Mircea Beuran

The epithelial to mesenchymal transition in pancreatic cancer: A systematic review

BACKGROUND/OBJECTIVES The present article summarizes and analyzes the current knowledge about the role of the epithelial to mesenchymal transition (EMT) in the systemic invasiveness of pancreatic cancer. METHOD An electronic search of PubMed/MEDLINE, EMBASE, and the Web of Science was used to identify relevant original articles and reviews. RESULTS The EMT represents a key step during normal embryogenesis. However, increasing evidence reveals its essential role in the local progression and metastasis of pancreatic cancer. Areas of interest are the cross-linking between cells undergoing the EMT and pancreatic cancer stem cells, and the correlation between the EMT and chemoresistance to standard therapies. During carcinogenesis, malignant pancreatic cells at the primary site acquire the ability to undergo the EMT, a transformation associated with increased mobility. The reverse process at secondary sites, the mesenchymal to epithelial transition (MET), has devastating consequences, allowing neoplastic epithelial cells to invade surrounding tissues and spread to distant sites. Consequences of the EMT are the loss of E-cadherin expression and the acquisition of mesenchymal markers including fibronectin or vimentin. Detailed knowledge of the molecular processes underlying the EMT has opened possibilities for new therapeutic agents. These include an EMT approach for patients with early cancers, to prevent invasion and dissemination, and anti-MET therapy for patients with established metastasis. CONCLUSIONS The current literature shows a strong correlation between the EMT and the systemic aggressiveness of pancreatic tumors. Individualized therapy, targeting the process of EMT and its cross-linking with cancer stem cells, may increase survival of patients with pancreatic cancer.

Extralevator vs conventional abdominoperineal resection for rectal cancer—A systematic review and meta-analysis

BACKGROUND The aim of this study was to compare the short-term morbidity and long-term oncologic benefits of extralevator abdominoperineal excision (ELAPE) with conventional abdominoperineal resection (CAPR) for patients with rectal cancer. METHODS Electronic search of the Cochrane Library, MEDLINE, EMBASE, Korean Journal, and J-EAST database from 2007 until August 2015 was carried out. We considered randomized controlled trials and nonrandomized comparative studies comparing ELAPE with CAPR to be eligible, if they included patients with rectal cancers. RESULTS A total of 1 randomized controlled trials and 10 nonrandomized comparative studies met the inclusion criteria, involving 1,736 patients in the ELAPE group and 1,320 in the CAPR group. The ELAPE was associated with a significantly lower intraoperative perforation rate. There were no differences regarding the circumferential margin involvement, R0 resections, and local recurrence rate. There was less blood loss in ELAPE patients. CONCLUSIONS The ELAPE significantly lowered the intraoperative perforation rate, with no benefits regarding circumferential resection margin involvement and local recurrence rate.

Natural orifice translumenal endoscopic surgery (NOTES) second-look peritoneoscopy for staging of limited peritoneal carcinomatosis

BACKGROUND Over the past decades, staging laparoscopy evolved as a useful tool in multimodality treatment of patients with abdominal malignancies, especially for detection of incurable peritoneal and liver metastasis. Natural orifice translumenal endoscopic surgery (NOTES) is a new, evolving technique which represents the next logical progression in minimally invasive surgery and has theoretical advantages in comparison with standard laparoscopic surgery. A review of the current literature revealed a continuous increasing number of fundamental and clinical studies addressing NOTES approach in multimodal management of oncologic patients. Technical possibility to use this new minimally invasive approach for oncological resection of abdominal malignancies was proved by some investigators. HYPOTHESIS NOTES can be used as an alternative method for staging patients with limited peritoneal carcinomatosis and may have better results compared to current imaging techniques for small diameter metastatic disease. CONCLUSIONS With the continuous development of the NOTES techniques and technology, the second-look peritoneoscopy by NOTES may become an alternative method for staging in patients with peritoneal carcinomatosis. Nevertheless, NOTES is at a very early stage of its development, and its implementation in oncologic surgery should be made very caution, and only after careful evaluation.

