Association analysis of the SOX10 polymorphism with Hirschsprung disease in the Han Chinese population

Background

Hirschsprung disease (HSCR, Online Mendelian Inheritance in Man 142623) is a typical developmental disorder of the enteric nervous system in which ganglion cells fail to innervate the lower gastrointestinal tract during embryonic development. SOX10 gene is involved in the normal development of the enteric nervous system. Heterozygous SOX10 mutations have been identified in patients with syndromic HSCR. However, no mutations have been reported to date to be associated to isolated HSCR patient. We thus sought to investigate whether mutations in the SOX10 are associated with isolated HSCR in the Chinese population.

Methods

Polymerase chain reaction amplification and direct sequencing were used to screen 4 exons of the SOX10 gene for mutations and polymorphisms in 104 patients with sporadic HSCR and 96 ethnically matched controls in Han Chinese populations.

Results

In this study, 4 single nucleotide polymorphisms (SNPs) were identified: SNP1: c.18C>T (GAC→GAT) in exon 2; SNP2: c.122G>T (GGC→GTC) in exon 2; SNP3: IVS2+10 (C→G) in intron 2; and SNP4: c.927T>C (CAT→CAC) in exon 4. SNP1 and SNP2 were novel described polymorphisms in the Chinese population. No SOX10 mutations were found in Han Chinese with isolated HSCR.

Conclusions

Our results revealed that there was no association between the 4 SNPs of the SOX10 gene and HSCR. This study showed that the SOX10 gene is unlikely to be a major HSCR gene in the Chinese Han population.     

RET proto-oncogene testing in infants presenting with Hirschsprung disease identifies 2 new multiple endocrine neoplasia 2A kindreds

Background

Multiple endocrine neoplasia 2A (MEN 2A) is a genetic syndrome manifesting as medullary thyroid carcinoma (MTC), hyperparathyroidism, and pheochromocytoma. Multiple endocrine neoplasia 2A results from mutations in the RET proto-oncogene. Hirschsprung disease (HSCR) is a rare manifestation of MEN 2A and has been described in known MEN 2A families.

Methods

Here we describe 2 MEN 2A families that were only identified after the diagnosis of HSCR.

Results

Kindred 1: A boy presented in infancy with HSCR. Genetic screening revealed a C609Y mutation, which is consistent with MEN 2A. Evaluation of his sister, father, and grandmother revealed the same mutation. All 3 had thyroidectomies demonstrating C-cell hyperplasia. The grandmother had a microscopic focus of MTC.Kindred 2: An infant boy and his sister were diagnosed with HSCR as neonates. Genetic testing demonstrated a C620R gene mutation consistent with MEN 2A. Total thyroidectomies revealed metastatic MTC in the father and C-cell hyperplasia in both children.

Conclusions

Hirschsprung disease can be the initial presentation of MEN 2A. We strongly recommend that genetic screening be performed in patients presenting with HSCR, looking for the known RET mutations associated with MEN 2A. If a mutation consistent with MEN 2A is detected, genetic screening of all first-degree relatives in the kindred is recommended.     

MNX1 (HLXB9) mutations in Currarino patients

Purpose

The combination of partial absence of the sacrum, anorectal anomalies, and presacral mass constitutes Currarino syndrome (CS), which is associated with mutations in MNX1 motor neuron and pancreas homeobox 1 (previously HLXB9).Here, we report on the MNX1 mutations found in a family segregating CS and in 3 sporadic CS patients, as well as on the clinical characteristics of the affected individuals.

Methods

MNX1 mutations were identified by direct sequencing the coding regions, intron/exon boundaries of MNX1 in 5 CS Japanese family members and 3 Chinese sporadic cases and their parents.

Results

There were 2 novel (P18PfsX37, R243W) and 2 previously described (W288G and IVS2 + 1G > A) mutations. These mutations were not found in 198 control individuals and are predicted to impair the functioning of the MNX1 protein.

Conclusions

The variability of the CS phenotype among related or unrelated patients bearing the same mutation advocates for differences in the genetic background of each individual and invokes the implication of additional CS susceptibility genes.     

Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China

Background

Hirschsprung disease (HSCR, OMIM 142623) is a complex congenital disorder characterized by intestinal obstructions caused by the absence of the intestinal ganglion cells of the nerve plexuses in variable lengths of the digestive tract. The PHOX2B gene is involved in neurogenesis and disruption of Phox2b in mice results in a HSCR-like phenotype. The first association study of the PHOX2B gene with HSCR derived from Chinese population in Hong Kong; here, we address the question of whether PHOX2B acts as a predisposing factor in HSCR pathogenesis in Chinese population in mainland.

Methods

To investigate the contribution of PHOX2B to the HSCR phenotype, polymerase chain reaction amplification and direct sequencing were used to screen PHOX2B coding regions and intron/exon boundaries for mutations and polymorphisms in 102 patients with HSCR and 96 ethnically matched controls, in Han Chinese populations of Southeastern China.

Results

In this study, we genotyped 4 single nucleotide polymorphisms (SNPs) (including 1 novel SNP) located within the PHOX2B gene. Statistically significant differences were found for c.701 A > G and IVS2 + 100 A > G, and the log-additive model was accepted as the best inheritance model (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.11-2.87) for IVS2 + 100 A > G. We also showed that the haplotype-A G A N composed of 4 SNPs exhibited significant association with the disease (P = .03); this haplotype was more frequently observed in cases than in controls (OR, 2.31; 95% CI, 1.11-4.82).

Conclusions

Our study provided further evidence that the PHOX2B gene is involved in the susceptibility to HSCR in the Han Chinese population. Our findings are in accordance with the involvement of PHOX2B in the signaling pathways governing the development of enteric neurons.     

Advantages of intraoperative semiquantitative evaluation of myenteric nervous plexuses in patients with Hirschsprung disease

Background

The reappearance of an occlusive syndrome after surgical treatment of patients with Hirschsprung disease is often caused by incomplete resection of the affected segment. Intraoperative examination of frozen biopsies assists surgery, but interpretation of biopsies in the transitional zone is difficult.

Methods

We performed retrospective semiquantitative evaluations of myenteric nervous plexuses at the proximal limits of resection specimens from 41 children who were treated for rectocolic Hirschsprung disease using intraoperative examination of transparietal biopsies. The results of the evaluations were correlated with the postoperative courses of the children.

Results

After formalin fixation, the mean length of the aganglionic segments was 8.9 cm (range, 1-37.5 cm). At the proximal limit, the percentage of the circumference of the muscularis propria that was composed of plexuses with ganglion cells was more than 95% in 7 children, 90% to 95% in 21 children, 40% to 80% in 6 children, and 30% or less in 7 children (17%), 4 of whom subsequently developed occlusive syndromes.

Conclusions

Semiquantitative intraoperative examination of the entire circumference of resected segments facilitates precise evaluation of intrinsic innervation at the level of the anastomosis and may reduce the frequency of recurrence of occlusive symptoms after surgery.     

Intrasphincteric botulinum toxin decreases the rate of hospitalization for postoperative obstructive symptoms in children with Hirschsprung disease

Background

Although most children with Hirschsprung disease do well after pull-through surgery, some continue to have persistent obstructive symptoms. The purpose of this study was to evaluate the effect of intrasphincteric botulinum toxin in the management of these children.

Methods

A retrospective review of patients with Hirschsprung disease treated over 10 years was performed.

Results

Twenty-two patients who had previously undergone pull-through surgery received a median number of 2 botulinum toxin injections (range, 1-23). The number of hospitalizations for obstructive symptoms significantly decreased from preinjection (median, 1.5; interquartile range [IQR], 1-3) to postinjection (median, 0; IQR, 0-1) (P = .0003). The number of injections was lower in children with a rectosigmoid transition zone (median, 1 injection; IQR, 1-3.5) than in those with long-segment disease (median, 3 injections; IQR, 1-15) (P = .04). Eighty percent of patients had a good response to the first dose of botulinum toxin, and 69% of them required additional injections. There were no short-term or long-term complications related to botulinum toxin.

Conclusions

Intrasphincteric botulinum toxin significantly decreased the need for obstruction-related hospitalization in children who had undergone pull-through surgery for Hirschsprung disease. Botulinum toxin should be strongly considered in the management algorithm for postoperative obstructive symptoms in children with Hirschsprung disease.     

