Impact of age on groin hernia profiles observed during laparoscopic transabdominal preperitoneal hernia repair.

BACKGROUND: How increasing age affects the characteristics of groin hernia remains uncertain. This study evaluated the association between age and the type of groin hernia, especially with respect to its multiplicity, observed during laparoscopic transabdominal preperitoneal (TAPP) hernia repair. METHODS: We retrospectively evaluated 634 consecutive patients with primary groin hernia who underwent laparoscopic TAPP repair between October 2000 and June 2017. Patients were stratified into 4 age groups: < 60 years, 60-69 years, 70-79 years, and 80 years or older. RESULTS: The incidence of occult contralateral hernia and multiple ipsilateral hernias increased significantly with each increasing age group: 7.3%, 10.4%, 12.7%, and 20.8% for occult contralateral hernia (p = 0.005), and 5.6%, 9.2%, 16.8%, and 21.7% for multiple ipsilateral hernias (p < 0.001), respectively. Univariate analyses showed that an older age (age ≥ 70 years) was the only factor significantly associated with the presence of multiple groin hernias (odds ratio, 2.69; 95% confidence interval, 1.89-3.81; p < 0.001). In patients with multiple ipsilateral hernias, the prevalent form in men was a pantaloons hernia, with an incidence of about 70% across all age groups, whereas in women it was groin hernias, with one component being a femoral hernia, an obturator hernia, or both. CONCLUSIONS: The multiple occurrence of groin hernias, either unilaterally or bilaterally, was a clinical feature in the elderly.

Contrast-enhancement ratio on multiphase enhanced computed tomography predicts recurrence of pancreatic neuroendocrine tumor after curative resection.

BACKGROUND/OBJECTIVE: No previous study has quantitatively investigated the degree of enhancement of pancreatic neuroendocrine tumors (pNETs) using a routine preoperative modality. The aim of this study was to evaluate the contrast-enhancement ratio (CER) of pNETs using multiphase enhanced CT and to assess the impact of the CER on disease recurrence after surgery. METHODS: A retrospective study was performed using data from 47 consecutive patients with pNETs who had undergone curative surgery. The CER of the tumor was calculated by dividing the CT attenuation value obtained during the maximum-enhanced phase by that obtained during the pre-enhanced phase. A region of interest was placed in the largest tumor dimension plane so as to cover as much surface of the tumor as possible while avoiding adjacent normal structures, calcification, and necrotic areas of the tumor. RESULTS: During a median follow-up period of 51 months (range, 1-132 months), a total of 4 patients (8.5%) developed disease recurrence. The median CER value was significantly lower for the patients with recurrence than for the patients without recurrence (2.9 vs. 4.3, P = 0.013). Univariate analyses showed that a CER ≤3.2 was significantly associated with disease recurrence (P < 0.001). All the patients with disease recurrence had tumors that were both large (>20 mm) and weakly enhanced (CER ≤ 3.2), whereas no recurrences were observed even in patients with tumors >20 mm when the CER was greater than 3.2. CONCLUSIONS: CER might be a useful predictor of disease recurrence in patients with pNETs.

Signal intensity of the pancreas on magnetic resonance imaging: Prediction of postoperative pancreatic fistula after a distal pancreatectomy using a triple-row stapler.

BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the impact of the pancreatic signal intensity (SI) on magnetic resonance imaging (MRI) findings for predicting the development of pancreatic fistula (PF) after a distal pancreatectomy (DP) involving a triple-row stapler closure. METHODS: A multivariate logistic regression analysis was used to identify risk factors for clinical PF, as defined by the International Study Group on Pancreatic Fistula grade B or C. The pancreas-to-muscle SI ratio was evaluated using fat-suppressed T1-weighted MRI. RESULTS: Of the 41 enrolled patients, 8 (19.5%) developed clinical PF. The pancreatic thickness (≥15 mm) and SI ratio (≥1.3) were identified as independent predictors of clinical PF in a multivariate analysis. Clinical PF was observed in one patient with a thick pancreas and a low SI ratio (14.3%), whereas it was observed in 60% of the patients with a thick pancreas and a high SI ratio. The area under the receiver operating characteristic curve for a predictive model consisting of the two factors was 0.87 (95% confidence interval, 0.75 to 0.99), the level of which tended to be greater than that for pancreatic thickness alone (0.81, p = 0.09). CONCLUSIONS: The SI ratio as evaluated using MRI might be useful for predicting clinical PF in patients with the pancreatic thickness ≥15 mm after DP involving a stapler closure.

