Association between low MCV in early pregnancy and perinatal mental health in the Japan Environment and Children's Study and the possible effect of iron deficiency.

BACKGROUND: Postpartum anemia and iron deficiency are associated with postpartum depression. This study investigated the association between a low mean corpuscular volume (MCV) without anemia (which implies early-stage iron deficiency) in early pregnancy and perinatal mental health outcomes. METHODS: The fixed data from the Japan Environment and Children's Study (JECS), a Japanese nationwide birth cohort, were used. Perinatal mental health was assessed using the Kessler 6-item psychological distress scale (K6) in mid-pregnancy and the Edinburgh Postnatal Depression Scale (EPDS) at 1- and 6-months postpartum. RESULTS: Among the 3635 women with MCVs <85 fL in early pregnancy, the proportions of women with K6 scores ≥13 in mid-pregnancy and EPDS scores ≥9 at 1- and 6-months postpartum were 2.7 %, 12.8 %, and 9.9 %, respectively, compared with the 33,242 women with MCVs ≥85 fL at 1.9 %, 11.9 %, and 9.0 %, respectively. Multivariate logistic regression models showed that an MCV <85 in early pregnancy was associated with a K6 score ≥ 13 in mid-pregnancy and an EPDS score ≥ 9 at 1- and 6-months postpartum (adjusted odds ratio (95 % confidence interval): 1.48 (1.16-1.87), 1.14 (1.01-1.28), and 1.09 (0.95-1.24), respectively). LIMITATIONS: Low MCV values do not necessarily represent iron deficiency. Ferritin, currently the best indicator of iron deficiency, was not measured in the JECS. CONCLUSIONS: This study results suggest that a low MCV without anemia in early pregnancy is associated with a slightly increased risk of perinatal mental health deterioration.

Stent Graft of Pseudoaneurysm Rupture After Subtotal Stomach-preserving Pancreaticoduodenectomy.

BACKGROUND/AIM: Pseudoaneurysm rupture (PR) after subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) is a potentially fatal complication. PATIENTS AND METHODS: This study included 122 patients who underwent SSPPD at the Matsuyama Red Cross Hospital between January 2016 and December 2021. RESULTS: PR occurred in five patients (4.1%) after SSPPD. Preoperative diagnoses were cancers of the pancreatic head, distal bile duct, and gallbladder. All patients had postoperative Grade B or C pancreatic fistulas. PR occurred on postoperative days 8, 13, 20, 45, and 46. Bleeding sites were at the gastroduodenal artery transection, left gastric artery, and right hepatic artery. Four patients underwent peripheral stent graft placement, and one underwent haemostasis by coiling. Stent grafts for the gastroduodenal artery transected stamp were placed in the common hepatic artery, and in the superior mesenteric artery for PR in the right hepatic artery. All patients who underwent stent graft placement were treated with antiplatelet therapy; no complications or stent occlusion were observed in these patients. However, two patients died of cancer recurrence, 4 and 8 months after stent graft placement. The longest survival post stent graft placement was 50 months. CONCLUSION: Peripheral stent graft placement for the treatment of PR after SSPPD can maintain peripheral blood flow and haemostasis.

Novel Functional Peptide for Next-Generation Vital Pulp Therapy.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography-tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

CA19-9 Reduction After 4 Months of Treatment Is a Prognostic Factor for Locally Advanced Pancreatic Cancer.

BACKGROUND/AIM: Carbohydrate antigen 19-9 (CA19-9) levels may aid in the determination of subsequent treatment in patients with unresectable locally-advanced pancreatic cancer (LAPC) treated with chemotherapy. However, the relationship between the timing and magnitude of CA19-9 changes and clinical outcomes remains unclear. This study was conducted to identify the timing and magnitude of CA19-9 changes, which are most strongly associated with outcomes in LAPC patients. PATIENTS AND METHODS: We retrospectively analyzed consecutive LAPC patients treated with gemcitabine plus nab-paclitaxel (GnP) or modified FOLFIRINOX (mFFX) as the first-line chemotherapy between March 2014 and December 2018 in our hospital. Multivariate analyses were performed to identify prognostic factors of chemotherapy in LAPC. RESULTS: Ninety-four patients were included (GnP/mFFX: 72/22). The median overall survival was 20.3 months, and the median progression-free survival was 8.8 months. CA19-9 values before treatment did not affect prognosis. However, CA19-9 <100 U/ml or more than a 70% reduction in CA19-9 four months after commencing treatment was associated with a good prognosis (hazard ratio=0.17; 95% confidence interval=0.09-0.33; p<0.01). CONCLUSION: CA19-9 values 4 months after commencing treatment are a significant prognostic factor in LAPC patients undergoing chemotherapy.