Fetal bovine serum suppresses apoptosis in the small intestine after total ischemia and reperfusion in mice

Background/Purpose

Total ischemia/reperfusion (I/R) of the small intestine induces cellular apoptosis. In this study, the authors investigated the effects of fetal bovine serum (FBS) on apoptosis and related proapoptotic and antiapoptotic factors in the I/R-injured small intestine of mice.

Methods

The mice underwent total I/R of the small intestine and were treated with oral gavages of normal saline or FBS for 3 days, concluding with total ischemia of the small intestine. Samples of the I/R-injured small intestine, representing various predefined time-points post-I/R (immediately before and after 1 hour of total ischemia and at 1, 6, and 24 hours after initiation of reperfusion), were subjected to terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining to study the cellular apoptosis, and Western blot analysis to measure expression of p53, bcl-2 and bax, with caspase-activity assay used to determine the activity of caspase 3.

Results

For the saline-treated mice, increased cellular apoptosis, suppressed expression of p53 and bcl-2 (with decreased bcl-2 to bax ratio) and increased caspase-3 activity were found for the I/R-injured small intestine. By contrast, FBS treatment suppressed cellular apoptosis, producing up-regulation of p53 and bcl-2 (with increased bcl-2 to bax ratio to 5.4-fold of the saline-treated group) and inhibiting the activity of caspase 3 (P < .05).

Conclusions

The results of our study suggest that I/R-induced apoptosis of the mouse small intestine may be related to p53 and bcl-2 suppression (with decreased bcl-2 to bax ratio) and activation of caspase 3 and that such apoptosis seems to be suppressed by FBS treatment.     

Redo surgery in Hirschsprung disease: what did we learn? Unicentric experience on 70 patients

Purpose

This article is aimed at describing a series of 70 patients who underwent a redo pull-through in the period between January 1991 and January 2007 and to compare them with a series of consecutive patients with Hirschsprung disease who underwent a single pull-through.

Methods

The notes were reviewed, and a comprehensive interview based on a disease-specific questionnaire for continence and quality of life was submitted to all eligible patients. We used a number of consecutive patients who underwent a single pull-through for Hirschsprung disease as control group.

Results

Seventy patients were included. Residual aganglionosis in pulled-through bowel or retained aganglionic rectum represented the indications to reoperation in most cases. Intestinal obstruction represented the leading symptom in more than 60% of patients. We adopted either the endorectal pull-through, the Duhamel, or the Swenson procedure. Thirty-six patients were assessed for long-term outcome. One third experienced complications. Long-term continence was satisfactory in 70%.Enterocolitis, soiling, and perineal excoriations were complained by 30%. Excellent to good perspectives were described by 94%, and excellent to good cosmetic results by 22%. The only significant difference with control group (109 patients) involved cosmetic appearance, whereas soiling, although more frequent, could not be considered significantly increased.

Conclusions

Patients who experience failure of a pull-through must go through multiple procedures to achieve definitive results. Although overall outcome does not significantly differ from that of a single effective pull-through, great efforts should be made to minimize complications and avoid the need for a redo, which requires experienced surgeons and highly committed families for a longer course of the disease.     

Reoperations in Hirschsprung disease

Background

We sought to identify causes of preventable complications related to operations for Hirschsprung disease.

Methods

We reviewed the cases of 51 patients with Hirschsprung disease who underwent a primary procedure elsewhere, had a complication, and were referred for reoperation.

Results

Thirty-five patients had 1 failed operation, 10 had 2, and 6 had 3. Initial operations were Soave (20), Duhamel (15), Swenson (5), transanal endorectal (4), myectomy (3), unknown (3), and laparoscopic Swenson (1). Thirty-one patients presented with a stoma. Patients without a stoma (20) had fecal impaction (8), recurrent enterocolitis (6), and fecal incontinence (6). None had both enterocolitis and incontinence. Reoperation was performed posterior sagittally (40) or transanally (5). Indications included stricture (21), megarectal Duhamel pouches (12), fistulae (11 [8 rectocutaneous, 2 rectourethral, and 1 rectovaginal]), pouchitis (2), and retained aganglionic bowel (8). After reoperation, 14 were continent, 11 had a stoma (8 permanent), 6 had voluntary bowel movements but soiled occasionally, 6 received rectal irrigations to avoid enterocolitis, 6 were incontinent but clean with bowel management, and 2 were lost to follow-up.