Functional differentiation of RAMP2 and RAMP3 in their regulation of the vascular system.

Adrenomedullin (AM) is a vasoactive peptide that possesses various bioactivities. AM receptors are dimers consisting of CLR with one of two accessory proteins, RAMP2 or RAMP3. The functional difference between CLR/RAMP2 and CLR/RAMP3 and the relationship between the two receptors remain unclear. To address these issues, we generated RAMP2 and RAMP3 knockout (-/-) mice and have been studying their physiological activities in the vascular system. AM-/- and RAMP2-/- mice die in utero due to blood vessel abnormalities, which is indicative of their essential roles in vascular development. In contrast, RAMP3-/- mice were born normally without any major abnormalities. In adult RAMP3-/- mice, postnatal angiogenesis was normal, but lymphangiography using indocyanine green (ICG) showed delayed drainage of subcutaneous lymphatic vessels. Moreover, chyle transport by intestinal lymphatics was delayed in RAMP3-/- mice, which also showed more severe interstitial edema than wild-type mice in a tail lymphedema model, with characteristic dilatation of lymphatic capillaries and accumulation of inflammatory cells. In scratch-wound assays, migration of isolated RAMP3-/- lymphatic endothelial cells was delayed as compared to wild-type cells, and AM administration failed to enhance the re-endothelialization. The delay in re-endothelialization was due to a primary migration defect rather than a decrease in proliferation. These results suggest that RAMP3 regulates drainage through lymphatic vessels, and that the AM-RAMP3 system could be a novel therapeutic target for controlling postoperative lymphedema.

Vascular endothelial adrenomedullin-RAMP2 system is essential for vascular integrity and organ homeostasis.

BACKGROUND: Revealing the mechanisms underlying the functional integrity of the vascular system could make available novel therapeutic approaches. We previously showed that knocking out the widely expressed peptide adrenomedullin (AM) or receptor activity-modifying protein 2 (RAMP2), an AM-receptor accessory protein, causes vascular abnormalities and is embryonically lethal. Our aim was to investigate the function of the vascular AM-RAMP2 system directly. METHODS AND RESULTS: We generated endothelial cell-specific RAMP2 and AM knockout mice (E-RAMP2(-/-) and E-AM(-/-)). Most E-RAMP2(-/-) mice died perinatally. In surviving adults, vasculitis occurred spontaneously. With aging, E-RAMP2(-/-) mice showed severe organ fibrosis with marked oxidative stress and accelerated vascular senescence. Later, liver cirrhosis, cardiac fibrosis, and hydronephrosis developed. We next used a line of drug-inducible E-RAMP2(-/-) mice (DI-E-RAMP2(-/-)) to induce RAMP2 deletion in adults, which enabled us to analyze the initial causes of the aforementioned vascular and organ damage. Early after the induction, pronounced edema with enhanced vascular leakage occurred. In vitro analysis revealed the vascular leakage to be caused by actin disarrangement and detachment of endothelial cells. We found that the AM-RAMP2 system regulates the Rac1-GTP/RhoA-GTP ratio and cortical actin formation and that a defect in this system causes the disruption of actin formation, leading to vascular and organ damage at the chronic stage after the gene deletion. CONCLUSIONS: Our findings show that the AM-RAMP2 system is a key determinant of vascular integrity and homeostasis from prenatal stages through adulthood. Furthermore, our models demonstrate how endothelial cells regulate vascular integrity and how their dysregulation leads to organ damage.

Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo-embolization.

