Rapid Onset of De Novo Rectal Prolapse Following Colpocleisis.

INTRODUCTION: The aim of this video case series is to demonstrate our experience of the clinical findings and the surgical management of the rapid onset de novo rectal prolapse (RP) following colpocleisis METHODS: This is a case series of three patients who developed de novo RP within 1 month after colpocleisis, which was repaired by laparoscopic ventral mesh rectopexy (LVMR). The video shows the physical, radiological, and intraoperative findings of these patients. A retrospective review of our surgical cases of RP was also performed to analyze the onset timing of de novo RP after various pelvic organ prolapse (POP) procedures. RESULTS: The pathological condition of all three patients' RP was evacuation enterocele, and LVMR was feasible without postoperative complications or recurrences. In the retrospective case review of 158 RP surgeries in our institution (June 2015 to September 2023), 18 cases (11.4%) occurred following POP surgery. De novo RP following colpocleisis developed significantly earlier than those following other procedures (average: 6.1 vs 66.4 months, p = 0.010). CONCLUSIONS: Although de novo RP following colpocleisis is relatively rare, this complication could have a detrimental effect on patients' quality of life. Preoperative informed consent may be advisable before planning colpocleisis.

Iliac vein variation in the sacral promontory on three-dimensional computed tomography angiography: a prospective observational study before laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Venous injury may occur during exposure of the anterior longitudinal ligament at the anterior sacral promontory (SP). We aimed to quantitatively measure the extent of the vascular window (VW) in front of the SP in patients with internal iliac vein (IIV) variations using preoperative three-dimensional computed tomography angiography (3DCTA). We hypothesized that patients with IIV variations would have a narrow VW. METHODS: This prospective observational study included patients scheduled for laparoscopic sacrocolpopexy (LSC) between July 2022 and April 2023 who underwent preoperative 3DCTA. The primary endpoint was the VW measurement in the standard and variant IIV groups using 3DCTA before LSC. The secondary endpoint was the difference between the two IIV groups adjusted for age, body mass index, hypertension, and diabetes using an analysis of covariance (ANCOVA) model. Multiple regression analysis was performed to analyze the effect of factors on the distance from the SP to great vascular bifurcations. RESULTS: There were 20 cases of IIV variation (20.2%). VW was 28.8 ± 12.4 mm in the variant group and 39.6 ± 12.6 mm in the standard group (p = 0.001). In the ANCOVA model, IIV variations affected VW (coefficient, -11.8; 95% confidence interval [CI], -18.4 to -5.08, p < 0.001). Multivariate analysis revealed that the aorta-SP distance decreased with age (coefficient, -0.44; 95% CI, -0.77 to -0.11, p = 0.009). CONCLUSIONS: One in five women has a vascular variant at the SP that restricts the "safe" zone of fixation to < 3 cm.

Generation and Coupling of Radical Species from α-Alkoxy Bridgehead Carboxylic Acid, Selenide, Telluride, Acyl Selenide, and Acyl Telluride.

α-Alkoxy bridgehead radicals enable intermolecular construction of sterically congested C-C bonds due to their sterically accessible nature. We implemented these radical species into total syntheses of various densely oxygenated natural products and demonstrated their exceptional versatility. Herein, we employed different precursors to generate the same α-alkoxy bridgehead radical and compared the efficacy of the precursors for coupling reactions. Specifically, the bridgehead radical of the trioxaadamantane structure was formed from α-alkoxy carboxylic acid, selenide/telluride, and acyl selenide/acyl telluride, and reacted with 4-((tert-butyldimethylsilyl)oxy)cyclopent-2-en-1-one and 5-oxo-1-cyclopentene-1-carbonitrile. The efficiency of the bridgehead radical formation and subsequent coupling reaction significantly depended on the structures of the precursors and acceptors as well as the reaction conditions. Our findings provide new insights for selecting the appropriate substrates of key coupling reactions in the total synthesis of complex natural products.

Unmasked insulinoma occasioned by severe hypoglycemic coma immediately postpartum: a case report.

