Use of Prone Positioning During Ventilatory Support Found Superior in ARDS.

In patients with acute respiratory distress syndrome (ARDS), use of the prone position during ventilatory support roughly doubled survival at the 1- and 3-month marks, according to a New England Journal of Medicinestudy.

Researchers followed outcomes in nearly 500 patients with severe ARDS who were randomized either to prone positioning for at least 16 consecutive hours a day, or to being left supine. By 28 days, mortality was 16% in the prone group, versus 33% in the supine group; at 90 days, the prone-positioning advantage held: 24% versus 41%.

An editorialist calls the results “compelling,” and the treatment effect “virtually unprecedented in modern medicine.” He cautions, however, that the logistics of turning patients to the prone position from supine requires teamwork to avoid kinking and extubation. The article includes a video showing how this can be accomplished with three people.

Source: NEJM 

Treating GERD Successfully: Beyond Heartburn Relief.

A short questionnaire helps identify whether patients on therapy for GERD are experiencing sleep disturbance and might benefit from an adjustment in therapy.

Gastroesophageal reflux disease (GERD) and sleep disturbance are highly prevalent conditions that occur together in many patients. Recent studies have demonstrated that effective treatment of GERD also ameliorates related sleep dysfunction. Proton-pump inhibitors (PPIs) have been demonstrated to improve quality of life, work productivity, and driving acuity (Am J Gastroenterol 2011; 106:421). However, data have been limited to gastroenterology practice settings. In the current primary-care–based, industry-funded, cluster-randomized, open-label study, researchers evaluated the performance of a questionnaire in identifying sleep disturbance in patients being treated for GERD and, secondarily, the efficacy of esomeprazole in improving sleep disturbance.

From 180 primary care centers in Canada, 1388 patients were administered the PPI Acid Suppression Symptom (PASS) test, a validated questionnaire of five questions that identifies symptoms in patients on continuing acid-suppression therapy for GERD. One item regards sleep disturbance. Among the 825 patients who described sleep disturbance at baseline, 534 patients at 111 centers were randomized to switch from their current antisecretory therapy to once-daily esomeprazole (20 mg or 40 mg; intervention), and 291 patients at 69 centers were randomized to continue current therapy (control). At 4 weeks, 23% of patients in the intervention group versus 55% in the control group reported continued sleep disturbance (odds ratio, 2.3; 95% confidence interval, 0.17–0.32). Mean improvements in quality-of-life scores and reflux symptom scores were higher in the intervention group than in the control group.

Comment: Primary care providers (and, I suspect, many gastroenterologists) need to better recognize the implications of inadequate gastroesophageal reflux disease treatment, including sleep disturbance, which in many patients will respond to a change in acid-suppressive therapy. Whether a formal questionnaire is necessary for screening versus pragmatic and attentive questioning probably depends on the provider. Defining successful treatment for GERD means setting appropriate endpoints beyond just heartburn relief.

 

Source: Journal Watch Gastroenterology

 

 

 

 

Metabolic syndrome: A novel high-risk state for colorectal cancer

Metabolic syndrome (MS) and related disorders, including cancer, are steadily increasing in most countries of the world. However, mechanisms underlying the link between MS and colon carcinogenesis have yet to be fully elucidated. In this review article we focus on the relationships between various individual associated conditions (obesity, dyslipidemia, diabetes mellitus type 2 and hypertension) and colon cancer development, and demonstrate probable related factors revealed by in vivo and in vitrostudies. Furthermore, molecules suggested to be involved in cancer promotion are addressed, and the potential for cancer prevention by targeting these molecules is discussed.

 

Source: cancer letters

 

 

 

 

A nanomedicine to treat ocular surface inflammation: performance on an experimental dry eye murine model.