PURPOSE: The aim of the present study was to evaluate whether serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) trends might be correlated with overall survival rates in patients with recurrent hepatocellular carcinoma (HCC) undergoing trans-catheter arterial chemo-embolization (TACE). METHODS: We performed a retrospective cohort study of 142 patients with recurrent HCC who were treated by TACE at our hospital from April 1990 to December 2011. Patients were divided into three groups, as follows, according to the trends of the two tumor markers AFP and DCP: the low group, comprising patients with tumor marker levels below the cutoff values (AFP 100 ng/mL and DCP 100 mAU/mL) both pre- and post-TACE; the decreased group, comprising patients with elevated tumor marker levels pre-TACE in whom the levels decreased post-TACE; and the elevated group, comprising patients with elevated tumor marker levels post-TACE. RESULT: Analysis using a Cox proportional hazards model identified the DCP trend (elevated group vs. low group, hazard ratio 8.47, 95 % confidence interval 4.53-15.84, p < 0.0001), but not the AFP trend, as an independent prognostic factor for survival. While the AFP trend was correlated only with the overall response rate assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST; p = 0.041), the DCP trend was strongly associated with both the overall response rate (p = 0.009) and the disease control rate (p = 0.004). CONCLUSION: The DCP trend might be useful for assessing treatment outcomes after TACE in patients with recurrent HCC.

A Case of Myxoid Pleomorphic Liposarcoma with Rhabdoid Cells: A Diagnostic Pitfall.

Myxoid pleomorphic liposarcoma (MPLS) is an extremely rare tumor listed in the fifth edition of the WHO classification (2020). Histologically, it mainly comprises a mixture of myxoid and pleomorphic liposarcoma-like components. Genetically, it lacks FUS/EWSR1::DDIT3 fusion and MDM2 amplification. Herein, we describe an example of MPLS with rhabdoid cells in a 10-year-old girl who presented with a growing mass in the right inguinal region. The specimen from the wide excision measured 68 mm × 55 mm × 43 mm, and a circumscribed and lobulated mass was observed in the subcutaneous tissue. Histologically, oval-to-short, spindle-shaped, proliferating tumor cells with moderate nuclear atypia and mesh-like capillaries against a myxoid background were noted. Adipocytes were observed focally, while rhabdoid cells were observed multifocally. Immunohistochemically, the tumor showed inconsistent reactivity for desmin but was negative for MYOD1, myogenin, MDM2, and CDK4. Fluorescence in situ hybridization revealed no DDIT3 rearrangement. Despite adjuvant chemotherapy, the tumor metastasized to the thoracic cavity 24 months after excision. The metastatic lesions contained abundant lipoblasts rather than rhabdoid cells, and we concluded this tumor was a MPLS. The presence of rhabdoid cells could be a diagnostic pitfall, and recognizing such a variation in histology would help improve diagnostic accuracy.

Giant spin-to-charge conversion at an all-epitaxial single-crystal-oxide Rashba interface with a strongly correlated metal interlayer.

The two-dimensional electron gas (2DEG) formed at interfaces between SrTiO3 (STO) and other oxide insulating layers is promising for use in efficient spin-charge conversion due to the large Rashba spin-orbit interaction (RSOI). However, these insulating layers on STO prevent the propagation of a spin current injected from an adjacent ferromagnetic layer. Moreover, the mechanism of the spin-current flow in these insulating layers is still unexplored. Here, using a strongly correlated polar-metal LaTiO3+δ (LTO) interlayer and the 2DEG formed at the LTO/STO interface in an all-epitaxial heterostructure, we demonstrate giant spin-to-charge current conversion efficiencies, up to ~190 nm, using spin-pumping ferromagnetic-resonance voltage measurements. This value is the highest among those reported for all materials, including spin Hall systems. Our results suggest that the strong on-site Coulomb repulsion in LTO and the giant RSOI of LTO/STO may be the key to efficient spin-charge conversion with suppressed spin-flip scattering. Our findings highlight the hidden inherent possibilities of oxide interfaces for spin-orbitronics applications.

[Meckel's diverticulum duplication revealed by acute operation of ileus: a case report].

