Surgical Strategy for T2 Gallbladder Cancer: Nationwide Multicenter Survey in Korea.

BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.

Topographical anatomy of the intestines during in utero physiological herniation.

Because most malrotations of the small intestine are thought to occur during repackaging, the location of the intestine should vary less during physiological herniation than afterward. Examination of serial sagittal sections of 27 embryos and fetuses (gestational age 6-9 weeks; crown-rump length 15-45 mm) during herniation showed that the jejunum and ascending colon passed through a small opening of the hernia sac at the levels of the stomach and pancreas in 16 specimens. Below the pancreas, a definite mesentery extended between the ascending and descending colon in the abdominal cavity. In the other 11 specimens, the descending colon passed through an opening of normal size and ran posteriorly along the urinary bladder, so the entire ilium, ascending colon, and transverse colon entered the sac. In these specimens, the duodenojejunal junction was usually situated in a window of the mesentery of the colon (internal herniation). The descending colon was observed at an outside location more frequently in earlier specimens. In contrast to our working hypothesis, the locations of the intestine were abnormal in 40.7% (11/27) of samples. In addition, no abnormal colon was observed in any of the seven specimens after repackaging. An outside location of the descending colon was not directly associated with malrotation because recovery was likely. However, the delayed development of the inferior mesenteric arterial branches could cause failure, including death in utero, during or after the repackaging associated with physiological herniation. Clin. Anat. 31:583-592, 2018. © 2017 Wiley Periodicals, Inc.

Fetal Development of Human Oral Epithelial Pearls With Special Reference to Their Stage-Dependent Changes in Distribution.

OBJECTIVE: To access detailed distribution and age-dependent changes of oral epithelial pearls. DESIGN: Investigation and analysis with human fetal serial sections. SETTING: Institute of Embryology. METHODS: This study examined serial frontal sections of the upper and lower jaws of 19 human fetuses at 12 to 18 weeks and of the lower jaws of four late-stage fetuses. RESULTS: The upper jaw contained more than 20 midline and more than 60 lateral pearls greater than 20 µm in diameter, whereas the lower jaw contained fewer than 30 pearls of the same size. Midline pearls in the upper jaw were often cylindrical or rugby-ball shaped, whereas all pearls in the lower jaw were small and spherical. Epithelial pearls in the upper jaw started developing along the upper midline until 12 weeks; lateral pearls and additional midline pearls (or strictly, paramedian pearls) developed until 15 weeks. In the lower jaw, however, pearl development started at 18 weeks and was almost always from the dental lamina. Some of the fetuses assessed had an open nasopalatine canal without a duct, but there was no fibrous connection between this canal and pearls. Similarly, the lip frenulum or incisive suture was not connected with these pearls. CONCLUSION: The timing and sequence of development suggest that postfusion rupture of the palate by midline pearls was unlikely.

Sectional Localization of a Small Hepatocellular Carcinoma in the Right Hepatic Lobe by Computed Tomography: Comparison between the Conventional and Portal Vein Tracing Methods.

PURPOSE: To compare the accuracy of the conventional and portal vein tracing methods in the right hepatic lobe in multidetector computed tomography (MDCT). MATERIALS AND METHODS: This retrospective study included patients with hepatocellular carcinoma (HCC) lesions in the right hepatic lobe who underwent multiphasic MDCT and C-arm CT hepatic arteriography (C-arm CTHA) for chemoembolization. The accuracies of the conventional and portal vein tracing methods were evaluated using C-arm CTHA as the gold standard. RESULTS: A total of 147 patients with 205 HCC nodules were included. The C-arm CTHA could identify all the tumour-feeding arteries and consequently demonstrated that 120 lesions were located in the anterior section, 78 in the posterior section, and 7 in the border zone. The accuracy rates of conventional vs. portal vein tracing methods were 71.7 % vs. 98.3 % for the anterior section lesions, 67.9 % vs. 96.2 % for the posterior section, and 28.6 % vs. 57.1 % for the border zone. The portal vein tracing method was more accurate than the conventional method (P<0.001). CONCLUSIONS: The portal vein tracing method should be used for sectional localization of HCCs in the right lobe, because it predicts the location more accurately than the conventional method. KEY POINTS: • Portal tracing method is more accurate than conventional method for tumour localization. • The conventional method is especially inaccurate in right anteroinferior or posterosuperior quadrants. • Scissurae between right anterior and posterior section may not be vertical but tilted.

