Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. METHODS: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. RESULTS: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (chi 2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 ( P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA. CONCLUSIONS: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. CLINICAL RELEVANCE: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.     

Paraparesis associated with ruptured anterior cerebral artery territory aneurysms

BACKGROUND: Paraparesis is a rare but characteristic manifestation of ruptured anterior communicating artery or anterior cerebral artery (ACA) aneurysms, but the pathogenesis remains unclear. This study investigated the neuroimaging and clinical features of patients with such paraparesis to evaluate possible causes. METHODS: Nine of 178 patients with ruptured anterior communicating artery or ACA aneurysms presented with paraparesis among 462 patients with subarachnoid hemorrhage (SAH) admitted between May 1996 and November 2001. Diffusion-weighted magnetic resonance (MR) imaging was performed within 48 hours of the onset of SAH in 4 of these 9 patients. The clinical course and neuroimaging studies of these 4 patients were retrospectively reviewed. RESULTS: Diffusion-weighted MR imaging revealed -intensity areas in the medial aspects of the bilateral frontal lobes, which were supplied by the ACAs and distal to the aneurysms, in all 4 patients. These high-intensity lesions had normal to subnormal values of apparent diffusion coefficient (ADC). Most of the high-intensity lesions recovered and did not result in the final lesions regardless of the ADC values, but some lesions with subnormal ADC values resulted in cerebral infarction. Paraparesis was transient and almost completely resolved in 3 patients. CONCLUSIONS: Diffusion-weighted MR imaging detected primary brain damage in the ACA territories caused by acute SAH, which was compatible with the clinical paraparesis. Primary brain damage caused by SAH may include 3 types of lesions: reversible with normal ADC value, reversible with subnormal ADC value, and irreversible with subnormal ADC value.     

Transjugular intrahepatic portosystemic shunt in a patient with cavernomatous portal vein occlusion

A 23-year-old woman with liver cirrhosis secondary to primary sclerosing cholangitis was referred to us for the treatment of recurrent bleeding from esophageal varices that had been refractory to endoscopic sclerotherapy. Her portal vein was occluded, associated with cavernous transformation. A transjugular intrahepatic portosystemic shunt (TIPS) was performed after a preprocedural three-dimensional computed tomographic angiography evaluation to determine feasibility. The portal vein system was recanalized and portal blood flow increased markedly after TIPS. Esophageal varices disappeared 3 weeks after TIPS. Re-bleeding and hepatic encephalopathy were absent for 3 years after the procedure. We conclude that with adequate preprocedural evaluation, TIPS can be performed safely even in patients with portal vein occlusion associated with cavernous transformation.     

Postoperative management using intensive patient-controlled epidural analgesia and early rehabilitation after an esophagectomy

Purpose  Patient-controlled epidural analgesia (PCEA) was developed for use after surgery for thoracic esophageal cancer to relieve wound pain, introduce early rehabilitation, and provide an uneventful postoperative recovery. Methods  This retrospective study investigated 22 patients who underwent esophageal surgery to determine the efficacy of postoperative management with PCEA. In the PCEA group (n = 12), patients had two epidural catheters inserted to cover both the thoracic and abdominal incision with a patient-controlled bolus capability. Results  Postoperative mechanical ventilation was administered in all cases in the control group (n = 10). On the other hand, this was only necessary in two patients in the PCEA group. The amount of time the patients stayed in the intensive care unit and the hospital was significantly shorter in the PCEA group than in the control group (P < 0.001 and P < 0.01, respectively). Respiratory complications occurred in four patients in the control group, and none in the PCEA group. The mean number of supplemental analgesics administered for breakthrough pain until the 7th postoperative day was 5.5 in the control group, and 1.3 in the PCEA group (P < 0.001). Conclusions  Early rehabilitation is facilitated with intensive PCEA, while it also improves postoperative management and reduces hospitalization after esophageal surgery.     

