A New and Alternative Leads Positioning for Complex Regional Pain Syndrome Treatment: Paraforaminal Stimulation

We present a case of a female patient suffering from type I complex regional pain syndrome (CRPS) who developed “mirror imaging” of her CRPS and was successfully treated with dual spinal cord stimulation (SCS) in the paraforaminal epidural space. This patient initially had unilateral pain that was unsuccessfully treated with midline SCS and single‐lead lateral epidural lead placement “paraforaminally.” One year later, because we believed that paraforaminal stimulation would preferentially stimulate primary sensitized afferents innervating the painful area, we reperformed SCS with two leads positioned laterally and paraforaminally close to the roots within the epidural space. After repositioning and after 1 year of paraforaminal stimulation, there was significant improvement in the patient's symptoms, resolving all unilateral and “mirrored” symptoms. We conclude that paraforaminal stimulation may be a valid therapeutic option for the treatment of CRPS.     

Detection of Apoptosis in Peripheral Blood Cells of 31 Subjects Affected by Down Syndrome Before and After Zinc Therapy

Thirty-one patients affected by Down syndrome (DS) were investigated to study the presence of apoptosis in peripheral blood cells in relation to the plasma levels of zinc. Twelve patients had undergone therapy with ZnSO₄, while the remaining 19 were untreated. The presence of programmed cell death was evaluated by means of electron microscopy, in situ nick translation (NT), and agarose gel electrophoresis of DNA. These approaches evidenced the presence of apoptosis in peripheral blood cells of patients before therapy with ZnSO₄, while after zinc supplementation there was a reduction in the number of apoptotic cells. These results suggest that the process of programmed cell death in peripheral blood cells of patients with Down syndrome is related to the plasma levels of zinc ion.     

Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.

Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored genetic alterations in the E-cadherin gene. Novel mutations predicted to significantly compromise protein function were found within 4 of these cancers, 2 of which harbored alterations resulting in biallelic inactivation of the gene product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting the presence of a homozygous abnormality. Notably, one germline E-cadherin mutation was also identified within these "sporadic" diffuse cancers. Significant gene mutations were not found in the 14 intestinal-type or histologically mixed cancer. Immunohistochemistry revealed aberrant or negative protein expression in seven diffuse-type tumors, four of which correlated with the genetic alterations. Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting that allelic loss at the locus is not a common mechanism for E-cadherin inactivation during gastric tumorigenesis. Our observations suggest that inactivation of the E-cadherin gene occurs only in a subset of diffuse-type gastric cancers, as the majority of cases did not contain genetic alterations or identifiable protein abnormalities. Germline E-cadherin alterations, although rare, may underlie some diffuse gastric cancer cases that have important biologic and practical implications     

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.     

Trends in stomach carcinoma. A statistical analysis of 1204 cases

The authors report a retrospective analysis of their experience of gastric cancer. One thousand two hundred and four patients, observed between 1977 and 1994, of whom 1,094 underwent surgery, were studied. Data analysis was performed, dividing this period as follows: 1977-1982, 1983-1988, 1989-1994. The results reveal that, over time, substantial changes occurred both in tumor characteristics and surgical approach. With regards to tumor characteristics, the disease weighs heavily, even if it is less frequent than in the past (25% reduction), striking younger subjects and presenting in increasingly more aggressive forms [higher frequency of proximal (+11.4%) and diffuse forms (+18.1%), reduction of advanced forms (-11.6%) not proportional to the increase of early forms (+64.5%), as well as increase of cases with a short clinical history (+15.2%)]. In terms of surgical approach, while the use of conservative surgery was reduced during the study period, extensive procedures were more widely used, particularly in the curative treatment of advanced tumors (subtotal gastrectomies: reduction of 39.5%; total gastrectomies: increase of 106%). The increasing use of extended surgery is linked to the modifications occurred in tumor characteristics and in pre and post-operative management rather then to changes in surgical approach. It must be noted, however, that such technical advances have not yielded an improvement in survival (p = n.s.); as such, it is likely that gastric cancer has became a more aggressive disease and, therefore, has counterbalanced the benefits of early diagnosis and extended exeresis.     

Factors influencing outcome in gastric cancer involving muscularis and subserosal layer.

AIMS: The prognostic factors for advanced gastric carcinoma without serosal invasion (pT2 AGC) are not clear. In terms of prognosis, pT2 AGC is considered intermediate between early gastric cancer (EGC) and gastric carcinoma with serosal invasion. METHODS: From January 1985 to December 2000, 182 patients with pT2 AGC underwent curative gastric resection in our Department. Prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: Univariate analysis demonstrated that gender, tumour location, lymph node involvement, Borrmann type, number of lymph nodes involved, venous infiltration and extent of lymphadenectomy were significantly related to the prognosis. Multivariate analysis revealed that extent of lymph node metastasis (N1 vs N0 relative risk (RR) of recurrences=3.96, p<0.05; N2 vs N0 RR=6.55, p<0.05), and extent of lymphadenectomy (D1 vs D2 RR=3.2, p<0.01) were independent prognostic factors. In a subset of patients in which venous infiltration was analysed, this factor was also significant (RR=3.9, p<0.05). CONCLUSIONS: Our study shows that lymph node involvement and venous infiltration are important prognostic factors for pT2 AGC and, as such, adjuvant chemotherapy could be useful in this group of patients. An extensive lymph node dissection, minimum D2, should always be performed in order to reduce the risk of recurrence.     

