Estrogen Receptor Expression in Pancreatic Adenocarcinoma: Time to Reconsider Evidence.

ABSTRACT: Pancreatic adenocarcinoma remains a chemotherapy-resistant and refractory malignancy with high mortality, unaffected by recent progress in anticancer treatment. Expression of estrogen receptors was detected almost 50 years ago, in both benign and malignant pancreatic cells. However, early preclinical studies in pancreatic cancer led to contradictory findings, and most clinical studies failed to demonstrate an effect with tamoxifen treatment. The identification of a second form of estrogen receptor seems to provide some explanation for these discrepancies. Predominantly expressed in malignant cells and structurally different from what was considered the only estrogen receptor, estrogen receptor ß was recognized as a negative prognostic factor and a possible therapeutic target in pancreatic ductal adenocarcinoma. Therefore, findings of research before the identification of estrogen receptor ß should be reconsidered, and further studies should be designed to reassess the expression and effect of this specific estrogen receptor type in pancreatic cancer.

Total Laparoscopic Excision of an Altman Type IV Sacrococcygeal Teratoma with the Assistance of Intraoperative Transrectal Sonography.

OBJECTIVE: To present the case of a young patient with an Altman type IV sacrococcygeal teratoma (Fig 1) managed exclusively with laparoscopy. DESIGN: A step-by-step demonstration of the technique. SETTING: A 24-year-old patient complaining of dysmenorrhea, deep dyspareunia, chronic constipation, dyschezia, and bladder atony was diagnosed with a 5-cm cystic tumor compressing the low rectum and overlying the left levator ani muscle. INTERVENTIONS: Laparoscopic excision of the tumor. At laparoscopy, significant bilateral pelvic venous congestion was found. The left medial and lateral pararectal fossa and the rectovaginal space were developed to the level of the pelvic floor. Several branches of the left internal artery and vein were dissected. The left hypogastric nerve and deep hypogastric plexus were dissected in an effort to preserve ipsilateral autonomic nerve supply to the rectum. Owing to the tumor's soft consistency and dense adherence to the surrounding structures, transrectal sonography facilitated dissection, which was performed medially to the mesorectal fascia and anteriorly to the presacral fascia. The middle sacral artery and peripheral branches of the internal iliac vasculature supplying the tumor were ligated. Part of the left levator ani had to be excised. The rectum was injured during the effort to detach the tumor from its lateral wall. The injury was repaired laparoscopically. The cut edge of the levator ani was used as a flap to reinforce the repair. CONCLUSION: Sacrococcygeal teratomas lying entirely in the pelvis (Altman type IV) are extremely rare [1,2]. Complete laparoscopic excision is challenging and potentially dangerous [3-5], but it is feasible with careful dissection.

Receptor-Binding Cancer Antigen Expression in Thyroid Neoplasms: A Retrospective Study.

Background: Receptor-binding cancer antigen (RCAS1) is a membrane protein, regarded as a tumor-associated antigen. Cancer cells evade immune response with RCAS1 up-regulation, inducing apoptosis to tumor infiltrating lymphocytes. Thyroid cancer incidence is rising and its accurate diagnosis in early stage is targeted. The aim of this study is to access RCAS1 expression in benign and malignant thyroid pathology. Methods: This is a retrospective study of 110 patients, who had thyroidectomy in a single tertiary referral centre between January 2008 until December 2014. Immunohistochemistry study for RCAS1 expression was carried out and correlation with clinical and histopathological data is attempted. Results: RCAS1 immunostaining was found positive in 81 out of 110 cases. Notably it was deemed positive in all malignant thyroid tissue samples (p 0.001). In thyroid malignancy, tumor size, thyroid capsule invasion and positive lymph nodes status were positively correlated with moderate and strong expression of RCAS1. For papillary thyroid carcinoma, the vast majority (35/37 cases, 94.6%) were also classified as having moderate or strong RCAS1 expression. Conclusions: RCAS1 expression can aid in differential diagnosis between benign and malignant thyroid pathology, while its strong expression correlates with worse oncological features.

Survivin expression in hepatocellular carcinoma. Correlation with clinicopathological characteristics and overall survival.

