Desmoplastic Reaction Influences Pancreatic Cancer Growth Behavior

Connective tissue growth factor (CTGF), which is regulated by transforming growth factor-ß (TGFß), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46-fold increase in CTGF mRNA expression (p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFß-induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation (p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) (p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFß, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.     

Radiofrequency ablation of the great saphenous vein with the ClosureFAST™ procedure: mid-term experience on 400 patients from a single centre

Introduction

Endovascular obliteration of the great saphenous vein (GSV) has been proposed as an alternative to conventional extirpative treatment of varicose veins.

Materials and methods

This report reviewed the initial experience with the ClosureFAST? procedure in 407 legs over a one-year period. Occlusion of the GSV was seen on 98 % of completion scans and in all patients within 1 week of the procedure. Persistent occlusion was documented in all cases. One had paresthesias and one had skin pigmentation. Three patients had transient superficial thrombophlebitis in a treated segment of a superficial collateral of the GSV. One patient was found to have extension of an asymptomatic, nonocclusive thrombus into the common femoral vein 1 week after the procedure.

Conclusion

Radiofrequency ablation of the GSV appears to be a safe alternative to conventional stripping and ligation. Randomised clinical trials and longer follow-up periods are required to establish the overall superiority of the procedure in comparison to conventional stripping.     

Study of the course of the incidence angle during growth

Standing posture is made possible by hip extension and lumbar lordosis. Lumbar lordosis is correlated with pelvic parameters, such as the declivity angle of the upper surface of the sacrum and the incidence angle, which determine the sagittal morphotype. Incidence angle, which is different for each individual, is known to be very important for upright posture, but its course during life has not yet been established. Incidence angle was measured on radiographs of 30 fetuses, 30 children and 30 adults, and results were analysed using the correlation coefficientr and Student's t test. A statistically significant correlation between age and incidence angle was observed. Incidence angle considerably increases during the first months, continues to increase during early years, and stabilizes around the age of 10 years. Incidence is a mark of bipedism, and its role in sagittal balance is essential.     

Endovascular treatment of a post-traumatic tibial pseudoaneurysm and arteriovenous fistula: case report and review of the literature

Here we report a rare case of a 74-year-old man with a pseudoaneurysm of the anterior tibial artery and a concomitant arteriovenous fistula (AVF). The patient was admitted because of increasing pain following the formation of a large mass located in the anterior mid-portion of the calf after a moderate non-penetrating blunt trauma. A polytetrafluoroethylene-covered stent was placed over the origin of the pseudoaneurysm, with complete exclusion of the pseudoaneurysm and disappearance of the AVF. One year after the procedure the mass had completely disappeared and the vascular anatomy of the calf is well preserved.     

The sentinel node biopsy in early gastric cancer: a preliminary study

Background and aims Sentinel node biopsy is currently used in surgery of malignant melanoma and breast cancer. The feasibility of sentinel node mapping in gastrointestinal cancers and its diagnostic sensitivity is unclear. It could be of particular value in the management of early gastric cancer in which radical D2 lymphadenectomy may be unnecessary. Materials and methods From January 2004 to June 2005, ten patients with preoperative diagnosis of early gastric cancer and no nodal involvement (cT1N0) were submitted to sentinel node biopsy using the dual mapping procedure with endoscopic blue dye and ^99mTc radio colloid injection. All the patients underwent standard radical gastrectomy and D2 lymphadenectomy. The resected nodes were evaluated by routine (hematoxylin–eosin) histopathological examination; the sentinel (blue or hot) nodes, in addition, were evaluated with immunohistochemistry for cytokeratin. Results The detection rate of this procedure was 100%. The preliminary results and perspectives for feasibility of sentinel node biopsy and its accuracy in predicting the nodal status in early gastric cancer are discussed.     

Primary therapy with ECF in combination with a GnRH analog in premenopausal women with hormone receptor-positive T2-T4 breast cancer

Patients with hormone receptor-positive tumors less often show a pathological complete response (pCR) than do those with hormone receptor-negative tumors. The addition of endocrine therapies may improve the clinical benefits of primary therapies in these patients. We investigated the efficacy of the epirubicin+cisplatin+fluorouracil (ECF) as continuous infusion) regimen in association with a gonadotropin-releasing hormone (GnRH) analog in 36 premenopausal women with T2-T4a-d N0-2 M0 ER and/or PgR-positive breast cancer. Median age was 39.5 years (range 26-53). Clinical response (complete or partial) was observed in 27 out of 36 patients (75% 95% CI 57.8-87.9%) and a pCR was observed in four patients (11%). Nine (25%) patients had stable disease and no progression was observed. Twenty-one patients (58%) were submitted for breast-conserving surgery and 15 had a radical mastectomy. No baseline clinical and biological characteristics significantly correlated with response. Thirty out of 31 patients evaluable for endocrine assessment had documented ovarian suppression, which occurred after a median of 28 days (range 20-43). We conclude that the combination of ECF and a GnRH analog is associated with a high response rate in the primary treatment of breast cancer. Further studies combining chemotherapy and endocrine agents are warranted in patients with hormone receptor-positive tumors.     

Management of 100 consecutive cases of pancreatic serous cystadenoma: wait for symptoms and see at imaging or vice versa?

