Cost-Effectiveness Analysis of Perioperative Oral Management after Cancer Surgery and an Examination of the Reduction in Medical Costs Thereafter: A Multicenter Study.

In April 2012, perioperative oral management (POM) was approved for inclusion in the national health insurance system of Japan to prevent the occurrence of pneumonia, a major complication in cancer patients. The subsequent decrease in the incidence of postoperative pneumonia indicated the prophylactic effect of POM. The constant increase in health expenditure necessitates a cost-effectiveness analysis. In addition, the effect of reducing healthcare costs owing to health technologies must be evaluated. In the present multi-institutional study, the cost-effectiveness analysis of POM was conducted by comparing the incidence of postoperative pneumonia and the healthcare costs between patients who received surgery for malignant tumors before (n = 11,886) and after (n = 13,668) the introduction of POM. Additionally, the effect of reducing healthcare costs was evaluated. Reductions in the number of patients who developed pneumonia, duration of hospitalization, and number of deaths were observed after the introduction of POM. The incremental cost-effectiveness ratio was 111,927 yen, hence the prevention of postoperative pneumonia needs 111,927 yen per patient in healthcare costs. Consequently, a maximum reduction of 250,368,129 yen in healthcare costs was observed between the incremental costs for pneumonia treatment and the cost of POM. These findings indicate that improvements in cost-effectiveness can be expected in the future through the development of procedure and system for POM.

Alternative transcription start sites of the enolase-encoding gene enoA are stringently used in glycolytic/gluconeogenic conditions in Aspergillus oryzae.

Gene expression using alternative transcription start sites (TSSs) is an important transcriptional regulatory mechanism for environmental responses in eukaryotes. Here, we identify two alternative TSSs in the enolase-encoding gene (enoA) in Aspergillus oryzae, an industrially important filamentous fungus. TSS use in enoA is strictly dependent on the difference in glycolytic and gluconeogenic carbon sources. Transcription from the upstream TSS (uTSS) or downstream TSS (dTSS) predominantly occurs under gluconeogenic or glycolytic conditions, respectively. In addition to enoA, most glycolytic genes involved in reversible reactions possess alternative TSSs. The fbaA gene, which encodes fructose-bisphosphate aldolase, also shows stringent alternative TSS selection, similar to enoA. Alignment of promoter sequences of enolase-encoding genes in Aspergillus predicted two conserved regions that contain a putative cis-element required for enoA transcription from each TSS. However, uTSS-mediated transcription of the acuN gene, an enoA ortholog in Aspergillus nidulans, is not strictly dependent on carbon source, unlike enoA. Furthermore, enoA transcript levels in glycolytic conditions are higher than in gluconeogenic conditions. Conversely, acuN is more highly transcribed in gluconeogenic conditions. This suggests that the stringent usage of alternative TSSs and higher transcription in glycolytic conditions in enoA may reflect that the A. oryzae evolutionary genetic background was domesticated by exclusive growth in starch-rich environments. These findings provide novel insights into the complexity and diversity of transcriptional regulation of glycolytic/gluconeogenic genes among Aspergilli.

Endocytosis of a maltose permease is induced when amylolytic enzyme production is repressed in Aspergillus oryzae.

In the filamentous fungus Aspergillus oryzae, amylolytic enzyme production is induced by the presence of maltose. Previously, we identified a putative maltose permease (MalP) gene in the maltose-utilizing cluster of A. oryzae. malP disruption causes a significant decrease in α-amylase activity and maltose consumption, indicating that MalP is a maltose transporter required for amylolytic enzyme production in A. oryzae. Although the expression of amylase genes and malP is repressed by the presence of glucose, the effect of glucose on the abundance of functional MalP is unknown. In this study, we examined the effect of glucose and other carbon sources on the subcellular localization of green fluorescence protein (GFP)-tagged MalP. After glucose addition, GFP-MalP at the plasma membrane was internalized and delivered to the vacuole. This glucose-induced internalization of GFP-MalP was inhibited by treatment with latrunculin B, an inhibitor of actin polymerization. Furthermore, GFP-MalP internalization was inhibited by repressing the HECT ubiquitin ligase HulA (ortholog of yeast Rsp5). These results suggest that MalP is transported to the vacuole by endocytosis in the presence of glucose. Besides glucose, mannose and 2-deoxyglucose also induced the endocytosis of GFP-MalP and amylolytic enzyme production was inhibited by the addition of these sugars. However, neither the subcellular localization of GFP-MalP nor amylolytic enzyme production was influenced by the addition of xylose or 3-O-methylglucose. These results imply that MalP endocytosis is induced when amylolytic enzyme production is repressed.