PURPOSE: Survivin expression is a potential prognostic indicator in various carcinomas. The prognostic value of Survivin for survival in hepatocellular carcinoma, (HCC) however, remains controversial. The aim of the study is to examine the expression of the inhibitor of apoptosis Survivin in HCC and investigate the correlation with the clinic-pathologic characteristics and overall survival (OS) following surgical resection. METHODS: Specimens from patients with resected HCC were examined by Immunohistochemical staining for Survivin and BCL-2expression. Clinical and histopathological data were retrieved from medical and pathology records, while OS was determined by reviewing records from the department of Oncology and personal communication with survivors. Bivariate analysis was performed using the Chi-square and Mann-Whitney U tests, while survival was estimated by Kaplan Meier method and compared with log-rank test. RESULTS: Sixty patients were included in the study. Survivin was expressed in 26 patients (43.3%). Survivin expression was significantly correlated to OS (p=0.014). A statistically significant negative correlation between Survivin and BCL-2 was also noted (p<0.001). CONCLUSIONS: Survivin expression reflects aggressive histological and clinical behavior of HCC and correlates with poorer OS. Further studies are required to confirm if Survivin can be used as a predictive biomarker to evaluate prognosis and target treatments for HCC.

Survivin expression as an independent predictor of overall survival in pancreatic adenocarcinoma.

CONTEXT: Survivin is an antiapoptotic protein with a role in tumorigenesis and suggested prognostic value in several proliferative diseases. AIMS: This study aimed to examine the role of survivin as a prognostic marker in pancreatic adenocarcinoma (PDAC). SETTINGS AND DESIGN: Fifty-one specimens of PDAC were assessed for survivin expression by immunohistochemistry. SUBJECTS AND METHODS: Overall survival and 1-, 3-, and 5-year survival were retrieved retrospectively. STATISTICAL ANALYSIS USED: Bivariate analysis was conducted using Chi-square and Mann-Whitney U tests, while survival analysis was conducted using Kaplan-Meier statistics. RESULTS: Of the 51 assessed cases, 49% were positive for survivin. Survivin expression was significantly correlated 1-year survival and overall survival, particularly in bcl-2 positive cases. CONCLUSIONS: Survivin may be implicated in the bcl-2 and p53 pathways and therefore in the biology of PDAC. Its potential use as a survival predictor and therapeutic target represent a promising field.

Contrast-Enhanced Color Doppler Ultrasonography for Preoperative Evaluation of Sentinel Lymph Node in Breast Cancer Patients.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard of care for breast cancer patients with non-palpable axillary lymph nodes. We evaluated the usefulness of contrast-enhanced ultrasonography in preoperative detection of malignant SLNs. METHODS: 50 patients with breast cancer (median age: 60 years) underwent a color power Doppler ultrasonography with intravenous contrast (Sonovue®) preoperatively, and findings suggestive of metastatic disease to the SLN were documented. The final histopathological report and the radiological preoperative record were compared. Finally, the sensitivity, specificity and diagnostic accuracy of this evolving diagnostic modality were calculated. RESULTS: Contrast-enhanced ultrasound scan identified a negative SLN in the axilla of 27 patients and final histopathology was negative for 30 cases in total, so negative predictive value was calculated as 90% and positive predictive value was 75%. Overall sensitivity was 83.33% and specificity was 84.38%. Moreover, the ability of contrast-enhanced ultrasound to differentiate between SLN status was only statistically significantly correlated with the actual final histopathological report (p < 0.001), while successful ultrasound prediction was not correlated with any factor. CONCLUSIONS: SLN status can be evaluated preoperatively using contrast-enhanced color Doppler ultrasonography with high accuracy.

Association of FokI and PvuII polymorphisms with breast cancer staging and survival among Caucasian women: a prospective study.

PURPOSE: Both vitamin D and estrogens play an important role in breast cell growth and differentiation. Therefore, we hypothesized that FokI polymorphism in the Vitamin D Receptor (VDR) gene, as well as PvuII polymorphism in the Estrogen Receptor (ESR) gene might be associated with progression of breast cancer. The aim of this study was to prospectively examine the association of these polymorphisms with histopathological features and prognosis among women with histologically proven breast cancer. METHODS: Patient characteristics, tumor histopathology, and genotyping of one VDR polymorphism variant (FokI) and one ER polymorphism variant (PvuII) were recorded. Patients were also routinely followed up. RESULTS: There was a significant difference regarding nodal stage (p<0.001) between the different genotypes of FokI polymorphisms (FF, Ff, ff), even though a trend was also detected in the frequency between ductal and lobular type, as well as tumor size (p=0.077). When further analysis was performed regarding patients whose polymorphism included the f allele, we found statistically significant differences in tumor size (p<0.001), nodal stage (p=0.03), tumor grade (p=0.04) and lymphovascular invasion (p<0.001), while no differences in nodal status, distant metastases and tumor stage were noticed. No significant associations were found between any of the PvuII polymorphism variants and tumor histopathology and stage. No statistical significance was proven between FokI polymorphism's variants or f allele and overall or progression-free survival. Statistically significant associations between overall and progression- free survival and PvuII polymorphism's variants was demonstrated (p<0.001). CONCLUSION: The f allele was associated with the presence of lymphovascular invasion and poorly differentiated tumors, whereas the PP genotype was associated with increased overall and progression-free survival, suggesting that this variant is related to a more favorable prognosis.

