Genotype–phenotype studies of VCP‐associated inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia

Valosin containing protein (VCP) disease associated with inclusion body myopathy, Paget disease of the bone and frontotemporal dementia is a progressive autosomal dominant disorder caused by mutations in Valosin containing protein gene. To establish genotype–phenotype correlations we analyzed clinical and biochemical markers from a database of 190 members in 27 families harboring 10 missense mutations. Individuals were grouped into three categories: symptomatic, presymptomatic carriers and noncarriers. The symptomatic families were further divided into ten groups based on their VCP mutations. There was marked intra and inter‐familial variation; and significant genotype–phenotype correlations were difficult to establish because of small numbers. Nevertheless when comparing the two most common mutations, R155C mutation was found to be more severe, with an earlier onset of myopathy and Paget (p = 0.03). Survival analysis of all subjects revealed an average life span after diagnosis of myopathy and Paget of 18 and 19 years respectively, and after dementia only 6 years. R155C had a reduced survival compared to the R155H mutation (p = 0.03).We identified amyotrophic lateral sclerosis (ALS) was diagnosed in 13 individuals (8.9%) and Parkinson's disease in five individuals (3%); however, there was no genotypic correlation. This study represents the largest dataset of patients with VCP disease and expands our understanding of the natural history and provides genotype–phenotype correlations in this unique disease.     

Rectum Sarcoma: Challenging Diagnostic and Therapeutic Modalities

Introduction

Sarcomas are malignant tumors that arise from mesenchymal tissue at any of the body sites. They incorporate the wide category of GISTs and are classified in various histological types. Histological grading is another indicator of the degree of malignancy, the probability of distant metastases, and survival but remains a poor definition of local recurrence.

Discussion

The size and depth of invasion are the most important prognostic factors. Since they grow within the intestinal wall, the symptoms are usually few or late, leading to delays in diagnosis. Most common signs are rectal bleeding, abdominal or anal pain, diarrhea, tenesmus and weight loss. The diagnostic and staging protocol of stromal tumors of the rectum includes mainly endoscopic surveillance, computed tomography, and magnetic resonance imaging. Therefore, rectum sarcoma (RS) consists one of the most biologically virulent cancers and is difficult to cure by conventional procedures. The treatment is primarily surgical, where possible, and should guarantee complete clearance of the tumor, which often requires an aggressive approach. Unfortunately, the minority of patients is eligible to undergo surgical intervention. In addition, surgical removal of RS does not necessarily indicate a patient's long-term recovery. Alternative therapies, such as radio- and chemotherapy, proved insufficient. Elucidation of its molecular basis may prove useful in developing and identifying prognostic biomarkers.     

Retroperitoneal Schwannomas: Dilemmas in Diagnostic Approach and Therapeutic Management

Introduction

Schwannomas are rare tumors arising from Schwan cells of the peripheral nerve sheath. The majority of the cases are sporadic and familial clustering is often observed in association with von Rechlinghausen’s disease. Cases of intrasacral (osseous) and spinal tumors have also been described. Histologically, schwannomas are distinguished by the presence of areas of high and low cellularity called Antoni A and B tissue, respectively.

Clinical Presentation

Clinical features are highly non-specific and depend on the location and size of the lesion, with abdominal pain and neurological deficit being the most common abnormalities. Radiological studies are fundamental in the diagnostic evaluation of RSs.

Therapeutic Management

Despite recent research on the therapeutic strategies against RS, surgical resection appears the only potentially curative approach. Unfortunately, a mere minority of patients is eligible to undergo surgical intervention. In addition, surgical removal of RS does not necessarily guarantee patient’s long-term survival. Laparoscopic approach and enucleation of the tumor have been suggested as well. Alternative therapies, such as radio- and chemotherapy often proved insufficient. The aim of this review was to evaluate the results of surgical treatment for RS with special reference to the extent of its histological spread and to analyze the recent literature in order to provide an update on the current concepts of therapeutic management of this entity.     

Evidence for a novel gene for familial febrile convulsions, FEB2, linked to chromosome 19p in an extended family from the Midwest

Febrile convulsions are a common form of childhood seizure. It is estimated that between 2 and 5% of children will have a febrile convulsion before the age of 5. It has long been recognized that there is a significant genetic component for susceptibility to this type of seizure. Wallace, Berkovic and co-workers recently reported linkage of a putative autosomal dominant febrile convulsion gene to chromosome 8q13-21. We report here another autosomal dominant febrile convulsion locus on chromosome 19p. Linkage analysis in this large multi- generational family gave a maximum pairwise lod score of 4.52 with marker Mfd120 at locus D19S177. Linkage to the chromosome 8 locus was excluded in this family. Haplotype analysis using both affected and unaffected family members indicates that this febrile convulsion gene, which we call FEB2 , can be localized to an 11.7 cM, 1-2 Mb section of chromosome 19p13.3, between loci D19S591 and D19S395.      

