Significance of the surgical hepatic resection margin in patients with a single hepatocellular carcinoma.

BACKGROUND: The impact of a wide surgical margin on the outcome of patients with hepatocellular carcinoma (HCC) has not been evaluated in relation to the type of liver resection performed, anatomical or non-anatomical. The aim of this study was to evaluate the impact of surgical margin status on outcomes in patients undergoing anatomical or non-anatomical resection for solitary HCC. METHODS: Data from patients with solitary HCC who had undergone non-anatomical partial resection (Hr0 group) or anatomical resection of one Couinaud segment (HrS group) between 2000 and 2007 were extracted from a nationwide survey database in Japan. Overall and recurrence-free survival associated with the surgical margin status and width were evaluated in the two groups. RESULTS: A total of 4457 patients were included in the Hr0 group and 3507 in the HrS group. A microscopically positive surgical margin was associated with poor overall survival in both groups. A negative but 0-mm surgical margin was associated with poorer overall and recurrence-free survival than a wider margin only in the Hr0 group. In the HrS group, the width of the surgical margin was not associated with patient outcome. CONCLUSION: Anatomical resection with a negative 0-mm surgical margin may be acceptable. Non-anatomical resection with a negative 0-mm margin was associated with a less favourable survival outcome.

ANTECEDENTES: El impacto de un margen quirúrgico (surgical margin, SM) amplio en el resultado de pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) no ha sido evaluado en relación con el tipo de resección hepática realizada: anatómica o no anatómica. El objetivo del presente estudio fue evaluar el impacto del estado del SM en los resultados en pacientes sometidos a resección anatómica o no anatómica por un HCC solitario. MÉTODOS: Los datos de pacientes con un HCC solitario sometidos a resección parcial no anatómica (grupo Hr0) o resección anatómica de un segmento de Couinaud (grupo HrS) entre 2000 y 2007 se obtuvieron a partir de una base de datos nacional de Japón. En los grupos Hr0 y HrS se evaluaron la supervivencia global y la supervivencia libre de recidiva asociadas al estado microscópico del SM y a la amplitud del SM. RESULTADOS: Se incluyeron un total de 4.457 pacientes en el grupo Hr0 y 3.507 en el grupo HrS. Un SM microscópico positivo se asoció con una pobre supervivencia global en ambos grupos. Un SM negativo, pero a una distancia de 0 mm se asoció con una peor supervivencia global y libre de recidiva en comparación con aquellos asociados a un SM más amplio, solo en el grupo Hr0. En el grupo HrS, la amplitud del SM no se asoció con los resultados del paciente. CONCLUSIÓN: La resección anatómica con un SM negativo a una distancia de 0 mm puede ser aceptable. La resección no anatómica con un SM negativo a una distancia de 0 mm se asoció con resultados de supervivencia menos favorables.

Ultra-low-loss nanofiber Fabry-Perot cavities optimized for cavity quantum electrodynamics.

We demonstrate the fabrication of ultra-low-loss, all-fiber Fabry-Perot cavities that contain a nanofiber section, optimized for cavity quantum electrodynamics. By continuously monitoring the finesse and fiber radius during the fabrication of a nanofiber between two fiber Bragg gratings, we were able to precisely evaluate taper transmission as a function of radius. The resulting cavities have an internal round-trip loss of only 0.31% at a nanofiber waist radius of 207 nm, with a total finesse of 1380, and a maximum expected internal cooperativity of ∼1050 for a cesium atom on the nanofiber surface. Our ability to fabricate such high-finesse nanofiber cavities may open the door for the realization of high-fidelity scalable quantum networks.

Noninvasive prenatal testing: benefits and limitations of the available tests.

BACKGROUND: The „gold standard“ for prenatal diagnosis of aneuploidies is provided by the karyotype, which has high accuracy, but is dependent on invasive procedures, which generate risk of fetal loss. Different methodologies of development of noninvasive prenatal genetic tests (NIPT) for tracking aneuploidies, including sex chromosomes, have been made available for clinical use, for some microdeletions and triploids and for exclusion of paternity. These exams make use of three methodological tools: s-MPS, t-MPS and SNP. Genetic tests, despite the high cost, cover a broader range of clinical applications, have the advantage that can be performed early, with high accuracy, and low false positive rate. Type of article: Review. SETTING: Department of Obstetrics and Gynecology, Science College of Santa Casa of São Paulo (FSMSCSP), São Paulo-SP, Brazil. DESIGN AND METHODS: This study was a non-asystematic review, which searched PubMed / MEDLINE as a research source and aimed at the compilation of data, which allowed approaching the evolution, the technical and methodological advances of the available tests, the recognition of its benefits, limitations and future perspectives on NIPT. CONCLUSION: NIPT stand out for being applied earlier during the pregnancy with high accuracy and low false-positive rates, including a broad spectrum of clinical applications. The t-MPS is a recent technique used to evaluate aneuploidy that shows greater accuracy and lower cost than the s-MPS, but that is limited to being applied only to the most common aneuploidies. The SNP technique can search for more genetic conditions, besides presenting better accuracy.