Fetal growth of the anal sinus and sphincters, especially in relation to anal anomalies.

PURPOSE AND METHODS: The anal sinuses, small furrows above the pectinate line, sometimes form perianal abscesses in adults. We examined the pattern of fetal growth of the anal sinus and sphincters using 22 mid-term (8-18 weeks) and 6 late-stage (30-38 weeks) fetuses. RESULTS: In mid-term fetuses, the external and internal sphincters gradually increased in thickness, depending on specimen size (from 0.2 to 1.5 mm), whereas the anteroposterior diameter of the anal canal at the epithelial junction was relatively stable (0.5-1.0 mm) irrespective of specimen size. Anal canal diameter increased less than twofold between mid-term and late-stage fetuses, from 0.5-1.0 to almost 2 mm, whereas sphincter thickness increased over tenfold, from 0.2-1.5 to almost 3.5 mm. The anal sinus often showed balloon-like enlargement when the sphincter muscle bundles were tightly packed in mid-term, but not in late-stage fetuses. CONCLUSIONS: Large concentric mechanical stress from the sphincters in late-stage fetuses apparently prevented the anal sinus from expanding in a balloon-like manner. Conversely, to avoid anal stenosis, the growing sinuses maintained a luminal space of the anal canal in response to stress from rapidly growing sphincters. The inferiorly extending sinus usually provided temporal double canals separated by a thick column. In the presence of double lumens, anal canal duplication is likely to develop without any abnormalities of the anal epithelium and sphincters.

Low-dose mycophenolate mofetil in tablet form or capsule form combined with tacrolimus in the early period after kidney transplantation: a prospective randomized trial
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AIMS: The tablet form (500 mg) of mycophenolate mofetil (MMF) provides more convenience of taking drugs and cost-effectiveness than the capsule form (250 mg). We examined the efficacy and safety of MMF in its different forms combined with tacrolimus in kidney transplant recipients. METHODS: This multicenter, 26-week, randomized trial was performed to compare the efficacy and safety of the tablet form of MMF versus the capsule form of MMF in 156 kidney transplant recipients. Allograft function, the incidence of efficacy failure (biopsy-proven acute rejection (BPAR), death, graft loss, or loss to follow-up), and adverse events were compared. RESULTS: The mean dose (mg/day) of MMF at 26 weeks was comparable: 1,052.6 ± 194.2 in the tablet group vs. 1,155.6 ± 298.1 in the capsule group (p = 0.063). Trough levels of tacrolimus at 26 weeks were comparable. The mean estimated glomerular filtration rate of the tablet group at 26 weeks post-transplant was not inferior to that of the capsule group. The incidence of efficacy failure was similar in the two groups: tablet group, 5.2% and capsule group, 7.7% (difference -2.5%; 95% confidence interval -5.22 - 10.21%). The incidence of BPAR until 26 weeks post-transplant in the tablet group was 3.9%, compared to 7.7% in the capsule group (p = 0.346). There was no significant difference in the incidence of discontinuations and serious adverse events between the groups. CONCLUSION: Low-dose MMF in tablet form combined with tacrolimus can be considered as an efficacious and safe immunosuppressive regimen in the early period after kidney transplantation.
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Topographical relationships of intramuscular nerves and vessels of the motor endplates in the thigh and gluteal regions of human fetuses: an immunohistochemical study.

PURPOSE: The aim of this study was to describe topography of vessels and nerves in striated muscles to understand individual muscle function. MATERIALS AND METHODS: Immunohistochemistry for nerve and artery was used to examine the thigh and gluteal muscles of six human midterm fetuses. RESULTS: The supplying nerves often accompanied arteries along epimysium bundling muscle fibers as well as in the covering fascia surrounding the entire muscle mass. However, courses of nerve twigs were usually independent of those of vessels in muscle bundles. Notably, irrespective of whether or not the vascular bundle accompanied the nerves at the muscle surface or hilus, most of the motor endplate bands did not accompany the vessels. CONCLUSION: Since the motor endplates were low vascularised, a chemical induction of vessels for nerve terminal development (or the reversed induction) seemed unlikely in striated muscles. In contrast to proprioceptive neuromuscular facilitation, manual stimulation of the endplate bands may stimulate muscle activity without sympathetic reflexes through vessel-accompanying nerves.

Lack of striated muscle fibers in the longitudinal anal muscle of elderly Japanese: a histological study using cadaveric specimens.

