Archive for July, 2010

Renal carcinoma infiltrating inferior vena cava and combined valvular heart disease - one-stage uro-cardiological procedure: a case report

Wednesday, July 28th, 2010

Standard treatment of patients with coexisting cardiac and non-cardiac diseases includes two separate operations. We report a case of 55-year-old man with combined valvular heart disease and renal carcinoma infiltrating inferior caval vein, who underwent one-stage cardio-urologic procedure. In the first step, mitral and tricuspid valvuloplasty were performed by cardiac surgeons. Then , urologists performed radical nephrectomy and thrombectomy. The postoperative course was uneventful. In twelve months follow-up the patient shows no signs of reccurrence and he had no symptoms of cardiac disease. To the best of our knowledge such a case has never been reported before in the literature.

CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion

Saturday, July 24th, 2010

Background:
Ovarian carcinoma (OvCa) is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells and its only natural ligand, CCL25, is largely expressed in the thymus, which involutes with age. Other than the thymus, CCL25 is expressed by the small bowel. Interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for OvCa cells. The current study shows OvCa tissue and cells significantly express CCR9, which interacts with CCL25 to support carcinoma cell migration and invasion.
Methods:
RT-PCR and flow cytometry techniques were used to quantify the expression CCR9 by OvCa cells. OvCa tissue microarrays (TMA) was used to confirm CCR9 expression in clinical samples. The Aperio ScanScope scanning system was used to quantify immunohistochemical staining. Cell invasion and migration assays were performed using cell migration and matrigel invasion chambers. Matrix metalloproteinase (MMP) mRNAs were quantified by RT-PCR and active MMPs were quantified by ELISA.
Results:
Our results show significantly (p < 0.001) higher expression of CCR9 by mucinous adenocarcinoma, papillary serous carcinoma, and endometriod ovarian carcinoma cases, than compared to non-neoplastic ovarian tissue. Furthermore, CCR9 expression was significantly elevated in OvCa cell lines (OVCAR-3 and CAOV-3) in comparison to normal adult ovarian epithelial cell mRNA. OvCa cells showed higher migratory and invasive potential towards chemotactic gradients of CCL25, which was inhibited by anti-CCR9 antibodies. Expression of collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), and stromelysins (MMP-3, -10, and -11) by OvCa cells were modulated by CCL25 in a CCR9-dependent fashion.
Conclusions:
These results demonstrate both biological significance and clinical relevance of CCL25 and CCR9 interactions in OvCa cell metastasis.

Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins

Tuesday, July 20th, 2010

AimThe aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components.
Methods:
23 cases of uterine MMMT identified from the Saskatchewan Cancer Agency (1970-1999) were evaluated. Immunohistochemical expression of Bad, Mcl-1, bcl-x, bak, mdm2, bax, p16, p21, p53, p27, EMA, Bcl-2, Ki67 and PCNA was correlated with clinico-pathological data including survival outcomes.
Results:
Histopathological examination confirmed malignant epithelial component with homologous (12 cases) and heterologous (11 cases) sarcomatous elements. P53 was strongly expressed (70-95%) in 15 cases and negative in 5 cases. The average survival in the p53+ve cases was 3.56 years as opposed to 8.94 years in p53-ve cases. Overexpression of p16 and Mcl-1 were observed in patients with longer survival outcomes (>2 years). P16 and p21 were overexpressed in the carcinomatous and sarcomatous elements respectively. Cyclin-D1 was focally expressed only in the carcinomatous elements.
Conclusions:
Our study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus.

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial).

Tuesday, July 20th, 2010

Background:
Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts’ opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects.
Methods:
A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I) A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days). II) A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey’s classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included.
Conclusion:
A clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach.Trial registration number : NCT01111253

Decompressive laparotomy with temporary abdominal closure versus percutaneous puncture with placement of abdominal catheter in patients with abdominal compartment syndrome during acute pancreatitis: background and design of multicenter, randomised, controlled study