Distinct mechanism of activation of two transcription factors, AmyR and MalR, involved in amylolytic enzyme production in Aspergillus oryzae.

The production of amylolytic enzymes in Aspergillus oryzae is induced in the presence of starch or maltose, and two Zn2Cys6-type transcription factors, AmyR and MalR, are involved in this regulation. AmyR directly regulates the expression of amylase genes, and MalR controls the expression of maltose-utilizing (MAL) cluster genes. Deletion of malR gene resulted in poor growth on starch medium and reduction in α-amylase production level. To elucidate the activation mechanisms of these two transcription factors in amylase production, the expression profiles of amylases and MAL cluster genes under carbon catabolite derepression condition and subcellular localization of these transcription factors fused with a green fluorescent protein (GFP) were examined. Glucose, maltose, and isomaltose induced the expression of amylase genes, and GFP-AmyR was translocated from the cytoplasm to nucleus after the addition of these sugars. Rapid induction of amylase gene expression and nuclear localization of GFP-AmyR by isomaltose suggested that this sugar was the strongest inducer for AmyR activation. In contrast, GFP-MalR was constitutively localized in the nucleus and the expression of MAL cluster genes was induced by maltose, but not by glucose or isomaltose. In the presence of maltose, the expression of amylase genes was preceded by MAL cluster gene expression. Furthermore, deletion of the malR gene resulted in a significant decrease in the α-amylase activity induced by maltose, but had apparently no effect on the expression of α-amylase genes in the presence of isomaltose. These results suggested that activation of AmyR and MalR is regulated in a different manner, and the preceding activation of MalR is essential for the utilization of maltose as an inducer for AmyR activation.

Can we predict the prognosis of resectable hepatoblastoma from serum alpha-fetoprotein response during preoperative chemotherapy?

PURPOSE: The objective of this study was to clarify whether the alpha-fetoprotein (AFP) reduction rate during preoperative chemotherapy represents a prognostic factor for hepatoblastoma. METHOD: We divided 14 hepatoblastoma patients who underwent preoperative chemotherapy and curative resection into Group A (no recurrence; n = 10) and Group B (recurrence; n = 4). We then compared AFP levels before and after preoperative chemotherapy between groups. RESULT: Mean AFP level after completing the first cycle of chemotherapy was reduced to 7.28 % (range 1.2-36.8 %) in Group A and 17.05 % (range 12.0-20.5 %) in Group B (p < 0.05). Mean AFP after total preoperative chemotherapy was reduced to 1.42 % (range 0.07-8.5 %) in Group A and 7.55 % (range 3.4-12.4 %) in Group B (p < 0.02). Eight patients in whom AFP levels decreased >1 log after the first cycle of preoperative chemotherapy survived without recurrence. CONCLUSION: A large, early decrease in AFP level during preoperative chemotherapy may offer a strong indicator of survival. Patients in whom AFP levels do not decrease easily during preoperative chemotherapy may have increased risk of recurrence and should be followed very closely.

Primary anastomosis for meconium peritonitis: first choice of treatment.