Hepatectomy for hepatocellular carcinoma after perioperative management of portal hypertension.

BACKGROUND: Indications for hepatectomy in patients with hepatocellular carcinoma (HCC) who have portal hypertension (PH) have been controversial. Some studies have concluded that PH is a contraindication to hepatectomy, whereas others have suggested that perioperative prophylactic management (PPM) can help overcome complications after hepatectomy associated with PH. The objective of this retrospective study was to assess the short- and long-term outcomes after hepatectomy for HCC in patients with PH, with or without PPM. METHODS: Records were reviewed of consecutive patients who underwent hepatectomy for HCC, with or without PPM of PH, in a single institution from 1994 to 2015. Patients were divided into three groups: those who received PPM for PH (PPM group), patients who had PH but did not receive PPM (no-PPM group) and those without PH (no-PH group). RESULTS: A total of 1259 patients were enrolled, including 123 in the PPM group, 181 in the no-PPM group and 955 in the no-PH group. Three- and 5-year overall survival rates were 74·3 and 53·1 per cent respectively in the PPM group, 69·2 and 54·9 per cent in the no-PPM group, and 78·1 and 64·2 per cent in the no-PH group (P = 0·520 for PPM versus no PPM, P = 0·027 for PPM versus no PH, and P < 0·001 for no PPM versus no PH). Postoperative morbidity and mortality rates were 26·0 and 0·8 per cent respectively in the PPM group, 29·8 and 1·1 per cent in the no-PPM group, and 20·3 and 0 per cent in the no-PH group. CONCLUSION: The present study has demonstrated acceptable outcomes among patients with HCC who received appropriate management for PH in an Asian population. Enhancement of the safety of hepatic resection through use of PPM may provide a rationale for expansion of indications for hepatectomy in patients with PH.

Inversion of Qubit Energy Levels in Qubit-Oscillator Circuits in the Deep-Strong-Coupling Regime.

We report on experimentally measured light shifts of superconducting flux qubits deep-strongly coupled to LC oscillators, where the coupling constants are comparable to the qubit and oscillator resonance frequencies. By using two-tone spectroscopy, the energies of the six lowest levels of each circuit are determined. We find huge Lamb shifts that exceed 90% of the bare qubit frequencies and inversions of the qubits' ground and excited states when there are a finite number of photons in the oscillator. Our experimental results agree with theoretical predictions based on the quantum Rabi model.

Identification of patterns of factors preceding severe or life-threatening asthma exacerbations in a nationwide study.

BACKGROUND: Reducing near-fatal asthma exacerbations is a critical problem in asthma management. OBJECTIVES: To determine patterns of factors preceding asthma exacerbations in a real-world setting. METHODS: In a nationwide prospective study of 190 patients who had experienced near-fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2-week period before admission. RESULTS: Three distinct clusters of symptoms were defined employing the self-reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle-aged patients with low Body mass index and tendency to depression who had stopped anti-asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle-aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long-acting beta-agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild-moderate symptoms. There were no differences in overuse of short-acting beta-agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters. CONCLUSION: To reduce severe or life-threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti-type 2 response-targeted therapies should be considered for cluster C.

The comparative anatomy of the folds, fossae, and adhesions around the duodenojejunal flexure in mammals.

BACKGROUND: Anatomical knowledge of the duodenojejunal flexure is necessary for abdominal surgeries, and also important for physiologic studies about the duodenum. But little is known about the anatomy of this region in mammals. Here, we examined comparative anatomy to understand the anatomical formation of the duodenojejunal flexure in mammals. MATERIALS AND METHODS: The areas around the duonenojejunal flexure were ob-served in mouse, rat, dog, pig, and human, and the anatomical structures around the duodenojejunal junction in the animals were compared with those in human. RESULTS: The superior and inferior duodenal folds, and the superior and inferior duodenal fossae were identified in all examined humans. In pig, the structures were not clearly identified because the duodenum strongly adhered to the retroperitoneum and to the mesocolon. In mouse, rat, and dog, only the plica duodenocolica, which is regarded as the animal counterpart of the superior duo-denal fold in human, was identified, and other folds or fossae were not observed, probably because the duodenum was not fixed to the parietal peritoneum in those animals. Transection of the plica duodenocolica could return the normally rotated intestine back to the state of non-rotation in rat. CONCLUSIONS: This study showed the anatomical similarities and dissimilarities of the duodenojejunal flexure among the mammals. Anatomical knowledge of the area is useful for duodenal and pancreatic surgeries, and for animal studies about the duodenum. (Folia Morphol 2018; 77, 2: 286-292).

