The prevalence of metabolic syndrome, hypertension, and diabetes has been increasing rapidly in Korea. The rate of increase has paralleled the replacement of Korean traditional diets (KTD), which emphasize vegetables and fermented foods, with western style dietary patterns that are rich in animal foods and saturated fat. We aimed to investigate the efficacy of the KTD in controlling fasting plasma glucose, blood pressure, and cardiovascular disease risk factors in hypertensive and type 2 diabetic (T2D) patients. Forty-one patients (61.8±1.5 years) who were taking medications prescribed for respective diseases were recruited from the Chonbuk National University Hospital for participation in a 12-week, parallel, controlled clinical trial. The control group (n=20) was advised to “eat as usual,” whereas the experimental KTD diet group (n=21) was fed the KTD three times a day for 12 weeks. At the end of the trial, both groups had lower body mass index, % body fat, and waist–hip ratio compared to the baseline values (P<.05). Compared to the control group, the KTD group had a greater mean change (P<.05) from the baseline for glycated hemoglobin (HbA1c) (−0.72% vs. −0.25%) and heart rate (−7.1 vs. +1.6). Regular consumption of the KTD for 12 weeks by hypertensive and T2D patients resulted in favorable changes in cardiovascular risk factors.
cardiovascular risk; diabetes; Korean traditional diet (KTD); hypertension; metabolic syndrome
Using 5 fetuses of gestational age (GA) of 15-16 weeks and 4 of GA of 22–25 weeks, we examined site- and stage-dependent differences in CD68-positive microglial cell distribution in human fetal brains. CD68 positive cells were evident in the floor of the fourth ventricle and the pons and olive at 15-16 weeks, accumulating in and around the hippocampus at 22–25 weeks. At both stages, the accumulation of these cells was evident around the optic tract and the anterior limb of the internal capsule. When we compared CD68-positive cell distribution with the topographical anatomy of GAP43-positive developing axons, we found that positive axons were usually unaccompanied by CD68-positive cells, except in the transpontine corticofugal tract and the anterior limb of the internal capsule. Likewise, microglial cell distribution did not correspond with habenulointerpeduncular tract. Therefore, the distribution of CD68-positive cells during normal brain development may not reflect a supportive role of these microglia in axonogenesis of midterm human fetuses.
Carbonic anhydrase type IX (CA9) is known to express in the fetal joint cartilage to maintain pH against hypoxia. Using paraffin-embedded histology of 10 human fetuses at 10-16 weeks of gestation with an aid of immunohistochemistry of the intermediate filaments, matrix components (collagen types I and II, aggrecan, versican, fibronectin, tenascin, and hyaluronan) and CA9, we observed all joints and most of the entheses in the body. At any stages examined, CA9-poisitive cells were seen in the intervertebral disk and all joint cartilages including those of the facet joint of the vertebral column, but the accumulation area was reduced in the larger specimens. Glial fibrillary acidic protein (GFAP), one of the intermediate filaments, expressed in a part of the CA9-positive cartilages. Developing elastic cartilages were positive both of CA9 and GFAP. Notably, parts of the tendon or ligament facing to the joint, such as the joint surface of the annular ligament of the radius, were also positive for CA9. A distribution of each matrix components examined was not same as CA9. The bone-tendon and bone-ligament interface expressed CA9, but the duration at a site was limited to 3-4 weeks because the positive site was changed between stages. Thus, in the fetal entheses, CA9 expression displayed highly stage-dependent and site-dependent manners. CA9 in the fetal entheses seemed to play an additional role, but it was most likely to be useful as an excellent marker of mechanical stress at the start of enthesis development.
Carbonic anhydrase type IX; Intermediate filaments; Joints; Enthesis; Human fetus
Multicystic biliary hamartoma (MCBH) is a very rare hamartomatous cystic nodule of the liver, which has recently been described as a new entity of a hepatic nodular lesion. We report a unique case of MCBH with a review of the literatures. A hepatic multicystic mass of segment 3 was detected in a 52-year-old male by abdominal computed tomography, and resection of this lesion was performed. Macroscopic examination revealed a 2.7×2.0 cm nodular mass with a multicystic honeycomb cut surface. Histologically, this lesion consisted of multiple dilated cystic ducts lined by biliary type epithelial cells, periductal glands and connective tissue, which included small amounts of hepatic parenchyma and blood vessels. Recognition of this unusual lesion is essential to avoid confusion with other cystic tumors of the liver, and to learn more about its natural history and response to treatment.