PURPOSE: Newborn surgery for meconium peritonitis (MP) is sometimes very difficult owing to severe adhesions and bleeding. The aim of this study was to reveal the benefit of primary anastomosis (PA) for MP by comparing PA with multistep operations (MO). PATIENTS AND METHODS: We retrospectively reviewed 38 patients with MP who underwent surgery in our institution from 1983 to 2009. From 1983 to 2000, we essentially used MO. After 2001, we used PA with the exception of 1 patient. We performed MO on 20 patients (group A) and PA on 18 patients (group B). RESULTS: Mortality was 4 in 20 in group A and 1 in 18 in group B. Three patients in group A and 2 in group B required reoperation because of complications. After 2001, 14 of 16 patients underwent PA. Of the 2 patients for whom PA could not be performed, one was postresuscitation from cardiopulmonary arrest and the other was an extremely low-birth-weight infant. The only mortality among the patients who underwent PA occurred in a very low-birth-weight infant who died from intraoperative hepatic hemorrhage. CONCLUSION: PA can be performed for almost all patients with MP except for extremely low-birth-weight infants.

Esophagogastric separation and abdominal esophagostomy via jejunal interposition: a new operation for extreme forms of pathologic aerophagia.

Pathologic aerophagia is sometimes seen in patients with neurologic disorders. It rarely causes massive bowel distention, ileus, and volvulus. Here, we report the use of esophagogastric separation and abdominal esophagostomy via jejunal interposition to prevent bowel distention caused by severe aerophagia in 2 patients with neurologic disorders in whom the usual nonoperative methods of management failed. In both cases, swallowed air was evacuated via the jejunostomy, eliminating bowel distention. This operation may be useful in patients with neurologic disorders associated with severe aerophagia.

Ovarian fibroma with marked ascites and elevated serum levels of CA-125 in a young girl.

We report a case of ovarian fibroma with marked ascites and elevated serum CA-125 levels in a young girl. Ovarian fibromas are rare in children. They usually present as a solid mass and may be associated with ascites and elevated serum CA-125 levels. Because of their solid nature and these associations, they can be mistaken for a malignant tumor, resulting in unnecessary oophorectomy. Ovarian fibromas are benign neoplasms, and the prognosis is extremely good. Surgical management should be an ovarian-sparing tumor excision. Although uncommon in pediatric patients, ovarian fibromas should be included in the differential diagnosis of ovarian mass in children.

Laryngotracheal separation using skin flap formation: a novel surgical procedure.

Laryngotracheal separation is often performed to prevent intractable aspiration for children with severe mental and physical disabilities. However, tracheo-innominate artery fistula after surgery can occur as a severe complication and cause fatal hemorrhage. We have therefore developed a novel procedure to prevent tracheo-innominate artery fistula. Surgery was performed by making an H-shaped incision and creating skin flaps. The trachea was not raised anteriorly and the skin flaps were sutured to the trachea. We performed this procedure on nine patients, and no major complications occurred in any case. This procedure can be expected to reduce the occurrence of tracheo-innominate artery fistula.

Recurrent pancreatitis caused by pancreatobiliary anomalies in children with annular pancreas.

PURPOSE: Annular pancreas (AP) is usually associated with duodenal obstruction in neonates. Pancreatitis with AP occurs frequently in adults but is rare in children. This article describes pancreatitis in children with AP and pancreatobiliary anomalies and its surgical treatment. PATIENTS AND METHODS: Six children who underwent duodenal bypass for AP subsequently developed recurrent pancreatitis. Three had trisomy 21. Duodenoduodenostomy had been performed in 5 patients and gastrojejunostomy in 1 patient for neonatal duodenal obstruction. We reviewed overall management, imaging, and surgical treatment in these children. RESULTS: All children subsequently complained of recurrent abdominal pain. Pancreatitis developed in 6 children, and magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed associated pancreatobiliary anomalies such as pancreas divisum, pancreatobiliary malunion, choledochocele, and intraluminal duodenal diverticulum. In 5 cases, surgery for recurrent or chronic pancreatitis was performed. The range of follow-up was 11 to 54 months, and all children who underwent surgery had excellent results. CONCLUSIONS: Children with AP occasionally require reoperation for recurrent pancreatitis because of associate pancreatobiliary anomalies. Magnetic resonance cholangiopancreatography and ERCP provide excellent images of pancreatobiliary anomalies. Intraoperative cholangiopancreatography is also essential for accurate depiction of the ductal structure and selection of the appropriate surgical procedure.