BACKGROUND: Insulinoma in women during pregnancy and postpartum is very rare; approximately 65% of cases are diagnosed early in pregnancy and ~ 35% immediately after delivery, few being found in middle or late pregnancy, likely due to increased insulin resistance seen after early-stage pregnancy. We successfully treated a case of insulinoma in which severe hypoglycemic coma immediately after delivery occasioned detailed investigation and diagnosis. CASE PRESENTATION: Our patient experienced hypoglycemic coma in the 3rd month of pregnancy (initially considered due to her hyperemesis gravidarum) that improved spontaneously during the gestational period. No abnormalities of plasma glucose or body weight were found in regular checkups during her pregnancy; however, recurrence of hypoglycemic coma after delivery led us to suspect insulinoma. While contrast enhanced computer tomography and endoscopic ultrasonography (EUS) initially failed to detect a tumor in the pancreas, selective arterial calcium stimulation test revealed an insulin-secreting tumor localized in the pancreatic body. She then underwent spleen-preserving distal pancreatectomy; a 10-mm tumor positive for chromogranin A, synaptophysin and insulin was identified. CONCLUSIONS: Although pregnancy can mask insulinoma-associated symptoms and make diagnosis challenging, hypoglycemic episodes during early pregnancy, which were observed in this case, are suggestive of insulinoma. Importantly, in this case, accurate preoperative localization of the tumor enabled prompt curative surgery after delivery. Thus, clinical vigilance for the occurrence of insulinoma and its localization is appropriate for pregnant women suffering severe hypoglycemia.

A case of familial hypocalciuric hypercalcemia type 1 due to CASR p.Pro55Leu mutation.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant disease, which requires differential diagnosis from relatively common primary hyperparathyroidism (PHPT) in order to avoid unnecessary surgery. CASE PRESENTATION: A 16-year-old female had been followed by the department of psychosomatic medicine at our institution. Throughout the follow-up period, her plasma calcium levels were high, plasma Pi levels were relatively low, and plasma intact PTH was relatively high. She was referred to our department to determine the cause of her hypercalcemia. Her 24 h urinary calcium excretion was as low as 100 mg/day, and calcium creatinine clearance ratio was below 0.01. Moreover, she had a family history of hypercalcemia (proband, her brother, and her father). The genetic testing for her family revealed that she, her brother, and her father were definitively diagnosed with FHH type 1 due to the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C > T:p.Pro55Leu). CONCLUSION: We experienced a 16-year-old female with FHH, in whom genetic testing identified the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C > T:p.Pro55Leu) as pathogenic, permitting a definitive diagnosis of FHH type 1. The genetic testing for calcium sensing receptor is beneficial to distinguish asymptomatic primary hyperparathyroidism from FHH.

Glucokinase-maturity onset diabetes mellitus in the young suggested by factory-calibrated glucose monitoring data: a case report.

Glucokinase has an important role in regulating glycolysis as a glucose sensor in liver and pancreatic ß cells. Glucokinase-maturity onset diabetes in young (GCK-MODY also known as MODY2) is caused by autosomal dominant gene mutation of the GCK gene; it is characterized by mild fasting hyperglycemia and small 2-h glucose increment during 75 g-oral glucose tolerance test (OGTT) as well as near-normal postprandial glucose variabilities. A 10-year-old girl with family history of diabetes visited her physician after being found positive for urinary glucose by school medical checkup. She received a diagnosis of diabetes based on the laboratory data: 75 g-OGTT (mild fasting hyperglycemia and small 2-h glucose increment) and factory-calibrated glucose monitoring (mild elevation of average glucose level and near-normal glycemic variability), which raised suspicion of GCK-MODY. She was then referred to our institution for genetic examination, which revealed a GCK heterozygous mutation (NM_000162: exon10: c.1324G>T: p.E442X) in the proband as well as in her mother and maternal grandmother, who had been receiving anti-diabetes medications without knowing that they had GCK-MODY specifically. GCK-MODY cases show incidence of microvascular and macrovascular diseases similar to that of normal subjects, and their glucose levels are adequately controlled without anti-diabetes drug use. Thus, early and definitive diagnosis of MODY2 by genetic testing is important to avoid unnecessary medication.

