Anal Canal Cancer

PURPOSE: This study was designed to obtain an updated population-based perspective on anal canal cancer incidence rates, demographics, and outcomes using a nationwide database. Eight-five percent of all carcinomas of the anus are anal canal cancers, and previous studies suggest that incidence rates may be rising. Although the most successful treatment for anal canal cancer has been chemoradiation, little information at the population-level exists regarding demographics, treatment, and survival. METHODS: All patients diagnosed with anal canal cancer from 1973 to 1998 in the Surveillance Epidemiology and End Results cancer registry were analyzed. Data regarding demographics, cancer characteristics, treatment, and survival were assessed. Univariate and multivariate survival analyses were performed. RESULTS: A total of 4,841 patients were studied (mean age was 61 years; 62 percent female). Female patients were significantly older than male patients (65 vs. 58 years; P < 0.0001). There was a yearly increase in incidence of anal canal cancers (from 1973–1998). Disease prevalence by stage was localized (53 percent), regional (38 percent), and distant (9 percent). Racial/stage differences were seen, because black patients had less localized disease than white patients (46 vs. 53 percent; P < 0.01). Overall five-year survival for the entire cohort was 53 percent, and cancer-specific survival was 84 percent. Survival improved per decade (based on year of diagnosis). Significant survival differences in race were noted, but were less when the receipt of treatment was considered. CONCLUSION: Although most anal canal cancer reviews are single institutional series, this study was performed with population-based data. The incidence of anal canal cancer is increasing, and overall survival rates are improving. Important disparities in care were identified, which need to be addressed.     

Ontogenetic transition in fetal wound transforming growth factor-beta regulation correlates with collagen organization

Fetal rat skin transitions from scarless fetal-type repair to adult-type repair with scar between day 16 (E16) and day 18 (E18) of gestation (term = 21.5 days). Deficient transforming growth factor (TGF)-beta 1 and -beta 2 injury response has been proposed as a mechanism for scarless fetal-type repair. However, previous fetal studies have inconsistently reported the degree of TGF-beta induction after injury. To minimize developmental variables in fetal versus adult TGF-beta regulation, we narrowed our study to wounded fetal animals. We hypothesize that TGF-beta ligand and receptor expression will be differentially regulated during the transition from early gestation (E16) wounds manifesting scarless fetal-type repair to late gestation (E19) wounds manifesting adult-type repair with scar. In this study, decreased and rapidly cleared TGF-beta 1 and -beta 2 expression accompanied by increased and prolonged TGF-beta 3 levels in wounded E16 animals correlated with organized collagen deposition. In contrast, increased and prolonged TGF-beta 1 and -beta 2 expression accompanied by decreased and delayed TGF-beta 3 expression in wounded E19 animals correlated with disorganized collagen architecture. Similarly, expression of TGF-beta receptors type I and II were also increased or prolonged in E19 animals. Our results implicate increased TGF-beta 1, -beta 2, and decreased TGF-beta 3 expression, as well as increased type I and II receptor expression in late gestation fetal scar formation.     

Comparison of minimally invasive and modified Ravitch pectus excavatum repair

Background/Purpose: Minimally invasive repair of pectus excavatum (MIRPE) has gained wide acceptance during the last 4 years. This study compares, retrospectively, the experience at 2 large hospitals, 1 using MIRPE and the other a modified Ravitch repair (MRR). Methods: From 1996 to 2000, 68 PE patients underwent MIRPE at one hospital, and 139 underwent MRR at another hospital. Ages ranged from 5 to 19 years (mean, 12) for MIRPE, and 3 to 51 years (mean, 17.3) for MRR. The mean pectus severity index was 4.2 for MIRPE and 4.9 for MRR (normal, 2.5). Results: There were no deaths after MIRPE or MRR. Complications included 6 reoperations for MIRPE and none for MRR. There were 8 rehospitalizations for MIRPE and none for MRR. Ninety percent of MIRPE complications occurred in the first 25 cases. The mean blood loss was under 90 mL for both MIRPE and MRR. Mean operating time was 75 minutes for MIRPE and 212 minutes for MRR. Ninety-six percent of MIRPE patients and no MRR patients had epidurals. Intravenous analgesics averaged 5 days for MIRPE and 1.7 days for MRR. Mean hospitalization was 6.5 days for MIRPE and 2.9 days for MRR. Mean time before return to work or school was 18 days for MIRPE and 12 days for MRR. The sternal bar was removed from 107 of 139 MRR patients (mean time, 19 minutes) and 18 of 68 MIRPE patients (mean time, 25 minutes). Conclusions: Both MIRPE and MRR provide excellent clinical results. MRR has a longer operating time but decreased hospital stay, complication rate, and use of pain medications. Attention to technical operative details and surgeon's experience are essential for optimal results using both techniques.     