Clinicopathological Characteristics of Four Cases of Adrenal Myelolipomas: A Rare Surgical Entity.

Myelolipomas are unusual benign tumors or tumor-like lesions, composed of hematopoietic cells and mature adipose tissue. They usually are asymptomatic and behave as non-functioning, unilateral, small adrenal tumors often found incidentally on imaging studies. We report the clinicopathological characteristics of four cases of adrenal myelolipomas treated in our hospital, worth to mention because of their rarity and their significant size. Myelolipomas were first described by Gierke in 1905, and the term myelolipoma was coined by Oberling in 1929. The adrenal gland is the most common site, but myelolipomas are also rarely present in extra-adrenal sites, including the pelvis, mediastinum, retroperitoneum, and paravertebral region, as an isolated soft tissue mass. These tumors account for 2.6% of the primary adrenal masses with equal sex distribution and in our reviewed material of a decade they constitute about 5% in a series of surgically treated adrenals for various neoplastic processes of the adrenals. Although usually small in size, in our series a remarkable large size of the tumors examined was observed, ranging from 7 - 15 cm. Adrenal myelolipoma is often an "incidentaloma", since its diagnosis is frequently based on autoptic findings or made during surgical interventions and imaging procedures performed for other purposes, as happened in our cases.

Managing injuries of hepatic duct confluence variants after major hepatobiliary surgery: an algorithmic approach.

AIM: To investigate injuries of anatomy variants of hepatic duct confluence during hepatobiliary surgery and their impact on morbidity and mortality of these procedures. An algorithmic approach for the management of these injuries is proposed. METHODS: During a 6-year period 234 patients who had undergone major hepatobiliary surgery were retrospectively reviewed in order to study postoperative bile leakage. Diagnostic workup included endoscopic and magnetic retrograde cholangiopancreatography (E/MRCP), scintigraphy and fistulography. RESULTS: Thirty (12.8%) patients who developed postoperative bile leaks were identified. Endoscopic stenting and percutaneous drainage were successful in 23 patients with bile leaks from the liver cut surface. In the rest seven patients with injuries of hepatic duct confluence, biliary variations were recognized and a stepwise therapeutic approach was considered. Conservative management was successful only in 2 patients. Volume of the liver remnant and functional liver reserve as well as local sepsis were used as criteria for either resection of the corresponding liver segment or construction of a biliary-enteric anastomosis. Two deaths occurred in this group of patients with hepatic duct confluence variants (mortality rate 28.5%). CONCLUSION: Management of major biliary fistulae that are disconnected from the mainstream of the biliary tree and related to injury of variants of the hepatic duct confluence is extremely challenging. These patients have a grave prognosis and an early surgical procedure has to be considered.

Sharp liver transection versus clamp crushing technique in liver resections: a prospective study.

BACKGROUND: Parenchymal liver transection constitutes an important phase of liver resection. Serious intraoperative bleeding, together with injuries to vital structures of the liver remnant, can occur during this stage. A method of sharp liver parenchymal transection with scalpel is compared in a prospective randomized manner with the widely used clamp crushing technique. METHODS: Patients scheduled for hepatectomy under selective hepatic vascular exclusion (N = 82) were allocated randomly to either the sharp transection group (n = 41) or the clamp crushing group (n = 41). Warm ischemic time, blood loss and transfusions, postoperative morbidity and mortality, and tumor-free margins were recorded in both groups and analyzed. RESULTS: When the sharp transection group was compared with the clamp crushing group, the two groups were similar in warm ischemic time (median 36 vs 34 minutes), total operative time (median 205 vs 211 minutes), intraoperative blood loss (median 500 vs 460 mL), blood transfusion requirements (median value 0 in both groups), and overall complication rate (44% vs 39%). However, sharp transection yielded better tumor-free margins compared with the clamp crushing technique (12 +/- 1.4 mm vs 8 +/- 1.5 mm, mean +/- SD, P < .05). CONCLUSION: Sharp liver parenchymal transection with a scalpel is equally safe in terms of blood loss and mortality compared with the clamp crushing method. Although it is a technically demanding method, requiring selective hepatic vascular occlusion, it may be recommended when the tumor-free margins are anticipated to be narrow.

