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.

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.

A case of neonatal mature teratoma transformed to malignancy in the neck extending to the mouth floor.

A case with neonatal teratoma originating from the cervicofacial region which transformed to be malignant during treatment is reported. The case is a full-term baby girl with swallowing difficulty and has a mass at the floor of her mouth with the right neck swelling. The mass was revealed to be multi-cystic and extending deep into the sublingual space and protruding outside. Puncture and marsupialisation of the cyst could not relieve her symptom and the tumor was resected in three occasions and was diagnosed as mature teratoma without malignant component. However, three months after the last resection, the solid right neck mass enlarged rapidly and the serum alpha-fetoprotein level was elevated. Biopsied specimen demonstrated the mass to be germ cell tumor with embryonal carcinoma and yolk sac tumor component. Eight courses of JEB regimen with recurrent mass resection successfully lead to complete regression without compromising patient growth as well as cosmetics. Head and neck teratomas in children are mostly benign amenable to curative excision but its rarity and site and size of the tumor make its treatment challenging. It is important to have multi-disciplinary management for the disease from neonatal period until growth has finished. There exists a relationship between the age at diagnosis and outcome of a patient with teratoma and head and neck teratomas in neonate are mostly benign but should be removed completely as soon as the patient condition is stabilized to reduce the risk of malignant change.

Managing prenatally diagnosed asymptomatic congenital cystic adenomatoid malformation.

AIM: To review our cases of congenital cystic adenomatoid malformation (CCAM) with special emphasis on the management of prenatally diagnosed asymptomatic CCAM (PDA-CCAM). METHODS: A total of 42 consecutive CCAM patients treated between 1990 and 2008 at our institution and affiliated hospitals were divided into four groups, according to whether prenatal diagnosis was made [PD (+) or (-)], whether patients were symptomatic [S (+) or (-)], whether there was any increase in size observed radiologically [R (+) or (-)], and whether surgical resection was performed [X (+) or (-)], to give a symptomatic early surgery group diagnosed prenatally (group A; n = 15): PD (+), S (+), R (+), X (+); an asymptomatic early surgery group diagnosed prenatally (group B; n = 8): PD (+), S (-), R (-), X (+); a conservative observation group diagnosed prenatally (group C; n = 6): PD (+), S (-), R (-), X (-); and a symptomatic surgery group diagnosed postnatally (group D; n = 13): PD (-), S (+), R (unknown), X (+). Patient demographics, effects of surgical stress, histopathology, and outcome were compared between the four groups. RESULTS: Groups A and B had surgery as neonates and mean duration of post-operative follow-up has been 15.7 months for group A and 63.3 months for group B. Group C has been under observation for a mean of 21.6 months (range: 10-40 months) with no incidence of infection. In group D, four had surgery as neonates after developing respiratory distress, and nine had surgery later (mean age: 4.1 years) after developing pneumonia (late onset group). Mean duration of follow-up for group D has been 48.0 months. In the late-onset group, pneumonia was successfully treated medically, and all nine had elective surgery with no intra- or post-operative complications. However, compared with group B (asymptomatic early surgery group diagnosed prenatally) the late-onset group had significantly longer duration of surgery (P < 0.05), significantly greater intraoperative blood loss (P < 0.01), and significantly higher peak post-operative C-reactive protein (P < 0.01), although there were no statistical differences for increase in white blood cell count ratios or length of hospitalization. Malignancy has not developed to date in any subject. CONCLUSION: Our data suggest that patients with PDA-CCAM may be observed safely until they become symptomatic or changes in size are observed radiologically.

TGF-beta isoform signaling regulates secondary transition and mesenchymal-induced endocrine development in the embryonic mouse pancreas.

