Successful Treatment of Transverse Testicular Ectopia by Laparoscopically Assisted Orchiopexy.

Transverse testicular ectopia (TTE) is a rare congenital malformation where both testes descend through the same inguinal canal and are located in the same hemiscrotum. It is usually treated with transseptal orchiopexy. In this article, we report the case of a 1-year-old boy diagnosed with TTE who was successfully treated with laparoscopically assisted orchiopexy by going through the anatomical conventional route. A four-month-old boy was referred to our department with bilateral empty scrotum. On the physical examination, the left testis was palpable in the left groin region and the right testis was impalpable. A follow up ultrasonography was performed after 4 months, and an oval-shaped testis-like structure was detected in left internal inguinal ring near the left testis. Right side TTE was suspected in the initial diagnosis. Laparoscopic surgery was performed at age one. The left testis was observed in the inguinal canal, and the right testis was ectopically located in the left opening inguinal canal above the left testis. Two spermatic cord and testes were separated respectively, and the right testis was pulled into abdominal space laparoscopically and brought down to the right hemiscrotum via the right inguinoscrotal canal. Bilateral orchiopexy was performed via the normal anatomical route. The postoperative course was uneventful, and testes were in the scrotum bilaterally one year after orchiopexy.

Laparoscopic Approach to Presacral Recurrence of Sacrococcygeal Teratoma.

A 6-month-old girl was presented to our hospital due to a presacral mass found 5 months after surgery of sacrococcygeal teratoma. The original tumor was a 63 x 50 mm sized round cyst connecting to the coccyx, observed with computed tomography. The initial operation was performed with en bloc removal of the tumor along with the coccyx in the prone position. During a routine follow up, ultrasonography indicated a possible local recurrence, 5 months after the initial operation. The magnetic resonance imaging revealed a polycystic formation with a diameter of 20 x 11 x 17 mm in the presacral space. The laparoscopic operation was conducted with the patient in the lithotomy and Trendelenburg position. The broad ligament of uterus was fixed to the abdominal skin and the rectum was mobilized to identify the tumor, which was resected laparoscopically. A histopathological examination showed the tumor to be a mature cystic teratoma. We observed her without any additional treatment and no recurrence is seen after 6 months.

Incidentally Detected Microcarcinoma of Thyroid in Surgical Specimens of the Goiter in Pediatric Patient: A Case Report.

A 14 year-old girl with a previous medical history of cholecystic polyps was referred to our department with throat discomfort during swallowing. The cervical ultrasound and magnetic resonance imaging revealed a massive polycystic formation with a diameter of 45 × 24 × 31 mm consistent with a right lobe goiter. However, there were no findings for suspected malignancy. Hemithyroidectomy was performed and the specimen was sent for histopathological assessment. Hematoxylin-eosin staining of the right lower nodule showed variably-sized follicles consistent with adenomatous goiter. The right upper nodule showed a growth of relatively compact sized follicles　with a thick fibrous capsule. A satellite nodule lying outside of the tumor capsule was consistent with minimally invasive follicular thyroid microcarcinoma. We observed her without any additional treatment and no recurrence is seen at present.

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients.

BACKGROUND: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. METHODS: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo bio-distribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. RESULTS: From January 2012 to June 2015, 20 pts. (median age 43 years [21-67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. CONCLUSIONS: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. TRIAL REGISTRATION: The study was registered on the NCT01469975 website with a registration code NCT01469975 on November the third, 2011.

Surgical Treatment of Inguinal Hernia with Prolapsed Ovary in Young Girls: Emergency Surgery or Elective Surgery.