Liver; Cysts; Hamartoma
Connexin-43, a major gap junction protein, and cytokeratin-19, one of the intermediate filament keratins, are known to be markers of well-differentiated epithelium. In this study, we investigated the expression of these markers in the head region, lungs, and abdominal organs of 10 human mid-term fetuses. The expression of connexin-43 was found to be restricted to the dura mater, kidney, and adrenal cortex. In the kidney, we found a clear site-dependent difference in the expression pattern of these markers: connexin-43 expression was observed in the tubules of the renal cortex whereas cytokeratin-19 was strongly expressed in the collecting ducts and renal pelvis. This difference remained unchanged throughout the fetal stages examined. Immunoreactivity was not observed for either of the markers in the intrarenal vessels, including the glomeruli, and mesangial cells. Connexin-43 expression seemed to be restricted to the metanephric vesicle-derived structures that differentiate in the urogenital ridge of the splanchnic mesoderm. The adrenal cortex also originates from the same para-aortic mesoderm. In contrast, in the urogenital organs, cytokeratin-19 seemed to be expressed in ducts derived from the urogenital sinus.
Connexin-43; Cytokeratin-19; Kidney; Immunohistochemistry; Human fetus
In the developing human musculoskeletal system, cell death with macrophage accumulation occurs in the thigh muscle and interdigital area. To comprehensively clarify the distribution of macrophages, we immunohistochemically examined 16 pairs of upper and lower extremities without the hip joint (left and right sides) obtained from 8 human fetuses at approximately 10-15 weeks of gestation. Rather than in muscles, CD68-positive macrophages were densely distributed in loose connective tissues of the flexor aspects of the extremities, especially in the wrist, hand and foot. In contrast, no or fewer macrophages were evident in the shoulder and the extensor aspects of the extremities. The macrophages were not concentrated at the enthesis of the tendon and ligament, but tended to be arranged along other connective tissue fibers. Deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling revealed apoptosis in the hand lumbricalis muscles, but not in the area of macrophage accumulation. Likewise, podoplanin-positive lymphatic vessels were not localized to areas of macrophage accumulation. Re-organization of the connective tissue along and around the flexor tendons of the hand and foot, such as development of the bursa or tendon sheath at 10-15 weeks, might require the phagocytotic function of macrophages, although details of the mechanism remain unknown.
CD68-positive macrophages; Hand and foot; Lymphatic vessels; Enthesis; Human fetus
Although the rectus abdominis and its sheath are well known structures, their development in the human fetus is poorly understood.
Materials and Methods
We examined rectus abdominis and sheath development in semiserial horizontal sections of 18 fetuses at 5-9 weeks of gestation.
Rectus muscle differentiation was found to commence above the umbilicus at 6 weeks and extend inferiorly. Until closure of the anterior chest wall via fusion of the bilateral sternal anlagen (at 7 weeks), the anterior rectal sheath originated from the external oblique and developed towards the medial margin of the rectus abdominis at all levels, including the supracostal part. After formation of the anterior sheath, fascial laminae from the internal oblique and transversus abdominis contributed to formation of the posterior rectus sheath. However, the posterior sheath was absent along the supracostal part of the rectus abdominis, as the transversus muscle fibers reached the sternum or the midline area. Therefore, it appeared that resolution of the physiological umbilical hernia (8-9 weeks) as well as chest wall closure was not required for development of the rectus abdominis and its sheath. Conversely, in the inferior part of the two largest fetal specimens, after resolution of the hernia, the posterior sheath underwent secondary disappearance, possibly due to changes in mechanical stress.
Upward extension of the rectus abdominis suddenly stopped at the margin of the inferiorly developing pectoralis major without facing the external intercostalis. The rectus thoracis, if present, might correspond to the pectoralis.
Rectus abdominis; rectus sheath; pectoralis; sternalis; sternum; rib
We recently demonstrated the morphology of the anococcygeal ligament. As the anococcygeal ligament and raphe are often confused, the concept of the anococcygeal raphe needs to be re-examined from the perspective of fetal development, as well as in terms of adult morphology.
Materials and Methods
We examined the horizontal sections of 15 fetuses as well as adult histology. From cadavers, we obtained an almost cubic tissue mass containing the dorsal wall of the anorectum, the coccyx and the covering skin. Most sections were stained with hematoxylin and eosin or Masson-trichrome solution.
The adult ligament contained both smooth and striated muscle fibers. A similar band-like structure was seen in fetuses, containing: 1) smooth muscle fibers originating from the longitudinal muscle coat of the anal canal and 2) striated muscle fibers from the external anal sphincter (EAS). However, in fetuses, the levator ani muscle did not attach to either the band or the coccyx. Along and around the anococcygeal ligament, we did not find any aponeurotic tissue with transversely oriented fibers connecting bilateral levator ani slings. Instead, in adults, a fibrous tissue mass was located at a gap between bilateral levator ani slings; this site corresponded to the dorsal side of the ligament and the EAS in the immediately deep side of the natal skin cleft.