A rare case of complex vascular reconstruction in liver transplantation.

Abnormalities of recipient or donor vascular structures are associated with reconstructive difficulties in liver transplantation. A patient with thrombosis of the right hepatic vein and associated stricture of the inferior vena cava (IVC), portal vein thrombosis and multiple aberrant arteries underwent orthotopic liver transplantation. The donor's suprahepatic IVC was anastomosed to the recipient's intrathoracic IVC. The portal vein flow was restored by venous graft interposition, while the arterial flow was ensured by interposing an iliac arterial graft anastomosed to the infrarenal aorta. In conclusion, graft function remains excellent more than 5 years postoperatively.

The role of central venous pressure and type of vascular control in blood loss during major liver resections.

BACKGROUND: Blood loss during liver resection constitutes the primary determinant of the postoperative outcome. Various techniques of vascular control and maintenance of a low central vein pressure (CVP) have been used in order to prevent intraoperative blood loss and postoperative complications. Our study aims at assessing the effects of different levels of CVP in relation to type of vascular control on perioperative blood loss and patient outcome. METHODS: The records of 102 consecutive patients who underwent a major hepatectomy were retrospectively analyzed. Forty-two patients were operated on with a CVP of 6 mm Hg or more and 60 patients had a CVP of 5 mm Hg or less. The Pringle maneuver was used in 45 patients and selective hepatic vascular exclusion (SHVE) in 57 patients. Blood loss, complications, and mortality were analyzed comparing the two CVP groups in relation to type of vascular control. RESULTS: The Pringle maneuver is associated with more blood loss when CVP is 6 mm Hg or more compared with CVP 5 mm Hg or less (1,250 mL [250 to 2,850] versus 780 mL [150 to 3,100]; P <0.05). Conversely, blood loss during SHVE is independent of the CVP levels. A significant difference in blood loss between the Pringle maneuver and SHVE was observed, only when CVP was 6 mm Hg or more (1,250 mL [250 to 2,850] versus 680 mL [150 to 1,260]; P <0.05). Hospital stay was also significantly longer in patients operated on with CVP 6 mm Hg or more (15 days [4 to 38] than in patients with CVP 5 mm Hg or less (10 days [4 to 32]; P <0.05). CONCLUSIONS: Elevated CVP during major liver resections results in greater blood loss and a longer hospital stay. The Pringle maneuver with CVP 5 mm Hg or less is associated with blood loss not significantly different from that with SHVE. The latter, though, has been shown not to be affected by CVP levels and should be used whenever CVP remains high despite adequate anesthetic management.

Effects of hepatovenous back flow on ischemic- reperfusion injuries in liver resections with the pringle maneuver.

BACKGROUND: Experimental findings have demonstrated a beneficial role of retrograde blood flow from hepatic veins that takes place during the Pringle maneuver in liver resections. The cytoprotective effect of hepatovenous back-perfusion has not been evaluated in humans. A randomized prospective study was designed to compare the response of liver cells to ischemic-reperfusion injury during the application of two different ischemic procedures: inflow versus inflow plus outflow vascular occlusion of the liver. STUDY DESIGN: Forty patients were randomly allocated to undergo liver resection using the continuous Pringle maneuver (n = 20) or inflow plus outflow vascular occlusion of the liver by selective hepatic vascular exclusion (n = 20). Liver function was assessed on postoperative days 1 to 6. Response of liver cells to I/R injury was evaluated by measuring interleukins IL-6 and IL-8 at 3, 12, 24, and 48 hours after reperfusion. Oxidative stress was assessed by measuring malondialdehyde levels. RESULTS: Both groups were comparable regarding ischemic time, operative time, and extent of liver resection. Patients in whom retrograde blood flow to the liver took place during the Pringle maneuver showed better liver function postoperatively and less severe hepatic I/R injuries compared with those undergoing liver resection using both inflow and outflow vascular occlusion. Oxidative stress was significantly lower in the Pringle maneuver group compared with the inflow plus outflow vascular occlusion group (mean [+/- SD] malondialdehyde 8 +/- 2.1 micromol/L in the Pringle group versus 14.7 +/- 1.8 micromol/L in the selective hepatic vascular exclusion group 30 min after reperfusion, p < 0.01). CONCLUSIONS: Back perfusion via hepatic veins contributes to attenuation of I/R damage during the Pringle maneuver and should be preferred if possible during liver resection.