Differences in lower limb muscle strength and balance ability between sarcopenia stages depend on sex in community-dwelling older adults.

AIM: This study aimed to compare motor function between sarcopenia stages with respect to sex in community-dwelling older adults. METHODS: The participants, comprising 2107 community-dwelling older adults (738 men and 1369 women), were classified into 4 groups and the groups were operationally defined-normal, low muscle mass, low physical function, and sarcopenia groups. Lower limb muscle strength and balance ability were assessed for evaluating motor function. To compare motor function between sarcopenia stages, an analysis of covariance adjusted for age and body mass index was performed. RESULTS: Lower limb muscle strengths were significantly lower not only in the sarcopenia group but also in the low muscle mass and low physical function groups than that in the normal group in both men and women. Low hip abductor muscle strength was observed in the low physical function group compared to the low muscle mass group in women, but not in men. Timed Up and Go test results in the sarcopenia and low function groups was lower than in the normal and low muscle mass groups for men and women. One-leg standing in the low physical function group was lower than that in the normal group, only for women. CONCLUSIONS: Reduced motor function was observed not only in older people with sarcopenia but also in older people with only low muscle mass or low physical function, and the decline in lower limb muscle strength and balance ability in the low function group were greater in older women than in older men.

Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report.

BACKGROUND: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. CASE PRESENTATION: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. CONCLUSIONS: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.

Flipper Probes for the Community.

This article describes four fluorescent membrane tension probes that have been designed, synthesized, evaluated, commercialized and applied to current biology challenges in the context of the NCCR Chemical Biology. Their names are Flipper-TR®, ER Flipper-TR®, Lyso Flipper-TR®, and Mito Flipper-TR®. They are available from Spirochrome.

A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the HNF1B gene.

Pancreatic tail hypoplasia is a common manifestation of maturity onset diabetes of the young (MODY) 5 that can cause reno-genito-urinary malformations such as renal cysts and bicornuate uterus. A 69-year-old female was admitted to our hospital for consultation on her relatively high HbA1c value. At age 20, she was diagnosed with uterus bicornis. At age 68, she was diagnosed with pancreas tail hypoplasia, renal cysts and non-functioning pancreatic neuroendocrine tumor (NET) in addition to right hydronephrosis due to multiple ureteral bladder carcinomas. She received total right nephrectomy, ureterectomy and partial cystectomy for multiple ureteral bladder carcinomas [non-invasive papillary urothelial carcinoma, low grade (G1), pTa, LV10, u-rtx, RM0, and pN0 (0/8)]. She also received distal pancreatomy for pancreatic NET [NET G1]. She then was referred to our department at age 69 due to increase in her HbA1c value from 6.2 to 7.2%; 75 g oral glucose tolerance test revealed impaired glucose tolerance. Her clinical characteristics (uterus bicornis, pancreas hypoplasia, and renal cysts) closely resembled the phenotype of MODY5, in which mutations in the HNF1B gene have been reported. Our genetic testing failed to detect any mutation or microdeletion in the coding or minimal promoter regions of the HNF1B gene. Although there remains a possibility that genetic mutations in introns and regulatory regions of the HNF1B gene might cause the MODY5-like manifestations in this patient, these results might suggest involvement of genes other than HNF1B in the pathogenesis of our patient's disease.

Age-related changes in muscle thickness and echo intensity of trunk muscles in healthy women: comparison of 20-60s age groups.

