Masahiko Sugiyama

An animal model study for tissue-engineered trachea fabricated from a biodegradable scaffold using chondrocytes to augment repair of tracheal stenosis

INTRODUCTION We have designed an engineered graft fabricated from a biodegradable scaffold using chondrocytes and applied this construct to augment repair of tracheal stenosis. This study investigated the feasibility of using such tissue-engineered airways with autologous chondrocytes in a rabbit model. MATERIAL AND METHODS Chondrocytes were isolated and expanded from the auricular cartilage of New Zealand white rabbits, then seeded onto composite 3-layer scaffolds consisting of a collagen sheet, a polyglycolic acid mesh, and a copolymer (l-lactide/epsilon-caprolactone) coarse mesh. The engineered grafts were implanted into a 0.5 x 0.8-cm defect created in the midventral portion of the cervical trachea. Gelatin sponges that slowly released basic fibroblast growth factor (b-FGF) were then placed on the constructs, which were retrieved 1 or 3 months after implantation. RESULTS The biodegradable scaffold seeded with chondrocytes could maintain airway structure up to 3 months after implantation. Tracheal epithelial regeneration occurred in the internal lumen of this composite scaffold. Three months after implantation, staining of the sections showed cartilage accumulation in the engineered tracheal wall. CONCLUSION This composite biodegradable scaffold may be useful for developing engineered trachea. A gelatin sponge slowly releasing b-FGF might enhance chondrogenesis.

Combination therapy with Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides dramatically improved the intestinal function in a girl with short bowel syndrome: a novel synbiotics therapy for intestinal failure.

It has been well known since ancient times that fermented milk produces beneficial effects on the consumer’s health. In the last few decades, these beneficial effects have been demonstrated to be due to the metabolic action of some bacterial species, including lactobaccilli, bifidobacteria, and streptococci (1–3). Lilly et al. first introduced the term probiotics for such bacteria in 1965 (4). Probiotics are widely used as a live microbial feed supplement that beneficially affects the host animals by improving their intestinal microbial balance (5). Additionally the term prebiotics has been adopted to refer to a nondigestive food ingredient that selectively targets the growth and/or activity of one or a limited number of bacteria in the colon and, thus, has the potential to improve host health. Several types of ingredients, such as fructooligosaccharides, galactooligosaccharides, and inulin, are used as prebiotics (2, 6). Furthermore, the combined use of probiotics and prebiotics is called synbiotics therapy, but few reports concerning synbiotics have been published (7, 8). Short bowel syndrome refers to seriously adverse symptoms that are seen in patients who have been subjected to a massive bowel resection. These patients are usually malnourished and have a dilated intestine that results in intestinal bacterial overgrowth syndrome (9, 10). Regulation of intestinal bacterial overgrowth, especially pathogenic bacterial overgrowth, is very important in patients with short bowel syndrome to attain any improvement in intestinal function. For this purpose, various antibiotics have been used to eliminate the intestinal bacteria selectively. An alternative strategy for regulating intestinal bacteria is to apply probiotics and/or prebiotics. In this report, we report the use of synbiotics therapy in the treatment of a 4-year-old girl suffering from short bowel syndrome. For the synbiotics therapy, we used Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides. This novel combination therapy was expected to act synergistically for the improvement of the subject’s health. We found that the patient’s intestinal absorptive function and motility were dramatically improved by this newly designed synbiotics therapy, and she progressed satisfactorily after 2 years of the therapy. Following the case report, we discuss the beneficial effects of the new synbiotics therapy for intestinal failure.

Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study

BACKGROUND In Japan, a nationwide programme between 1984 and 2003 screened all infants for urinary catecholamine metabolites as a marker for neuroblastoma. Before 1989, this was done by qualitative spot tests for vanillylmandelic acid in urine, and subsequently by quantitative assay with high-performance liquid chromatography (HPLC). However, the Japanese government stopped the mass-screening programme in 2003, after reports that it did not reduce mortality due to neuroblastoma. We aimed to assess the effectiveness of the programme, by comparing the rates of incidence and mortality from neuroblastomas diagnosed before 6 years of age in three cohorts. METHODS We did a retrospective population-based cohort study on all children born between 1980 and 1998, except for a 2-year period from 1984. We divided these 22,289,695 children into three cohorts: children born before screening in 1980-83 (n=6,130,423); those born during qualitative screening in 1986-89 (n=5,290,412); and those born during quantitative screening 1990-98 (n=10,868,860). We used databases from hospitals, screening centres, and national cancer registries. Cases of neuroblastoma were followed up for a mean of 78.7 months. FINDINGS 21.56 cases of neuroblastoma per 100,000 births over 72 months were identified in the qualitatively screened group (relative risk [RR] 1.87, 95% CI 1.66-2.10), and 29.80 cases per 100,000 births over 72 months in the quantitatively screened group (RR 2.58, 2.33-2.86). The cumulative incidence of neuroblastoma in the prescreening cohort (11.56 cases per 100,000 births over 72 months) was lower than that in other cohorts (p<0.0001 for all comparisons), but more neuroblastomas were diagnosed after 24 months of age in this cohort (p=0.0002 for qualitative screening vs prescreening, p<0.0001 for quantitative screening vs prescreening). Cumulative mortality was lower in the qualitative screening (3.90 cases per 100,000 livebirths over 72 months) and quantitative screening cohorts (2.83 cases) than in the prescreening cohort (5.38 cases). Compared with the prescreening cohort, the relative risk of mortality was 0.73 (95% CI 0.58-0.90) for qualitative screening, and 0.53 (0.42-0.63) for quantitative screening. Mortality rates for both the qualitative and quantitative screening groups were lower than were those for the prescreening cohort (p=0.0041 for prescreening vs qualitative screening, p<0.0001 for prescreening vs quantitative screening). INTERPRETATION More infantile neuroblastomas were recorded in children who were screened for neuroblastoma at 6 months of age than in those who were not. The mortality rate from neuroblastoma in children who were screened at 6 months was lower than that in the prescreening cohort, especially in children screened by quantitative HPLC. Any new screening programme should aim to decrease mortality, but also to minimise overdiagnosis of tumours with favourable prognoses (eg, by screening children at 18 months).

Lymph node metastasis from cancer of the esophagogastric junction, and determination of the appropriate nodal dissection

PurposeBoth squamous cell carcinomas and adenocarcinomas can develop in the esophagogastric junction. To clarify the appropriate lymph node dissection range, lymph node metastases from cancers in the esophagogastric junction were investigated.MethodsThe nodal metastases were analyzed in 64 patients with squamous cell carcinoma and 129 with adenocarcinoma according to Siewert’s classification, which is based on topographic anatomical criteria for adenocarcinoma.ResultsThe squamous cell carcinomas located above the esophagocardial junction had more frequent metastasis to the lower and middle mediastinal lymph nodes in proportion to the depth of the tumor. Nodal metastasis was also often detected in the abdominal lymph nodes. In contrast, adenocarcinomas metastasized less frequently to the mediastinal lymph nodes, and the metastatic rates in the abdominal nodes were higher than those from squamous cell carcinoma.ConclusionEsophagectomy with mediastinal and abdominal lymph node dissection is considered to be an appropriate approach for surgical resection of squamous cell carcinomas, whereas transhiatally extended gastrectomy with lower mediastinal and abdominal lymph node dissection is recommended for the treatment of adenocarcinomas.

Impact of perioperative peripheral blood values on postoperative complications after esophageal surgery

PurposePrediction of the postoperative course of esophagectomy is an important part of the strict perioperative management of patients undergoing surgery for esophageal cancer.MethodsTo evaluate their clinical importance, peripheral blood values, including white blood cell count (WBC), lymphocyte count, and the levels of total protein, transferrin, factor XIII, D-dimer, fibrin, and fibrinogen degradation products (FDP) were measured before and after esophagectomy for esophageal cancer in 24 patients.ResultsThe preoperative WBC and the pre- and postoperative lymphocyte count were decreased remarkably in patients who received preoperative chemoradiotherapy. The values of perioperative serum transferrin were significantly lower in patients with postoperative pneumonia than in those without. The activity of plasma factor XIII was suppressed on postoperative day (POD) 7 in patients with pneumonia and on POD 14 in patients with leakage.ConclusionsThese results suggest that patients who receive preoperative chemoradiotherapy are potentially immunosuppressed, the preoperative serum transferrin level is a possible predictive marker of postoperative pneumonia, and suppression of factor XIII activity is related to anastomotic insufficiency.

