simulation and experimental results are used to show the usefulness of the proposal.

Tuning of a dead-time compensator focusing on industrial processes.

This paper proposes tuning rules for the Simplified Dead-Time Compensator (SDTC), which is intended to deal with stable, unstable and integrative dead-time processes. The main contribution is the proposal of new guidelines for the tuning of the robustness filter. The new set of rules allow for the use of lower order filters which are able to simultaneously account for closed-loop robustness and noise attenuation. Through illustrative examples, it is shown that the proposed approach provides enhanced disturbance rejection and noise attenuation in the control of industrial processes when compared with other recently published works. Furthermore, the internal temperature of an in-house thermal chamber is controlled to evaluate the applicability of the strategy on real processes.

Endoscopic retrograde cholangiopancreatography, but not esophagogastroduodenoscopy or colonoscopy, significantly increases portal venous pressure: direct portal pressure measurements through endoscopic ultrasound-guided cannulation.

BACKGROUND AND STUDY AIMS: Changes in portal pressure during endoscopy have not been previously evaluated. The aims of this study were to assess the effect of esophagogastroduodenoscopy (EGD), colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP) on portal vein, inferior vena cava (IVC), and systemic pressures. PATIENTS AND METHODS: Five acute experiments were performed on 50-kg pigs utilizing endoscopic ultrasound (EUS)-guided catheterization of the portal vein and IVC. Systemic, intra-abdominal, IVC, and portal vein pressures were monitored during colonoscopy, EGD, and ERCP with endoscopic sphincterotomy. After endoscopy the animals were sacrificed for necropsy. The main outcome measure was pressure change during each type of endoscopic procedure. RESULTS: There were no significant changes in heart rate or systemic pressure during all endoscopic procedures. Intra-abdominal pressure increased during colonoscopy ( P = 0.02) and ERCP ( P = 0.007). However, mean portal venous pressure was significantly elevated only after the injection of contrast into the common bile duct, reaching its peak value at the time of biliary sphincterotomy (39.0 +/- 15.2 mm Hg vs. 13.4 +/- 3.6 mm Hg at baseline, P = 0.006). Mean peak IVC pressure was also elevated during ERCP, but it did not reach statistical significance (24.0 +/- 10.7 mm Hg vs. 12.6 +/- 4.1 mm Hg at baseline, P = 0.06). CONCLUSION: EGD and colonoscopy did not cause significant changes in portal vein, IVC, or systemic pressures. ERCP with biliary sphincterotomy increased portal pressure with only limited effect on IVC and systemic pressures. These new data indicate a possible connection between ERCP with sphincterotomy and portal pressure, and may be clinically important for patients with liver disease and other causes of portal hypertension who undergo this procedure.

Severity of post-ERCP pancreatitis directly proportional to the invasiveness of endoscopic intervention: a pilot study in a canine model.

BACKGROUND AND STUDY AIMS: Pancreatitis complicates 1% - 22% of endoscopic retrograde cholangiopancreatography procedures. The study aims were to develop a reproducible animal model of post-ERCP pancreatitis (PEP), and investigate the impact of endoscopic technique on severity of PEP. PATIENTS AND METHODS: ERCP was carried out in six male hound dogs. Pancreatitis was induced by one of three escalating methods: 1) pancreatic acinarization with 20 - 30 mL of contrast; 2) acinarization + ductal balloon occlusion + sphincterotomy; 3) acinarization + intraductal synthetic bile injection + ductal balloon occlusion + sphincterotomy. Dogs 5 and 6 received a pancreatic stent. Necropsy was performed on postoperative day 5. All pancreatic specimens were graded by two blinded pathologists according to a validated scoring system. All dogs were compared with three control dogs. RESULTS: Dogs 1 - 4 developed clinical pancreatitis and hyperamylasemia (11 736 vs. 722 U/L, P = 0.02). Total injury scores were significantly elevated compared with controls (6.85 vs. 1.06, P = 0.004). There was significant increase in acinar cell necrosis (0.86 vs. 0.06, P = < 0.001), and all other categories (except fibrosis) demonstrated elevated injury scores . Dogs 5 and 6 developed clinical pancreatitis without significant hyperamylasemia; total injury scores were elevated compared with controls (4.83 vs. 1.06, P = 0.01), but lower than in Dogs 1 - 4 (4.83 vs. 6.85, P = 0.25). There was escalating severity of pancreatic injury from Dogs 1 to 4 correlating with the method of endoscopic injury used. CONCLUSION: Severity of PEP is directly proportional to invasiveness of endoscopic intervention. Pancreatic acinarization, even without balloon occlusion and sphincterotomy, can be used as a reliable animal model for future studies investigating therapy and prevention of disease.