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.

Results for 79 patients with neuroblastoma detected through mass screening at 6 months of age in a single institute.

BACKGROUND: In Japan, mass screening for neuroblastoma has been performed at 6 months of age to improve the prognosis of this condition for more than 20 years. In recent years, most neuroblastomas detected by mass screening were considered to have favorable biological features and sometimes tend to regress spontaneously. METHODS: The authors established non-treated observation criteria in 1997 and criteria for observation of residual tumor after first-line chemotherapy in 1999, and have made an effort to reduce the intensity of medical treatment for neuroblastoma. The authors examined outcomes of 79 patients who were found in the Shizuoka neuroblastoma mass screening at 6 months of age and who received medical treatment or underwent observation in Shizuoka Children's Hospital, Shizuoka, Japan, between December 1981 and December 2004. RESULTS: A total of 77 patients survived but the remaining two patients died from complications of medical treatment. None of the patients died due to progression of neuroblastoma. In the cases, non-treated observation was performed in 17. Of those, 12 patients are now under non-treated observation. Of their tumors, two have disappeared, nine have become smaller and another one has not change in size. Observation of residual tumor after first-line chemotherapy was performed in 15 cases, and three disappeared and the other 12 cases became smaller. Medical treatment-related complications were observed in 20 of 67 patients who received medical treatment, and 18 of the 20 patients were seen before establishing non-treated observation criteria. CONCLUSION: Non-treated observation and observation of residual tumor after first-line chemotherapy were useful to reduce medical treatment-related complications.

Laparoscopic splenopexy for wandering spleen: extraperitoneal pocket splenopexy.

Wandering spleen is a very rare disease. It is a very dangerous condition due to the risk of splenic ischemia from persistent pedicle torsion. Here, we describe a case of wandering spleen diagnosed by ultrasound and computed tomography scans in an 11-year-old boy who suffered from frequent urination and enuresis. A laparoscopic splenopexy was successfully performed with fixation of the spleen in an extraperitoneal pocket. Since the operation, the organ has remained in place with good perfusion. The details of the procedure are described.

Spontaneous regression of metastases including meningeal metastasis after gross resection of primary tumor in an infant with stage 4 neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in childhood. Spontaneous regression has been well described in infants, especially in those with stage 4S and those with low-stage neuroblastoma detected by screening. However, neuroblastoma presenting with intracranial metastasis is generally considered to need a postoperative chemotherapy. Here, we report a 3-month-old girl with stage 4 neuroblastoma presenting with spontaneous regression of metastatic tumor including meningeal metastasis after gross resection of primary tumor. Further investigation may be required to detect patients of this kind without the need of postoperative chemotherapy regardless of their stage at diagnosis.

Thymidine phosphorylase expression and efficacy of adjuvant doxifluridine in advanced colorectal cancer patients.

To clarify the correlation between the expression level of thymidine phosphorylase (TP) and efficacy of doxifluridine (5'-DFUR) and 5-fluorouracil (5-FU), samples from 177 colorectal cancer patients who underwent curative resection were evaluated by immunohistochemical staining using a newly developed monoclonal antibody 1C6-203. Patients were randomly given either oral 5'-DFUR or 5-FU as postoperative adjuvant chemotherapy. In Dukes' C staged colon cancer patients treated with 5'-DFUR, better survival was observed in the high TP patients than the low TP patients (P=0.025 by the log-rank test). The observed 5-year survival rates were 91.2 and 74.8%, respectively. No correlation between TP expression and patient prognosis was detected in the 5-FU group. In Dukes' C stage colon patients with high TP expression, the 5'-DFUR group had slightly better survival than the 5-FU group. These findings suggest that TP may be a chemosensitive marker for 5'-DFUR as postoperative adjuvant chemotherapy for advanced colon cancer patients.