A 29-year-old man was admitted with abdominal pain. Peritonitis symptoms appeared on the day after of hospitalization and emeregency surgery was performed. A Meckel diverticulum adhered to the mesenterium of the sigmoid colon which was strangulated for a length of 30cm. Additionally, a second Meckel diverticulum was present on the oral side of the first one. The length of these were 3cm and 5cm, and the longer one caused the strangulation. The letter diverticulum contained a crab shell about 2cm in size, which was considered to be the cause of adhesion. Our search of the literature revealed only one report of two Meckel diverticula. This type of our case is extremely rare.

Cystic mixed adenoneuroendocrine carcinoma of the pancreas: A case report.

INTRODUCTION: Pancreatic mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor. We report herein a case of pancreatic MANEC with cystic features. PRESENTATION OF CASE: A 67-year-old woman presented with jaundice. A CT scan revealed an 18-mm mass at the pancreatic head that obstructed the common bile duct and another 35-mm cystic lesion containing a mural nodule in the pancreatic body, which was suspected to be an intraductal papillary mucinous carcinoma. A biopsy of the head mass led to the diagnosis of adenocarcinoma. The patient underwent pancreatoduodenectomy, and the body cyst was resected with the head mass. A histopathological analysis revealed that the body cyst had two components, ductal adenocarcinoma and neuroendocrine tumor. We diagnosed the cystic tumor as MANEC. DISCUSSION: Cases of MANEC have been reported as originating from the stomach, small intestine, and colon, but pancreatic MANEC is rare. The histogenesis and the therapeutic strategy for pancreatic MANEC are controversial. CONCLUSION: The clinicopathological features of pancreatic MANEC remain unclear; therefore, more reports of cases of pancreatic MANEC are necessary for a complete analysis.

[A case of recurrent gastric cancer with obstructive jaundice successfully treated by docetaxel].

Recently, treatment by taxane regimen for advanced gastric cancer as second-line chemotherapy has been increasingly reported. A 58-year-old man underwent distal gastrectomy for advanced gastric cancer on November 25, 2002. There was permeation through the duodenum side, and a Billroth II operation was done for repair. Although a relapse was not clear from the picture image, due to the tumor marker increase since July 2004, chemotherapy using TS-1 100 mg/day was given. On February 2005, liver dysfunction and obstructive jaundice appeared, and the patient was diagnosed with a recurrence in the hilar lymph node of the liver through PET and CT. Because of the Billroth II operation for repair, ERBD was impossible, and we performed PTCD to decrease jaundice. Treatment by docetaxel 60 mg/m(2) every three weeks was given since March 15. After two courses of chemotherapy with docetaxel, the insertion of the guide wire was possible from the part of PTCD. Implantation of the stent became possible after four courses. PTCD could be removed, and the patient QOL has effectively improved. Outpatient treatment became possible for him in January 2006.

The suppression of maternal-fetal leukemia inhibitory factor signal relay pathway by maternal immune activation impairs brain development in mice.

Recent studies in rodents suggest that maternal immune activation (MIA) by viral infection is associated with schizophrenia and autism in offspring. Although maternal IL-6 is though t to be a possible mediator relating MIA induced these neuropsychiatric disorders, the mechanism remains to be elucidated. Previously, we reported that the maternal leukemia inhibitory factor (LIF)-placental ACTH-fetal LIF signaling relay pathway (maternal-fetal LIF signal relay) promotes neurogenesis of fetal cerebrum in rats. Here we report that the maternal-fetal LIF signal relay in mice is suppressed by injection of polyriboinosinic-polyribocytidylic acid into dams, which induces MIA at 12.5 days post-coitum. Maternal IL-6 levels and gene expression of placental suppressor of cytokine signaling 3 (Socs3) increased according to the severity of MIA and gene expression of placental Socs3 correlated with maternal IL-6 levels. Furthermore, we show that MIA causes reduction of LIF level in the fetal cerebrospinal fluid, resulting in the decreased neurogenesis in the cerebrum. These findings suggest that maternal IL-6 interferes the maternal-fetal LIF signal relay by inducing SOCS3 in the placenta and leads to decreased neurogenesis.