Repair using the pectoralis major muscle flap for anastomotic leakage after esophageal reconstruction via the subcutaneous route

BACKGROUND Anastomotic leakage with an intractable cutaneous fistula frequently develops after an esophagectomy and reconstruction via the subcutaneous route. METHODS A pectoralis major muscle (PMM) flap was used for the treatment of 6 patients with esophageal cancer who developed anastomotic leakage with fistula after reconstruction via the subcutaneous route. A gastric tube and colon had been used for reconstruction in 2 and 4 patients, respectively. A trimming and repair of the leakage site was initially performed and the anastomotic site was then covered with a muscle flap. RESULTS Recurrent anastomotic leakage did not develop in 5 patients. Among these patients, oral intake was initiated from 11-15 days after the repair operation in 4 patients. A patient having recurrent anastomotic leakage after a repair operation recovered well with conservative therapy. CONCLUSION The coverage with a PMM flap over the repair site is a simple method for preventing the development of recurrent leakage after a repair operation. Even when recurrent anastomotic leakage has occurred after this operation, healing is normally expected by means of conservative treatment. We, therefore, recommend this method for the repair of intractable anastomotic leakage after reconstruction via the subcutaneous route for esophageal cancer.

A Female Infant Who Had both Complete VACTERL Association and MURCS Association : Report of a Case

A 41-day-old female infant with VACTERL association was transferred to the pediatric intensive care unit of our hospital. She had been delivered at 36 weeks gestation by spontaneous vaginal delivery and weighed 2340 g. Esophageal atresia type A with long gap, anal atresia, cardiac anomaly (atrial septal defect and patent ductus arteriosus), thoracic vertebral dysplasia, left renal agenesis, and minor anomalies (left-side facial nerve palsy, left-side difficulty in hearing, and the absence of the right thenar) had been diagnosed by various examinations. She was transferred to our hospital to receive treatment for heart failure due to a cardiac anomaly. We recognized vaginal atresia during a radical operation for anal atresia (rectovestibular fistula) at 8 months of age. Furthermore, magnetic resonance imaging (MRI) revealed agenesis of the uterus. MURCS association includes Mullerian duct aplasia or hypoplasia, renal aplasia, and cervicothoracic somite dysplasia. This is the first case of complete VACTERL association combined with MURCS association.

Safe laparoscopic resection of a gastric gastrointestinal stromal tumor close to the esophagogastric junction

Laparoscopic gastrectomy is commonly performed for gastrointestinal stromal tumors (GISTs). Partial gastrectomy is usually achieved with a wedge resection to preserve gastric function; however, performing a wedge resection to excise a large tumor located close to the esophagogastric junction (EGJ) can result in deformation of the stomach and/or the stenosis of the EGJ if the gastric wall resection is excessive. We describe our procedure, in which the whole layer of the gastric wall was cut, maintaining a sufficient margin and confirming the distance between the tumor and the EGJ, by endoscopy and laparoscopy. The defect in the gastric wall was closed using linear staplers by hanging up the stay sutures. Five patients with GIST close to EGJ underwent this procedure, followed by a good postoperative course. Thus, we consider our procedure to be safe and effective for gastric GISTs close to the EGJ.

Long-Term Survival of a Baby with Body Stalk Anomaly: Report of a Case

Body stalk anomaly is characterized by severe scoliosis, severe pulmonary hypoplasia, and giant omphalocele. The prognosis of the disease is poor and most obstetricians consider it fatal. Very few patients with body stalk anomaly survive. We report the case of a baby diagnosed with body stalk anomaly in fetal life, who was saved by intensive care after birth. We closed the giant omphalocele successfully by placing karaya gum sheets over it, which created a humidified environment and promoted natural skin epithelization over the skin defect.

Laparoscopic Fundoplication for Gastroesophageal Reflux Disease in Infants and Children

The number and types of minimally invasive surgical procedures being performed in children have increased exponentially in the last 15 years. Laparoscopic fundoplication is commonly performed for gastroesophageal reflux disease (GERD), although the population of patients who undergo this procedure is different in adults and children. In Japan, laparoscopic fundoplication has become a standard procedure, even for children with neurological impairment; however, its indications remain controversial. In this article we review the status of laparoscopic antireflux surgery for infants and children, looking at its indications, the procedures available, the complications, and the training required to perform the procedure safely and effectively.