Anatomical basis of antropyloric transposition for fecal incontinence in humans: the infrapyloric approach

Purpose

Antropylorus transposition in the perineum for end-stage anal incontinence has shown to be feasible in humans. Vascular anatomy of the antro-pyloro-duodenal area is critical in preventing complications and increasing pyloric graft survival. This study was undertaken to examine the vascular anatomy of antro-pyloro-duodenal area in an attempt to safeguard the graft blood supply and improve its survival.

Methods

After obtaining preoperative CT angiography to delineate the infrapyloric artery (IP a.), bench dissection of resected pancreaticoduodenectomy specimens was performed in 12 patients. Ex vivo angiography of these specimens were also performed. Subsequent to the information obtained from these dissections, the method of antropylorus mobilization during transposition was modified in terms of the site of division of the right gastroepiploic a. (Rt GEA). Perioperative outcomes (graft related complications, fecal incontinence scores, Doppler flow studies, and manometry studies of the graft) were compared between the two groups.

Results

IP a. originated only from the Rt GEA in 8 cases (66 %) and from both the gastroduodenal a. and the Rt GEA in the rest. However, its origin solely from the gastroduodenal a. was not observed. The pyloric graft survival, pyloric valve pressures and Doppler flow velocities were significantly (p < 0.05) better when the infrapyloric a. was preserved following this refinement. However, no immediate significant difference in incontinence scores was observed.

Conclusions

Careful preservation of the pyloric valve vascularity by preserving the IP a. by dividing the Rt GEA at its origin increases vascularity, survival and contractility of the pyloric graft in perineum.     

On the Role of Ultrasonography and CT Scan in the Diagnosis of Acute Appendicitis

The purposes of this study were to revisit the utility of ultrasonography (USG) as a primary imaging modality in acute appendicitis (AA) and to establish the role of CT scan as a second-line/problem-solving modality. All cases of suspected AA were referred for urgent USG. USG was done with standard protocol for appendicitis. Limited computed tomographic (CT) scan [NCCT ± CECT (IV contrast only)] was done for the lower abdomen and pelvis where sonographic findings were equivocal. One hundred and twenty-one patients were referred for USG for suspected appendicitis. Eight-four patients underwent surgery for AA based on clinical as well as imaging findings, of whom 76 had appendicitis confirmed at histopathology. Three patients were misdiagnosed (3.6 %) on USG as appendicitis. Of 76 patients of appendicitis confirmed histopathologically, 63 (82.8 %) had features of appendicitis on USG and did not require any additional imaging modality. Of 121 patients, 12 (10 %) needed CT scan because of atypical features on USG. Of these 12 patients, seven had retrocecal appendicitis, and three high-up paracolic appendicitis. USG alone had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 81, 88, 92.6, 71.6, and 83 %, respectively. When combined with CT scan in select cases, the sensitivity, specificity, PPV, NPV, and accuracy of combined USG + CT scan were 96 % (P?=?0.0014), 89 %, 93 %, 93.5 % (P?=?0.0001), and 93 % (P?=?0.0484), respectively. Twenty-eight (23 %) patients were given alternative diagnosis on USG. Dedicated appendiceal USG should be used as a primary imaging modality in diagnosing or excluding AA. Appendiceal CT can serve as a problem-solving modality.     

Structurally Specific Heparan Sulfates Support Primitive Human Hematopoiesis by Formation of a Multimolecular Stem Cell Niche

Stem cell localization, conservation, and differentiation isbelieved to occur in niches in the marrow stromal microenvironment. Ourrecent observation that long-term in vitro human hematopoiesis requiresa stromal heparan sulfate proteoglycan (HSPG) led us to hypothesizethat such HSPG may orchestrate the formation of the stem cell niche. Wecompared the structure and function of HS from M2-10B4, ahematopoiesis-supportive cell line, with HS from a nonsupportive cellline, FHS-173-We. Long-term culture-initiating cell (LTC-IC)maintenance was enhanced by PG from supportive cells but not by PG fromnonsupportive cells (P < .005). The supportive HS weresignificantly larger and more highly sulfated than the nonsupportiveHS. Specifically, supportive HS contained higher 6-O-sulfation on theglucosamine residues. In agreement with these observations, purified6-O-sulfated heparin and highly 6-O-sulfated bovine kidney HS similarlymaintained LTC-IC. In contrast, completely desulfated heparin,N-sulfated heparin, and unmodified heparin did not support LTC-ICmaintenance. Moreover, the supportive HS promoted LTC-IC maintenancebut not differentiation of CD34⁺/HLA-DRcells into colony-forming cells (CFCs) and mature bloodcells. The supportive HS but not the nonsupportive HS bound bothcytokines and matrix components critical for hematopoiesis, includinginterleukin-3 (IL-3), macrophage inflammatory protein-1 (MIP-1),and thrombospondin (TSP). Significantly more CD34⁺ cellsadhered directly to immobilized O-sulfated heparin than to N-sulfatedor desulfated heparin. Thus, hematopoiesis-supportive stromal HSPGpossessing large, highly 6-O-sulfated HS mediate the juxtaposition ofhematopoietic progenitors with stromal cells, specific growth-promoting(IL-3) and growth-inhibitory (MIP-1 and platelet factor 4 [PF4])cytokines, and extracellular matrix (ECM) proteins such as TSP. Weconclude that the structural specificity of stromal HSPG thatdetermines the selective colocalization of cytokines and ECM componentsleads to the formation of discrete niches, thereby orchestrating thecontrolled growth and differentiation of stem cells. These findings mayhave important implications for ex vivo expansion of and gene transferinto primitive hematopoietic progenitors.     