MUC5AC is a glycoprotein with gel-forming properties, whose altered expression has been implicated in the pathogenesis of dry eye disease. The aim of our study was to achieve an efficient in vivo transfection of MUC5AC, restore its normal levels in an inflamed ocular surface and determine whether restored MUC5AC levels improve ocular surface inflammation. Cationized gelatin-based nanoparticles (NPs) loaded with a plasmid coding a modified MUC5AC protein (pMUC5AC) were instilled in healthy and experimental dry eye (EDE) mice. MUC5AC expression, clinical signs, corneal fluorescein staining and tear production were evaluated. Ocular specimens were processed for histopathologic evaluation, including goblet cell count and CD4 immunostaining. Neither ocular discomfort nor irritation was observed in vivo after NP treatment. Expression of modified MUC5AC was significantly higher in ocular surface tissue of pMUC5AC-NP-treated animals than that of controls. In healthy mice, pMUC5AC-NPs had no effect on fluorescein staining or tear production. In EDE mice, both parameters significantly improved after pMUC5AC-NP treatment. Anterior eye segment of treated mice showed normal architecture and morphology with lack of remarkable inflammatory changes, and a decrease in CD4+ T-cell infiltration. Thus, pMUC5AC-NPs were well tolerated and able to induce the expression of modified MUC5A in ocular surface tissue, leading to reduction of the inflammation and, consequently improving the associated clinical parameters, such as tear production and fluorescein staining. These results identify a potential application of pMUC5AC-NPs as a new therapeutic modality for the treatment of dry eye disease.

 

Source:Nature

 

Current status on the diagnosis and evaluation of pancreatic tumour in Asia with particular emphasis on the role of endoscopic ultrasound.

In Asia, the incidence of pancreatic cancer in some countries has been increasing. Owing to most cases being diagnosed late, prognosis for pancreatic cancer remains dismal. It is clear the future for pancreatic cancer is early detection. While the possible presence of pancreatic masses is often first raised by non-invasive abdominal imaging such as computerized tomography (CT) and magnetic resonance imaging (MRI), smaller lesions and locoregional lymph node metastases are often not detectable by these means. Endoscopic ultrasonography (EUS) offers a higher sensitivity (93-100%) for the detection of small potentially curable pancreatic masses than other existing imaging modalities. It is also recommended to evaluate portal vein confluence, portal vein, celiac axis and SMA origin, and exclude respectability. Due to the closer proximity of EUS to the target structure, and lower rate of needle tract seeding, EUS-guided fine needle aspiration (FNA) of pancreatic mass is considered the most suitable tissue acquisition technique. Lastly, EUS also enables the performance of endoscopic interventions. Its performance can be further enhanced with newer techniques, including contrast enhanced ultrasound and elastrography. It is anticipated that in the near future, molecular technologies may make it possible to detect microscopic amounts of cancer in tissue or blood, predict relapse and survival after therapy, as well as determine optimal therapy.

• Source: http://onlinelibrary.wiley.com

 

 

 

 

Hepatobiliary and Pancreatic: Detection of early hepatocellular carcinoma by enhanced magnetic resonance imaging..

 

A woman, aged 75, with cirrhosis caused by hepatitis C had a routine ultrasound study for surveillance for hepatocellular carcinoma. A possible nodule was identified in segment VI but it was difficult to identify the contours or margins of the nodule. A contrast-enhanced ultrasound (US) study with perfluorobutane (Sonazoid®) showed no enhancement or washout of the nodule in either the vascular or Kupffer phases. Computed tomography (CT) during hepatic arteriography (CTHA) or arterial portography (CTAP) also failed to show a liver lesion (Figure 1, left and middle panel). In contrast, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) clearly revealed a low-signal nodule during the hepatobiliary phase (Figure 1, right). The appearance was consistent with either a dysplastic nodule or a well-differentiated hepatocellular carcinoma. As the nodule could not be detected on US or CT, we performed real-time virtual sonography synchronizing B-mode US images with the hepatobiliary phase of enhanced MRI which allowed for the same area to be displayed in real time as both MR and B-mode US images (Figure 2). Using this technique, the nodule was clearly visualized and an aspiration biopsy was performed. Histology revealed a well-to-moderately differentiated hepatocellular carcinoma that was treated by percutaneous radiofrequency ablation guided by real-time virtual sonography with contrast-enhanced MRI.

Radiofrequency ablation is widely used for the treatment of hepatocellular carcinoma. However, to achieve successful ablation, it is important to have a clear view of the margins of the nodule. Although most larger hepatocellular carcinomas are hypervascular, early carcinomas can be hypovascular and can be difficult to detect with contrast-enhanced US, contrast-enhanced CT or CT during hepatic arteriography. The recent introduction of contrast-enhanced MRI appears to have improved the detection of early liver tumors and may be helpful for the differentiation of early hepatocellular carcinoma from dysplastic nodules. Real-time virtual sonography is a system in which a B-mode US image can be synchronized with CT images. To our knowledge, this is the first report of the successful use of real-time virtual sonography with enhanced MRI for the detection and treatment of an early hepatocellular carcinoma. This technology may facilitate the diagnosis and treatment of hepatocellular carcinoma at an earlier stage.