Transforming growth factor-beta (TGF-beta) superfamily signaling has been implicated in many developmental processes, including pancreatic development. Previous studies are conflicting with regard to an exact role for TGF-beta signaling in various aspects of pancreatic organogenesis. Here we have investigated the role of TGF-beta isoform signaling in embryonic pancreas differentiation and lineage selection. The TGF-beta isoform receptors (RI, RII and ALK1) were localized mainly to both the pancreatic epithelium and mesenchyme at early stages of development, but then with increasing age localized to the pancreatic islets and ducts. To determine the specific role of TGF-beta isoforms, we functionally inactivated TGF-beta signaling at different points in the signaling cascade. Disruption of TGF-beta signaling at the receptor level using mice overexpressing the dominant-negative TGF-beta type II receptor showed an increase in endocrine precursors and proliferating endocrine cells, with an abnormal accumulation of endocrine cells around the developing ducts of mid-late stage embryonic pancreas. This pattern suggested that TGF-beta isoform signaling may suppress the origination of secondary transition endocrine cells from the ducts. Secondly, TGF-beta isoform ligand inhibition with neutralizing antibody in pancreatic organ culture also led to an increase in the number of endocrine-positive cells. Thirdly, hybrid mix-and-match in vitro recombinations of transgenic pancreatic mesenchyme and wild-type epithelium also led to increased endocrine cell differentiation, but with different patterns depending on the directionality of the epithelial-mesenchymal signaling. Together these results suggest that TGF-beta signaling is important for restraining the growth and differentiation of pancreatic epithelial cells, particularly away from the endocrine lineage. Inhibition of TGF-beta signaling in the embryonic period may thus allow pancreatic epithelial cells to progress towards the endocrine lineage unchecked, particularly as part of the secondary transition of pancreatic endocrine cell development. TGF-beta RII in the ducts and islets may normally serve to downregulate the production of beta cells from embryonic ducts.

Serum monocyte chemotactic protein-1 levels in congenital diaphragmatic hernia.

To measure serum monocyte chemotactic protein-1 (MCP-1) in patients with congenital diaphragmatic hernia (CDH) and investigate its relationship to the development of persistent pulmonary hypertension (PPH). Serum MCP-1 was measured in 13 neonates with high risk for CDH at the time of diagnosis and postoperatively, and in five age-matched controls using an ELISA system. The 13 CDH subjects were divided into four groups according to the presence of PPH and outcome. Group I (severe-pre group): subjects with severe PPH who died prior to surgery (n = 5); Group II (mild-pre group): subjects with mild PPH controlled by medications (n = 8); Group IIa (severe-post group): subjects who subsequently developed severe PPH postoperatively and died (n = 3); and Group IIb (mild-post group): subjects who continued to have mild PPH controlled by medications. We also examined nitrofen-induced hypoplastic lungs from five rat fetuses with CDH and five control lung specimens for MCP-1 using immunohistochemistry. Mean serum MCP-1 in Group I was (1038.0 +/- 95.8 pg/ml), which was significantly higher than Group II (444.9 +/- 39.7 pg/ml) (P < 0.0001) and controls (147.3 +/- 11.3 pg/ml) (P < 0.0001). Postoperatively, Group IIa was significantly higher than Group IIb from 24 to 120 h postoperatively (P < 0.001). In Group IIb serum MCP-1 did not rise at all between 24 and 120 h postoperatively. Hypoplastic fetal rat CDH lungs had strong expression of MCP-1 compared with control lungs. Up-regulated expression and high circulating levels of MCP-1 in CDH patients with PPH suggest that MCP-1 may play a role in the development of PPH in CDH.

Mesenchymal epimorphin is important for pancreatic duct morphogenesis.

Epithelial-mesenchymal interactions are crucial for the proper development of many organs, including the pancreas. Within the pancreas, the ducts are thought to harbor stem/progenitor cells, and possibly to give rise to pancreatic ductal carcinoma. Little is known about the mechanism of formation of pancreatic ducts in the embryo. Pancreatic mesenchyme contains numerous soluble factors which help to sustain the growth and differentiation of exocrine and endocrine structures. Here, we report that one such morphoregulatory mesenchymal protein, epimorphin, plays an important role during pancreatic ductal proliferation and differentiation. We found that epimorphin is expressed in pancreatic mesenchyme during early stages of development, and at mesenchymal-epithelial interfaces surrounding the ducts at later stages. Strong upregulation of epimorphin expression was seen during in vitro pancreatic duct differentiation. Similarly, in vitro pancreatic duct formation was inhibited by a neutralizing antibody against epimorphin, whereas addition of recombinant epimorphin partially rescued duct formation. Together, our study demonstrates the role of epimorphin in pancreatic ductal morphogenesis.