Reliable gastric closure after natural orifice translumenal endoscopic surgery (NOTES) using a novel automated flexible stapling device.

BACKGROUND: Reliable closure of the translumenal incision is one of the main challenges facing natural orifice translumenal endoscopic surgery (NOTES). This study aimed to evaluate the use of an automated flexible stapling device (SurgASSIST) for closure of the gastrotomy incision in a porcine model. METHODS: A double-channel gastroscope was advanced into the stomach. A gastric wall incision was made, and the endoscope was advanced into the peritoneal cavity. After peritoneoscopy, the endoscope was withdrawn into the stomach. The SurgASSIST stapler was advanced orally into the stomach. The gastrotomy edges were positioned between the opened stapler arms using two endoscopic grasping forceps. Stapler loads with and without a cutting blade were used for gastric closure. After firing of the stapler to close the gastric wall incision, x-ray with contrast was performed to assess for gastric leakage. At the end of the procedure, the animals were killed for a study of closure adequacy. RESULTS: Four acute animal experiments were performed. The delivery and positioning of the stapler were achieved, with technical difficulties mostly due to a short working length (60 cm) of the device. Firing of the staple delivered four rows of staples. Postmortem examination of pig 1 (when a cutting blade was used) demonstrated full-thickness closure of the gastric wall incision, but the cutting blade caused a transmural hole right at the end of the staple line. For this reason, we stopped using stapler loads with a cutting blade. In the three remaining animals (pigs 2-4), we were able to achieve a full-thickness closure of the gastric wall incision without any complications. CONCLUSIONS: The flexible stapling device may provide a simple and reliable technique for lumenal closure after NOTES procedures. Further survival studies are currently under way to evaluate the long-term efficacy of gastric closure with the stapler after intraperitoneal interventions.

Preliminary pneumoperitoneum facilitates transgastric access into the peritoneal cavity for natural orifice transluminal endoscopic surgery: a pilot study in a live porcine model.

BACKGROUND AND STUDY AIMS: Safe entrance into the peritoneal cavity through the gastric wall is paramount for the successful clinical introduction of natural orifice transluminal endoscopic surgery (NOTES). The aim of the study was to develop alternative safe transgastric access to the peritoneal cavity. PATIENTS AND METHODS: We performed 11 survival experiments on 50-kg pigs. In sterile conditions, the abdominal wall was punctured with a Veress needle. The peritoneal cavity was insufflated with 2 L carbon dioxide (CO (2)). A sterile endoscope was introduced into the stomach through a sterile overtube; the gastric wall was punctured with a needle-knife; after balloon dilation of the puncture site, the endoscope was advanced into the peritoneal cavity. Peritoneoscopy with biopsies from abdominal wall, liver and omentum, was performed. The endoscope was withdrawn into the stomach. The animals were kept alive for 2 weeks and repeat endoscopy was followed by necropsy. RESULTS: The pneumoperitoneum, easily created with the Veress needle, lifted the abdominal wall and made a CO (2)-filled space between the stomach and adjacent organs, facilitating gastric wall puncture and advancement of the endoscope into the peritoneal cavity. There were no hemodynamic changes or immediate or delayed complications related to pneumoperitoneum, transgastric access, or intraperitoneal manipulations. Follow-up endoscopy and necropsy revealed no problems or complications inside the stomach or peritoneal cavity. CONCLUSIONS: Creation of a preliminary pneumoperitoneum with a Veress needle facilitates gastric wall puncture and entrance into the peritoneal cavity without injury to adjacent organs, and can improve the safety of NOTES.

A new stapler-based full-thickness transgastric access closure: results from an animal pilot trial.