Superior mesenteric artery first approach versus standard pancreaticoduodenectomy: a systematic review and meta-analysis

BACKGROUND The superior mesenteric artery (SMA) first approach was proposed recently as a new modification of the standard pancreaticoduodenectomy. Increasing evidence showed that a periadventiceal dissection of the SMA with early transection of the inflow during pancreaticoduodenectomy associates better early perioperative results, and setup the scene for long-term oncological benefits. The objectives of the current study are to compare the operative results and long-term oncological outcomes of SMA first approach pancreaticoduodenectomy (SMA-PD) with standard pancreaticoduodenectomy (S-PD). DATA SOURCES Electronic search of the PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Library was performed until July 2015. We considered randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) comparing SMA-PD with S-PD to be eligible if they included patients with periampullary cancers. RESULTS A total of one RCT and thirteen NRCSs met the inclusion criteria, involving 640 patients with SMA-PD and 514 patients with S-PD. The SMA-PD was associated with less intraoperative bleeding, less blood transfusions and higher rate of associated venous resections. The pancreatic fistula and delayed gastric emptying had a significantly lower rate in the SMA-PD group. There were no differences between the two approaches regarding overall complications, major complication rates and in-hospital mortality. There was no difference regarding R0 resection rate, and one-, two- or three-year overall survival. The SMA-PD was associated with a lower local, hepatic and extrahepatic metastatic rate. CONCLUSIONS The SMA-PD is associated with better perioperative outcomes, such as blood loss, transfusion requirements, pancreatic fistula, and delayed gastric emptying. Although the one-, two- or three-year overall survival rate is not superior, the SMA-PD has a lower local and metastatic recurrence rate.

MicroRNA-21 as a Prognostic Biomarker in Patients with Pancreatic Cancer – A Systematic Review and Meta-Analysis

OBJECTIVES The aim of this systematic review and meta-analysis is to summarize the current knowledge regarding microRNA-21 and to evaluate its prognostic impact in patients with pancreatic cancer. METHODS We conducted an electronic literature search to identify all published studies in PubMed/MEDLINE, Scopus and Google Scholar databases from 2000 until August 2016. RESULTS A total of 17 studies involving 1471 patients met the inclusion criteria for the quantitative synthesis. The microRNA-21 upregulation was significantly associated with poorer overall survival, disease-free survival, and progression-free survival. The subgroup analysis revealed that microRNA-21 overexpression has a significant higher prognostic value for patients who receive adjuvant chemotherapy. Increased microRNA-21 was associated with a statistically significant higher rate of metastatic lymph nodes and poorly differentiated tumors. CONCLUSIONS MicroRNA-21 upregulation in pancreatic cancer is associated with a significantly poorer overall survival, disease-free survival, and progression-free survival. MicroRNA-21 may be a useful prognostic biomarker, allowing stratification for chemotherapy administration, and being a component of precision medicine in patients with pancreatic cancer.

Most small bowel cancers are revealed by a complication.

ABSTRACT Objective To characterize the pattern of primary small bowel cancers in a tertiary East-European hospital. Methods A retrospective study of patients with small bowel cancers admitted to a tertiary emergency center, over the past 15 years. Results There were 57 patients with small bowel cancer, representing 0.039% of admissions and 0.059% of laparotomies. There were 37 (64.9%) men, mean age of 58 years; and 72 years for females. Out of 57 patients, 48 (84.2%) were admitted due to an emergency situation: obstruction in 21 (38.9%), perforation in 17 (31.5%), upper gastrointestinal bleeding in 8 (14.8%), and lower gastrointestinal bleeding in 2 (3.7%). There were 10 (17.5%) duodenal tumors, 21 (36.8%) jejunal tumors and 26 (45.6%) ileal tumors. The most frequent neoplasms were gastrointestinal stromal tumor in 24 patients (42.1%), adenocarcinoma in 19 (33.3%), lymphoma in 8 (14%), and carcinoids in 2 (3.5%). The prevalence of duodenal adenocarcinoma was 14.55 times greater than that of the small bowel, and the prevalence of duodenal stromal tumors was 1.818 time greater than that of the small bowel. Obstruction was the complication in adenocarcinoma in 57.9% of cases, and perforation was the major local complication (47.8%) in stromal tumors. Conclusion Primary small bowel cancers are usually diagnosed at advanced stages, and revealed by a local complication of the tumor. Their surgical management in emergency setting is associated to significant morbidity and mortality rates.