Colorectal cancer emergencies during pregnancy case reports

Colorectal carcinoma emergencies during pregnancy are exceptionally rare. Three women 38, 31 and 36 years old, in the third trimester of gestation received treatment, respectively, for acute abdomen due to perforation of rectal carcinoma, ileus due to a sigmoid tumor, and deep venous thrombosis (DVT) from a cecal tumor compromising the right iliac vein. In the first two patients urgent cesarean sections were carried out with Hartmann's procedure and a loop colostomy was performed to resolve the ensuing intraabdominal sepsis and ileus, respectively. In the third patient, a cesarean section was carried out to treat the underlying DVT more aggressively, while right colectomy was postponed for three weeks. Restoration of the alimentary tract was achieved two months later in the first case, while in the second and third cases total colectomy due to familial polyposis and right colectomy were performed three weeks after the cesarean section. An overview of the clinical features, diagnostic pitfalls and therapeutic approaches to manage complications of colorectal cancer during pregnancy are discussed.     

Anesthetic and perioperative management of intestinal and multivisceral allograft recipient in nontransplant surgery.

As the survival rate of the intestinal and multi-visceral transplant recipients continues to improve, an increasing number of these patients present for either elective or emergency surgery related or unrelated to transplantation. The aim of this review is to focus on clinical issues related to the anesthetic and perioperative management of the intestinal or multi-visceral transplant recipient for nontransplant surgery. Specific issues concerning perioperative assessment and medications, choice of anesthetic drugs and techniques, and postoperative care management are reviewed.     

Total thyroidectomy as the single surgical option for benign and malignant thyroid disease: a surgical challenge

Introduction

Total thyroidectomy has been the treatment of choice for patients with malignant thyroid disease. However, the efficacy and safety of this procedure for patients with benign disease is still a matter of debate. The aim of this study is to show that total thyroidectomy can be safely performed for both malignant and benign disease.

Material and methods

A retrospective study on 216 patients was conducted. Once an indication for surgery was established, our single surgical treatment was total thyroidectomy. Age, sex, nature of thyroid disease, final pathology and postoperative complications were recorded.

Results

For both benign and malignant disease, total thyroidectomy resulted in no permanent laryngeal nerve injury and no permanent hypoparathyroidism. Temporary laryngeal nerve palsy occurred in 0.9% and 3% of patients with benign and malignant disease respectively (p = 0.245). Six percent of patients with benign and 10.0% of patients with malignant thyroid disease suffered temporary hypoparathyroidism (p = 0.280). Immediate reoperation for postoperative hemorrhage was performed in 1.7% of patients with benign disease and in 1.0% of patients with malignancy with an uneventful outcome (p = 0.650).

Conclusions

When performed by surgeons experienced in endocrine surgery, total thyroidectomy may be considered as the treatment of choice for both malignant and benign thyroid disease requiring surgical treatment. Total thyroidectomy virtually eliminates the requirement of completion thyroidectomy for incidentally diagnosed thyroid carcinoma and significantly reduces the rate of reoperation for recurrent disease, as it provides an immediate and permanent cure for all benign thyroid diseases, with a low incidence of postoperative complications.     

Small Liver Remnants Are More Vulnerable to Ischemia/Reperfusion Injury after Extended Hepatectomies: A Case–Control Study

Background

There is evidence that small-for-size liver grafts are more vulnerable to ischemia/reperfusion injury after liver transplantation. We hypothesized that ischemic injury is more pronounced in small liver remnants after major hepatectomies.

Methods

Fifteen patients underwent extended hepatectomy with remnant liver mass less than 30 % of standard liver weight (study group). These patients were matched with patients who underwent minor liver resection, with liver remnants equal to or more than 70 % of standard liver weight (control group). Ischemia/reperfusion injury was assessed by tissue caspase-3 activity postoperatively as well as peak aspartate aminotransferase (AST) values and a-glutathione S-transferase (α-GST) levels adjusted for remnant liver weight. In addition, caspase-3 activity and adjusted serum markers of hepatocyte injury were correlated with the degree of postoperative portal hypertension.

Results

Caspase-3 activity was higher in patients with small liver remnants (22.66 ± 6.57 vs. 12.60 ± 4.06 count per high-power field, p < 0.001). Serum markers of hepatocyte injury, when adjusted per gram of liver remnant, were found to be higher in the study group than in the control group (AST: 1.26 ± 0.25 vs. 0.54 ± 0.11 IU g^?1, p < 0.001; α-GST: 0.14 ± 0.02 vs. 0.08 ± 0.01 IU g^?1, p < 0.001). Tissue caspase-3 expression in the small liver remnant group correlated with both AST and α-GST levels adjusted per gram of liver remnant (r ² = 0.51, p = 0.005 and r ² = 0.71, p < 0.001, respectively). Significant correlations between postoperative portal hypertension and the same markers as well as caspase-3 activity were also demonstrated.

Conclusion

Liver remnants less than 30 % of standard liver weight are much more susceptible to ischemia/reperfusion injury than controls twice the size. Adjustment of serum markers of hepatocyte injury to the liver remnant weight depicts injury more accurately.