Source: http://onlinelibrary.wiley.com

Gastrointestinal: Esophageal metastasis from hepatocellular carcinoma.

 

A 63-year-old man visited our hospital because he was undergoing treatment of hepatocellular carcinoma (HCC) in 2007. Multinodular HCC had been detected, and he had been treated 8 times with transcatheter arterial chemoembolization and twice with radiofrequency ablation. In addition, he received endoscopic variceal ligation (EVL) and endoscopic injection therapy due to esophageal varices. Three years after commencing treatment, the patient represented with melena. Bleeding esophageal varices were diagnosed and EVL was performed. At this time, abdominal CT demonstrated multinodular-type HCC in both lobes of the liver, with tumor thrombi in the portal vein. Follow-up upper endoscopy revealed a post-EVL ulcer at the esophagogastric junction (Figure 1). Two months later, upper endoscopy was performed due to slight progression of anemia. Endoscopic examination showed two whitish polypoid masses at the site of EVL (Figure 2a), and a submucosal tumor-like protrusion was recognized on the oral side of the polypoid lesions (Figure 2b). Biopsy specimens obtained from the polypoid mass showed a tumor that was histologically consistent with HCC (Figure 3a) and that was focal positive staining for alphafetoprotein (Figure 3b) and glypican-3 (Figure 3c). After biopsy specimens were taken, argon plasma coagulation was performed at the biopsy site. The patient died of progressive hepatic failure one month later.

HCC is a common malignancy worldwide and extrahepatic metastasis in patients with HCC occurs frequently, in 30–75% of patients. Gastrointestinal involvement is seldom found, in only 4–12% of cases in autopsy series, whereas it has been reported that premortem-diagnosed gastrointestinal tract involvement is found in 0.5–2% of cases. The most commonly involved site was the duodenum, followed by the stomach, the colon, and the jejunum.

Portal blood flow can be reversed by increased intrahepatic resistance and arteriovenous communications in patients with liver cirrhosis associated with HCC, which may cause retrograde metastasis of HCC via the portal system. There are two different hypotheses concerning the way HCC metastasizes to the esophagus: either by direct invasion of the gastrointestinal tract via contiguation between the serosal side of a liver tumor and the esophagus, or via the hematogenous spread of tumor emboli infiltrating via the portal vein system and being disseminated by hepatofugal portal blood flow to the esophagus.

In our patient, the therapy for esophageal varices may have caused the esophageal metastasis of HCC. Tumor emboli in the portal system may have been trapped at the site where the variceal bloodstream was interrupted by EVL, and the metastatic tumor then could have grown and broken through the ulcer base due to EVL. The metastatic tumor from HCC in the esophagus showed a rapid increase in size, and it changed to the appearance of a submucosal mass. As the tumor size increased further, the shape of the esophageal metastasis appeared to change from a submucosal mass to a polypoid mass.

Source: http://onlinelibrary.wiley.com

Vaginal Bleeding.

70-year-old woman was seen in this hospital because of vaginal bleeding. An endometrial-biopsy specimen showed a poorly differentiated malignant neoplasm that was suggestive of mixed müllerian tumor (carcinosarcoma). A diagnostic and therapeutic procedure was performed.

The underlying cause of abnormal vaginal bleeding is age-dependent. Ten percent of premenopausal women with abnormal bleeding have a malignant tumor. In contrast, 75% of women over 70 years of age with postmenopausal bleeding have cancer, and the risk rises with age in postmenopausal women.

Clinical Pearls

• What is the typical presentation of carcinosarcoma of the uterus?

Postmenopausal vaginal bleeding is the most common manifestation of carcinosarcoma. Patients with carcinosarcoma also frequently present with the classic triad of painful postmenopausal bleeding, an enlarged uterus, and prolapsed tumor visible at the cervical os.

• Under what circumstances is surgery not the primary treatment for uterine cancer?