Leukocyte Cell Population Data for Hematology Analyzer-Based Distinction of Clonal-versus-Non-Clonal Lymphocytosis: A Real-World Testing Experience

Automated blood counts revealing lymphocytosis necessitate smear reviews. Even expert morphological evaluation may however, fail to differentiate a benign-versus-malignant etiology without further testing. Automated analyser-derived quantitative data on leukocyte cell populations remain undertested for distinguishing such etiologies. Instrument manufacturers claim that if successful, they may be used to generate software flags that help under-resourced laboratories better triage hemogram specimens requiring further testing. We tested the diagnostic accuracy of volume-conductivity-scatter (VCS) indices together with complete blood count (CBC) parameters in such scenarios. We compared LH780-derived (Beckman Coulter, FL, USA) CBC + VCS parameters from patients with clonal lymphoproliferations (n = 42, including 30 chronic lymphocytic leukemia cases) versus 83 controls with absolute or relative lymphocytosis (derivation cohort). Diagnostic performances of 11 logistic regression equations derived were subsequently evaluated on two specific validation cohorts (n = 130 and n = 1465). Clonal lymphocytoses showed significantly lower hemoglobin and higher leukocyte counts but similar lymphocyte percentages (LY %) vis-à-vis controls. The most significant, albeit overlapping predictor of clonality was the absolute lymphocyte count, LY# (47.8 ± 48.4 × 10⁹/L vs. 2.9 ± 1.4 × 10⁹/L in clonal vs. benign cases). In eleven logistic regression equations constructed using four combinatorial approaches, only the models with LY# (highest sensitivity/specificity of 99.3%/100%) and the lymphocytic VCS parameters alone (highest sensitivity/specificity of 76.2%/90.2%) performed consistently in both validation cohorts. Lymphocytic VCS parameters were moderately successful in distinguishing benign-versus-malignant lymphocytes. Other approaches of CBC-plus-VCS parameters did not sustain their initial excellent performances in the validation cohorts, highlighting a need for careful appraisal and better standardization of automated cellular analysis technologies.     

The Preoperative Evaluation of Infective Endocarditis via 3-Dimensional Transesophageal Echocardiography

Transesophageal echocardiography continues to have a central role in the diagnosis of infective endocarditis and its sequelae. Recent technological advances offer the option of 3-dimensional imaging in the evaluation of patients with infective endocarditis. We present an illustrative case and review the literature regarding the potential advantages and limitations of 3-dimensional transesophageal echocardiography in the diagnosis of complicated infective endocarditis.A 51-year-old man, an intravenous drug user who had undergone bioprosthetic aortic valve replacement 5 months earlier, presented with prosthetic valve endocarditis. Preoperative transesophageal echocardiography with 3D rendition revealed a large abscess involving the mitral aortic intervalvular fibrosa, together with a mycotic aneurysm that had ruptured into the left atrium, resulting in a left ventricle-to-left atrium fistula. Three-dimensional transesophageal echocardiography enabled superior preoperative anatomic delineation and surgical planning. We conclude that 3-dimensional transesophageal echocardiography can be a useful adjunct to traditional 2-dimensional transesophageal echocardiography as a tool in the diagnosis of infective endocarditis.     

Design principles of chemical penetration enhancers for transdermal drug delivery

Chemical penetration enhancers (CPEs) are present in a large number of transdermal, dermatological, and cosmetic products to aid dermal absorption of curatives and aesthetics. This wide spectrum of use is based on only a handful of molecules, the majority of which belong to three to four typical chemical functionalities, sporadically introduced as CPEs in the last 50 years. Using >100 CPEs representing several chemical functionalities, we report on the fundamental mechanisms that determine the barrier disruption potential of CPEs and skin safety in their presence. Fourier transform infrared spectroscopy studies revealed that regardless of their chemical make-up, CPEs perturb the skin barrier via extraction or fluidization of lipid bilayers. Irritation response of CPEs, on the other hand, correlated with the denaturation of stratum corneum proteins, making it feasible to use protein conformation changes to map CPE safety in vitro. Most interestingly, the understanding of underlying molecular forces responsible for CPE safety and potency reveals inherent constraints that limit CPE performance. Reengineering this knowledge back into molecular structure, we designed >300 potential CPEs. These molecules were screened in silico and subsequently tested in vitro for molecular delivery. These molecules significantly broaden the repertoire of CPEs that can aid the design of optimized transdermal, dermatological, and cosmetic formulations in the future.     

Plasma Exchange for Hemolytic Crisis and Acute Liver Failure in Wilson Disease

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism which primarily involves the liver and the central nervous system. Rarely, WD can present as acute liver failure (ALF) and this disease is universally fatal in the absence of liver transplantation. The authors report a young girl with WD ALF, who showed signs of recovery after prompt initiation of plasma exchange (PE) and chelation therapy. Though liver transplantation could not be done in this child and the child died 8 d after stopping PE, this case highlights that PE can be a successful medical treatment in WD ALF and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.