Acquired Downregulation of Donor-Specific Antibody Production After ABO-Incompatible Kidney Transplantation.

The mechanism of long-term B cell immunity against donor blood group antigens in recipients who undergo ABO-incompatible (ABOi) living-donor kidney transplantation (LKTx) is unknown. To address this question, we evaluated serial anti-A and anti-B antibody titers in 50 adult recipients. Donor-specific antibody titers remained low (≤1:4) in 42 recipients (84%). However, antibodies against nondonor blood group antigens were continuously produced in recipients with blood type O. We stimulated recipients' peripheral blood mononuclear cells in vitro to investigate whether B cells produced antibodies against donor blood group antigens in the absence of graft adsorption in vivo. Antibodies in cell culture supernatant were measured using specific enzyme-linked immunosorbent assays (ELISAs). Thirty-five healthy volunteers and 57 recipients who underwent ABO-compatible LKTx served as controls. Antibody production in vitro against donor blood group antigens by cells from ABOi LKTx patients was lower than in the control groups. Immunoglobulin deposits were undetectable in biopsies of grafts of eight recipients with low antibody titers (≤1:4) after ABOi LKTx. One patient with blood type A1 who received a second ABOi LKTx from a type B donor did not produce B-specific antibodies. These findings suggest diminished donor-specific antibody production function in the setting of adult ABOi LKTx.

Severe or life-threatening asthma exacerbation: patient heterogeneity identified by cluster analysis.

BACKGROUND: Severe or life-threatening asthma exacerbation is one of the worst outcomes of asthma because of the risk of death. To date, few studies have explored the potential heterogeneity of this condition. OBJECTIVES: To examine the clinical characteristics and heterogeneity of patients with severe or life-threatening asthma exacerbation. METHODS: This was a multicentre, prospective study of patients with severe or life-threatening asthma exacerbation and pulse oxygen saturation < 90% who were admitted to 17 institutions across Japan. Cluster analysis was performed using variables from patient- and physician-orientated structured questionnaires. RESULTS: Analysis of data from 175 patients with severe or life-threatening asthma exacerbation revealed five distinct clusters. Cluster 1 (n = 27) was younger-onset asthma with severe symptoms at baseline, including limitation of activities, a higher frequency of treatment with oral corticosteroids and short-acting beta-agonists, and a higher frequency of asthma hospitalizations in the past year. Cluster 2 (n = 35) was predominantly composed of elderly females, with the highest frequency of comorbid, chronic hyperplastic rhinosinusitis/nasal polyposis, and a long disease duration. Cluster 3 (n = 40) was allergic asthma without inhaled corticosteroid use at baseline. Patients in this cluster had a higher frequency of atopy, including allergic rhinitis and furred pet hypersensitivity, and a better prognosis during hospitalization compared with the other clusters. Cluster 4 (n = 34) was characterized by elderly males with concomitant chronic obstructive pulmonary disease (COPD). Although cluster 5 (n = 39) had very mild symptoms at baseline according to the patient questionnaires, 41% had previously been hospitalized for asthma. CONCLUSIONS & CLINICAL RELEVANCE: This study demonstrated that significant heterogeneity exists among patients with severe or life-threatening asthma exacerbation. Differences were observed in the severity of asthma symptoms and use of inhaled corticosteroids at baseline, and the presence of comorbid COPD. These findings may contribute to a deeper understanding and better management of this patient population.

Electron-Beam Mapping of Vibrational Modes with Nanometer Spatial Resolution.

We demonstrate that a focused beam of high-energy electrons can be used to map the vibrational modes of a material with a spatial resolution of the order of one nanometer. Our demonstration is performed on boron nitride, a polar dielectric which gives rise to both localized and delocalized electron-vibrational scattering, either of which can be selected in our off-axial experimental geometry. Our experimental results are well supported by our calculations, and should reconcile current controversy regarding the spatial resolution achievable in vibrational mapping with focused electron beams.

Laser frequency locking with 46 GHz offset using an electro-optic modulator for magneto-optical trapping of francium atoms.