BACKGROUND AND STUDY AIMS: Reliable closure of the transluminal incision is the crucial step for natural orifice transluminal endoscopic surgery (NOTES) procedures. The aim of this study was to evaluate the feasibility and effectiveness of transgastric access closure with a flexible stapling device in a porcine survival model. PATIENTS AND METHODS: We carried out four experiments (two sterile and two nonsterile) on 50 kg pigs. The endoscope was passed through a gastrotomy made with a needle knife and an 18-mm controlled radial expansion dilating balloon. After peritoneoscopy, a flexible linear stapling device (NOLC60, Power Medical Interventions, Langhorne, Pennsylvania, USA) was perorally advanced over a guide wire into the stomach, positioned under endoscopic guidance, and opened to include the site of gastrotomy between its two arms; four rows of staples were fired. One animal was sacrificed 24 hours after the procedure (progression of pre-existing pneumonia). The remaining animals were survived for 1 week and then underwent repeat endoscopy and postmortem examination. RESULTS: Peroral delivery and positioning of the stapling device involved some technical difficulties, mostly due to the short length (60 cm) of the stapling device. The stapler provided complete leak-resistant gastric closure in all pigs. None of the surviving animals had any clinical signs of infection. Necropsy demonstrated an intact staple line with full-thickness healing of the gastrotomy in all animals. Histologic examination confirmed healing, but also revealed intramural micro-abscesses within the gastric wall after nonsterile procedure. CONCLUSIONS: Gastrotomy closure with a perorally delivered flexible stapling device created a leak-resistant transmural line of staples followed by full-thickness healing of the gastric wall incision. Increasing the length of the instrument and adding device articulation will further facilitate its use for NOTES procedures.

Hybrid minimally invasive surgery--a bridge between laparoscopic and translumenal surgery.

BACKGROUND: The peroral transluminal approach to the peritoneal cavity appears safe, feasible, and may further reduce the invasiveness of surgery. However, flexible endoscopes have multiple limitations inside the peritoneal cavity, which can potentially be overcome by blending the use of both a laparoscope and a flexible upper endoscope--a hybrid approach. The goal of the present study was to evaluate a hybrid minimally invasive technique for cholecystectomy in a porcine model. METHODS: Hybrid cholecystectomies were performed in acute experiments on 50-kg pigs under general anesthesia. Pneumoperitoneum was created with a Veress needle, and a laparoscopic 10-mm port was inserted. Under laparoscopic observation, the gastric wall incision was done with an endoscopic needle-knife and sphincterotome, and the upper endoscope was advanced into the peritoneal cavity. A laparoscopic 10-mm port was inserted into the right upper quadrant of the abdomen for gallbladder traction to facilitate exposure of the cystic duct and artery. Via the biopsy channel of the flexible endoscope, and using a knife with an isolated tip, a needle knife, and clips, both the cystic duct and artery were identified, clipped, and transected. The gallbladder itself was then dissected and retracted through the mouth, and the gastric wall incision was closed with endoscopic clips. RESULTS: Five hybrid cholecystectomies were performed without complications. The laparoscopic port enabled a stable pneumoperitoneum, good traction and counter-traction, and improved spatial orientation and visualization. Necropsy did not reveal any intraperitoneal complications. CONCLUSIONS: The hybrid approach increases safety of initial gastric puncture and gastric wall incision, improves orientation and navigation of the flexible endoscope inside the peritoneal cavity, simplifies peroral transgastric cholecystectomy, and could be used to decrease invasiveness of laparoscopic surgery and to facilitate development and clinical introduction of transgastric endoscopic procedures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00464-007-9329-2) contains supplementary material, which is available to authorized users.

The utility of contrast-enhanced endoscopic ultrasound in monitoring ethanol-induced pancreatic tissue ablation: a pilot study in a porcine model.

BACKGROUND AND STUDY AIMS: Pancreatic ablation is gaining popularity for the treatment of focal pancreatic lesions. The aim of our study was to evaluate local effects of intrapancreatic alcohol injection and the utility of contrast-enhanced endoscopic ultrasound (EUS) for its monitoring in a porcine model. METHODS: We performed four survival experiments on 50-kg pigs. Under linear EUS guidance, 0.5 mL of 50% ethanol plus purified carbon particle solution (GI Spot) was injected into the pancreatic body to create a focal area of pancreatic necrosis. The animals survived for 24-48 hours (pigs # 1, # 2, and # 3) and 7 days (pig # 4). EUS was then repeated with and without perflutren lipid microspheres (Definity) administration through the peripheral vein. Standard and microsphere-enhanced images of the pancreas were compared. Afterwards the animals were euthanized for necropsy. RESULTS: Alcohol injection caused focal pancreatic necrosis, which was barely seen by standard EUS as a subtle hypoechoic lesion 1 cm in diameter. Color and power Doppler EUS of this region did not reveal any blood flow. After intravenous injection of microspheres, color Doppler EUS revealed marked contrast enhancement of normal pancreatic parenchyma with a clearly delineated avascular alcohol-treated area, which on postmortem examination corresponded to the discrete necrotic area marked with carbon particles. CONCLUSIONS: EUS-guided alcohol injection consistently causes focal areas of pancreatic necrosis. Contrast-enhanced EUS with microspheres improves visualization of altered pancreatic vascular perfusion and can be used to facilitate detection of small pancreatic lesions and its follow-up post-ablation.