We hypothesize that a classically described raphe corresponds to the specific subcutaneous tissue on the superficial or dorsal side of the anococcygeal ligament.
Anal canal; rectum; smooth muscle; embryology; anatomy; histology
To evaluate the pattern of right gastric venous drainage by use of digital subtraction angiography.
Materials and Methods
A series of 100 consecutive patients who underwent right gastric arteriography during transcatheter arterial chemoembolization for hepatocellular carcinoma were included in this study. Angiographic findings were retrospectively analyzed with respect to the presence or absence of the right and aberrant gastric veins, multiplicity of draining veins, aberrant right gastric venous drainage sites, and the termination pattern of aberrant right gastric veins (ARGVs). We also compared the relative size of the right and left gastric veins.
A total of 49 patients collectively had 66 ARGVs. The common drainage sites for the ARGVs included the hepatic segment IV (n = 35) and segment I (n = 15). The termination pattern of ARGV could be classified into 4 different types. The most common type was termination as a superficial parenchymal blush formation in small areas without demonstrable portal branches. A statistically significant difference was found for the dominancy of the right gastric vein in gastric venous drainage between the two groups with or without ARGV (p < 0.05, Fisher's exact test). In the group of patients without ARGV (n = 51), the right gastric vein was equal to (n = 9) or larger than (n = 17) the left gastric vein in 26 patients (26 of 51, 51%).
The incidence of ARGV is higher than expected with four distinct types in its termination pattern. The right gastric vein may play a dominant role in gastric venous drainage.
Aberrant gastric vein; Gastric vein; Angiography
Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a rare subtype of primary liver cancer. We investigated the histopathologic features of transitional or intermediate areas in 21 combined HCC-CCs and immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c-kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval-shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an abundant stroma, small cells with an antler-like anastomosing pattern, and solid nests of intermediate hepatocyte-like cells surrounded by small cells in periphery, in order of frequency. The intermediate area of one tumor was composed predominantly of spindle cells arranged in short fascicles. Immunophenotype of tumor cells with intermediate morphology suggested a progenitor cell origin for this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and serum alpha-fetoprotein levels showed a significant association with poor patient survival. Serum alpha-fetoprotein level was an independent prognostic indicator in multivariate analysis. In conclusion, an awareness of the clinicopathologic features, specifically the various morphologic features of intermediate areas in this tumor, is essential for prevention of potential misdiagnosis as another tumor.
Carcinoma; Hepatocellular; Cholangiocarcinoma
Computer-assisted three-dimensional reconstruction of the fetal human pancreas was prepared to reconsider topographical relation between the dorsal/ventral anlagen and the vascular supply.
Tissue sections from the upper abdominal viscera of three fetuses were examined. Sections were immunohistochemically stained to determine pancreatic polypeptide expression, a marker of the ventral pancreas.
The immunohistochemical findings were used to create three-dimensional computer-assisted reconstructions to identify pancreatic arteries. The narrowest part of the pancreas, or the neck, corresponding to a part of the dorsal pancreas, was located on the left side of the common bile duct, portal vein and gastroduodenal artery (GDA). The posterior arterial arcade accompanied the ventral pancreas, whereas the anterior arcade did not. In contrast to the GDA, the splenic artery was clearly separated from the neck in fetuses. The GDA appears to be the primary and stable arterial supply for the neck of the pancreas.
This observation may have implications for the preservation of the neck with the GDA during pancreaticoduodenectomy for benign and low-grade malignant diseases.
Gastroduodenal artery; Dorsal pancreas; Pancreatic polypeptide immunohistochemistry; Human fetus
The molecular mechanisms of CC (cholangiocarcinoma) oncogenesis and progression are poorly understood. This study aimed to determine the genome-wide expression of genes related to CC oncogenesis and sarcomatous transdifferentiation.
Genes that were differentially expressed between CC cell lines or tissues and cultured normal biliary epithelial (NBE) cells were identified using DNA microarray technology. Expressions were validated in human CC tissues and cells.
Using unsupervised hierarchical clustering analysis of the cell line and tissue samples, we identified a set of 342 commonly regulated (>2-fold change) genes. Of these, 53, including tumor-related genes, were upregulated, and 289, including tumor suppressor genes, were downregulated (<0.5 fold change). Expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPARγ, KRT17, UCHL1, IGFBP7 and SPARC proteins was immunohistochemically verified in human and hamster CC tissues. Additional unsupervised hierarchical clustering analysis of sarcomatoid CC cells compared to three adenocarcinomatous CC cell lines revealed 292 differentially upregulated genes (>4-fold change), and 267 differentially downregulated genes (<0.25 fold change). The expression of 12 proteins was validated in the CC cell lines by immunoblot analysis and immunohistochemical staining. Of the proteins analyzed, we found upregulation of the expression of the epithelial-mesenchymal transition (EMT)-related proteins VIM and TWIST1, and restoration of the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 during sarcomatoid transdifferentiation of CC.