Epidermolysis bullosa simplex associated with pyloric atresia is a novel clinical subtype caused by mutations in the plectin gene (PLEC1).

Epidermolysis bullosa (EB) is an inherited mechano-bullous disorder of the skin, and is divided into three major categories: EB simplex (EBS), dystrophic EB, and junctional EB (JEB). Mutations in the plectin gene (PLEC1) cause EBS associated with muscular dystrophy, whereas JEB associated with pyloric atresia (PA) results from mutations in the alpha6 and beta4 integrin genes. In this study, we examined three EB patients associated with PA from two distinct families. Electron microscopy detected blister formation within the basal keratinocytes leading to the diagnosis of EBS. Surprisingly, immunohistochemical studies using monoclonal antibodies to a range of basement membrane proteins showed that the expression of plectin was absent or markedly attenuated. Sequence analysis demonstrated four novel PLEC1 mutations. One proband was a compound heterozygote for a nonsense mutation of Q305X and a splice-site mutation of 1344G-->A. An exon-trapping experiment suggested that the splice-site mutation induced aberrant splicing of the gene. The second proband harbored a heterozygous maternal nonsense mutation, Q2538X and homozygous nonsense mutations R1189X. Analysis of the intragenic polymorphisms of PLEC1 suggested that R1189X mutations were due to paternal segmental uniparental isodisomy. These results indicate that PLEC1 is a possible causative gene in this clinical subtype, EBS associated with PA. Furthermore, two patients out of our three cases died in infancy. In terms of clinical prognosis, this novel subtype is the lethal variant in the EBS category.

Toldt's fascia flap: a new technique for repairing large diaphragmatic hernias.

The most popular techniques for repairing large diaphragmatic defects involve the use of synthetic patches. We present an alternative approach using living tissue. We reviewed our cases of congenital diaphragmatic hernia (CDH) diagnosed within the first 24 h of life from 1991 to 2003. Toldt's fascia (TF) flap was used to repair defects that were too large to repair primarily even though the anterior rim of the diaphragm was present. After confirming that a small medial muscle remnant of the diaphragm was present, its mesothelial covering was incised, and the incision was extended to the TF far enough to create a flap sufficiently large to repair the defect. The TF flap, consisting of the small medial muscle remnant, TF, peritoneum, and retroperitoneal connective tissue, was mobilized carefully from the ipsilateral kidney and adrenal gland, and the repair completed with interrupted sutures using nonabsorbable material. We used this TF flap approach in seven of 43 patients with CDH. Two had right-sided CDH. Six survived. The mean size of the diaphragmatic defects in the seven TF flap cases was 5.43+/-0.53 x 3.86+/-1.07 cm, which was significantly larger than the defects in direct primary repair cases (3.40+/-0.77 x 2.03+/-0.59 cm) (p<0.01). The six survivors had good outcomes, and none of them have had recurrence of herniation or required any additional surgical intervention (mean follow-up period: 4.7 years). To the best of our knowledge, this is the first report of TF being used to repair large diaphragmatic hernias. Our technique is simple and has proven to be reliable for durable restoration of the diaphragm, suggesting that it could reduce the dependence on synthetic patch repair, which is associated with certain long-term complications.

Neuroblastoma detected by mass screening: the Tumor Board's role in its treatment.