Impact of advanced age on the short- and long-term outcomes in patients undergoing hepatectomy for hepatocellular carcinoma: a single-center analysis over a 20-year period.

BACKGROUND: The purpose of this study was to analyze the influence of age on both the risk of hepatectomy and the prognosis in patients with hepatocellular carcinoma (HCC). METHODS: Patients undergoing an initial hepatectomy for HCC were classified into 2 age groups: 75 years or over (n = 113) and less than 75 years (n = 499). RESULTS: A zero 90-day mortality was achieved in the elderly. Although the recurrence rate and recurrence sites were almost similar between the 2 groups, the 5-year survival rate in the elderly patients was significantly lower than that in the younger patients (46.0% vs 57.6%; P = .018), possibly because of the higher incidence of deaths from other causes (26.8% vs 10.4%; P = .011) in the elderly. CONCLUSION: Selected elderly HCC patients can undergo a hepatectomy safely and can benefit from long-term HCC control comparable with that of their younger counterparts.

Hepatocellular carcinoma associated with sarcoidosis.

INTRODUCTION: The association of hepatic sarcoidosis with hepatocellular carcinoma (HCC) is considerably rare. Here we report a rare case of HCC associated with sarcoidosis. PRESENTATION OF CASE: A 75-year-old male with no history of alcohol addiction or viral hepatitis was referred to our hospital because of an abnormal liver mass. Subsegmentectomy of the liver was performed for the diagnosis of HCC. A histopathological examination revealed small non-necrotizing granulomas with a tendency to coalesce that were scattered in and around the carcinoma. No features of cirrhosis, steatohepatitis, and any other liver diseases were observed. Furthermore, swelling of the bilateral lung hilar lymph nodes with uptake of 18F-fluorodeoxyglucose was found on positron emission tomography/computed tomography and the tuberculin reaction test results were negative. On the basis of these findings, the final diagnosis of HCC associated with sarcoidosis was confirmed. DISCUSSION: By reviewing previous cases, we found only five cases that described patients diagnosed with HCC associated with sarcoidosis. Of these, four patients died within two years after diagnosis because of ruptures or inoperable huge tumors. In contrast, radical hepatectomy was performed at an earlier stage of disease in two patients, including ours, and both these patients have remained healthy with no recurrences or metastases at the latest follow-up visit. CONCLUSION: Periodic checkups of the liver should be conducted for patients with systemic sarcoidosis, regardless of the presence of liver cirrhosis.

Efficacy of self-expanding metallic stent for right-sided colonic obstruction due to carcinoma before 1-stage laparoscopic surgery.

PURPOSE: The aim of this small study was to assess the clinical outcomes of self-expanding metallic stent (SEMS) placement followed by 1-stage laparoscopic resection for treatment of acute right-sided colonic obstruction due to carcinoma. METHOD: From January 2012 to December 2012, we performed 1-stage laparoscopic colectomy after placement of SEMS for right-sided obstructive colon carcinoma in 4 patients. RESULTS: SEMS placement was technically successful in all cases and symptoms were immediately relieved. The presence of the endoluminal stent did not prevent a laparoscopic approach; moreover, decompression of the bowel obstruction provided a wide field of view and working space for the laparoscopic procedure. There were no cases of conversion to laparotomy and no intraoperative complications. CONCLUSION: One-stage laparoscopic surgery, as a minimally invasive therapy, can be safely performed by SEMS placement in patients with acute right-sided colonic obstruction due to carcinoma. A large sample study is required to confirm the efficacy of this procedure.

Retroperitoneal dedifferentiated liposarcoma with osteosarcomatous components: a case report.

We report a rare case of recurrent retroperitoneal dedifferentiated liposarcoma with osteosarcomatous components. An 82-year-old male diagnosed with recurrent retroperitoneal liposarcoma underwent a tumor resection. Histologically, osseous matrix with osteoid and mature hyaline cartilaginous tissues with high cellularity were observed in a fibrous background through most of the tumor, and scattered MDM2- and CDK4-positive atypical hyperchromatic stromal cells were detected surrounding the dedifferentiated areas. Dedifferentiation occurs in up to 10% of well-differentiated liposarcomas, frequently resembling a malignant fibrous histiocytoma-like pleomorphic sarcoma. In contrast, divergent differentiation with osteosarcomatous components is considered to be extremely rare.