Comparison of intraabdominal pressures using the gastroscope and laparoscope for transgastric surgery.

BACKGROUND: The peroral transgastric endoscopic approach for intraabdominal procedures appears to be feasible, although multiple aspects of this approach remain unclear. This study aimed to measure intraperitoneal pressure in a porcine model during the peroral transgastric endoscopic approach, comparing an endoscopic on-demand insufflator/light source with a standard autoregulated laparoscopic insufflator. METHODS: All experiments were performed with 50-kg female pigs under general anesthesia. A standard upper endoscope was advanced perorally through a gastric wall incision into the peritoneal cavity. The peritoneal cavity was insufflated with operating room air from an endoscopic light source/insufflator. Intraperitoneal pressure was measured by three routes: (1) through the endoscope biopsy channel, (2) through a 5-mm transabdominal laparoscopic port, and (3) through a 16-gauge Veress needle inserted into the peritoneal cavity through the anterior abdominal wall. The source of insufflation alternated between on-demand manual insufflation through the endoscopic light source/insufflator using room air and a standard autoregulated laparoscopic insufflator using carbon dioxide (CO(2)). RESULTS: Six acute experiments were performed. Intraperitoneal pressure measurements showed good correlation regardless of measurement route and were independent of the type of insufflation gas, whether room air or CO(2). On-demand insufflation with the endoscopic light source/insufflator resulted in a wide variation in pressures (range, 4-32 mmHg; mean, 16.0 +/- 11.7). Intraabdominal pressures using a standard autoregulated laparoscopic insufflator demonstrated minimal fluctuation (range, 8-15 mmHg; mean, 11.0 +/- 2.2 mmHg) around a predetermined value. CONCLUSION: Use of an on-demand unregulated endoscopic light source/insufflator for translumenal surgery can cause large variation in intraperitoneal pressures and intraabdominal hypertension, leading to the risk of hemodynamic and respiratory compromise. Safety may favor well-controlled intraabdominal pressures achieved with a standard autoregulated laparoscopic insufflator.

Is blood the ideal submucosal cushioning agent? A comparative study in a porcine model.

BACKGROUND AND STUDY AIMS: Creation of a submucosal cushion before endoscopic mucosal resection (EMR) significantly reduces perforation risk. We evaluated six solutions as cushioning agents in live pigs. MATERIAL AND METHODS: 5 ml of normal saline, normal saline plus epinephrine, albumin 12.5 %, albumin 25 %, hydroxypropyl methylcellulose, and the pig's own whole blood were endoscopically injected into the porcine esophageal submucosa. Blood was obtained from a peripheral vein immediately before injection. Injections were made every 4 cm from the gastroesophageal junction. The time from completion of the injection to disappearance of the cushion was recorded. Endoscopy was repeated at 48 hours post injection. Two EMRs were performed after blood injection. Statistical analysis employed one-way analysis of variance followed by pairwise T test comparisons using the Bonferroni correction. RESULTS: Five animal experiments were completed. The mean time to dissipation of the submucosal cushion was shortest for saline plus epinephrine sites (2.87 minutes, SD 2.21) followed by the saline (4.8 minutes, SD 1.56), albumin 12.5 % (5.68 minutes, SD 3.48), albumin 25 % (7.83 minutes, SD 2.02), hydroxypropyl methylcellulose (9.77 minutes, SD 1.55), and blood sites (38.6 minutes, SD 6.07). Injection of blood resulted in significantly longer mucosal elevation than any other solution ( P < 0.0007). Blood from the cushion did not hamper visualization and facilitated EMR. CONCLUSION: Blood produces the most durable cushion compared with standard agents, also having the advantages of being readily available and without cost. Albumin 25 % provides as durable a cushion as hydroxypropyl methylcellulose.

Compliance with CPAP therapy in older men with obstructive sleep apnea.