Abstract Pancreatic serous cystadenomas have a low malignancy rate. When nonsymptomatic, in selected patients, they can be managed without surgery; however, a high degree of diagnostic reliability is crucial. We admitted 100 consecutive cases (87 women with a median age of 51.86 years). Of these, 44 were symptomatic and 56 were diagnosed incidentally. Ultrasound correctly diagnosed 53% of the cases, incorrectly 31%, and was nondiagnostic in 16%. Computed tomography scan had similar rates (54%, 34% and 12%, respectively), while magnetic resonance imaging improved diagnostic accuracy to 74% and reduced incorrect diagnoses to 26%. In 21 cases, exploratory needle aspiration of the cyst was carried out; only 8 samples (38%) resulted in a diagnosis; in 12 patients (57%) insufficient material was acquired to allow for diagnosis, one case demonstrated epithelial dysplasia. In 1 patient an exploratory puncture resulted in a very serious bleeding. Sixty-eight patients were treated surgically, the 44 symptomatic cases and another 24 patients with ill-defined oligocystic lesions that could not be differentiated as serous or mucinous in the preoperative period. Two patients underwent resection because of frank tumor growth. In the two time periods analyzed (the first 7 years and the subsequent 6.5 years) the relationship between cases observed/operated on did not significantly change. Twenty-one (30.8%) distal pancreatectomies, 14 (20.5%) intermediate resections, 10 (14.7%) pancreaticoduodenectomies 4 (5.8%) enucleations, and 1 (1.4%) duodenum-preserving pancreatic head resection were carried out. Nine patients (13.2%), underwent exploratory laparotomy with a diagnostic biopsy. Another 9 underwent decompressive interventions with cystojejunostomies. The morbidity was 27.9%, with a reoperation rate of 7.3% and zero mortality. In general the patient’s pain resolved in the postoperative period. Median follow-up was 43 months (range, 4–191 months). One patient died from other causes, and all others are currently alive. In the group of 32 patients who did not undergo operation, the median follow-up is 69 months (range, 8–164 months). Until more sophisticated technologies can be developed, the current diagnostic work-up will not result in increased preoperative diagnosis of serous-cystic tumors of the pancreas. This is mainly relevant to the oligocystic forms, which account for about one fourth of all serous tumors observed. Electronic Publication     

Nipple-sparing mastectomy for breast cancer and risk reduction: oncologic or technical problem?

BACKGROUND: We evaluated the risks and benefits of nipple-sparing mastectomy in a multiinstitutional experience in the settings of risk-reducing surgery and breast cancer treatment. STUDY DESIGN: We analyzed data on 123 patients who had undergone nipple-sparing mastectomy with breast reconstruction for prophylaxis (n=55), treatment of breast cancer (n=41), or both (n=27) at four large centers. RESULTS: Median patient age was 45 years (range 22 to 70 years). There were 192 procedures (69 bilateral, 54 unilateral). Forty-four patients had invasive cancer; 20 had ductal carcinoma in situ (DCIS); 4 had phyllodes tumor. In all of these patients, the nipple tissue was cancer free on pathologic review. Median followup was 24.6 months (range 2.0 to 570.4 months). Local recurrence developed in two patients: one had DCIS in the upper-outer quadrant, with 71.8 months of followup; the other's cancer was invasive, in the upper-outer quadrant, with 6 months of followup. Distant metastasis developed in a third patient, who died 50 months after the procedure. Breast cancer developed in two patients after prophylactic mastectomy: one in the upper-outer quadrant at 61.8 months; one in the axillary tail at 24.4 months. No patients had recurrences in the nipple-areolar complex. Necrosis of the nipple was reported in 22 of 192 patients (11%) and it was judged minimal (less than one-third total skin of nipple) in 13 of 22 patients (59%). Overall cosmesis was judged by the patient and surgeon as good to excellent in the majority of patients. Level of satisfaction with cosmetic results was similar between prophylactic and treatment patients. CONCLUSIONS: The risk of local relapse was very low in our series of nipple-sparing mastectomies performed for DCIS or invasive cancer. Nipple-sparing mastectomy in the risk-reducing and breast cancer-treatment settings may be feasible in selected patients and should be the subject of additional prospective clinical trials.     

Contrast-enhanced intraoperative ultrasonography during hepatectomies for colorectal cancer liver metastases

Preliminary reports showed that contrast-enhanced intraoperative ultrasonography (CEIOUS) provides information on primary or metastatic tumors of the liver that is not obtainable with conventional intraoperative ultrasonography (IOUS). This study validates the impact of CEIOUS, focusing on resective surgery for colorectal cancer (CRC) liver metastases. Twenty-four consecutive patients underwent liver resection using IOUS and CEIOUS for CRC liver metastases. CEIOUS was accomplished with intravenous injection of 4.8 mL of sulphur-hexafluoride microbubbles. CEIOUS found lesions missed at preoperative imaging and at IOUS in four patients and confirmed all of the new findings of IOUS in four patients. In addition, CEIOUS helped to define the tumor margins of the main lesion in 29% of patients with CRC liver metastases. No adverse effects were observed in relation with CEIOUS. In conclusion, CEIOUS improves IOUS accuracy with a significant impact on surgical strategy and radicality in patients who undergo surgery for CRC liver metastases. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).