The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis.
The purpose of this study is to provide better understanding as to how the "double" vascular arcades, in contrast to other intestinal marginal vessels, develop along the right margin of the pancreatic head.
Materials and Methods
In human fetuses between 8-30 weeks, we described the topographical anatomy of the vessels, bile duct, duodenum as well as the ventral and dorsal primordia of the pancreatic head with an aid of pancreatic polypeptide immunohisto-chemistry.
The contents of the hepatoduodenal ligament crossed the superior side of the pylorus. Moreover, the right hepatic artery originating from the superior mesenteric artery ran along the superior aspect of the pancreatic head. An arterial arcade, corresponding to the posterior pancreaticoduodenal arteries, encircled the superior part of the pancreatic head, whereas another arcade, corresponding to the anterior pancreaticoduodenal arteries, surrounded the inferior part. The dorsal promordium of the pancreas surrounded and/or mixed the ventral primordium at 13-16 weeks. Thus, both arterial arcades were likely to attach to the dorsal primordium.
The fetal anatomy of the pancreaticoduodenal vascular arcades as well as that of the hepatoduodenal ligament were quite different from adults in topographical relations. Thus, in the stage later than 30 weeks, further rotation of the duodenum along a horizontal axis seemed to be required to move the pylorus posterosuperiorly and to reflect the superior surface of the pancreatic head posteriorly. However, to change the topographical anatomy of the superior and inferior arterial arcades into the final position, re-arrangement of the pancreatic parenchyma might be necessary in the head.
Pancreaticoduodenal arterial arcades; ventral pancreas; pancreatic polypeptide immunohistochemistry; human fetus
Arteriovenous fistula (AVF) involving the inferior mesenteric vessels is rare, and the affected patients usually present with abdominal pain, mass, or features of established portal hypertension. Colonic ischemia is a less common and more serious manifestation of AVF. We report a case of ischemic colitis secondary to inferior mesenteric AVF in a patient who underwent a previous liver transplantation, subsequently developed portal vein stenosis, and then presented with acute lower gastrointestinal bleeding. He underwent percutaneous transhepatic placement of a portal vein stent and left colectomy.
Ischemic colitis; Inferior mesenteric; Arteriovenous fistula; Portal vein stenosis
Reactive lymphoid hyperplasia (RLH) of the liver is a rare entity and has also been termed nodular lymphoid lesion or pseudolymphoma of the liver. We report a case of hepatic RLH exhibiting unusual histiocyte-rich histologic features in a 47-yr-old woman in conjunction with a renal cell carcinoma. A follow-up computed tomography scan was done 14 months after a right radical nephrectomy for renal cell carcinoma revealed a nodular lesion in segment 5 of the liver. The lesion was interpreted as metastatic renal cell carcinoma or hepatocellular carcinoma based on the history of the patient and radiologic findings. Wedge resection of segment 5 was done with sufficient distance from the mass. Microscopically, the lesion was composed predominantly of peculiar histiocytic proliferation and was characterized by lymphoid aggregates forming a lymphoid follicle with germinal centers. The present case and prior cases reported in the literature suggest that RLH of the liver appear to be a heterogenous group of reactive inflammatory lesions that are often associated with autoimmune disease or malignant tumors.
Pseudolymphoma; Liver Neoplasms; Lymphoid Hyperplasia, Reactive
Although reports of hypoplasia or absence of the liver of left lobe are not few, descriptions of the intrahepatic vessels are rare but valuable for discussion of the pathogenesis. The present report demonstrates a case of the left surgical lobe hypoplasia that is characterized by 1) the scar-like lobe with few parenchymal tissue and dilated bile ducts, 2) no Spiegel's lobe with the portal vein stuck to the inferior vena cava, 3) unusual configurations of the right hepatic vein and the 8th segmental portal vein branch, 4) the hepatic groove on S8, and 5) the trifurcation pattern of the portal vein primary division. According to the macroscopic and histological observations, we hypothesized that the secondary abnormal peritoneal fusion occurred in utero and/or during the postnatal growth, and that it involved the left portal vein and other adjacent structures, resulting in severe atrophy of the left surgical lobe.
Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 ± 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy.
Branch Duct Type Intraductal Papillary Mucinous Neoplasm (IPMN); Cyst Size; Mural Nodule; CEA; Malignancy; Invasive Carcinoma