In only a few circumstances is surgery not the primary treatment for uterine cancer — when there is a desire to preserve fertility, high operative risk, and unresectable disease. The goals of surgical treatment are excision of all disease with at least a 1-cm margin and staging of the tumor. The initial spread is to regional lymph nodes; therefore, standard treatment is a radical total abdominal hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. Endometrial cancers have several potential patterns of spread: direct invasion and expansion of the primary tumor, lymphatic invasion, hematogenous spread, and intraperitoneal dissemination. Because metastasis is common, preoperative combination positron-emission tomography and computed tomography (PET-CT) and a meticulous exploratory laparotomy are standard practice.

Morning Report Questions

Q: What features affect the overall prognosis of patients with carcinosarcoma?

A: Diagnostic features of malignant mixed mullerian tumor (carcinosarcoma) include the finding of a biphasic malignant tumor that is composed of high-grade carcinoma (most commonly endometrioid or serous) and sarcoma and is typically homologous (arising from mesenchymal tissue normally found in the uterus), although in up to 50% of cases, the tumor has a heterologous component (most commonly rhabdomyosarcoma or chondrosarcoma). There is no transition between the two components. Tumor stage is the most important prognostic factor in these tumors, although histologic features also affect outcome. The finding of serous or clear-cell carcinoma is associated with a more aggressive course. Sarcomatous components adversely affect the overall prognosis of patients with stage I tumors (5-year survival is 30% among patients with heterologous elements as compared with 80% among patients with homologous elements); myometrial and lymphovascular invasion are also associated with a poor prognosis.

Q: What are the treatment options for carcinosarcoma?

A: Carcinosarcoma is thought to require multiple methods of treatment. Radiation therapy has been shown to reduce the rates of local recurrence in the pelvis but does not increase the survival benefit among patients with carcinosarcoma. Adjuvant chemotherapy has not been shown to have an effect on recurrence rates or progression-free or overall survival among patients with carcinosarcoma. Hormonal therapy is of no use, since estrogen and progesterone receptors do not control tumor growth, even though they are typically present in patients with carcinosarcoma.

 

Sorce: NEJM

Impact of global cerebral atrophy on clinical outcome after subarachnoid hemorrhage.

Abstract

OBJECT

Atrophy in specific brain areas correlates with poor neuropsychological outcome after subarachnoid hemorrhage (SAH). Few studies have compared global atrophy in SAH with outcome. The authors examined the relationship between global brain atrophy, clinical factors, and outcome after SAH.

METHODS

This study was a post hoc exploratory analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial, a randomized, double-blind, placebo-controlled trial of 413 patients with aneurysmal SAH. Patients with infarctions or areas of encephalomalacia on CT, and those with large clip/coil artifacts, were excluded. The 97 remaining patients underwent CT at baseline and 6 weeks, which was analyzed using voxel-based volumetric measurements. The percentage difference in volume between time points was compared against clinical variables. The relationship with clinical outcome was modeled using univariate and multivariate analysis.

RESULTS

Older age, male sex, and systemic inflammatory response syndrome (SIRS) during intensive care stay were significantly associated with brain atrophy. Greater brain atrophy was significantly associated with poor outcome on the modified Rankin scale (mRS), severity of deficits on the National Institutes of Health Stroke Scale (NIHSS), worse executive functioning, and lower EuroQol Group–5D (EQ-5D) score. Adjusted for confounders, brain atrophy was not significantly associated with Mini-Mental State Examination and Functional Status Examination scores. Brain atrophy was not associated with angiographic vasospasm or delayed ischemic neurological deficit.

CONCLUSIONS

Worse mRS score, NIHSS score, executive functioning, and EQ-5D scores were associated with greater brain atrophy and older age, male sex, and SIRS burden. These data suggest outcome is associated with factors that cause global brain injury independent of focal brain injury.

Source: JNS

 

 

The use of surgery in mesothelioma.