PURPOSE: The objective of this study was to investigate the age-related changes in muscle thickness and muscle echo intensity of trunk in subjects including wide range of age groups. METHODS: The subjects were 112 healthy women (age range 20-60s). The rectus abdominis, external oblique, internal oblique, transversus abdominis, erector spinae, and lumbar multifidus muscles were examined. To confirm the differences among the age groups, the linear mixed effect models were performed. RESULTS: There were significant decreases in muscle thickness of the rectus abdominis and external oblique muscles in the 50s and 60s age groups compared to those in the 20s age group, and a significant decrease in muscle thickness of the erector spinae muscle in the 60s age group compared to those in the 20s age group. However, there was no significant difference among the age groups in muscle thickness of other trunk muscles. There were significant increases in echo intensity of the abdominal muscles in other age groups compared to those in the 20s age group, and significant increases in echo intensity of the back muscles in the age groups over 40 compared to those in the 20s group. CONCLUSION: Our study revealed that muscle quality may be more affected by age than muscle quantity and the effects of aging differ among muscles.

Effect of different knee flexion angles with a constant hip and knee torque on the muscle forces and neuromuscular activities of hamstrings and gluteus maximus muscles.

PURPOSE: This study examined the effect of different knee flexion angles with a constant hip and knee torque on the muscle force and neuromuscular activity of the hamstrings and gluteus maximus. METHODS: Twenty healthy males lay in prone position and held their lower limb with hip flexion at 45° and knee flexion at either 10° or 80°. At these angles, the hip and knee torques are identical. Under three load conditions: passive (referred to as Unloaded), active (Loaded), and active with 3-kg weight added to the shank (Loaded + 3 kg), the muscle stiffness (i.e., an indicator of muscle force) and neuromuscular activity of the hamstrings and gluteus maximus were measured using shear wave elastography and surface electromyography. RESULTS: The muscle stiffness and neuromuscular activity of the hamstrings and gluteus maximus increased significantly with the load. Muscle stiffness in the hamstrings was significantly lower at knee flexion of 80° than at 10° for Unloaded, but not for either Loaded or Loaded + 3 kg. The neuromuscular activity of the hamstrings was significantly greater at knee flexion of 80° than at 10° for both Loaded and Loaded + 3 kg. The muscle stiffness or neuromuscular activity of the gluteus maximus showed no significant differences between knee angles. CONCLUSIONS: When the passive force in the hamstrings decreases with knee flexion, sufficient muscle force to maintain the hip and knee torques against an external load is generated by preferentially increasing the neuromuscular activity of the hamstrings, rather than increasing the synergetic muscle force.

Total Synthesis of Resiniferatoxin Enabled by Radical-Mediated Three-Component Coupling and 7-endo Cyclization.

Resiniferatoxin (1) belongs to a daphnane diterpenoid family and has strong agonistic effects on TRPV1, a transducer of noxious temperature and chemical stimuli. The densely oxygenated trans-fused 5/7/6-tricarbocycle (ABC-ring) of 1 presents a daunting challenge for chemical synthesis. Here we report the development of a novel radical-based strategy for assembling 1 from three components: A-ring 9, allyl stannane 18b, and C-ring 17b. The 6-membered 17b, prepared from d-ribose derivative 19, was designed to possess the caged orthoester structure with α-alkoxy selenide as a radical precursor. Upon treatment of 17b with 18b, 9, and V-40, the potently reactive α-alkoxy bridgehead radical was generated from 17b and then sequentially coupled with 9 and 18b to yield 16b. This first radical reaction formed the hindered C9,10-linkage between the A and C-rings and extended the C4-chain on the A-ring in a stereoselective fashion. After derivatization of 16b into 15, the remaining 7-membered B-ring was cyclized in the presence of n-Bu3SnH and V-40 by utilizing the xanthate on the C-ring as the radical precursor and the allylic dithiocarbonate as the terminator. The second radical reaction thus enabled not only the 7-endo cyclization but also construction of the C8-stereocenter and the C6-exo olefin. Tricycle 14 was elaborated into the targeted 1 by a series of highly optimized chemoselective reactions. The present total synthesis of 1 demonstrates the advantages of radical reactions for linking hindered bonds within carbocycles without damaging preexisting functionalities, thereby offering a new strategic design for multistep target-oriented synthesis.

