Laparoscopy assisted transjejunal endoscopic retrograde cholangiography for treatment of intrahepatic duct stones in a post Roux-en-Y patient

We report a case of a 17-year-old female patient, who was operated on for choledocal cyst with Roux-en Y hepatojejunostomy. She was admitted to hospital with recurrent attacks of acute ascending cholangitis due to left intrahepatic duct stones. After a failed attempt at conventional endoscopic retrograde cholangiopancreatography through the anatomical route, she was treated successfully with laparoscopy assisted transjejunal endoscopic retrograde cholangiography.Endoscopic access to the biliary system can be difficult in patients with surgically altered anatomy of the upper gastrointestinal tract (GIT), such as Roux-en-Y reconstruction, because of the changed anatomy. However, endoscopic retrograde cholangiopancreatography (ERCP) is challenging in cases such as our patient;1,2 this is due to the distance needed to be traversed and looping. Our objective in presenting this particular case is to describe and highlight a laparoscopy assisted transjejunal ERCP to permit successful treatment and removal of intrahepatic duct stones in a post Roux-en-Y patient, and to minimize surgical inetervention to reduce unnecessary risks to the patient.     

Long-term compliance with continuous positive airway pressure in Saudi patients with obstructive sleep apnea: A prospective cohort study

Objectives:

To evaluate continuous positive airway pressure (CPAP) compliance and define predictors of CPAP compliance among Saudi patients with obstructive sleep apnea (OSA) after applying an educational program.

Methods:

This prospective cohort study included consecutive patients diagnosed to have OSA based on polysomnography between January 2012 and January 2014 in King Saud University, Riyadh, Kingdom of Saudi Arabia. All patients had educational sessions on OSA and CPAP therapy before sleep study, and formal hands-on training on CPAP machines on day one, day 7, and day 14 after diagnosis. The follow-up in the clinic was carried out at one, 4, and 10 months after initiating CPAP therapy. Continuous positive airway pressure compliance was assessed objectively. Logistic regression model was used to assess the predictors of CPAP adherence.

Results:

The study comprised 156 patients with a mean age of 51.9±12.1 years, body mass index of 38.4±10.6 kg/m², and apnea hypopnea index of 63.7±39.3 events/hour. All patients were using CPAP at month one, 89.7% at month 4, and 83% at month 10. The persistence of CPAP-related side effects and comorbid bronchial asthma remained as independent predictors of CPAP compliance at the end of the study.

Conclusion:

With intensive education, support, and close monitoring, more than 80% of Saudi patients with OSA continued to use CPAP after 10 months of initiating CPAP therapy.Continuous positive airway pressure (CPAP) is a standard, safe, and efficacious treatment for obstructive sleep apnea (OSA), a common disorder with established harm to quality of life and adverse consequences for cardiovascular health.1 Obstructive sleep apnea is characterized by recurrent partial (hypopnea) or complete (apnea) upper airway obstruction during sleep. These recurrent respiratory events usually cause intermittent hypoxemia and sleep fragmentation.2 Recent data demonstrated that the estimated prevalence of moderate to severe OSA ranges from 10-17% in middle-aged and elderly men.3 In Saudi Arabia, 3 out of 10 middle-aged Saudi men and 4 out of 10 middle-aged Saudi women are at high risk of having OSA.4,5 The mainstay medical treatment for OSA is CPAP therapy.6 Among various available therapeutic modalities for OSA, CPAP remains the most effective treatment.6 Continuous positive airway pressure is a machine that applies positive airway pressure to the upper air passages via a mask fitted on the mouth or nose to keep the throat open.6 Previous studies in Western countries showed that OSA patients on CPAP therapy use their machines on average from 4.5 to 5.5 hours per night with compliance rates ranging from 30-85%.7,8 Several studies have been conducted to define factors that influence, or predict CPAP use and adherence, and reported conflicting results.6 Moreover, several studies reported that race might influence CPAP adherence. For example, available data suggest lower CPAP adherence among African Americans than Caucasians.9 An earlier study that assessed CPAP compliance subjectively (self-reports) among Saudi patients with OSA after 3 months of initiation of CPAP therapy revealed an overall compliance rate of 39%.10 However, self-reports have been shown to overestimate CPAP use by approximately one hour/night when compared with objectively measured CPAP use.11 In general, there are very few data on objectively assessed long-term CPAP compliance in the literature. Moreover, there is a lack of previous study objectively addressing the rate of CPAP compliance, the predictors of good compliance, and the side effects of CPAP treatment in Saudi OSA patients. Therefore, we established in our center an educational program for patients with OSA and easily accessible medical support, and close follow-up of CPAP compliance. This study was conducted to evaluate CPAP compliance and to define predictors of CPAP compliance among Saudi patients with OSA after applying the new educational program.     