Conclusion

Stricture, megarectal pouch, fistula, and retained aganglionic bowel are preventable complications. Enterocolitis is partially preventable but can occur after a technically correct procedure. Fecal incontinence is a preventable complication likely because of anal canal damage.     

A prospective observational study examining quality of life in patients with malignant gastric outlet obstruction

Background

Gastric outlet obstruction (GOO) often complicates advanced malignancy. Palliative options include surgical bypass, endoscopic stent, percutaneous gastrostomy (PEG), or percutaneous jejunostomy (PEJ).

Methods

We enrolled 50 patients with GOO secondary to unresectable primary or metastatic cancer in a study examining palliative interventions. Validated instruments assessed quality of life (QOL) at baseline, 1 month, and 3 months following intervention.

Results

Median overall survival was 64 days. A shorter hospital stay and trend to lower mortality were observed after stent placement; solid food intake and rates of secondary intervention were comparable. Both stent and surgical bypass were associated with acceptable QOL outcomes. Fifteen patients refused participation at 1 month and 28 died of disease before 3 months, so 10 patients completed all surveys.

Conclusions

Although malignant GOO is associated with poor survival, there are reasonable alternatives for palliation. QOL studies are difficult to complete in this population due to severity of illness and short life expectancy.     

Hepatocyte growth factor treatment ameliorates diarrhea and bowel inflammation in a rat model of inflammatory bowel disease

Background/purpose

Transfection of the HLA-B27 gene into normal Fischer rats induces phenotypic changes similar to inflammatory bowel disease (IBD). This study investigated the benefits of 2 doses of hepatocyte growth factor (HGF) on the manifestations of IBD in this rat model.

Methods

Fischer rats and HLA-B27 rats were divided into 4 groups: Fischer rats treated with saline, HLA-B27 rats treated with saline, HGF at 150 μg/kg/d, and HGF at 300 μg/kg/d. HGF or saline was infused for 14 days via an osmotic pump attached to a catheter in the internal jugular vein. After treatment, rats were evaluated for diarrhea and reduction in gross and microscopic bowel inflammation. Statistics were determined using analysis of variance (ANOVA). A P value ≤ .05 was considered significant.

Results

Administration of HGF at 150 μg/kg/d decreased diarrhea by 40%, gross inflammation by 41%, and microscopic inflammation by 72% (P ≤ .05). At 300 μg/kg/d HGF decreased diarrhea by 46%, gross inflammation by 45%, and microscopic inflammation by 54% (P ≤ .05).

Conclusions

HGF administration reduces the clinical manifestations of IBD in this rat model. Similar effects were seen at both doses of HGF administration, implying that there is a plateau above which further increases in HGF levels provides no added benefit. HGF administration may be clinically useful in the management of IBD.     

Analgesic efficacy of ultrasound-guided regional anesthesia: a meta-analysis

Study Objective

To determine if the use of ultrasound guidance (vs non-ultrasound techniques) improves the success rate of nerve blocks.

Design

Meta-analysis of randomized controlled trials (RCTs) in the published literature.

Setting

University medical center.

Measurements

16 RCTs of patients undergoing elective surgical procedures were studied. Patients underwent ultrasound-guided or non-ultrasound techniques (nerve stimulation, surface landmark) for peripheral nerve blocks. Success rates were measured.

Main Results

Ultrasound guidance (vs all non-ultrasound techniques) was associated with a significant increase in the success rate of nerve blocks [relative risk (RR) = 1.11 (95% confidence interval [CI]: 1.06 to 1.17, P < 0.0001]). When compared with nerve stimulator techniques only, ultrasound guidance was still associated with an increase in the success rate (RR = 1.11 [95% CI: 1.05 to 1.17, P = 0.0001]). For specific blocks, ultrasound guidance (vs all non-ultrasound) was associated with a significant increase in successful brachial plexus (all) nerve blocks (RR = 1.11 [95% CI: 1.05 to 1.20, P = 0.0001]), sciatic popliteal nerve block (RR = 1.22 [95% CI: 1.08 to 1.39, P = 0.002]) and brachial plexus axillary nerve block (RR = 1.13 [95% CI: 1.00 to 1.26, P = 0.05]) but not brachial plexus infraclavicular nerve block (RR = 1.25 [95% CI: 0.88 to 1.76, P = 0.22]).