PURPOSE AND METHODS: The aim of this study is to investigate variations in the longitudinal anal muscle (LAM), especially in the meeting pattern between the levator ani and rectum at the origin of the LAM. We examined the histology of the anal canal and the lower rectum of 50 cadavers (25 males, 25 females) of elderly Japanese individuals with the aid of immunohistochemistry. RESULTS: We observed two patterns in the meeting site between the levator ani and the rectum. In type 1, observed in 26 specimens, the smooth muscle-rich fascia lining the internal or medial aspect of the levator ani (i.e., the fascia pelvis parietalis or endopelvic fascia) was connected to the external muscle layer. In type 2, observed in 24 specimens, multiple intramuscular septa of the levator ani were attached to a smooth muscle mass, with the latter joining the external smooth muscle layer of the rectum. However, 21 specimens (6 type 1 and 15 type 2) carried few smooth muscles at the meeting site. We did not find any striated muscle in the LAM, although this might have been the result of age-associated degeneration. Thus, active traction of the pelvic viscera by the LAM seemed unlikely in elderly Japanese. CONCLUSIONS: Rather than playing an active role, as suggested by the integral pelvic floor theory, the LAM seemed to be an elastic skeleton that maintains the shape of the anal canal.

Topographic anatomy of the fetal inferior vena cava, coronary sinus, and pulmonary veins: Variations in Chiari's network.

To understand anomalies in Chiari's network better, we assessed the topographical anatomy of the fetal inferior vena cava (IVC), coronary sinus, and atria. We examined sagittal serial paraffin sections of 15 human fetuses of crown-rump length 24-36 mm, corresponding to a gestational age of 8 weeks. Although their outflow tract morphologies were similar, these 15 specimens could be classified into two groups. In eight specimens, the left common cardinal vein reached the body wall, whereas in the other seven the vein was obliterated near the left pulmonary vein. Irrespective of the group in which the specimen was included, the anteroposterior arrangement of the coronary sinus, the sinus septum (septum), and the right sinus valve (right valve) could be classified into three types: the right valve-septum-coronary sinus arrangement in seven specimens; the right valve-coronary sinus-septum arrangement in five; and the coronary sinus-right valve-septum arrangement in three. Depending on differences in topographical anatomy, the sinus septum separated the coronary sinus opening from either the right or the left atrium. Likewise, the coronary sinus opening was either adjacent to or distant from the IVC terminal. Rather than the counter-side position of the right valve being at the IVC terminal, the left sinus valve protruded leftward, forming an incomplete interatrial septum. Fetal variations seemed to be closely connected with individual variations and a high frequency of Chiari's network anomalies in adults.

Denonvilliers' fascia revisited.

Although several studies have reported that the peritoneum does not contribute to the formation of a fascia between the urogenital organs and rectum, Denonvilliers' fascia (DF), a fascia between the mesorectum and prostate (or vagina) in adults, is believed to be a remnant of the peritoneum. Remnants of the peritoneum, however, were reportedly difficult to detect in other fusion fasciae of the abdominopelvic region in mid-term fetuses. To examine morphological changes of the pelvic cul-de-sac of the peritoneum, we examined 18 male and 6 female embryos and fetuses. A typical cul-de-sac was observed only at 7 weeks, whereas, at later stages, the peritoneal cavity did not extend inferiorly to the level of the prostatic colliculus or the corresponding structure in females. The cul-de-sac had completely disappeared in front of the rectum at 8 weeks and homogeneous and loose mesenchymal tissue was present in front of the rectum at the level of the colliculus at 12-16 weeks. We found no evidence that linearly arranged mesenchymal cells developed into a definite fascia. Therefore, the development of the DF in later stages of fetal development may result from the mechanical stress on the increased volumes of the mesorectum, seminal vesicle, prostate and vagina and/or enlarged rectum. Therefore, we considered the DF as a tension-induced structure rather than a fusion fascia. Fasciae around the viscera seemed to be classified into (1) a fusion fascia, (2) a migration fascia and (3) a tension-induced fascia although the second and third types are likely to be overlapped.

Surgical strategy for T1 gallbladder cancer: a nationwide multicenter survey in South Korea.