Simultaneous generation of cytomegalovirus-specific CD8+ and CD4+ T lymphocytes by use of dendritic cells comodified with pp65 mRNA and pp65 protein

Cytomegalovirus (CMV) disease remains a severe complication in patients who have undergone transplantation. Viremia can be prevented and treated by the adoptive transfer of donor-derived CMV-directed T cells. To ensure long-term protection against CMV disease, it is important to transfer CMV antigen-specific T cells that represent both the CD8+ and the CD4+ subsets. In the present study, we used as stimulators dendritic cells (DCs) that were electroporated with in vitro-transcribed 5'-capped polyadenylated messenger RNA (mRNA) that encoded the CMV pp65 protein (i.e., pp65 mRNA). These DCs could efficiently activate CMV-directed CD8+ T cells, as assayed by tetramer staining, interferon- gamma production, and cytolytic activity. We also used DCs that were pulsed with a recombinant pp65 protein to activate CMV-directed CD4+ T cells. When DCs were comodified with pp65 mRNA and pp65 protein, large numbers of CMV-directed CD8+ and CD4+ T cells were generated simultaneously. The approach outlined in the present study can be adapted for a clinical protocol that circumvents potential virus-related biohazards and is available to all patients independently of their human leukocyte antigen haplotype.     

Accuracy of transrectal ultrasound after preoperative radiochemotherapy compared to computed tomography and magnetic resonance in locally advanced rectal cancer

Introduction

The aim of the present study was to compare the restaging results obtained by transrectal ultrasound (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) performed after preoperative chemoradiation with pathologic staging of the operative specimen.

Methods

From January 2008 to December 2009, all the consecutive patients with locally advanced rectal cancer that underwent neoadjuvant therapy at our department were evaluated. The results of diagnostic examinations and the definitive pathological examination were considered and compared.

Results

Thirty-seven patients were included in the study (27 males, 73%), mean age was 65.5?years (range 45–82?years). In all the patients TRUS and CT and in 20 patients MRI were performed before and after the treatment. Concerning the depth of invasion after treatment TRUS agreed with histopathology in 25/37 patients (67.5%), CT agreed in 22/37 cases (59.5%), and MRI in 12/20 cases (60%). Considering only neoplasia with stage T3, TRUS agreed in 23/24 cases (96%), CT in 19 cases (79%), and MRI in 10/12 cases (83.5%). Considering the tumors that did not exceed the rectal wall (T0, T1, and T2), TRUS agreed with histology in 2/13 cases (15.5%), CT in 3/13 cases (23%), and MRI 2/8 cases (25%). Concerning the presence of positive lymph nodes TRUS agreed with histology in 28/37 cases (75.5%), while CT agreed in 21/37 cases (56.5%) and MRI in 11/20 cases (55%). The concordance between the techniques was found to be low.

Conclusions

Transrectal ultrasonography resulted as the most accurate method to determine neoplastic wall infiltration and lymph node involvement even after radiochemotherapy. In most cases, considering the poor correlation between the diagnostic procedures and the disagreement of the results, a restaging performed only with TRUS could be proposed, limiting the use of the other imaging methods to selected cases.     

Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia

Overexpression, polymorphisms, and mutations of the WT1 gene have been reported in several human tumors including acute myeloid leukemia (AML) and variably correlated with prognosis. Acute promyelocytic leukemia (APL) represents the AML subset disclosing higher WT1 expression levels; however, no WT1 studies specifically focused on APL have been conducted. We screened for the presence of mutations, SNP rs16754, and expression levels of WT1 gene in 103 adult patients with newly diagnosed APL. Fms-like tyrosine kinase (FLT3) mutations were analyzed as well. WT1 mutations were identified in four (4?%) patients. At least one copy of the minor SNP rs16754 allele (WT1 ^AG or WT1 ^GG) was detected in 30 (29?%) patients. Six patients (6?%) were homozygous for the minor allele (WT1 ^GG ) and this genotype was associated with higher WT1 mRNA copies (p?=?0.018). FLT3 mutations were found in 37?% of patients and correlated with high WT1 mRNA expression (p?=?0.004). Patients heterozygous or homozygous for the minor allele and patients homozygous for major (WT1 ^AA) allele did not differ in terms of presenting features. In adult APL, WT1 gene mutational and polymorphic profile shows similarities with pediatric AML rather than with adult AML.