We demonstrate frequency offset locking between two laser sources using a waveguide-type electro-optic modulator (EOM) with 10th-order sidebands for magneto-optical trapping of Fr atoms. The frequency locking error signal was successfully obtained by performing delayed self-homodyne detection of the beat signal between the repumping frequency and the 10th-order sideband component of the trapping light. Sweeping the trapping-light and repumping-light frequencies with keeping its frequency difference of 46 GHz was confirmed over 1 GHz by monitoring the Doppler absorption profile of I2. This technique enables us to search for a resonance frequency of magneto-optical trapping of Fr.

Analysis of Genetic Diversity of Fusarium tupiense, the Main Causal Agent of Mango Malformation Disease in Southern Spain.

Mango malformation disease (MMD) has become an important global disease affecting this crop. The aim of this study was to identify the main causal agents of MMD in the Axarquía region of southern Spain and determine their genetic diversity. Fusarium mangiferae was previously described in the Axarquía region but it represented only one-third of the fusaria recovered from malformed trees. In the present work, fusaria associated with MMD were analyzed by arbitrary primed polymerase chain reaction (ap-PCR), random amplified polymorphic DNA (RAPD), vegetative compatibility grouping (VCG), a PCR screen for mating type idiomorph, and phylogenetic analyses of multilocus DNA sequence data to identify and characterize the genetic diversity of the MMD pathogens. These analyses confirmed that 92 of the isolates were F. tupiense, which was previously only known from Brazil and Senegal. In addition, two isolates of a putatively novel MMD pathogen were discovered, nested within the African clade of the Fusarium fujikuroi species complex. The F. tupiense isolates all belonged to VCG I, which was first described in Brazil, and the 11 isolates tested showed pathogenicity on mango seedlings. Including the prior discovery of F. mangiferae, three exotic MMD pathogenic species have been found in southern Spain, which suggests multiple independent introductions of MMD pathogens in the Axarquía region.

Cholestatic Liver Injury After Biliary Reconstruction Impairs Transplanted Islet Viability and Function.

Islet autotransplantation following total pancreatectomy differs from allograft transplantation with respect to the requirement of biliary reconstruction. Although it is known that careful consideration should be given to postoperative cholestatic liver injury after biliary reconstruction, its direct effects on transplanted islets have not been completely elucidated. In this study, we developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with islet autotransplantation that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue. Therefore, patients should be intensively managed after total pancreatectomy with islet autotransplantation to preserve viability and function of the transplanted islets.

Enhanced ultrasonography using a nano/microbubble contrast agent for islet transplantation.

Recent basic and clinical studies have assessed the use of highly sensitive imaging modalities for visualizing transplanted islets. We investigated the utility of enhanced ultrasonography, combined with fluorescent acoustic liposome nano/microbubbles (FALs), for evaluating angiogenesis and the endocrine function of transplanted islets. BALB/c mice were classified into three groups: Diabetic mice that underwent syngeneic islet transplantation into the subrenal capsule and achieved normoglycemia (Tx group); those that failed to achieve normoglycemia (Tx-DM group); and those not receiving any treatment (DM group). Mice were examined by FAL-enhanced high frequency ultrasonography. The echogenicity of the islets increased rapidly within the first minute after injection of FALs and remained at a higher level in the Tx group, while small increases were observed in the other two groups. In histological assessments, fluorescently stained erythrocytes could be seen in and around the transplanted islets, indicating that the transplanted islets were enhanced by infusion of FALs via vessel networks between the engrafted islets and tissue. Furthermore, the echogenicity correlated significantly with endocrine parameters, including blood glucose (BG), serum insulin, and the BG change in the glucose tolerance test. In conclusion, the echogenicity of the islets under FAS-enhanced ultrasonosonography correlated with the endocrine status of transplanted islets.

Differential diagnosis of liver tumours using intraoperative real-time tissue elastography.