Regulation of adrenomedullin and its family peptide by RAMP system--lessons from genetically engineered mice.

Adrenomedullin (ADM), originally identified as a vasodilating peptide, is now recognized to be a pleiotropic molecule involved in both the pathogenesis of cardiovascular diseases and circulatory homeostasis. Homozygotes of ADM knockout mice (ADM-/-) were lethal at mid-gestation with abnormalities of vascular development and this finding clarified the angiogenic potency of ADM. Calcitonin gene-related peptide (CGRP), which has a structure and function similar to that of ADM, has been identified as a family peptide of ADM. Unlike ADM-/-, CGRP-/- were apparently normal. Therefore, the study of knockout mice first clarified the distinctly different physiological roles between ADM and CGRP. In contrast, heterozygotes of ADM knockout mice (ADM+/-) were alive but showed blood pressure elevation, reduced neovascularization, and enhanced neointimal formation by arterial injury. Based on these observations, there was hope ADM would have a therapeutic use. However, ADM has a short half-life in the blood stream and its application in chronic disease has limitations. Therefore, we focused on the ADM receptor system. The calcitonin-receptor-like receptor (CLR), which is the ADM receptor, associates with one of the accessory proteins, called receptor activity-modifying proteins (RAMPs). By interacting with RAMP1, CLR exhibits a high affinity for CGRP, whereas by interacting with either RAMP2 or -3, CLR exhibits a high affinity for ADM. We generated RAMP knockout mice and found that vascular phenotypes similar to ADM-/- were reproduced only in RAMP2-/-. This shows that RAMP2 is the key determinant of the vascular functions of ADM. RAMP2 could be an attractive therapeutic target in cardiovascular diseases.

Porphyrin-containing electrospun nanofibers: positional control of porphyrin molecules in nanofibers and their catalytic application.

Polyacrylonitrile nanofibers containing a series of porphyrin molecules were prepared by an electrospinning method. We first succeeded in controlling the position of porphyrin molecules in the nanofibers by considering porphyrin characteristics and the electrospinning conditions. It was concluded that positive charge of cationic porphyrin, TMPyP, and higher applied voltages were effective to locate the porphyrin molecules on the polymer nanofiber surfaces because of the electrostatic repulsion among the molecules during the electrospinning process. The polymer nanofibers with cationic manganese-porphyrin (Mn-TMPyP) on their surface repeatedly showed superoxide dismutase (SOD) activity, which is a catalytic activity to work as antioxidant in various biochemical fields. The positional control of functional molecules in nanofibers demonstrated a new possibility of nanofiber applications.

Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling.

Embryonic stem cells (ESCs) are a useful source for various cell lineages. So far, however, progress toward reconstitution of mature liver morphology and function has been limited. We have shown that knockout mice deficient in adrenomedullin (AM), a multifunctional endogenous peptide, or its receptor-activity modifying protein (RAMP2) die in utero due to poor vascular development and hemorrhage within the liver. In this study, using embryoid bodies (EBs)-culture system, we successfully induced liver sinusoidal endothelial-like cells by modulation of AM-RAMP2. In an EB differentiation system, we found that co-administration of AM and SB431542, an inhibitor of transforming growth factor ß (TGFß) receptor type 1, markedly enhanced differentiation of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)/stabilin-2-positive endothelial cells. These cells showed robust endocytosis of acetylated low-density lipoprotein (Ac-LDL) and upregulated expression of liver sinusoidal endothelial cells (LSECs)-specific markers, including factor 8 (F8), Fc-γ receptor 2b (Fcgr2b), and mannose receptor C type 1 (Mrc1), and also possessed fenestrae-like structure, a key morphological feature of LSECs. In RAMP2-null liver, by contrast, LYVE-1 was downregulated in LSECs, and the sinusoidal structure was disrupted. Our findings highlight the importance of AM-RAMP2 signaling for development of LSECs.