Malignant pleural mesothelioma is an aggressive cancer of the pleura that is associated with exposure to fibrous minerals in the environment, such as asbestos or erionite. Because asbestos is ubiquitous in building material, the worldwide incidence of the disease continues to rise; rates in Europe are expected to increase by 5—10% per year for the next 25 years.1 Left untreated, the prognosis of malignant pleural mesothelioma is poor, with median overall survival of 7 months.1 Diagnosis of early disease is rare, because symptoms, such as dyspnoea or chest wall pain, often do not occur until later stages. Suspicion must be high to make the diagnosis, because the disease often presents as a pleural effusion or pleural thickening on imaging, or both, making it difficult to differentiate from other diseases.2

Once malignant pleural mesothelioma is suspected, a tissue sample is obtained in the operating room via pleuroscopy or video-assisted thoracoscopy, with incisions placed in a potential future thoracotomy site.1 Pleural fluid cytology and needle biopsy are often insufficient, because adequate specimens are needed to establish whether invasion is present and distinguish malignant disease from fibrous exudate or proliferating mesothelial cells. Additionally, enough tissue should be obtained to identify the histological subtype: epithelial, sarcomatoid, or mixed (biphasic).2, 3

Prognostic factors that portend increased survival include epithelial histology, female sex, and earlier stage. In a retrospective study of 945 patients,4 longer survival was associated with these characteristics, as well as no history of smoking or asbestos exposure, and left-sided tumours. The longest survival is recorded in women younger than 50 years and those with epithelial disease, for whom median survival exceeds 30 months.5 The difference between the sexes is a consistent finding and suggests that circulating oestrogen might affect tumour biology.3, 5, 6

While trials assess the roles of neoadjuvant or adjuvant chemotherapy, radiation therapy, intracavitary chemotherapy, photodynamic therapy, and other systemic options, the standard of care is resection and adjuvant therapy with radiation or chemotherapy, or both.6 Most studies have suggested that patients with favourable disease characteristics benefit from surgery with curative intent in the context of multimodality therapy.1, 2, 7

The two options for surgical resection are extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). With EPP, the pleural envelope is resected along with its contents, including the lung, diaphragm, and pericardium. P/D is a similar radical resection, but preserves the lung. Until 10 years ago, many surgeons preferred EPP for macroscopic complete resection, even in early-stage disease, as long as the patient had adequate cardiopulmonary function. Critics of EPP suggested that it was associated with high risk and did not offer a clear survival benefit. The Mesothelioma and Radical Surgery trial8 was designed to assess the role of EPP in malignant pleural mesothelioma, but its design was not feasible due to the high morbidity associated with EPP, and subsequent exploratory analyses were done with sample sizes that did not have adequate power to draw meaningful conclusions.

Many surgeons have recognised that macroscopic complete resection can be accomplished with P/D and with less morbidity than with EPP, particularly for early-stage disease. A multi-institutional retrospective study of 663 patients9 showed that, when undertaken as part of a multimodality treatment plan with curative intent, cumulative survival for early-stage disease was higher for P/D than for EPP. For later-stage disease, survival was higher with EPP. A subsequent study3 assessed 42 patients with International Mesothelioma Interest Group stage III disease undergoing P/D and adjuvant chemoradiation. Macroscopic complete resection was possible in 26 (62%), and median survival after this procedure was 35 months compared with 13 months in the 16 patients with incomplete resections.3 These data suggest that, as long as macroscopic resection of gross disease can be achieved, which operation to undertake depends on the individual patient’s tumour and functional status.7 This conclusion is reflected in the most recent clinical guidelines that were formulated by the 2012 International Mesothelioma Interest Group Congress (panel).10 Moreover, as techniques and perioperative management have improved, the mortality rates associated with these procedures—which were once prohibitively high—are now only 2·2—7% for EPP and 1—5% for P/D.2, 7, 9

Panel

Surgical recommendations discussed at the 2012 International Mesothelioma Interest Group Congress10

• Surgical macroscopic complete resection and control of micrometastatic disease have an important role in the multimodality therapy of malignant pleural mesothelioma, as for other solid malignancies.
• Surgical cytoreduction is indicated when macroscopic complete resection is deemed achievable.
• The type of surgery (extrapleural pneumonectomy or pleurectomy/decortication) depends on clinical factors and on individual surgical judgment and expertise.
• All patients with the diagnosis of malignant pleural mesothelioma should be initially assessed in a multidisciplinary setting, by medical oncology, radiation oncology, and surgical teams.
• Clinical staging (lymph-node sampling, PET, and MRI) should be done before treatment.
• The histological subtype should be identified by tissue biopsy before initiation of treatment.

Source: Lancet