Conclusions

Ultrasound-guided peripheral nerve block is associated with an increased overall success rate when compared with nerve stimulation or other methods. Ultrasound-guided techniques also increase the success rate of some specific blocks.     

Is complete resection of the aganglionic bowel in extensive total aganglionosis up to the middle ileum always necessary?

Background/Purpose

Total colonic aganglionosis is an unusual form of Hirschsprung disease, reflected by the small number of published case studies. The goal of this study was to analyze our cases of the last 22 years and report on our experience with 3 cases of extended total aganglionosis proximal to the middle ileum in which remaining aganglionic bowel was left in situ.

Materials and Methods

In a period of 22 years (from January 1988 to April 2010), we operated on 15 children with total aganglionosis. These children were among 163 children with Hirschsprung disease. In 3 patients with extended aganglionosis proximal to the middle ileum, remaining aganglionic bowel was left in situ. Data were collected from the medical records, including each patient's demographics, medical history, primary treatment, complications, and follow-up.

Results

Eleven of the 15 children received an ileostomy as first treatment, and 4 children underwent a primary Duhamel procedure. Early postoperative complications included an abscess after an open procedure in a patient with trisomy 21 syndrome and an incorrect leveling resection that required an ileostomy. There were 2 deaths at 6 and 16 months postoperatively. The mortality rate was 13.3%. Of the 15 patients, 7 (46%) presented with at least 1 episode of postoperative enterocolitis, and only 2 of these patients had more than 3 episodes. We treated 3 patients with extended aganglionosis up to midileum (20%) in which the proximal resection level was in the aganglionic segment of ileum at the level of the ileostomy. The ileostomies were shown to be functioning satisfactorily before the pull through, so going more proximal to the ileostomy might have meant that the patient would present short bowel problems. These 3 patients had good bowel function postoperatively.

Conclusion

In principle, resection of the aganglionic bowel is mandatory to relieve obstruction and subsequent complications. There are situations, however, where the complications of a short bowel begin to outweigh the benefits of resection. In these cases, leaving remaining aganglionic bowel in situ may be an advantageous option for the patients with total aganglionosis extending to the midileum whose ileostomy functions well.     

A prospective, randomized trial for use of prednisolone in patients with facial nerve paralysis after parotidectomy

Background

A high rate of facial nerve paralysis (FNP) develops after parotid surgery, but there have been few clinical trials on treatments to improve recovery times. This study evaluated the efficacy of prednisolone in these patients.

Methods

A total of 123 patients who underwent parotidectomy without injury to the facial nerve were assessed prospectively for postoperative FNP. These patients were assigned randomly to treatment with prednisolone or placebo for 10 days. FNP was evaluated by House-Brackmann grades. Recovery rates and adverse effects were monitored regularly for 6 months after surgery.

Results

Of the 123 patients, 45 had postoperative FNP. All FNPs were grades II to IV, mostly on 1 or 2 facial areas. The incidence of FNP was increased significantly with malignant pathology, increased parotidectomy extent, and neck dissection (P < .01). Of 44 evaluable patients, 43 showed full recovery of FNP after 6 months, whereas 1 patient had permanent FNP. Recovery rates were equal in both groups, and there was no evidence of major adverse effects.

Conclusions

Prednisolone was ineffective in early recovery from postparotidectomy FNP.     

Neural Stem Cell Transplantation Rescues Rectum Function in the Aganglionic Rat

Background

Neural stem cell (NSC) transplantation is a promising tool for restoring the nervous system in a variety of neurodegenerative disorders. The aim of this study was to determine the potential of NSC transplantation as a therapeutic strategy for neuronal replacement of the enteric nervous system of the rectum in an aganglionic rat.

Materials and Methods

Rat central nervous system-derived NSCs (CNS-NSCs) obtained from the cortex of the fetal brain (E16) were transplanted into the benzalkonium chloride (BAC)-induced rat aganglionic rectum. Survival and differentiation of the implanted cells were assessed at 8 weeks posttransplantation using immunostaining and Western blotting. The rectoanal inhibitory reflex (RAIR) was also be measured.