OBJECTIVE: Inguinal ovarian hernias are common in young girls. Many articles in medical literature recommend early surgery for inguinal ovarian hernia because of the risk of torsion of the prolapsed ovary. However, since many irreducible herniated ovaries in newborn infants and during early infancy undergo spontaneous reduction by the age of 9 months, the policy at our institute is to obtain informed consent from the patient's family and then wait to perform surgery until after 9 months of age. In the present study, we assessed the indications for surgery for inguinal ovarian hernia in newborn infants and during early infancy. METHODS: Between 2003 and 2011, a total of 673 girls with inguinal hernias (age at the time of onset of symptoms: mean, 42.5 months; median, 39 months) were brought to our outpatient clinic for consultation. We reviewed their age at the time of the onset of hernia symptoms and their age at the time of surgery, their history of surgery, and their history of inguinal ovarian hernia using information obtained from their medical records. RESULTS: Among the 673 outpatients, 71 patients (mean/median age at the time of onset of symptoms: 11.2/1.5 months) were diagnosed as having an inguinal ovarian hernia at the time of diagnosis. Among these patients, surgery was performed for 58 patients (mean/median age at the time of surgery: 21.3/11 months). Of these patients, the ovary had already spontaneously reduced into the abdomen in 35 cases (mean/median age at the time of surgery: 24.1/12months), whereas the ovaries were on the wall of the hernia sac in 22 cases (mean/median age at the time of surgery: 17.3/10 months). In one case, a testis instead of an ovary was observed in the hernia sac at the time of surgery. Surgeries were performed in 611 of the 673 patients (mean/median age at the time of surgery: 54/50 months). In 35 cases (mean/median age at the time of surgery: 21.6/10 months), the ovary was still on the hernia sac wall at the time of surgery, but an inguinal ovarian hernia had not been diagnosed before surgery in 13 of these cases. A severe complication occurred in only one case, in which a hernia sac that contained a fallopian tube and ovary was ligated. None of the cases exhibited torsion of the ovary within the inguinal canal. CONCLUSION: Since the ovary can be expected to undergo spontaneous reduction into the abdomen by late infancy in many young patients with inguinal ovarian hernias, patients with inguinal ovarian hernias can be treated by elective surgery at the most convenient age, after 9 months of age.

Protein-losing Enteropathy Caused by Spontaneous Reduction of Intussusception with Meckel's Diverticulum.

Protein-losing enteropathy (PLE) is a relatively rare condition. In this article, we report the case of a 6-year-old boy diagnosed with PLE who developed intussusception, in whom at operation Meckel's diverticulum was identified in his intestine. Spontaneous reduction of intussusception is thought to relate to the mechanism of PLE.

Morphology-based investigation of metachronous inguinal hernia after negative laparoscopic evaluation - is it acquired indirect inguinal hernia?

PURPOSE: Patients who developed apparent metachronous contralateral inguinal hernia (MCIH) after negative laparoscopic diagnosis have been reported. We performed this study to investigate the morphological characteristics and etiology of this phenomenon. PATIENTS AND METHODS: A consecutive series of 1,747 patients (858 boys and 889 girls) with symptomatic unilateral inguinal hernia were studied. During laparoscopic percutaneous completely extraperitoneal closure, morphological appearances at the asymptomatic groin were inspected for contralateral patent processus vaginalis (CPPV) with definitive criteria. If positive CPPV was identified, it was closed by the same technique used for the affected side. The patients were reviewed for occurrence of metachronous contralateral hernia. RESULTS: A total of 755 patients (43.2%) had positive CPPV. Of the 992 patients whose CPPVs were evaluated as true negative, eight (seven boys, one girl) developed MCIH (time taken, three months to five years six months). During second-look operations, morphological appearances of the CPPV that was originally considered as true negative CPPV was found to be wide open. CONCLUSIONS: Despite a true negative evaluation by laparoscopy, there was a 0.8% chance of developing a MCIH. This phenomenon was male-oriented and may be acquired indirect inguinal hernia without preceding of CPPV.

Tapping but not massage enhances vasodilation and improves venous palpation of cutaneous veins.

This paper investigated whether tapping on the median cubital vein or massaging the forearm was more effective in obtaining better venous palpation for venipuncture. Forty healthy volunteers in their twenties were subjected to tapping (10 times in 5 sec) or massage (10 strokes in 20 sec from the wrist to the cubital fossa) under tourniquet inflation on the upper arm. Venous palpation was assessed using the venous palpation score (0-6, with 0 being impalpable). Three venous factors-venous depth, cross-sectional area, and elevation-were also measured using ultrasonography. The venous palpation score increased significantly by tapping but not by massage. Moreover, all 3 venous measurements changed significantly by tapping, while only the depth decreased significantly by massage. The three venous measurements correlated significantly with the venous palpation score, indicating that they are useful objective indicators for evaluating vasodilation. We suggest that tapping is an effective vasodilation technique.

The characteristics of healthy adults with hardly palpable vein--Relations between easy venous palpation and physical factors.

This study aimed to investigate relations between ease of venous palpation and various venous factors, and to elucidate characteristics of hardly palpable veins. Healthy adult volunteers (n = 110) were enrolled. The ease of venous palpation was scored from 0: impalpable to 3: well palpable. Venous factors, namely venous depth, elevation, area and minimal pressure that starts to collapse vein, were measured using an ultrasonography before and after tourniquet inflation at 60 mmHg for 60 s. Tourniquet inflation significantly increased the venous area and venous palpation score. The four venous factors correlated significantly with venous palpation score with the following correlation coefficient: Depth (r = -0.542), Elevation (0.486), area (0.258) and start-to-collapse pressure (-0.220). The characteristics of hardly palpable veins were small size, deep location and little elevation. Although vasodilatation facilitated venous palpation, venous depth and elevation were also important and should be included in future studies in which vasodilatation methods are evaluated.