Sonographic organometry in Brazilian and Sudanese patients with hepatosplenic schistosomiasis mansoni and its relation to the risk of bleeding from oesophageal varices.

Fifty-nine patients with hepatosplenic schistosomiasis mansoni were investigated by sonography in Northeast Brazil and Central Sudan. The sizes of the organs usually involved in this disease were quantitatively assessed according to a standardized protocol, and measurements were adjusted to the body height of the individual. The results were compared with those of healthy controls matched by sex, age, geographical origin and socio-economic status. Considerable differences were found between patients and controls as well as between residents from the two areas. The liver of both patients and controls from the Sudan was significantly smaller than that of patients and controls from Brazil. Only in Brazil, but not in the Sudan, was the left liver lobe larger in patients than in the controls. The diameter of the portal and the splenic vein, the spleen size and the thickness of the gallbladder wall were significantly increased in patients from both areas. The increase of the portal and splenic vein diameter was significantly correlated with the degree of hepatic periportal fibrosis and the frequency of bleeding from endoscopically proven oesophageal varices in the patients, irrespective of their geographic origin. In contrast, such correlations were not found for the degree of splenomegaly nor for the degree of gallbladder-wall thickening. It is concluded that standardized sonographic organometry permits the assessment of morbidity in hepatosplenic schistosomiasis mansoni under different endemic conditions. Especially the measurement of the portal vein diameter may allow estimation of the risk of gastrointestinal haemorrhage in these patients.     

Treatment sequencing strategy for hepatic epithelioid haemangioendothelioma

Background

The biology of hepatic epithelial haemangioendothelioma (HEHE) is variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary owing to the rarity of the disease and frequent misdiagnosis.

Methods

Between 1989 and 2013, patients retrospectively identified with HEHE from a single academic cancer centre were analysed to evaluate clinicopathological factors and initial treatment regimens associated with survival.

Results

Fifty patients with confirmed HEHE had a median follow-up of 51 months (range 1–322). There was no difference in 5-year survival between patients presenting with unilateral compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P = 0.1), localized compared with metastatic disease (69% versus 78.3%, respectively; P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9). However, 5-year survival for patients treated with chemotherapy at any point during their disease course was decreased compared with those who did not receive any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9–10.7), P = 0.02].

Conclusions

HEHE frequently follows an indolent course, suggesting that immediate treatment may not be the optimal strategy. Initial observation to assess disease behaviour may better stratify treatment options, reserving surgery for those who remain resectable/transplantable. Prospective cooperative trials or registries may confirm this strategy.     

Interleukin-3-Deficient Mice Have Increased Resistance to Blood-Stage Malaria

The contribution of interleukin-3 (IL-3), a hematopoietic growth factor and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting IL-3-deficient (knockout [KO]) mice with Plasmodium berghei NK65. Male IL-3 KO mice, but not female mice, were more resistant to infection than wild-type (WT) mice, as evidenced by lower peak parasitemia and prolonged survival. Both male and female IL-3 KO mice had increased splenomegaly and were more anemic than corresponding WT mice. Anemia was compensated for by an increase in bone marrow and splenic erythropoiesis in IL-3 KO mice, as evidenced by higher levels of erythroid progenitors. Plasma levels of gamma interferon (IFN-γ) and CXCL9 (monokine induced by IFN-γ [MIG]) were found to be significantly reduced in IL-3 KO mice during early stages of infection. In contrast, granulocyte colony-stimulating factor (G-CSF) levels were significantly higher, and the percentage of peripheral blood neutrophils lower, in infected IL-3 KO mice than in WT counterparts. Overall, our results indicate that IL-3 plays a critical role in suppressing protective immunity to P. berghei NK65 infection and that it is involved in inhibiting the development of splenomegaly, anemia, and erythropoiesis. IL-3 also influences IFN-γ, CXCL9, and G-CSF production in response to infection. The abnormal responses seen in infected IL-3 KO mice may be due to the lack of IL-3 during development, to the lack of IL-3 in the infected mature mice, or to both.     