Anaesthetic and perioperative management of paediatric organ recipients in nontransplant surgery.

The number and success rate of paediatric organ transplantation continue to improve yearly, and the number of transplanted children presenting for either elective or emergency nontransplant surgery is expected to increase accordingly. The general considerations related to any transplant recipient are the physiological and pharmacological problems of allograft denervation, the side effects of immunosuppression, the risk of infection, and the potential for rejection. Preoperative assessment of transplant recipients undergoing non-transplant surgery should focus on graft function, the risk of infection, and function of other organs. Local, regional, or general anaesthesia can be safely delivered to transplant recipients. Specific anaesthetic considerations related to the type of transplantation, have an impact directly on anaesthetic and perioperative management. Since anaesthetists and surgeons in hospitals who are not involved in transplantations, may be required to manage paediatric transplant recipients, the reviews of the existing experience in this field will be valuable tools in their hands.

Selective hepatic vascular exclusion versus Pringle maneuver in major liver resections: prospective study.

Selective hepatic vascular exclusion (SHVE) and the Pringle maneuver are two methods used to control bleeding during hepatectomy. They are compared in a prospective randomized study, where 110 patients undergoing major liver resection were randomly allocated to the SHVE group or the Pringle group. Data regarding the intraoperative and postoperative courses of the patients are analyzed. Intraoperative blood loss and transfusion requirements were significantly decreased in the SHVE group, and postoperative liver function was better in that group. Although there was no difference between the two groups regarding the postoperative complications rate, patients offered the Pringle maneuver had a significantly longer hospital stay. The application of SHVE did not prolong the warm ischemia time or the total operating time. It is evident from the present study that SHVE performed by experienced surgeons is as safe as the Pringle maneuver and is well tolerated by the patients. It is much more effective than the Pringle maneuver for controlling intraoperative bleeding, and it is associated with better postoperative liver function and shorter hospital stay.

Hemodynamic interaction between portal vein and hepatic artery flow in small-for-size split liver transplantation.

In split-liver transplantation, the entire portal flow is redirected through relatively small-for-size grafts. It has been postulated that excessive portal blood flow leads to graft injury. In order to elucidate the mechanisms of this injury, we studied the hemodynamic interactions between portal vein- and hepatic artery flow in an experimental model in pigs. Six whole pig liver grafts were implanted in Group 1 ( n=6) and six whole liver grafts were split into right and left grafts and transplanted to Groups 2 ( n=6) and 3 ( n=6), respectively. The graft-to-recipient liver volume ratio was 1:1, 2:3 and 1:3 in Groups 1, 2 and 3, respectively. Portal vein- and hepatic artery flows were measured with an ultrasonic flow meter at 60,120 and 180 min after graft reperfusion. Portal vein pressure was also recorded at the same time intervals. Graft function was assessed at 3,6h and 12h, and morphological changes at 12h after reperfusion. Following reperfusion, portal vein flow showed an inverse relationship to graft size, while hepatic artery flow was reduced proportionately to graft size. The difference was significant among the three groups ( P<0.05). Portal vein pressure was significantly higher in group 3, compared to groups 1 and 2 ( P<0.05). Hepatic artery buffer response was significantly higher in Group 3, compared to Groups 1 and 2 in relation to pre-occlusion values ( P<0.05). Split-liver transplantation, when resulting in small-for-size grafts, is associated with portal hypertension, diminished arterial flow, and graft dysfunction. Arterial flow impairment appears to be related to increased portal vein flow.

Total versus selective hepatic vascular exclusion in major liver resections.

BACKGROUND: Total hepatic vascular exclusion (THVE) and selective hepatic vascular exclusion (SHVE) are two effective techniques for bleeding control in major hepatic resections. Outcomes of the two procedures were compared. METHODS: Patients undergoing major liver resection were randomly allocated to the THVE and SHVE groups. Intraoperative hemodynamic changes and the postoperative course of the two groups were compared. RESULTS: During vascular clamping, the THVE group showed a significant elevation in pulmonary vascular resistance, systemic vascular resistance, intrapulmonary shunts, and a significant reduction in cardiac index, compared with the SHVE group (P <0.05). Patients undergoing THVE received more crystalloids and blood, showed more severe liver, renal and pancreatic dysfunction, and had a longer hospital stay than the SHVE group (P <0.05). CONCLUSIONS: Both techniques are equally effective in bleeding control in major liver resections. THVE is associated with cardiorespiratory and hemodynamic alterations and may be not tolerated by some patients. SHVE is well tolerated with fewer postoperative complications and shorter hospitalization time.