Relationship between tourniquet pressure and a cross-section area of superficial vein of forearm.

This study investigated the appropriate tourniquet pressure (TP) and duration of tourniquet application for venipuncture by calculating the venous cross-section (VCS) area on ultrasonography. Twenty healthy volunteers without cardiovascular risk factors were enrolled in this study. A target vein (either a cephalic or median cubital vein) was selected on ultrasonography. The pneumatic tourniquet was inflated using a rapid cuff inflator system at setting pressure for 120 sec. TP strength was varied from 20 mmHg to 100 mmHg, in 20 mmHg increments. The order of TP was randomized. Comparisons among more than 3 groups were performed by one-way repeated-measures ANOVA and the Bonferroni method. The VCS area increased rapidly until 10 sec after tourniquet inflation. The VCS area then increased gradually until 30 sec after tourniquet inflation. After that, the VCS area did not increase remarkably. The VCS area increased with TP strength up to 80 mmHg, but the VCS area at TP 100 mmHg decreased to less than that at TP 40 mmHg. Based on these results, we recommend a tourniquet pressure of 60 mmHg, and duration of tourniquet application is 30 to 60 sec for venipuncture.

A long-term survival case of tracheal agenesis: management for tracheoesophageal fistula and esophageal reconstruction.

Tracheal agenesis is a very rare disorder which leads to severe respiratory disorders immediately after birth. Reports are very limited on long-term survival cases. We report here a long-term survival case with Floyd's type I tracheal agenesis. During the neonatal stage, the patient underwent abdominal esophageal banding to substitute esophagus for trachea and transection at the cervical esophagus with esophagostomy. Subsequently, airway management was difficult due to a fragile tracheoesophageal fistula, but the fistula was conservatively treated and stabilized with the patient's growth. This patient is a very rare case in whom oral feeding was achieved after esophageal reconstruction using a gastric tube. For this case, we describe mainly (1) the management method of the tracheoesophageal fistula and (2) esophageal reconstruction without thoracotomy.

Synthesis and biological evaluation of vitamin K derivatives as angiogenesis inhibitor.

Ten vitamin K(3) derivatives were synthesized and screened for anti-angiogenic activity. Results indicated that amine derivatives (1a-d) exerted a stronger inhibition effect on angiogenesis compared to alkyl derivatives (2a-d). In addition to being the most potent inhibitor, 1b also suppressed human umbilical vein endothelial cell tube formation and proliferation. These results suggest that vitamin K(3) amine derivatives with shorter alkyl chains, such as 1b, could be useful for developing anti-angiogenic agents.

1,4-Naphthoquinone is a potent inhibitor of human cancer cell growth and angiogenesis.

Angiogenesis inhibitors are beneficial for the prevention and treatment of angiogenesis-dependent diseases including cancer. Vitamin K2 and K3, which are naphthoquinone derivatives, inhibit angiogenesis. We examined the anti-cancer and anti-angiogenic effects of naphthoquinones and its structurally related compounds. Among these 13 compounds, 1,4-naphthoquinone strongly inhibited both human colon cancer cell (HCT116) growth and angiogenesis. To clarify the anti-angiogenic mechanism, the effects of 1,4-naphthoquinone on human umbilical vein endothelial cell (HUVEC) tube formation, proliferation and chemotaxis were examined. Consequently, 1,4-naphthoquinone inhibited HUVEC functions. These results suggest that 1,4-naphthoquinone may be useful to cancer therapy.

Immunohistochemical detection of sphingosine-1-phosphate receptor 1 in vascular and lymphatic endothelial cells.

Sphingosine-1-phosphate receptor 1 (S1P(1)), a receptor for sphingosine-1-phosphate, has been shown to play an important role in the migration, proliferation, and survival of several types of cell including endothelial cells. Given that S1P(1) signaling could serve as a therapeutic target, we evaluate the expression of S1P(1) in formalin-fixed and paraffin-embedded sections from human tissues, using automated immunostainers (Ventana). The specificity of the polyclonal rabbit anti-human S1P(1) antibody used in this study was defined by immunostaining of the vasculature in S1P ( 1 ) ( -/- ) and S1P ( 1 ) ( +/- ) mouse embryos. The antibody stained the newly formed vasculatures ex vivo in a serum-free matrix culture model using rat aortic rings. In human specimens, S1P(1) was strongly expressed on the cell surface membrane of endothelial cells of blood and lymphatic vessels in all tissues examined. The expression of S1P(1) was confirmed by the flow cytometric analysis and real time RT-PCR of an angiosarcoma cell line. This study indicates that S1P(1) can be used as an immunohistochemical marker for human tissue endothelial cells.