Surgical management of pectus carinatum: 30 years' experience

Pectus carinatum is an uncommon malformation that is often more symptomatic than the appearance suggests, and one that physicians often do not refer for surgical correction. Hospital records of 90 patients who underwent repair of pectus carinatum deformities between 1970 and 2000 were reviewed. During the same period another 445 patients underwent repair of excavatum deformities. Minimal deformity was observed before the age of 10 years for 81 of 90 patients; only 7 of the 90 underwent repair before age 11 years. All patients were symptomatic; 84 had exertional dyspnea and exercise limitation, 52 had frequent respiratory infections, 24 had asthma, and 38 had chest discomfort. The mean pectus severity score (width of chest divided by the distance between the sternum and spine) was 1.73 (the normal chest is 2.56). The type of repair varied with the type of deformity, consisting of subperiosteal resection of the deformed cartilages, transverse osteotomy of the anterior sternum with insertion of a cartilage wedge, and support with a steel strut for 4 to 6 months in 76 of 90. There were no deaths within 1 year after the repair. Complications included hypertrophic scar (n= 13), wound seroma (n= 5), pleural effusion (n= 3), and pneumothorax (n= 2). The mean blood loss was 78 ml, and the mean hospital stay was 2.6 days. With a mean follow-up of 12.8 years, all patients experienced alleviation of respiratory symptoms and chest discomfort and diminished exercise limitation; 88 of 90 patients experienced a very good to excellent long-term result. One patient required reoperation. Pectus carinatum often causes more severe respiratory symptoms and exercise limitation than is generally recognized. Repair in 90 patients with carinatum deformities has resulted in marked clinical improvement in all patients, with low morbidity and short hospitalization.     

Anal canal cancer: a population-based reappraisal

PURPOSE: This study was designed to obtain an updated population-based perspective on anal canal cancer incidence rates, demographics, and outcomes using a nationwide database. Eight-five percent of all carcinomas of the anus are anal canal cancers, and previous studies suggest that incidence rates may be rising. Although the most successful treatment for anal canal cancer has been chemoradiation, little information at the population-level exists regarding demographics, treatment, and survival. METHODS: All patients diagnosed with anal canal cancer from 1973 to 1998 in the Surveillance Epidemiology and End Results cancer registry were analyzed. Data regarding demographics, cancer characteristics, treatment, and survival were assessed. Univariate and multivariate survival analyses were performed. RESULTS: A total of 4,841 patients were studied (mean age was 61 years; 62 percent female). Female patients were significantly older than male patients (65 vs. 58 years; P < 0.0001). There was a yearly increase in incidence of anal canal cancers (from 1973-1998). Disease prevalence by stage was localized (53 percent), regional (38 percent), and distant (9 percent). Racial/stage differences were seen, because black patients had less localized disease than white patients (46 vs. 53 percent; P < 0.01). Overall five-year survival for the entire cohort was 53 percent, and cancer-specific survival was 84 percent. Survival improved per decade (based on year of diagnosis). Significant survival differences in race were noted, but were less when the receipt of treatment was considered. CONCLUSION: Although most anal canal cancer reviews are single institutional series, this study was performed with population-based data. The incidence of anal canal cancer is increasing, and overall survival rates are improving. Important disparities in care were identified, which need to be addressed.     