Prevalence of Synchronous Colorectal Neoplasms Detected by Colonoscopy in Patients with Gastric Cancer

Purpose Our purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC). Methods The study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC. Results We studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC. Conclusions The possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.     

Intraoperative radiotherapy for oncological and function-preserving surgery in patients with advanced lower rectal cancer

Backgrounds Pelvic autonomic nerve preservation (PANP) with lateral lymph node dissection (LLND) has been introduced in rectal cancer surgery in Japan; however, its indication has not been standardized yet. Materials and methods Forty-four patients with advanced lower rectal cancer were randomized to either the standard treatment group (control group) or the intraoperative radiotherapy (IORT) group. All patients underwent potentially curative resection of the rectum with total mesorectal excision. The control group underwent bilateral LLND and limited PANP. The IORT group underwent bilateral LLND, complete PANP, and IORT. Patients allocated to the IORT group received IORT to the bilateral preserved pelvic nerve plexuses. Patients’ clinicopathologic parameters, postoperative complications, voiding function, and prognosis were compared between the two groups. Results Among 44 patients enrolled, three patients were excluded from the analysis, resulting in 19 patients in the IORT group and 22 patients in the control group. Patients’ demographic and pathological parameters and postoperative complications were well balanced between the two groups. Oncological outcomes including overall and disease-free survival were also similar. Local recurrence was observed in one patient in each group. Among the 34 patients not complicated with intrapelvic abscess, the mean duration of urinary catheter indwelling was 8 days in the IORT group and 13 days in the control group (p = 0.055). In the long term, medication for urination was necessitated in four patients in the control group, whereas in none in the IORT group (p = 0.059). Discussions Oncological outcomes in the IORT group are equal to those in the control group, and voiding functions in the IORT group are superior to those in the control group. These results suggest that IORT may be useful to expand the indication of complete PANP with LLND for advanced lower rectal cancer.     

Inspection of Safety and Accuracy of D2 Lymph Node Dissection in Laparoscopy-Assisted Distal Gastrectomy

Background  There is a consensus on the indication of laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer that needs D1 + α or D1 + β lymph node dissection. However, many gastrointestinal surgeons consider D2 lymph node dissection in LADG to be difficult, therefore, only a few medical institutions have performed D2 lymph node dissection in LADG. We examined the safety and accuracy of D2 dissection in LADG by comparing with open distal gastrectomy (ODG), as the first step to operate on advanced gastric cancer. Methods  The study population comprised 53 and 67 patients who underwent D2 dissection in LADG or ODG, respectively; with the diagnosis of preoperative depth grade SM, between 2004 and 2006. In D2 lymph node dissection, difficult points are dissections of lymph node along the superior mesenteric vein (No. 14v), along the hepatic artery (No. 12a), and along the proximal splenic artery (No. 11p). We performed these lymph nodes dissection in a fixed process, which was achieved through all improvements. Results  No significant difference was observed in age, sex, American Society of Anesthesiology (ASA) classification, body mass index (BMI), and operative time between two groups. Bleeding volume was significantly lower in LADG (96.5 ± 126.3 ml) than in ODG (221.9 ± 174.8 ml). There was no significant difference in number of dissected lymph nodes between ODG (44.8 ± 15.6) and LADG (49.2 ± 16.1), with no significant difference in degree of pathological stage. The postoperative complication rate was 16.4% for ODG and 5.7% for LADG, and postoperative hospital stay was significantly shorter for LADG (16.7 ± 5.6 days) than for ODG (21 ± 11.4 days). Conclusions  D2 dissection in LADG can be performed without problems with safety and accuracy, if the surgical team is skilled in the procedures of LADG.     