Inhibitory effects of vitamin K3 on DNA polymerase and angiogenesis.

Vitamins play essential roles in cellular reactions and maintain human health. Recent studies have revealed that some vitamins including D3, B6 and K2 and their derivatives have an anti-cancer effect. As a mechanism, their inhibitory effect on cancer-related angiogenesis has been demonstrated. Vitamin K2 (menaquinones) has an anti-cancer effect in particular for hepatic cancer and inhibits angiogenesis. In the current study, we demonstrated that sole vitamin K3 (menadione) selectively inhibits the in vitro activity of eukaryotic DNA polymerase gamma, which is a mitochondrial DNA polymerase, and suppresses angiogenesis in a rat aortic ring model. The anti-angiogenic effect of vitamin K3 has been shown in angiogenesis models using human umbilical vein endothelial cells (HUVECs) with regard to HUVEC growth, tube formation on reconstituted basement membrane and chemotaxis. These results suggest that vitamin K3 may be a potential anti-cancer agent like vitamin K2.

Epicatechin conjugated with fatty acid is a potent inhibitor of DNA polymerase and angiogenesis.

Anti-cancer and anti-angiogenesis effects of green tea catechins have been demonstrated. It has been found that chemical modification of tea catechins improves their biological activities. We examined the chemical modification of epicatechin enhanced anti-cancer and anti-angiogenic effects. Epicatechin conjugated with fatty acid (acyl-catechin) strongly inhibited DNA polymerase activity, HL-60 cancer cell growth and angiogenesis. Epicatechin conjugated with palmitic acid ((2R,3R)-3',4',5,7-tetrahydroxyflavan-3-yl hexadecanoate, epicatechin-C16) was the strongest inhibitor in DNA polymerase alpha, beta, lambda and angiogenesis assays. Epicatechin-C16 also suppressed human endothelial cell (HUVEC) tube formation on reconstituted basement membrane, suggesting that it affected not only DNA polymerase activity but also the signal transduction pathways needed for the tube formation in HUVECs. These results suggest that acylation of epicatechin is an effective chemical modification to improve the anti-cancer activity of epicatechin.

Antiangiogenic activity of brown algae fucoxanthin and its deacetylated product, fucoxanthinol.

The antiangiogenic effects of fucoxanthin and a deacetylated product, fucoxanthinol, were examined. Fucoxanthin significantly suppressed HUVEC proliferation and tube formation at more than 10 microM, but it had no significant effect on HUVEC chemotaxis. The formation of blood vessel-like structures from CD31-positive cells was evaluated using embryonic stem cell-derived embryoid bodies. Fucoxanthin effectively suppressed the development of these structures at 10-20 microM, suggesting that it could suppress differentiation of endothelial progenitor cells into endothelial cells involving new blood vessel formation. Fucoxanthin and fucoxanthinol suppressed microvessel outgrowth in an ex vivo angiogenesis assay using a rat aortic ring, in a dose-dependent manner. These results imply that fucoxanthin having antiangiogenic activity might be useful in preventing angiogenesis-related diseases.

Establishment of lymphotoxin beta receptor signaling-dependent cell lines with follicular dendritic cell phenotypes from mouse lymph nodes.

Follicular dendritic cells (FDCs) have been shown to play a crucial role in the positive selection of high-affinity B cells that are generated by somatic hypermutation in germinal center (GC). Because of technical difficulties in preparing and maintaining pure FDCs, a role for FDCs in this complicated process has not been fully elucidated. In this study, we established a cell line designated as pFL that retained major FDC phenotypes from a three-dimensional culture of mouse lymph node cells. pFL cells proliferated slowly in response to an agonistic anti-lymphotoxin beta receptor mAb and TNF-alpha. A more rapidly growing clone, named FL-Y, with similar requirements for growth was isolated from a long-term culture of pFL. Analysis of surface markers in these two cell lines by immunostaining, flow cytometry, and DNA microarray revealed the expression of genes, including those of CD21, FcgammaRIIB, lymphotoxin beta receptor, ICAM-1, VCAM-1, IL-6, and C4, which have been shown to be characteristic of FDCs. In addition, B cell-activating factor was expressed in these two cell lines. At the pFL or FL-Y:B cell ratio of 1:100, the cell lines markedly sustained B cell survival and Ab production during 2 wk of culture, while most B cells collapsed within 1 wk in the absence of the FDC-like cells. Interestingly, expression of typical GC markers, Fas and GL-7, was notably augmented in B cells that were cocultured with Th cells on these two cell lines. Thus, pFL and FL-Y cells may be useful for providing insight into the functional role for FDCs in GC.