OBJECTIVES: Factors specifically affecting compliance with continuous positive airway pressure (CPAP) in older patients with obstructive sleep apnea (OSA) have not been described. The purpose of this study is to determine which factors are associated with compliance and noncompliance in older patients, a growing segment of the population. DESIGN: A retrospective chart review of older male patients prescribed CPAP therapy for OSA over an 8-year period. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: All patients age 65 and older for whom CPAP therapy had been prescribed for treatment of OSA in the past 8 years. MEASUREMENTS: Records of all older male patients prescribed CPAP therapy for OSA over the last 8 years were reviewed. Compliance was defined by time-counter readings averaging 5 or more hours of machine run-time per night. RESULTS: Of 33 older male patients with OSA studied, 20 were found to be compliant and 13 noncompliant with nasal CPAP therapy. The mean age (+/- SEM) at the time of diagnosis of OSA in the compliant group was 68 (+/-1) years, whereas that of the noncompliant group was 72 (+/-1) years (P <.05). Of the compliant patients, 95% attended a CPAP patient education and support group, whereas only 54% of noncompliant patients attended (P =.006). Resolution of initial symptoms of OSA with CPAP therapy was significantly associated with compliance. Symptom resolution occurred in 90% of compliant patients and in only 18% of noncompliant patients (P <.0002). Factors that were significantly associated with noncompliance with CPAP were cigarette smoking, nocturia, and benign prostatic hypertrophy (BPH). Of noncompliant patients, 82% complained of nocturia, whereas only 33% of compliant patients complained of nocturia (P =.02). BPH was diagnosed in 62% of noncompliant patients and in only 15% of compliant patients (P =.004). Diuretic use was more common in the compliant group and, therefore, was not a cause of increased nocturia in noncompliant patients. CONCLUSION: In older male patients with OSA, compliance with CPAP therapy is associated with attendance at a patient CPAP education and support group. Resolution of symptoms with therapy also appears to be associated with enhanced compliance. In addition, we found an association between nocturia and the existence of BPH in older men with OSA who are not compliant with nasal CPAP. Larger observational studies should be performed to confirm these findings, and, if so confirmed, then further studies to determine whether treatment of BPH in older men with OSA improves compliance with CPAP.

Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction.

Inhaled corticosteroid therapy has proven efficacy for asthmatics, but the benefit for patients with chronic obstructive pulmonary disease (COPD) is less well supported. We hypothesized that withdrawal of inhaled steroids in elderly patients with severe irreversible airway obstruction would not lead to a deterioration in respiratory function. We designed a prospective, double-blind, randomized, placebo-controlled, crossover study to follow spirometry, quality of life questionnaire, six-minute (6-min) walk test, and sputum markers of inflammation during a 6-wk placebo treatment period and a 6-wk treatment period with beclomethasone dipropionate (BDP), 336 microg/d. There were 24 men receiving BDP who entered the study; 15 completed the study. Their mean age was 66.9 +/- 1.9 yr, and mean FEV(1) was 1.61 +/- 0.1 L (47% of predicted). There was a significant decrease in the mean FEV(1 )while using the placebo inhaler (1.70 L versus 1.60 L, baseline versus placebo: 95% CI, 0.002 to 0.195; p < 0.05). There was a decrease in the mean percentage change in FEV(1) for the study subjects during the placebo treatment period as compared with the BDP treatment period (-6.28 versus 5.03%, placebo versus BDP: 95% CI, -23.38 to 0.76; p = 0.06). Six-minute walk test results and sputum analysis for cell count and differential were not significantly different during placebo and BDP treatment periods. Borg scale assessment of dyspnea after exercise was increased while using the placebo inhaler as compared with baseline, and decreased during the BDP treatment period. Chronic Respiratory Disease Questionnaire (CRQ) scores revealed no significant difference between placebo and BDP. This study has demonstrated that in elderly patients with severe irreversible airway obstruction, withdrawal of inhaled corticosteroid therapy leads to a deterioration in ventilatory function and increased exercise-induced dyspnea.

New approaches to pulmonary hypertension.

Careful evaluation will often reveal secondary--and perhaps reversible--factors contributing to pulmonary hypertension. For primary disease, there are now a variety of treatments, ranging from calcium channel blockers to lung transplantation.

Leucemia mielóide aguda e gravidez / Acute myelocytic leukemia and pregnancy

Os autores analisaram dois casos de leucemia mielóide aguda durante a gravidez, atendidos na Clínica Obstétrica do HULW., da Universidade Federal da Paraíba. Chama-se atençao para a elevada incidência de complicaçoes maternas, decorrentes sobretudo do agravamento do estado de anemia e da presença de processos infecciosos recorrentes. Das complicaçoes fetais observadas no primeiro feto analisado, destacaram-se o sofrimento fetal agudo e o crescimento intra-uterino retardado. Finalizam, enfatizando as repercussoes ominosas dessa associaçao para o binômio materno-fetal.