Treatment of lower limb deformities and limb-length discrepancies with the external fixator in Ollier's disease

Background In this study, we addressed two questions on the treatment for Ollier's disease: (1) how much callus formation occurs when an osteotomy is performed intralesionally and (2) how is the stability of the wires and half-pins that are inserted intralesionally. Methods Four children with Ollier's disease underwent treatment of 12 lower limb segments using distraction osteogenesis until completion of their growth. All osteotomies were performed at the centers of the deformities, resulting in a total of seven osteotomies performed intralesionally. Results Full correction of the deformity and full restoration of length were achieved in all cases, but a residual limb-length discrepancy of <10 mm remained. The mean external fixation index in the intralesional distraction osteogenesis group was 39.7 days/cm versus 30.8 days/cm in the extralesional distraction osteogenesis group. Conversion from abnormal cartilage to normal regenerate bone was seen in only one segment. Although approximately two-thirds of the wires and half-pins were inserted intralesionally, in all but one case (in which an iatrogenic fracture occurred) the wires and half-pins were well stabilized throughout the external fixation period. Conclusions Although deformity and limb-length discrepancies due to Ollier's disease were successfully resolved by distraction osteogenesis, enchondroma may arise in distracted calluses when osteotomized intralesionally. However, the stability of the external fixator was sufficient to lengthen limbs and correct deformities even when wires and half-pins were inserted intralesionally.     

Comparison of maxillary stability after Le Fort I osteotomy for occlusal cant correction surgery and maxillary advanced surgery.

OBJECTIVE: To compare postoperative maxillary stability following Le Fort I osteotomy for the correction of occlusal cant as compared with conventional Le Fort I osteotomy for maxillary advancement. STUDY DESIGN: The subjects were 40 Japanese adults with jaw deformities. Of these, 20 underwent a Le Fort I osteotomy and intraoral vertical ramus osteotomy (IVRO) to correct asymmetric skeletal morphology and inclined occlusal cant. The other 20 patients underwent a Le Fort I osteotomy and sagittal split ramus osteotomy (SSRO) to advance the maxilla. Lateral and posteroanterior cephalograms were taken postoperatively and assessed statistically. Thereafter, the 2 groups were followed for time-course changes. RESULTS: There was no significant difference between the 2 groups with regard to time-course changes during the immediate postoperative period. CONCLUSION: This suggests that maxillary stability after Le Fort I osteotomy for cant correction does not differ from that after Le Fort I osteotomy for maxillary advancement.     

Evaluation of upper lip hypoesthesia with a trigeminal somatosensory-evoked potential following Le Fort I osteotomy in combination with mandibular osteotomy.

PURPOSE: The purpose of this study was to objectively evaluate hypoesthesia of the upper lip following Le Fort I osteotomy in combination with mandibular osteotomy with trigeminal somatosensory evoked potential (TSEP). SUBJECTS AND METHODS: The subjects consisted of 25 patients with mandibular prognathism with maxillary retrognathism mandibular prognathism with or without asymmetry, who underwent Le Fort I osteotomy in combination with sagittal split ramus osteotomy (SSRO) or intraoral vertical ramus osteotomy (IVRO).Trigeminal nerve hypoesthesia at the region of the upper lip was assessed bilaterally by the TSEP method. The electrodes were placed exactly above the highest point of the vermilion border and on the mucosa of the upper lip. An electroencephalograph recording system (Neuropack Sigma; Nihon Koden Corp., Tokyo, Japan) was used to analyze the potentials. Each patient was evaluated preoperatively and then postoperatively at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year. RESULTS: The average measurable period and standard deviation of TSEP of the upper lip was 7.8 +/- 10.7 weeks following Le Fort I osteotomy, TSEP of the lower lip was 4.6 +/- 9.2 weeks in the patients who underwent SSRO with Le Fort I osteotomy, and 1.2 +/- 0.4 weeks in the patients who underwent IVRO with Le Fort I osteotomy. CONCLUSION: This study objectively proved that hypoesthesia could appear in the upper lips following Le Fort I osteotomy with TSEP. The measurable period for the upper lip following Le Fort I osteotomy tended to be longer than that for the lower lip in the patients who underwent SSRO and IVRO with Le Fort I osteotomy.