Tissue adhesives for repairing inguinal hernia: a preliminary study.

AIM: To investigate the efficacy of tissue adhesives for closing the orifice of the inguinal hernia sac (IHS) as an alternative method for treating inguinal hernia. METHODS: Five-week-old male Lewis rats (n=4) were used, because Lewis rats have a large patent IHS. The rats were divided into 9 groups (n=6 in each) according to the type of tissue adhesive used: G1, fibrin glue (Beriplast); G1b, Beriplast plus blood; G2, microfibrillar collagen hemostat (Avitene); G2b, Avitene plus blood; G3, fibrinogen-based sealant (TachoComb); G3b, TachoComb plus blood; G4, synthetic absorbable sealant (Advaseal); G5, bilateral single port laparoscopic injection of octylcyanoacrylate (Dermabond); and G6, sham operation (control group). In G1-G4, surgery was performed through a midline lower abdominal incision. In G5, a 5-mm laparoscope was inserted in the epigastrium, a fine catheter was passed through the side port of the laparoscope into the right HIS, and 0.2 mL Dermabond was injected. The left IHS was treated in the same way. All rats were sacrificed 3 months after treatment, and IHS patency was examined macroscopically. All rats in G5 and G6 were mated 50 days after treatment to check fertility. RESULTS: All rats survived until sacrifice. At sacrifice, all IHS were patent in G6. All IHS were also patent in G1-G4, but all IHS were closed at the internal ring in G5. In G5 there were no adhesions between the orifice of the closed sac and the small bowel in 5/6, and only minor adhesions in 1/6. G5 fertility (5/6: 83%) was the same as for the control group (G6). CONCLUSION: Our results suggest that laparoscopic injection of Db into the IHS is simple, safe, reliable, virtually scarless, and may be a reasonable alternative to standard open surgical inguinal hernia repair.

Cross-talk between bone morphogenetic protein and transforming growth factor-beta signaling is essential for exendin-4-induced insulin-positive differentiation of AR42J cells.

A key goal of cellular engineering is to manipulate progenitor cells to become beta-cells, allowing cell replacement therapy to cure diabetes mellitus. As a paradigm for cell engineering, we have studied the molecular mechanisms by which AR42J cells become beta-cells. Bone morphogenetic proteins (BMPs), implicated in a myriad of developmental pathways, have not been well studied in insulin-positive differentiation. We found that the canonical intracellular mediators of BMP signaling, Smad-1 and Smad-8, were significantly elevated in AR42J cells undergoing insulin-positive differentiation in response to exendin-4 treatment, suggesting a role for BMP signaling in beta-cell formation. Similarly, endogenous BMP-2 ligand and ALK-1 receptor (activin receptor-like kinase-1; known to activate Smads 1 and 8) mRNAs were specifically up-regulated in exendin-4-treated AR42J cells. Surprisingly, Smad-1 and Smad-8 levels were suppressed by the addition of BMP-soluble receptor inhibition of BMP ligand binding to its receptor. Here, insulin-positive differentiation was also ablated. BMP-2 ligand antisense also strongly inhibited Smad-1 and Smad-8 expression, again with the abolition of insulin-positive differentiation. These results demonstrate a previously unrecognized key role for BMP signaling in mediating insulin-positive differentiation through the intracellular Smad signaling pathway. In short, BMP signaling may represent a novel downstream target of exendin-4 (glucagon-like peptide 1) signaling and potentially serve as an upstream regulator of transforming growth factor-beta isoform signaling to differentiate the acinar-like AR42J cells into insulin-secreting cells.

Synergistic endocrine induction by GLP-1 and TGF-beta in the developing pancreas.