BACKGROUND: The aim of this study was to investigate the clinical features and clinical outcomes of T1 gallbladder (GB) cancer and to determine an appropriate surgical strategy for T1 GB cancer. METHODS: A nationwide multicenter study, in which 16 University Hospitals in Korea participated, was performed from 1995 to 2004. A total of 258 patients, 117 patients with T1a and 141 patients with T1b disease were enrolled. Clinicopathologic findings and long-term follow-up results were analyzed after a consensus meeting of the Korean Pancreas Surgery Club was held. RESULTS: Simple cholecystectomy was performed in 95 patients (81.2 %) with T1a tumor and in 89 patients (63.1 %) with T1b tumor (p < 0.01). Lymph node metastasis was observed in 2.9 % of T1a patients and in 9.9 % of T1b patients (p = 0.391). A significant difference in 5-year disease-specific survival (DSS) rates was observed between T1a and T1b patients (96.4 vs 84.8 %, respectively, p = 0.03). However, no significant 5-year DSS rate difference was observed between those who underwent simple cholecystectomy or extended cholecystectomy, regardless of whether lymph node dissection was performed or whether lymph node metastasis was present. There was no significant difference in recurrence-free survival between simple cholecystectomy and extended cholecystectomy. CONCLUSIONS: There was no superiority of extended cholecystectomy over simple cholecystectomy in the aspect of survival and recurrence especially in T1b gallbladder cancer. Furthermore, the effectiveness of regional lymphadenectomy for treatment purpose remains questionable. Therefore, simple cholecystectomy could be recommended as a surgical strategy of T1 gallbladder cancer.

Endoscopic stenting in bile duct cancer increases liver volume.

BACKGROUND: Objective evaluation tools for assessing the effectiveness of stenting in palliative treatment of malignant biliary obstruction are not satisfactory. Effects of biliary stenting on liver volume change have never been studied. OBJECTIVE: We aimed to use volumetry to analyze liver volume changes after endoscopic stenting in bile duct cancer according to the location and number of stents. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS: Patients with a diagnosis of hilar or distal bile duct cancer and who underwent biliary metal stenting. INTERVENTIONS: ERCP with self-expandable metal stent placement. MAIN OUTCOME MEASUREMENTS: Liver volume change after biliary stenting and its comparison according to the location (hilar vs distal common bile duct) and number (hilar bilateral vs hilar unilateral). RESULTS: There were 60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean follow-up duration was 11.7 ± 4.9 weeks. Liver volume increased 17.4 ± 24.1%. The rate of liver growth was rapid during the early period from 4 to 8 weeks. Stenting in hilar bile duct cancer tended to increase liver volume more than distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer, unilateral and bilateral stents showed similar liver volume increases (20.1% and 25.8%, respectively; P = .512). LIMITATIONS: Single center, retrospective. CONCLUSIONS: Biliary stenting markedly increased liver volume in both hilar and distal bile duct cancer. Our data suggest that liver volume assessment could be a useful tool for evaluating stent efficacy.

Region-specific differences in the human myenteric plexus: an immunohistochemical study using donated elderly cadavers.

PURPOSE AND METHODS: To identify site-dependent and individual differences in neuronal nitric oxide synthase (nNOS)-positive nerves of the myenteric plexus, we examined full-thickness walls of the stomach, pylorus, duodenum, ileum, colon, and rectum in 7 male and 8 female cadavers (mean ages, 80 and 87 years, respectively). RESULTS: The areas occupied by nNOS-positive nerve fibers in the myenteric plexus were fragmentary and overlapped with areas occupied by vasoactive intestinal polypeptide-positive fibers. The nNOS-positive fiber-containing areas per 1-mm length of intermuscular space tended to be larger at more anal sites, with positive areas four times greater in the rectum than in the stomach. Interindividual differences in rectal areas were extremely large, ranging from 0.017 mm(2) in one 80-year-old man to 0.067 mm(2) in another 80-year-old man. Similarly, the numbers of nNOS-positive ganglion cell bodies per 1-mm length in the rectum ranged from 4 to 28. These areas and numbers were weakly correlated (r = 0.62; p = 0.02). Interindividual differences in the rectum appeared not to depend on either age or gender. CONCLUSIONS: Anatomic studies using donated cadavers carried the advantage of obtaining any parts of intestine within an individual, in contrast to surgically removed specimens. We speculated excess control of evacuation with laxatives as one of causes of atrophy of the rectal myenteric plexus.

Ectopic choroid plexus found in fetal sections: a case report with literature consideration.