Remote loading of curcumin-in-modified β-cyclodextrins into liposomes using a transmembrane pH gradient

Curcumin (CRM) is a natural polyphenol with antioxidative, anti-inflammatory, and anticancer therapeutic properties. However, CRM therapeutic potential is limited by low water solubility and bioavailability. Intraliposomal remote loading describes the retention of drugs in liposome cores in response to transmembrane pH gradient. The current study describes for the first time the remote loading of CRM into liposomes using secondary (E-βCD) and tertiary (D-βCD) amino-modified β-cyclodextrins (βCDs) as carriers and solubilizers. βCDs were chemically modified to prepare the ionizable weak base functional group followed by forming a guest-host complex of CRM in the modified βCDs hydrophobic cavities via a solvent evaporation encapsulation technique. These complexes were then actively loaded into preformed liposomes, composed of DPPC/cholesterol (65/35 molar ratio) via pH gradient. The formation of CRM-βCDs inclusion complexes was characterized using UV-Vis spectroscopy, thermal analysis, and NMR spectroscopy. The complex stoichiometric ratio was determined to be 1 : 1 of CRM-βCDs based on Job''s plot which was also confirmed by the modified Benesi–Hildebrand equation with increasing probability of forming the 1 : 2 ratio of CRM-βCDs. The apparent formation constants (K_f) of 51.6, 100.9 and 55.4 mM⁻² were determined for CRM-βCD, CRM-E-βCD, and CRM-D-βCD complexes, respectively. Liposome size, charge and polydispersity index indicate the presence of a homogeneous population before and after active loading. The encapsulation efficiencies of CRM-βCD complexes into pH gradient preformed liposomes were 16.5, 51.1, and 41.7 for CRM-βCD, CRM-E-βCD, and CRM-D-βCD, respectively, showing more than 5 fold increase compared to normal liposomes. The current study provides a novel remote loading approach utilizing chemically modified cyclodextrins to incorporate hydrophobic drugs into liposomes.

The current study provides a novel remote loading approach utilizing chemically modified cyclodextrins to incorporate hydrophobic drugs into liposomes.     

Disseminated Sporothrix brasiliensis infection with endocardial and ocular involvement in an HIV-infected patient

Disseminated sporotrichosis occurs in individuals with impaired cellular immunity, such as in cases of neoplasia, transplantation, diabetes, and especially, acquired immunodeficiency syndrome. This report presents a 32-year-old Brazilian human immunodeficiency virus (HIV)-infected patient who developed a protracted condition of disseminated sporotrichosis with endocarditis, bilateral endophthalmitis, and lymphatic involvement. He needed cardiac surgery to replace the mitral valve. Sporothrix brasiliensis isolates were recovered from cultures of subcutaneous nodules and mitral valve fragments. Species identification was based on classical and molecular methods. The patient received amphotericin B for 52 days and subsequently, oral itraconazole. He remains asymptomatic, and he is on maintenance therapy with itraconazole. Despite his positive clinical outcome, he developed bilateral blindness. To our knowledge, this case is the first report of endocarditis and endophthalmitis caused by S. brasiliensis.     

Risk of venous thromboembolism outweighs post-hepatectomy bleeding complications: analysis of 5651 National Surgical Quality Improvement Program patients

Background

Historically, liver surgeons have withheld venous thromboembolism (VTE) chemoprophylaxis due to perceived postoperative bleeding risk and theorized protective anticoagulation effects of a hepatectomy. The relationships between extent of hepatectomy, postoperative VTE and bleeding events were evaluated using the National Surgical Quality Improvement Program (NSQIP) database.

Methods

From 2005 to 2009, all elective open hepatectomies were identified. Factors associated with 30-day rates of VTE, postoperative transfusions and returns to the operating room (ROR), were analysed.

Results

The analysis included 5651 hepatectomies with 3376 (59.7%) partial, 585 (10.4%) left, 1134 (20.1%) right, and 556 (9.8%) extended. Complications included deep vein thrombosis (DVT) (1.93%), pulmonary embolism (PE) (1.31%), venous thromboembolism (VTE) (2.88%), postoperative transfusion (0.76%) and ROR with transfusion (0.44%). VTE increased with magnitude of hepatectomy (partial 2.13%, left 2.05%, right 4.15%, extended 5.76%; P < 0.001) and outnumbered bleeding events (P < 0.001). Other factors independently associated with VTE were aspartate aminotransferase (AST) ≥27 (P= 0.022), American Society of Anesthesiologists (ASA) class ≥3 (P < 0.001), operative time >222 min (P= 0.043), organ space infection (P < 0.001) and length of hospital stay ≥7 days (P= 0.004). VTE resulted in 30-day mortality of 7.4% vs. 2.3% with no VTE (P= 0.001).

Conclusions

Contrary to the belief that transient postoperative liver insufficiency is protective, VTE increases with extent of hepatectomy. VTE exceeds major bleeding events and is strongly associated with mortality. These data support routine post-hepatectomy VTE chemoprophylaxis.