Initial experience of laparoscopic pelvic exenteration and comparison with conventional open surgery.

BACKGROUND: Generalization of laparoscopic pelvic surgery has brought about profound knowledge of the pelvic anatomy and has encouraged expansion of indications for laparoscopic surgery to extended pelvic surgery. Pelvic exenteration (PE) is still a demanding surgical procedure and remains an essential technique for pelvic surgery although minimally invasive and function-preserving surgery is in the mainstream of surgical treatment. However, the techniques of laparoscopic PE (LPE) have been rarely explained nor has its feasibility been fully evaluated. The aim of this study was to describe important technical points and to assess the feasibility of LPE for pelvic malignancies. METHODS: Data on 67 patients with pelvic malignancies, who underwent PE between June 2006 and August 2014, were analyzed retrospectively. LPE has been indicated since 2013. Patients were divided into the LPE group (n = 9) and the conventional open PE (OPE) group (n = 58). RESULTS: Operative time in the LPE and OPE groups was similar (935 vs. 883 min, p = 0.398). Intraoperative blood loss in the LPE group was significantly less than that in the OPE group (830 vs. 2769 ml, p = 0.003). Pathological R0 resection rate was similar in both groups (77.8 vs. 75.9%). Overall incidence of any complication and major complications were much lower in the LPE group (66.7 and 0%) compared to the OPE group (89.7 and 32.8%), although not statistically significant (p = 0.094 and 0.053, respectively). Postoperative hospital stay was significantly shorter in the LPE group than in the OPE group (27 vs. 43 days, p = 0.003). CONCLUSIONS: We confirmed that LPE for pelvic malignancies resulted in less blood loss, a lower complication rate, and shorter postoperative hospital stay compared to OPE. LPE performed by an experienced pelvic surgeon was safe and efficient, and might be a promising option for carefully selected patients.

The feasibility of laparoscopic extended pelvic surgery for rectal cancer.

PURPOSE: The present study aimed to assess the safety and feasibility of laparoscopic extended pelvic surgery for primary or recurrent rectal cancer. METHODS: The data on 77 patients, who underwent extended pelvic surgery between February 2008 and June 2014, were retrospectively analyzed. The patients were divided, based on their treatment history, into an open surgery (OS) group (n = 41) and a laparoscopic surgery (LS) group (n = 36). RESULTS: The operative time in the LS group was significantly longer than that in the OS group (766 vs. 561 min; p < 0.001). In contrast, the LS group was associated with a significantly lower volume of intraoperative blood loss (195 vs. 923 ml; p < 0.001), fluid balance (5.38 vs. 8.23 ml/kg/h; p < 0.001) and rate of complications (40.0 vs. 68.3 %; p = 0.035), and a significantly shorter postoperative hospital stay. The postoperative levels of colloid osmotic pressure and albumin were significantly higher in the LS group. CONCLUSION: The operative time of the LS group was longer than that of the OS group; however, the LS group experienced less blood loss and fewer complications. Moreover, LS was associated with a reduction in intraoperative infusions and a reduced fluid balance, which maintained homeostasis.

Fat and carbohydrate in western diet contribute differently to hepatic lipid accumulation.

We investigated the contributions of dietary fat and dietary carbohydrate to the development of fatty liver induced by western diet (WD). Compared with WD-fed wild type (WT) mice, livers of WD-fed ChREBP(-/-) mice showed lipid droplets of varying sizes around the hepatic lobules, while hepatic triglyceride and cholesterol contents were only modestly decreased. Inflammation and fibrosis were suppressed in ChREBP(-/-) mice. In addition, compared with WD-fed WT mice, ChREBP(-/-) mice showed decreased ß-oxidation, ketogenesis and FGF21 production, increased intestinal lipid absorption, and decreased VLDL secretion. These findings suggest that dietary fat and carbohydrate contribute differently to the development of fatty liver.

Clinical Significance of Para-Aortic Lymph Node Dissection for Advanced or Metastatic Colorectal Cancer in the Current Era of Modern Chemotherapy.