We incidentally found an ectopic choroid plexus (CP) attached to the posterior side of the cervicothoracic spinal cord (C4-T6) in a 16-week aborted fetus. The cytoarchitecture of the cord and segmental nerves showed normal development. The fourth ventricle did not contain the usual CP but a red blood cell cluster due to hemorrhage, although the cause, whether spontaneous or traumatic, was unknown. The ectopic CP was associated with thick neuroepithelium that was strongly positive for glial fibrillary acidic protein, vimentin, nestin, and proliferating cell nuclear antigen, but did not contain any CD34-positive vessels. Thus, the ectopic neuroepithelium seemed not to carry growth factor for vascular development. On the inferior side of the ectopic CP, the lower thoracic cord was wavy, folded, and packed in a limited space as a folding fan. Despite the strange gross appearance, however, we found no abnormality in the dorsal root ganglion, the spinal nerve root, or the cytoarchitecture of the lower thoracic cord. Therefore, the abnormality in the lower thoracic cord seemed to be secondarily induced by trophic factor(s) from the ectopic CP and/or the associated neuroepithelium. This may be the first report on an ectopic CP associated with ectopic neuroepithelium.

Fetal development of ligaments around the tarsal bones with special reference to contribution of muscles.

Through a histological examination of eight mid-term human fetuses (10-15 weeks) and seven late-stage fetuses (30-34 weeks), we attempted to determine how and when fetal ligaments around the tarsal bones form the regular arrangement seen in adults. Ligaments along the dorsal aspect of the tarsal bones developed early as an elongation of the perichondrium, in contrast to the late development of the plantar-sided ligaments. In contrast, a distal elongation of the tibialis posterior tendon was a limited plantar ligament in the early stage; finally, it extended from the navicular, ran obliquely to cross the dorsal side of the fibularis longus tendon, and inserted to the lateral cuneiform and fourth metatarsal. In the late stage, the adductor hallucis muscle origin provided multiple ligamentous structures along the cuneiforms and metatarsals. The tarsal sinus contained multiple fibrous bundles (possibly, the putative interosseous talocalcanean ligaments) that were derived from (1) insertion tendons of the extensor digitorus brevis muscle and (2) the fibrous sheath of the extensor digitorus longus tendon. The aponeurotic origin of the quadratus plantae muscle seemed to contribute to formation of the long plantar ligament. Therefore, tarsal ligaments appeared likely to develop from the long tendons, their fibrous sheaths and aponeuroses and intramuscular tendons of the proper foot muscles. Under in utero conditions with little or no stress from the plantar side of the foot, the muscle-associated connective tissue seems to play a crucial role in providing a regular arrangement of the ligaments in accordance with tensile stress from muscle contraction.

Duodenal window revisited: A histological study using human fetuses.

To assess the development of the duodenal window in fetuses, we examined semiserial histological sections of 59 human fetuses with a crown-rump length of 27-156 mm (∼4-18 weeks of gestation). In 44 of the 54 fetuses with horizontal sections, the duodenal window was formed by interdigitation of the anterior and posterior muscle slips from the proper duodenal circular muscle coat. The anterior slips approached the common bile duct from the anterior side and wound around the bile duct from the right aspect, whereas the posterior slips approached the main pancreatic duct from the posterior side, reaching the left or outer aspect of the duct without winding. These slips may become longitudinal muscles in the ampulla after birth. Six specimens showed variations in this typical pattern, in that the posterior muscle slips as well as the duodenal longitudinal muscle coat wound around the bile duct. In the remaining four specimens, we observed an abnormal union of the bile and pancreatic ducts, with the duodenal circular muscles suddenly ending along the window or slightly inserted into the right side of the common duct after joining. In all later-stage fetuses, the common sphincter surrounded both the bile and pancreatic ducts in the ampulla. Consequently, at and along the duodenal window, the proper duodenal circular muscle seemed to contribute to fetal sphincter formation. The window was not a simple hiatus but a functional interface between the sphincter and the duodenal wall.

Retropancreatic fascia is absent along the pancreas facing the superior mesenteric artery: a histological study using elderly donated cadavers.

To determine the fascial configuration between the superior mesenteric artery and vein and the posterior aspect of the pancreas, we examined histological sections of 10 elderly donated cadavers without pathology in the abdomen. The retropancreatic fascia was absent along the pancreatic parenchyma facing the artery and vein. Abundant nerves along the artery were separated from the pancreas by loose tissue almost 10 mm in thickness. In addition, anterior renal fasciae facing the pancreatic body were not evident in these specimens, possibly due to the degeneration of the left adrenal gland with age. Thus, a definite renal fascia was restricted on the lateral and posterior sides of the left kidney. These findings suggest that interactions between a pancreatic tumor and nerves would require migration of cancer cells over a long distance. Conversely, attachment of the enlarged tumor mass to the nerves may be necessary for the invasion. The anterior renal fascia may fuse with the retropancreatic fascia.