Comparison of the Antiemetic Effect of Aprepitant/granisetron and Palonosetron Combined with Dexamethasone in Gynecological Cancer Patients Treated with Paclitaxel and Carboplatin Combination Regimen.

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Impact of Histological Features on Adjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Carcinoma.

BACKGROUND/AIM: This study evaluated the efficacy of adjuvant chemotherapy (AC) for intraductal papillary mucinous carcinoma (IPMC). PATIENTS AND METHODS: We retrospectively analyzed patients who underwent pancreatectomy for invasive IPMC from January 2007 to June 2020. We evaluated outcomes of AC in the entire cohort and in patients with known prognostic factors. RESULTS: A total of 51 patients with invasive IPMC underwent surgery, of which 35 received AC. In the entire cohort, there was no significant difference in median overall survival (OS) between the AC and surgery alone (SA) group [hazard ratio (HR)=0.54; p=0.232]. For patients with poorly differentiated adenocarcinoma, median OS was significantly longer in the AC group (HR=0.27; p=0.022). For patients with lymph node metastasis, median OS was significantly higher in the AC group (HR=0.07; p<0.001). CONCLUSION: AC may be effective for selected invasive IPMC patients.

Linker Threonine-phosphorylated Smad2/3 Is a Biomarker of Colorectal Neoplastic Stem-like Cells that Correlates With Carcinogenesis.

BACKGROUND/AIM: This study analysed threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr) expression and investigated whether pSmad2/3L-Thr is related to the transition from human colorectal adenoma (CRA) to carcinoma (CRC). MATERIALS AND METHODS: Immunofluorescent staining was performed forß-catenin, p53, CDK4, Ki67, Sox9, aldehyde dehydrogenase (ALDH) 1, and pSmad2/3L-Thr. RESULTS: We analysed specimens of diffuse p53-positive CRCs arising from p53-negative CRAs. Percentage of p53, nuclear ß-catenin, Ki67, CDK4, and pSmad2/3L-Thr-positive cells at the site of CRCs was significantly higher than that at the site of CRAs. At the site of normal colorectal mucosae, few epithelial cells were stained positively for pSmad2/3L-Thr. At the site of CRCs, pSmad2/3L-Thr-positive cells showed co-localization with p53, nuclear ß-catenin, and ALDH1. At any site, pSmad2/3L-Thr-positive cells showed co-localization with CDK4. CONCLUSION: pSmad2/3L-Thr correlates with human CRC carcinogenesis, and pSmad2/3L-Thr-positive cells show human colorectal stem cell-like and cancer stem cell characteristics.

Orbital haematoma after orbital fracture repair using silicone, polytetrafluorethylene, and poly-L-lactic acid/hydroxyapatite implants.

The purpose of this paper was to report the incidence of orbital haematoma formation following the repair of orbital fractures with silicone, polytetrafluorethylene (PTFE), and poly-L-lactic acid/hydroxyapatite (PLLA/HA) implants. This retrospective review examined 234 patients (235 sides) who underwent repair of orbital wall fractures over a six-year period. Of these, 36 patients received a silicone sheet; 49 patients received a silicone sheet with superimposed PTFE implant; and 149 patients (150 sides) received PTFE with or without an underlying PLLA/HA implant. Orbital haematomas were documented in 13 out of 36 patients (36.1%) who underwent fracture repair with a silicone sheet; seven out of 49 patients (14.3%) who had a silicone sheet with a superimposed PTFE implant; and three out of 150 sides (2.0%) with PTFE with or without underlying PLLA/HA. The difference in incidence of orbital haematoma formation was significant among the groups (p < 0.001, Pearson's chi squared test). In the silicone sheet group, haematomas formed within two weeks of surgery in 11 patients (84.6%). In the silicone sheet with superimposed PTFE implant group, five patients (71.4%) developed orbital haematomas no earlier than after two weeks postoperatively. This study showed that the incidence of orbital haematoma formation following orbital fracture repair is different among the implant materials. The use of PTFE and PLLA/HA implants may minimise this complication.

Difference in surgical outcomes of rectal cancer by study design: meta-analyses of randomized clinical trials, case-matched studies, and cohort studies.