Surgical aspects of dialysis in newborns and infants weighing less than ten kilograms

PURPOSE: Renal failure occurs in children with moderate frequency. Surgical aspects of establishing and maintaining dialysis access in small infants are exceptionally challenging. The purpose of this review is to evaluate the authors' experience with dialysis access for infants less than 10 kg, particularly with respect to the surgical care required. METHODS: A retrospective review was conducted between 1991 and 1999 of all pediatric dialysis patients weighing 10 kg or less (n = 29). Age at start of dialysis, duration of dialysis, modes of dialysis, and complications specific to peritoneal (PD) and hemodialysis (HD) were examined. RESULTS: The mean age at start of dialysis was 10.4 months and continued for an average duration of 16.3 months. Seventy-two percent of all patients required both modes of dialysis. HD and PD duration averaged 7.8 and 10.5 months, respectively. Catheter durability was 3.1 and 4.5 months per catheter for HD and PD, respectively. There was no significant difference in complications when comparing HD and PD. Patients who weighed 5 to 10 kg had significantly longer PD catheter durability than patients 0 to 5 kg (P = .001). Forty-one percent of patients terminated dialysis after transplantation, whereas 24% died awaiting transplantation. CONCLUSION: Despite a large number of operations required, infants less than 10 kg can be bridged successfully, by surgical intervention and subsequent dialysis, to transplantation.     

Differential expression of fibromodulin, a transforming growth factor-beta modulator, in fetal skin development and scarless repair

Transforming growth factor-beta (TGF-beta1, -beta2, and -beta3) has been implicated in the ontogenetic transition from scarless fetal repair to adult repair with scar. Generally, TGF-beta exerts its effects through type I and II receptors; however, TGF-beta modulators such as latent TGF-beta binding protein-1 (LTBP-1), decorin, biglycan, and fibromodulin can bind and potentially inhibit TGF-beta activity. To more fully explore the role of TGF-beta ligands, receptors, and potential modulators during skin development and wound healing, we have used a rat model that transitions from scarless fetal-type repair to adult-type repair with scar between days 16 and 18 of gestation. We showed that TGF-beta ligand and receptor mRNA levels did not increase during the transition to adult-type repair in fetal skin, whereas LTBP-1 and fibromodulin expression decreased. In addition, TGF-beta1 and -beta3; type I, II, and III receptors; as well as LTBP-1, decorin, and biglycan were up-regulated during adult wound healing. In marked contrast, fibromodulin expression was initially down-regulated in adult repair. Immunostaining demonstrated significant fibromodulin induction 36 hours after injury in gestation day 16, but not day 19, fetal wounds. This inverse relationship between fibromodulin expression and scarring in both fetal and adult rat wound repair suggests that fibromodulin may be a biologically relevant modulator of TGF-beta activity during scar formation.     

Craniosynostosis in transgenic mice overexpressing Nell-1

Previously, we reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with craniosynostosis (CS), one of the most common congenital craniofacial deformities. Here we describe the creation and analysis of transgenic mice overexpressing Nell-1. Nell-1 transgenic animals exhibited CS-like phenotypes that ranged from simple to compound synostoses. Histologically, the osteogenic fronts of abnormally closing/closed sutures in these animals revealed calvarial overgrowth and overlap along with increased osteoblast differentiation and reduced cell proliferation. Furthermore, anomalies were restricted to calvarial bone, despite generalized, non-tissue-specific overexpression of Nell-1. In vitro, Nell-1 overexpression accelerated calvarial osteoblast differentiation and mineralization under normal culture conditions. Moreover, Nell-1 overexpression in osteoblasts was sufficient to promote alkaline phosphatase expression and micronodule formation. Conversely, downregulation of Nell-1 inhibited osteoblast differentiation in vitro. In summary, Nell-1 overexpression induced calvarial overgrowth resulting in premature suture closure in a rodent model. Nell-1, therefore, has a novel role in CS development, perhaps as part of a complex chain of events resulting in premature suture closure. On a cellular level, Nell-1 expression may modulate and be both sufficient and required for osteoblast differentiation.