BACKGROUND: Real-time tissue elastography is an innovative tool that informs the surgeon about tissue elasticity by applying the principle of ultrasonography. The aim of this study was to investigate the accuracy of intraoperative real-time tissue elastography (IORTE) for the detection and characterization of liver tumours. METHODS: Between October 2010 and November 2011, IORTE was performed for liver lesions after the completion of routine B-mode intraoperative ultrasonography (IOUS). The elasticity images of all tumours, except those of cysts, were classified into six categories according to modified criteria (types 1-6), according to the degree of strain contrast with the surrounding liver. The concordance of IORTE with pathological examination of the tumour, B-mode IOUS and clinical diagnosis after follow-up was assessed. RESULTS: Images were obtained from 92 hepatocellular carcinomas (HCCs), 92 adenocarcinomas, 19 other malignant tumours and 18 benign tumours in 158 patients. Using a minilinear probe, 73 of 88 HCCs were classified as having a 'HCC pattern' (type 3, 4 or 5), resulting in a sensitivity of 83·0 per cent, a specificity of 67·2 per cent and an accuracy of 73·7 per cent. Some 66 of 90 adenocarcinomas were classified as 'adenocarcinoma pattern' (type 6), resulting in a sensitivity of 73·3 per cent, specificity of 95·1 per cent and accuracy of 85·9 per cent. IORTE detected seven new lesions (8 per cent). CONCLUSION: IORTE is useful for the detection and characterization of liver tumours.

Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis.

BACKGROUND: Ixekizumab, an anti-IL-17A monoclonal antibody, demonstrated a high level of efficacy in moderate-to-severe plaque psoriasis (PP) patients. OBJECTIVE: To evaluate the efficacy and safety of open-label ixekizumab in Japanese patients with moderate-to-severe PP, erythrodermic psoriasis (EP) and generalized pustular psoriasis (GPP). METHODS: Patients received 160-mg subcutaneous ixekizumab injection at Week 0, 80-mg every 2 weeks through Week 12 and 80-mg every 4 weeks through Week 24. Efficacy and safety are reported through 24 weeks; additional safety data are available for some patients. RESULTS: A total of 78 patients with PP, 8 with EP and 5 with GPP enrolled. In PP patients, PASI75 and PASI90 response rates were 98.7% (77/78) and 83.3% (65/78) at Week 12 respectively. In EP patients, PASI75 and PASI90 were 100.0% (8/8) and 62.5% (5/8) and in GPP patients were 80.0% (4/5) and 60.0% (3/5). Overall, 84.0% (76/91) had a treatment-emergent AE through ≥24 weeks. There were no serious AEs, deaths, cases of tuberculosis or invasive fungal infections. LIMITATIONS: No control group and small sample sizes, especially for EP and GPP. CONCLUSION: By Week 12, nearly all patients with PP, EP and GPP achieved PASI75. The safety profile was consistent with reported results and no unexpected safety signals were observed.

Adult right living-donor liver transplantation with special reference to reconstruction of the middle hepatic vein.

Two hundred fifty-three consecutive living-donor liver transplant recipients with a right liver graft (RLG) were divided into three groups: an extended right liver graft (ERLG) group (n = 47) in which the middle hepatic vein (MHV) trunk was included in the graft, a modified right liver graft (MRLG) group (n = 114) in which the MHV tributaries were reconstructed with cryopreserved homologous veins and a simple RLG group (n = 92) in which the MHV tributaries were sacrificed. The volume of the anterior sector was significantly impaired in the RLG group compared to the other two groups, whereas the volume of the posterior sector was significantly improved in the RLG group, indicating that the impaired anterior sector regeneration by MHV deprivation was compensated by the posterior sector regeneration. The regeneration rate of the anterior sector was highest in the ERLG group (92%), moderate in the MRLG group (71%) and lowest in the RLG group (52%). The whole graft regeneration rate of the ERLG group was significantly higher than that of the other two groups. Poor regeneration, however, was not correlated with delayed functional recovery or long-term outcome. Short-term, the patency of reconstructed MHV tributaries was over 90%, but occlusion occurred frequently over the long-term, especially in V5.

Surgical resection of peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma.

BACKGROUND: Peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma (HCC) occur occasionally after biopsy, percutaneous therapy or resection, and spontaneously, with no effective treatment available. The objective of this study was to clarify the indications for, and benefits of, surgical resection of such HCC implants. METHODS: This was a retrospective analysis of patients who underwent resection for peritoneal or chest wall implants from HCC over 14 years (1997-2011). Indications for surgery for implanted HCC were: limited number of implanted lesions including those found incidentally during surgery; intrahepatic lesion absent or predicted to be locally controllable; and absence of ascites with sufficient hepatic functional reserve. Prognostic factors affecting survival after resection were determined by univariable and multivariable analysis. RESULTS: A total of 32 patients underwent 36 resections. Cumulative 1-, 3- and 5-year overall survival rates were 71, 44 and 39 per cent respectively, with a median survival time of 34.5 months. Univariable and multivariable analysis revealed that poor perioperative intrahepatic disease control was associated with poor survival. CONCLUSION: Surgical resection of implanted HCC may improve long-term survival in selected patients as long as intrahepatic disease is absent or well controlled.