BACKGROUND/AIMS: Surgical resection is not generally indicated for para-aortic lymph node (PALN) metastasis from colorectal cancer. However, the clinical significance of PALN dissection (PALND) in the current era of modern chemotherapy has not been fully discussed. METHODS: Between November 2006 and February 2013, 14 patients underwent PALND for colorectal cancer and were proven as having pathological PALN metastasis. The median follow-up was 33.2 months. RESULTS: Primary location was the right-colon in 2 patients, and the left-colon or rectum in 12 patients. The timing of metastasis was metachronous in 5 patients and synchronous in 9 patients. Eleven patients (79%) received perioperative aggressive modern chemotherapy. Neoadjuvant chemotherapy with targeted drugs was introduced in 9 patients (64%) and 6 patients received adjuvant chemotherapy. Recurrence after PALND occurred in 12 patients (86%). The most common site was the lung in 6 patients (43%). The 1- and 3-year disease-free survivals were 39.3 and 7.9%, respectively. The 3-year overall survival were 41.2%. CONCLUSION: The recurrence rate after PALND for strictly selected patients was quite high even in the current era of modern chemotherapy. However, some patients achieved long-term survival or could be cured. Therefore, we should re-evaluate the efficacy of PALND in a larger prospective study.

Molecular identification of Heterakis spumosa obtained from brown rats (Rattus norvegicus) in Japan and its infectivity in experimental mice.

Heterakis spumosa is a nematode of invasive rodents, mainly affiliated with Rattus spp. of Asian origin. Despite the ecological importance and cosmopolitan distribution, little information is available on the genetic characteristics and infectivity to experimental animals of this roundworm. Heterakis isolates obtained from naturally infected brown rats caught in 2007 in the city of Sagamihara, east central Honshu, Japan, and maintained by laboratory passages were subjected to mitochondrial sequence analysis and experimental infection in mice. Sequencing of the cox1 gene revealed that nucleotides of H. spumosa and previously examined Heterakis isolonche isolates from gallinaceous birds in Japan differed by 11.2-12.2% that conforms to the range expected for interspecific differences. The two H. spumosa isolates differed by a single 138T/C non-synonymous substitution in the 393-bp mt sequence. In a dendrogram, the H. spumosa samples formed a subcluster with members of the nematode superfamily Heterakoidea, H. isolonche and Ascaridia galli. In an experimental infection study, ICR, AKR, B10.BR and C57BL/6 mice strains were inoculated with 200 H. spumosa eggs/head and necropsied at 14 and 90 days post-inoculation (DPI) when the number of worms was recorded. Eggs were initially detected in faeces from 32-35 DPI in ICR, AKR and B10.BR mice and the highest mean number of eggs per gram of faeces (EPG) was 4,800 at 38 DPI, 2,200 at 58 DPI and 800 at 44 and 72 DPI in ICR, AKR and B10.BR mice, respectively. No eggs were observed in faeces of the C57BL/6 mouse strain during the experiment. A similar number of juvenile worms were isolated from all mouse strains at 14 DPI, whereas no adult worms were detected in C57BL/6 mice at 90 DPI.

[A patient with paclitaxel hypersensitivity treated with nab-paclitaxel].

A 63-year-old man with multiple liver metastases from gastric cancer was treated with S-1 plus cisplatin; however, the number of multiple liver metastases increased. The patient received paclitaxel(PTX)treatment, but a hypersensitivity reaction occurred after administering the second dose; therefore, he received docetaxel treatment. A hypersensitivity reaction occurred after administering the first dose of docetaxel; therefore, he received irinotecan treatment. However, irinotecan administration was stopped because of severe diarrhea and weight reduction. Subsequently, at the patient's request, nab-PTX treatment was initiated by administering a premedication regimen of dexamethasone(8mg)and chlorpheniramine(10mg); no hypersensitivity reactions were reported thereafter. Nab-PTX is a contraindication; however, it might be possible to use nab-PTX for treating patients with PTX hypersensitivity.