BACKGROUND: RCTs are considered the standard in surgical research, whereas case-matched studies and propensity score matching studies are conducted as an alternative option. Both study designs have been used to investigate the potential superiority of robotic surgery over laparoscopic surgery for rectal cancer. However, no conclusion has been reached regarding whether there are differences in findings according to study design. This study aimed to examine similarities and differences in findings relating to robotic surgery for rectal cancer by study design. METHODS: A comprehensive literature search was conducted using PubMed, Scopus, and Cochrane CENTRAL to identify RCTs, case-matched studies, and cohort studies that compared robotic versus laparoscopic surgery for rectal cancer. Primary outcomes were incidence of postoperative overall complications, incidence of anastomotic leakage, and postoperative mortality. Meta-analyses were performed for each study design using a random-effects model. RESULTS: Fifty-nine articles were identified and reviewed. No differences were observed in incidence of anastomotic leakage, mortality, rate of positive circumferential resection margins, conversion rate, and duration of operation by study design. With respect to the incidence of postoperative overall complications and duration of hospital stay, the superiority of robotic surgery was most evident in cohort studies (risk ratio (RR) 0.83, 95 per cent c.i. 0.74 to 0.92, P < 0.001; mean difference (MD) -1.11 (95 per cent c.i. -1.86 to -0.36) days, P = 0.004; respectively), and least evident in RCTs (RR 1.12, 0.91 to 1.38, P = 0.27; MD -0.28 (-1.44 to 0.88) days, P = 0.64; respectively). CONCLUSION: Results of case-matched studies were often similar to those of RCTs in terms of outcomes of robotic surgery for rectal cancer. However, case-matched studies occasionally overestimated the effects of interventions compared with RCTs.

No significant association between stable iodine intake and thyroid dysfunction in children after the Fukushima Nuclear Disaster: an observational study.

PURPOSE: Stable iodine prophylaxis helps prevent childhood thyroid cancer in nuclear emergencies; however, there is limited information on its effect on thyroid function. This study aimed to examine thyroid function and autoimmunity among children and adolescents that took stable iodine after the Fukushima Nuclear Disaster. METHODS: For this observational study, data were obtained from children and adolescents that underwent thyroid cancer screening at Hirata Central Hospital from April 2012 to March 2018. Participant characteristics, including possible hypothyroidism and hyperthyroidism, were compared between the prophylaxis and no-prophylaxis groups. Multivariable logistic regression models were used to assess for possible hypothyroidism, autoantibodies positive, and hyperthyroidism. RESULTS: A total of 1,225 participants with stable iodine prophylaxis and 3,946 without prophylaxis were enrolled. Of those participants, blood samples were available for 144 and 1,201 participants in the prophylaxis and no-prophylaxis groups, respectively. There were 17 (11.8%) and 146 cases (12.2%) of possible hypothyroidism or autoantibodies positive cases in the prophylaxis and no-prophylaxis groups, respectively, and there were no cases and 3 cases (0.2%) of possible hyperthyroidism in those two groups, respectively. Multivariable analysis for possible hypothyroidism revealed no association between stable iodine intake and possible hypothyroidism or autoantibodies positive [odds ratio 0.716 (95% confidence interval 0.399-1.284)] (p = 0.262). We did not perform multivariable analysis for hyperthyroidism due to the limited number of cases. CONCLUSION: Significant adverse effects of stable iodine intake on thyroid function were not observed among children and adolescents 7 years after the Fukushima Nuclear Disaster.

Detailed Arterial Anatomy and Its Anastomoses of the Sphenoid Ridge and Olfactory Groove Meningiomas with Special Reference to the Recurrent Branches from the Ophthalmic Artery.

BACKGROUND AND PURPOSE: Detailed arterial anatomy of the sphenoid ridge and olfactory groove meningiomas is complicated due to the fine angioarchitecture and anastomoses between each feeder. Herein, we present details of the arterial anatomy and the relationships of feeders in these lesions. MATERIALS AND METHODS: This study included 20 patients admitted to our department between April 2015 and March 2020. Conditions of subjects consisted of 16 sphenoid ridge meningiomas and 4 olfactory groove meningiomas. We mainly analyzed arterial anatomy using 3D rotational angiography and slab MIP images of these lesions. We also analyzed the anastomoses of each feeder. RESULTS: We found that 19 (95%), 15 (75%), and 15 (75%) lesions had feeders from the ophthalmic, internal carotid, and external carotid arteries, respectively. As feeders from the ophthalmic artery, recurrent meningeal arteries were involved in 18 lesions (90%). Fifteen lesions (75%) had anastomoses between each feeder. CONCLUSIONS: Most of the meningiomas in the sphenoid ridge and olfactory groove had feeders from the ophthalmic and internal carotid arteries. There were various anastomoses between each feeder. This is the first report to demonstrate the detailed arterial anatomy and frequency of recurrent branches from the ophthalmic artery and their anastomoses using detailed imaging techniques.