Morphology of the ligament of Treitz likely depends on its fetal topographical relationship with the left adrenal gland and liver caudate lobe as well as the developing lymphatic tissues: a histological study using human fetuses.

To investigate the factors affecting the development of the ligament of Treitz, we examined sagittal and frontal histological sections of 35 human fetuses with a crown-rump length of 100-300 mm (approximately 16-38 weeks of gestation). The retropancreatic fascia consistently extended in a layer behind the pancreatic body and the splenic artery and vein, and also in front of the left renal vein and left adrenal. In 18 specimens, a connective tissue band was seen originating from the diaphragmatic crus around the esophageal opening and ending at the retropancreatic fascia to the left of the origin of the celiac artery. In 10 of these 18 specimens, these putative upper parts of the ligament contained striated muscles, or so-called Hilfsmuskel. Although most of other 17 specimens were larger fetuses, the left adrenal, the liver caudate lobe and the celiac ganglion made space for the ligament very limited. In 22 specimens including the above 18, the retropancreatic fascia extended inferiorly to approach the fourth portion of the duodenum (D4) or the duodenojejunal junction (DJJ). However, in 11 of the 22 examples of the putative lower part of the ligament, the connection between the duodenal muscle coat and the fascia was interrupted by developing lymphatic tissues. Consequently, the ligament of Treitz seemed to develop from both pleuroperitoneal membrane-derived cells and the retropancreatic fusion fascia, although the morphology was markedly modified by adjacent structures such as the adrenal gland. The ligament may "recover" after the adrenal becomes reduced in size after birth.

The anatomy of fetal peripheral lymphatic vessels in the head-and-neck region: an immunohistochemical study.

Using D2-40 immunohistochemistry, we assessed the distribution of peripheral lymphatic vessels (LVs) in the head-and-neck region of four midterm fetuses without nuchal edema, two of 10 weeks and two of 15 weeks' gestation. We observed abundant LVs in the subcutaneous layer, especially in and along the facial muscles. In the occipital region, only a few LVs were identified perforating the back muscles. The parotid and thyroid glands were surrounded by LVs, but the sublingual and submandibular glands were not. The numbers of submucosal LVs increased from 10 to 15 weeks' gestation in all of the nasal, oral, pharyngeal, and laryngeal cavities, but not in the palate. The laryngeal submucosa had an extremely high density of LVs. In contrast, we found few LVs along bone and cartilage except for those of the mandible as well as along the pharyngotympanic tube, middle ear, tooth germ, and the cranial nerves and ganglia. Some of these results suggested that cerebrospinal fluid outflow to the head LVs commences after 15 weeks' gestation. The subcutaneous LVs of the head appear to grow from the neck side, whereas initial submucosal LVs likely develop in situ because no communication was evident with other sites during early developmental stages. In addition, CD68-positive macrophages did not accompany the developing LVs.

Hispidin analogue davallialactone attenuates carbon tetrachloride-induced hepatotoxicity in mice.

In this study the protective effects of davallialactone (1), isolated from Inonotus xeranticus, have been examined against carbon tetrachloride (CCl4-induced acute liver injury. Mice received subcutaneous injection of 1 (2.5, 5, and 10 mg/kg) for three days before CCl4 injection (1 mg/kg). Protection from liver injury by 1 was confirmed by the observation of decreased serum transaminases and diminished necrosis of liver tissue. Reduced hepatic injury was very similar to that observed with silymarin, a known hepatoprotective drug used in this work for comparison. The groups treated with 1 had reduced reactive oxygen species (ROS), reduced serum malonyldialdehyde levels, and increased levels of liver Cu/Zn superoxide dismutase, as compared to the CCl4 control group. The expression of heme oxygenase-1 in the liver tissue was increased and the activity of liver cytochrome P4502E1 was restored in the mice treated with 1. In addition, levels of serum tumor necrosis factor-alpha (TNF-α), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), numbers of macrophage, and cleaved caspase-3-positive hepatocytes were reduced in the groups treated with 1. These findings suggest that davallialactone has protective effects against CCl4-induced acute liver injury, and this protection is likely due to the suppression of ROS-induced lipid peroxidation and inflammatory response.