Japan has a nationwide mass-screening program for neuroblastoma in 6-month-old infants. Neuroblastoma can regress spontaneously, and some institutions observe selected cases. We evaluated the management of screened neuroblastoma at our hospital since 1997 when an observation program was introduced. Criteria for the observation program were stage-I, stage-II, or stage-IVs tumors, urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels <40 microg/mg creatinine, tumor <5 cm in diameter, no invasion to the intraspinal canal or great vessels, and parental consent to participate. Patients who did not meet observation criteria underwent surgery or mild chemotherapy according to the location of the tumor. If patients met observation criteria after chemotherapy, surgical intervention was no longer performed. Thirty-six patients attended our hospital for screened neuroblastoma from 1997 to 2002. Thirty-three patients who were managed at our hospital participated in this study. Ten subjects met observation criteria. Tumors regressed in 7 patients (mean follow-up period 36.3 months) with corresponding decreases in VMA and HVA levels (group A). Three underwent surgery (group B) because of increasing VMA and HVA levels, increase in tumor size, or guardian's request. Twenty-three subjects did not meet observation criteria. Four patients underwent primary surgery (group C), and 19 patients had chemotherapy initially. Fourteen patients met observation criteria after chemotherapy and two are still having chemotherapy (group D). Three patients required surgery due to insufficient regression of their tumors (group E). Fourteen subjects in group D had marked decreases in VMA and HVA levels and tumor size (mean follow-up period 29.1 months), and tumors were not detected using imaging techniques in 8 patients. Histological examination of all resected specimens during the study period showed favorable histology and no N-myc amplification. There was no evidence of unfavorable prognosis in any of the 33 subjects, although 1 patient who underwent primary surgery had a vanishing kidney 1 year later and 1 patient had multiple bony metastases after complete resection of tumor, which was treated by chemotherapy. Until the real significance of mass screening for neuroblastoma as a public health measure is confirmed, observation with careful follow-up should be adopted more extensively because it has a favorable outcome in many cases, and is associated with minimal therapeutic complications.

Congenital diaphragmatic hernia: efficacy of ultrasound examination in its management.

To date, uniform standards for congenital diaphragmatic hernia (CDH) management have not existed. The purpose of this study was to evaluate the evolving clinical outcome of the patients with CDH and to present our recent management protocol using echocardiography. Sixty patients treated for CDH at our hospital from 1978 through 2001 were reviewed. Periods of treatments were divided arbitrarily into three periods;1978-1991 (period I, n=26), 1992-1994 (period II, n=6), 1995-2001 (period III, n=28). Immediate repair was performed during period I. We performed preoperative stabilization and delayed repair since the start of period II, and nitric oxide (NO) was introduced in period III. In period III, our management strategy was the use of fentanyl for sedation and analgesia; vasoactive agents such as dopamine, dobutamine, and prostaglandin E1 in selected cases; the use of high-frequency oscillating ventilation (HFOV), inhaled NO; and venovenous extracorporeal membrane oxygenation (ECMO) if indicated. The details of stabilization management and the timing of surgery were determined using echocardiography to evaluate pulmonary hypertension (PH) by measuring dimension and shunt patterns through the ductus arteriosus (DA), right pulmonary artery (rPA) and left pulmonary artery (lPA). Overall, 42 of 60 patients survived (70%). The number of patients surviving in each period was 14 of 26 (54%) in period I, 4 of 6 (67%) in period II, and 24 of 28 (86%) in period III. Seventeen of 28 patients in period III required inhaled NO (group A). Of these 17 patients, 5 required ECMO; of these 5, 3 were long-term survivors. The remaining 11 patients from period III who were managed without NO (group B) survived. In left-sided CDH cases, the dimension of DA at admission in group A (5.07+/-1.79 mm) was significantly larger than in group B (2.99+/-1.68 mm) (P<0.01). The dimension of rPA in group A (3.37+/-0.80 mm) was significantly smaller as compared with group B (4.28+/-0.72 mm) (P<0.01). Although the dimension of lPA was not significantly different between group A (3.03+/-0.74 mm) and group B (3.46+/-0.48 mm), lPA blood flow was noticeably stronger in group B. DA shunt patterns were bi-directional (53%), right-to-left (40%) and left-to-right (7%) in group A, whereas no patients in group B showed a right-to-left shunt pattern. After confirmation of closure of DA or dominant left-to-right shunt, and marked increase of pulmonary arterial blood flow, patients in both group A and B underwent surgery successfully. In four non-survivors, findings of improving PH were not observed. We conclude that echocardiographic examination is useful to manage persistent pulmonary hypertension with recent treatment modalities including NO and HFOV and to determine the proper timing of surgery, which contributes to an improved outcome of CDH.