New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.

Regional pancreatoduodenectomy versus standard pancreatoduodenectomy with portal vein resection for pancreatic ductal adenocarcinoma with portal vein invasion.

BACKGROUND: Pancreatoduodenectomy (PD) with portal vein resection (PVR) is a standard operation for pancreatic ductal adenocarcinoma (PDAC) with portal vein (PV) invasion, but positive margin rates remain high. It was hypothesized that regional pancreatoduodenectomy (RPD), in which soft tissue around the PV is resected en bloc, could enhance oncological clearance and survival. METHODS: This retrospective study included consecutive patients who underwent PD with PVR between January 2005 and December 2016 in a single high-volume centre. In standard PD (SPD) with PVR, the PV was skeletonized and the surrounding soft tissue dissected. In RPD, the retropancreatic segment of the PV was resected en bloc with its surrounding soft tissue. The extent of lymphadenectomy was similar between the procedures. RESULTS: A total of 268 patients were included (177 SPD, 91 RPD). Tumours were more often resectable in patients undergoing SPD (60·5 per cent versus 38 per cent in those having RPD; P = 0·014), and consequently they received neoadjuvant therapy less often (7·9 versus 25 per cent respectively; P < 0·001). R0 resection was achieved in 73 patients (80 per cent) in the RPD group, compared with 117 (66·1 per cent) of those in the SPD group (P = 0·016), although perioperative outcomes were comparable between the groups. Median recurrence-free (RFS) and overall (OS) survival were 17 and 32 months respectively in patients who had RPD, compared with 11 and 21 months in those who had SPD (RFS: P = 0·003; OS: P = 0·004). CONCLUSION: RPD is as safe and feasible as SPD, and may increase the survival of patients with PDAC with PV invasion.

ANTECEDENTES: La duodenopancreatectomía (pancreaticoduodenectomy, PD) con resección de la vena porta (portal vein resection, PVR) es una operación estándar para el adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) con invasión de la vena porta (portal vein, PV); sin embargo, las tasas de margen positivo siguen siendo altas. Nuestra hipótesis fue que la duodenopancreatectomía regional (regional pancreaticoduodenectomy, RPD) en la que el tejido blando alrededor de la PV se reseca en bloque podría mejorar el resultado oncológico y la supervivencia. MÉTODOS: Este estudio retrospectivo incluyó pacientes consecutivos que se sometieron a PD con PVR entre enero de 2005 y diciembre de 2016 en un solo centro de alto volumen. En la PD estándar (SPD) con PVR, la PV se esqueletizó disecando el tejido blando circundante. En la RPD, el segmento retropancreático de la PV se resecó en bloque con el tejido blando circundante. La extensión de la linfadenectomía fue similar en ambos procedimientos. RESULTADOS: Se incluyeron un total de 268 pacientes (177 sometidos a SPD y 91 a RPD). Los pacientes sometidos a SPD presentaron con mayor frecuencia tumores resecables (35 (38%) versus 107 (61%), P = 0,014)) y recibieron con mayor frecuencia terapia neoadyuvante (23 (25%) versus 14 (8%), P < 0,001)) que los pacientes sometidos a RPD. La resección R0 se logró en 73 (80%) pacientes pertenecientes al grupo RPD, en comparación con 117 (66%) pacientes sometidos a SPD (P = 0.011), aunque los resultados perioperatorios fueron comparables entre los grupos. La mediana de supervivencia libre de recidiva (recurrence-free survival, RFS) y de supervivencia global (overall survival, OS) fueron 17 meses y 31 meses, respectivamente, en pacientes sometidos a RPD, en comparación con 11 meses y 21 meses en pacientes sometidos a SPD, (P = 0,003 para RFS y P = 0,004 para la OS). CONCLUSIÓN: La RPD es tan segura y factible como la SPD y puede aumentar la supervivencia de pacientes con PDAC con invasión de la PV.

Preparation and evaluation of orally disintegrating tablets containing taste masked microparticles of acetaminophen.