Friday, July 16th, 2010

Background:
Development of abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) has a strong impact on the course of disease. Number of patients with this complication increases during the years due more aggressive fluid resuscitation, much bigger proportion of patients who is treated conservatively or by minimal invasive approach, and efforts to delay open surgery. There have not been standard recommendations for a surgical or some other interventional treatment of patients who develop ACS during the SAP. The aim of DECOMPRESS study was to compare decompresive laparotomy with temporary abdominal closure and percutaneus puncture with placement of abdominal catheter in these patients.
Methods:
One hundred patients with ACS will be randomly allocated to two groups: I) decompresive laparotomy with temporary abdominal closure or II) percutaneus puncture with placement of abdominal catheter. Patients will be recruited from five hospitals in Belgrade during two years period. The primary endpoint is the mortality rate within hospitalization. Secondary endpoints are time interval between intervention and resolving of organ failure and multi organ dysfunction syndrome, incidence of infectious complications and duration of hospital and ICU stay. A total sample size of 100 patients was calculated to demonstrate that decompresive laparotomy with temporary abdominal closure can reduce mortality rate from 60% to 40% with 80% power at 5% alfa.
Conclusion:
DECOMPRESS study is designed to reveal a reduction in mortality and major morbidity by using decompresive laparotomy with temporary abdominal closure in comparison with percutaneus puncture with placement of abdominal catheter in patients with ACS during SAP.

Axillary sentinel lymph node biopsy after mastectomy: a case report

Sunday, July 11th, 2010

Background:
Sentinel lymph node biopsy has been established as the preferred method for staging early breast cancer. A prior history of mastectomy is felt to be a contraindication.Case presentationA patient with recurrent breast cancer in her skin flap was discovered to have positive axillary sentinel nodes by sentinel lymph node biopsy five years after mastectomy for ductal carcinoma in situ.
Conclusion:
A prior history of mastectomy may not be an absolute contraindication to sentinel lymph node biopsy.

The combined effect of erythropoietin and granulocyte macrophage colony stimulating factor on liver regeneration after major hepatectomy in rats

Wednesday, July 7th, 2010

Background:
The liver presents a remarkable capacity for regeneration after hepatectomy but the exact mechanisms and mediators involved are not yet fully clarified. Erythropoietin (EPO) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) have been shown to promote liver regeneration after major hepatectomy.Aim of this experimental study is to compare the impact of exogenous administration of EPO, GM-CSF, as well as their combination on the promotion of liver regeneration after major hepatectomy.
Methods:
Wistar rats were submitted to 70% major hepatectomy. The animals were assigned to 4 experimental groups: a control group (n=21) that received normal saline, an EPO group (n=21), that received EPO 500IU/kg, a GM-CSF group (n=21) that received 20mcg/kg of GM-CSF and a EPO+GMCSF group (n=21) which received a combination of the above. Seven animals of each group were killed on the 1st, 3rd and 7th postoperative day and their remnant liver was removed to evaluate liver regeneration by immunochemistry for PCNA and Ki 67.
Results:
Our data suggest that EPO and GM-CSF increases liver regeneration following major hepatectomy when administered perioperatively. EPO has a more significant effect than GM-CSF (p<0.01). When administering both, the effect of EPO seems to fade as EPO and GM-CSF treated rats have decreased regeneration compared to EPO administration alone (p<0.01).
Conclusion:
EPO, GM-CSF and their combination enhance liver regeneration after hepatectomy in rats when administered perioperatively. However their combination has a weaker effect on liver regeneration compared to EPO alone. Further investigation is needed to assess the exact mechanisms that mediate this finding.

A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part(R) Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

Wednesday, July 7th, 2010

Background:
Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.
Methods:
This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part(R) Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (+/-14 days) after surgery.DiscussionThis trial aims to assess, whether the intra-peritoneal application of A-Part(R) Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.Trial registrationNCT00646412

Unusually young age distribution of primary hepatic leiomyosarcoma: case series and review of the adult literature

Saturday, July 3rd, 2010

Background:
Primary hepatic leiomyosarcoma is a rare disease diagnosed in older aged adults with a median age of 58 and occasionally in children with a history of immunosuppression.
Methods:
From 1998 to 2009, 215 patients were diagnosed with primary hepatic malignancies at our institution, 4 of which were diagnosed with primary hepatic sarcoma (1.8%). Three cases were primary hepatic leiomyosarcomas (LMS) and one case was primary undifferentiated embryonal sarcoma of the liver; median age 30 (range 20-39) years.
Results:
One patient is currently 12 months post-resection with no evidence of recurrence. Two patients passed away at 19 days and 22 months from small for size liver and tumor recurrence respectively.
Conclusion:
We have presented 3 cases of primary hepatic leiomyosarcoma diagnosed at our institution with an unusually young age distribution and no evidence of immunosuppression. These cases highlight the diagnostic and therapeutic challenges of this rare tumour.