OBJECTIVES: Glucagon-like peptide-1 (GLP-1) is known to stimulate glucose-dependent insulin production and secretion by pancreatic beta-cells. Preliminary evidence suggests that GLP-1 may also influence endocrine differentiation from pancreatic progenitor cells. Additionally, TGF-beta signaling can also control endocrine differentiation by both inhibiting proliferation and enhancing differentiation of endocrine progenitor cells to become mature beta-cells. Here we document synergy of these two signaling pathways in the differentiation of endocrine cells in the developing pancreas. METHODS: Embryonic pancreas was harvested from mice at day 11.5 and cultured for six days with GLP-1 agonist, exendin-4, and/or TGF-beta1 ligand. Also, a pan-neutralizing TGF-beta isoform antibody was used alone or with exendin-4 to study TGF-beta inhibition in this system. Pancreatic cultures were processed for immunohistochemistry. RESULTS: Exogenous TGF-beta1 and exendin-4 each individually enhanced both insulin and glucagon differentiation dose-dependently. However, when combined there was an additive effect to a 4.5-fold increase in insulin-positive differentiation. We also saw suppression of amylase-positive differentiation. Surprisingly, TGF-beta pan-neutralizing antibody also gave an augmentation of endocrine differentiation by 1.5 to 2-fold, but no synergistic effect was seen with exendin-4. CONCLUSION: We conclude that TGF-beta isoforms have a specific synergistic role with GLP-1 pathway signaling in early pancreatic development, toward endocrine differentiation and away from acinar differentiation.

Laparoscopic injection of dermabond tissue adhesive for the repair of inguinal hernia: short- and long-term follow-up.

PURPOSE: Is laparoscopic injection of 2-octyl-cyanoacrylate tissue adhesive (Dermabond: Db) into the inguinal hernia sac (IHS) effective for inguinal hernia repair? METHODS: Thirty male 4-week-old Lewis rats were used as subjects for this study. In the right Db (R-Db) group (n = 10), a fine catheter was passed through an 18-guage indwelling intravenous cannula inserted in the right lower quadrant, and 0.2 mL Db was injected into the right IHS under laparoscopic control. The left side was not treated. Both IHSs were treated in the bilateral Db (B-Db) group (n = 10). In the no Db (N-Db or control) group (n = 10), only laparoscope insertion was performed. Herniography was performed before death. B-Db and N-Db rats were mated 50 days after treatment. Half of all rats were killed 2 months after treatment and the remaining half 12 months after treatment. RESULTS: All rats survived until killing. Macroscopic findings postdeath confirmed herniography results; treated IHS were closed, and untreated IHS were patent. There were minor adhesions in 3 of 20 treated rats. Sperm were identified in the vaginas of all mated rats. CONCLUSIONS: These results suggest that our new technique is simple, safe, and reliable as an alternative to standard operative repair for inguinal hernia.

Laparoscopically assisted anorectovaginoplasty for selected types of female anorectal malformations.

PURPOSE: The aim of this study was to describe laparoscopically assisted anorectovaginoplasty (LAARVP) for the repair of selected types of female anorectal malformation. METHODS: Five cases (case 1, rectovaginal fistula with a high rectum; case 2, rectovestibular fistula with double vagina; case 3, rectovestibular fistula with absent vagina; case 4, anovestibular fistula with absent vagina; case 5, cloaca) were reviewed. RESULTS: Patient 4 had undergone a posterior sagittal anorectoplasty without vaginoplasty at another hospital after misdiagnosis of simple anovestibular fistula. Mean age at LAARVP was 15.4 months. At LAARVP, the fistula was divided in cases 1 through 4 and dissected as low as possible in case 5. In cases 3 and 4, the distal fistula was used to create the neovagina. In cases 1 through 3, the proximal rectum was mobilized and brought through the pelvic floor sphincter muscles using Georgeson's laparoscopically assisted colon pull-through technique through a minimal perineal incision. A posterior sagittal incision was required in cases 4 and 5. However, the initial laparoscopic approach was very helpful in both cases. Currently, all patients are well after a mean follow-up period of 32.2 months. Mean current age is 4.0 years. Patients 1 through 3 are continent, patient 4 is incontinent with soiling, and patient 5 is too young to be evaluated. CONCLUSIONS: LAARVP helps to achieve low dissection of the fistula, gives optimal view of the pelvic organs, provides accurate placement of the anorectal pull-through, and minimizes abdominal perineal scars.

Huge lymphangioma of the tongue: a case report.

Lymphangioma of the tongue is relatively rare and may cause facial structural deformity. Using a combination of a V-shaped and central resection, we successfully treated a 6-year-old girl who had massive lymphangioma of the tongue. Postoperatively, her tongue was located completely within her mouth with good cosmetic results. Sensory and motor nerves to the tongue appeared to be intact. Her speech was also improved.