In the present work, taste masked particles of acetaminophen (AAP), a highly soluble bitter tasting drug, were developed and ODT containing the taste masked particles were prepared. Taste masked particles of AAP were prepared using different amounts of tetraglycerol polyricinoleate (TGPR) and Eudragit ®E100. Although the drug content ratio and drug recovery decreased with increasing TGPR, drug release from AAP-CR100 particles containing a large amount of TGPR was mostly suppressed for 2 min. Hence, AAP-CR100 was incorporated into ODT as taste masked particles for AAP. Three major disintegrants were used for ODT, and it was confirmed that the tensile strength of all formulations showed applicable hardness for handling. The AAP-CR100-CP(40) formulation containing crospovidone showed the shortest disintegration time and the drug release from AAP-CR100-CP(40) into pH 6.8 test solution was suppressed compared with commercial AAP tablets. Because the drug release from AAP-CR100-CP(40) into the pH 1.2 test solution was rapid, it was suggested that drug release from AAP-CR100-CP(40) is suppressed in the oral cavity, and the drug is released promptly in the stomach. Thus AAP-CR100-CP(40) may be useful as an ODT in which the dissolution of AAP in the oral cavity is suppressed.

Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND AND PURPOSE: Tapering immunosuppressants is desirable in patients with well-controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction-associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody-positive MG, and to determine the factors that predict exacerbations. METHODS: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction-associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. RESULTS: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction-associated exacerbation than in those without exacerbation. The cut-off values determined in a receiver-operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. CONCLUSION: Tapering of tacrolimus was possible in most patients with well-controlled anti-acetylcholine receptor antibody-positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.

Insulin secretion and sensitivity before and after surgical treatment for aldosterone-producing adenoma.

AIM: Primary aldosteronism, which is usually caused by an aldosterone-producing tumour, affects glucose metabolism. The effects of this condition on insulin secretion and insulin sensitivity have remained unclear, however. To gain insight into the influence of primary aldosteronism on glucose tolerance, various parameters related to insulin secretion or insulin sensitivity in patients with an aldosterone-producing tumour were comprehensively analyzed. METHODS: To assess 14 patients with an aldosterone-producing tumour, hyperglycaemic and hyperinsulinaemic-euglycaemic clamp tests as well as oral glucose tolerance tests (OGTTs) were performed before and after tumour excision. Time between presurgical analysis and surgery was 27-559 (194±132) days, and 14-142 (51±38) days between surgery and postsurgical analysis. Various parameters related to insulin secretion or sensitivity as determined by OGTT as well as hyperglycaemic and hyperinsulinaemic-euglycaemic clamp analyses were evaluated. RESULTS: Surgical treatment of tumours ameliorated hypokalaemia and reduced plasma aldosterone levels. First and second phases of insulin secretion during the hyperglycaemic clamp, as well as the insulinogenic index and total insulin secretion measured during OGTT, were also improved after surgery. In addition, the insulin sensitivity index determined during the hyperinsulinaemic-euglycaemic clamp was reduced after surgery. CONCLUSION: Primary aldosteronism impairs insulin secretion.

Possible underestimation of blood loss during laparoscopic hepatectomy.

Background: Previous studies have documented potential advantages of laparoscopic hepatectomy in decreasing blood loss compared with open surgery. This study aimed to compare intraoperative blood loss estimated using four different methods in open versus laparoscopic hepatectomy. Methods: Patients undergoing liver resection between 2014 and 2017 were evaluated prospectively, differentiating between the laparoscopic and open approach. Groups were compared using univariable and multivariable analyses. Intraoperative blood loss was estimated using three formulas based on the postoperative decreases in haematocrit, haemoglobin or red blood cell volume, and using the conventional method of the sum of suction fluid amounts and gauze weight. In addition, blood loss per hepatic transection area was calculated to compare groups. Results: Some 125 patients who underwent hepatectomy were selected, including 56 open hepatectomies and 69 laparoscopic liver resections. Intraoperative blood loss per hepatic transection area estimated by the conventional method was significantly less in the laparoscopic than the open group (3·6 (range 0·2-50·0) versus 6·6 (1·2-82·5) ml/cm2 respectively; P < 0·001). In contrast, there were no significant differences between groups in blood loss estimated based on the decrease in haematocrit (12·9 (0-65·2) versus 8·1 (0-123·7) ml/cm2; P = 0·818), haemoglobin or red blood cell volume. Blood loss estimation using three formulas showed significant linear correlations with the blood loss estimated by the conventional method in the open group (r s = 0·758 to 0·762), but not in the laparoscopic group (r s = -0·019 to 0·031). Conclusion: The conventional method of calculating blood loss in laparoscopic hepatectomy can underestimate losses.