Results

Eight weeks following transplantation, grafted CNS-NSCs differentiated into neurons and glial cells in the aganglionic rectum. The protein expression of neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT) were significantly increased and the RAIR restored after cell implantation.

Conclusions

CNS-NSC transplantation may provide a viable therapeutic option for disorders of the enteric nervous system.     

Insulinlike growth factor I gene expression is increased in the fetal lung after tracheal ligation

Background/Purpose

The mortality and morbidity in congenital diaphragmatic hernia are mainly caused by pulmonary hypoplasia. To improve clinical results, further methods inducing lung growth may have to be used. The aim of this report was to evaluate the expression of insulinlike growth factor I (IGF-I), estrogen receptor α, estrogen receptor β, growth hormone receptor, and thioredoxin in a rat model of hypoplastic, hyperplastic, and normal fetal lungs to improve understanding of lung growth.

Methods

Hypoplastic diaphragmatic hernia lungs were created by giving nitrofen by gavage to pregnant rats on day 9.5. Hyperplastic lungs were achieved by intrauterine tracheal ligation of rat fetuses on day 19. All lungs were harvested on gestational day 21. Total nucleic acids were extracted by proteinase K digestion and extraction in phenol/chloroform. The total nucleic acids mixture was hybridized with radioactively labeled RNA probes, and the radioactivity of the hybrids was compared with the respective standard curve of known amounts of in vitro synthesized mRNA. Immunohistochemistry staining was performed for IGF-I.

Results

The IGF-I mRNA was significantly (P < .01) higher in hyperplastic lungs compared with control and hypoplastic lungs. The latter 2 did not differ. No difference was found between the other mRNA levels in the study groups.

Conclusions

IGF-I is involved in the accelerated lung growth seen after intrauterine tracheal ligation.     

Clinical features and HLXB9 gene mutation of a sporadic Chinese Currarino's syndrome case

Background/Purpose

The Currarino's syndrome (CS), which is characterized by sacral bony anomalies, anorectal malformation, and a presacral mass, is associated with mutations of HLXB9 gene. The aim of this study was to clearly define the clinical manifestations and molecular anomalies of CS in China.

Methods

We studied the medical history and clinical manifestations of a child with presacral mass. Genomic DNA was extracted from lymphocytes, and mutation analysis of the HLXB9 gene was conducted by using polymerase chain reaction and direct sequencing in the child and her parents.

Results

A previously unreported heterozygous missense mutation of HLXB9 gene was detected in the child.

Conclusions

The HLXB9 gene mutation could take place in sporadic cases of CS without a typical hemisacrum.     

Identifying the best candidate for radical prostatectomy among patients with high-risk prostate cancer

Background

The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial.

Objective

To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated.

Design, setting, and participants

We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA] >20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease—namely, pT2-pT3a, node negative PCa with negative surgical margins.

Intervention

All patients underwent radical retropubic prostatectomy and PLND.

Measurements

Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates.

Results and limitations

Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p ≤ 0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p < 0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram.

Conclusions

Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters.     

The effect of neoadjuvant chemoradiation therapy on the prognostic value of lymph nodes after rectal cancer surgery

Background

Neoadjuvant therapy may affect the prognostic impact of total lymph node harvests and lymph node positivity after surgery for rectal cancer.

Methods

We performed a retrospective review of 390 consecutive patients with histologically confirmed rectal cancer. Postoperative follow-up evaluation and survival were confirmed via medical record review. The impacts of lymph node positivity and total lymph node harvest on survival and recurrence are reflected as proportional hazard ratios (HRs).

Results

A total of 221 patients underwent neoadjuvant therapy, of whom 75 had positive nodes. Node-positive patients showed a significantly shorter survival time (HR, 2.89; P = .002) and time to local recurrence (HR, 6.36; P = .031) compared with patients without positive nodes. Survival and recurrence were not significantly different between patients with a total harvest of fewer than 12 nodes and patients with a higher lymph node harvest.

Conclusions

After neoadjuvant treatment and total mesorectal excision, lymph node positivity is associated with significantly shorter survival and time to local recurrence in rectal cancer patients, whereas absolute total lymph node harvests likely have little impact on prognosis.