Surgical Anatomy of the Superior Mesenteric Vessels Related to Pancreaticoduodenectomy: a Systematic Review and Meta-Analysis

Background and PurposeMesopancreas dissection with central vascular ligation and the superior mesenteric artery (SMA)-first approach represent the cornerstone of current principles for radical resection for pancreatic head cancer. The surgeon dissecting around the SMV and SMA should be aware regarding the anatomical variants in this area. The aims of this systematic review and meta-analysis are to detail the surgical anatomy of the superior mesenteric vessels and to propose a standardized terminology with impact in pancreatic cancer surgery.MethodsWe conducted a systematic search to identify all published studies in PubMed/MEDLINE and Google Scholar databases from their inception up to March 2017.ResultsSeventy-eight studies, involving a total of 18,369 specimens, were included. The prevalence of the mesenteric-celiac trunk, replaced/accessory right hepatic artery (RRHA), common hepatic artery, and SMV inversion was 2.8, 13.2, 2.6, and 4.1%, respectively. The inferior pancreaticoduodenal artery has its origin into the first jejunal artery, SMA, and RRHA, in 58.7, 35.8, and 1.2% of cases, respectively. The SMV lacks a common trunk in 7.5% of cases. The first jejunal vein has a trajectory posterior to the SMA in 71.8% of cases. The left gastric vein drains into the portal vein in 58%, in splenic vein (SV) in 35.6%, and into the SV-PV confluence in 5.8% of cases.ConclusionsComplex pancreaticoduodenal resections require detailed knowledge of the superior mesenteric artery and vein, which is significantly different from the one presented in the classical textbooks of surgery. We are proposing the concept of the first jejunopancreatic vein which impacts the current oncological principles of pancreatic head cancer resection.

Surgical Anatomy of the Superior Mesenteric Vessels Related to Colon and Pancreatic Surgery: A Systematic Review and Meta-Analysis

The surgeon dissecting the base of the mesenterium, around the superior mesenteric vein (SMV) and artery, is facing a complex tridimensional vascular anatomy and should be aware of the anatomical variants in this area. The aim of this systematic review is to propose a standardized terminology of the superior mesenteric vessels, with impact in colon and pancreatic resections. We conducted a systematic search in PubMed/MEDLINE and Google Scholar databases up to March 2017. Forty-five studies, involving a total of 6090 specimens were included in the present meta-analysis. The pooled prevalence of the ileocolic, right colic and middle colic arteries was 99.8%, 60.1%, and 94.6%, respectively. The superior right colic vein and Henle trunk were present in 73.9%, and 89.7% of specimens, respectively. In conclusion, the infra-pancreatic anatomy of the superior mesenteric vessels is widely variable. We propose the term Henle trunk to be used for any venous confluence between gastric, pancreatic and colic veins, which drains between the inferior border of the pancreas and up to 20 mm downward on the right-anterior aspect of the SMV. The term gastrocolic trunk should not be synonymous, but a subgroup of the Henle trunk, together with to gastropancreatocolic, gastropancreatic, or colopancreatic trunk.

Laparoscopic vs open complete mesocolic excision with central vascular ligation for colon cancer: A systematic review and meta-analysis

AIM To compare the effectiveness of laparoscopic complete mesocolic excision (CME) with central vascular ligation (L-CME) with its open (O-CME) counterpart. METHODS We conducted an electronic search of the PubMed/MEDLINE, Excerpta Medica Database, Web of Science Core Collection, Cochrane Center Register of Controlled Trails, Cochrane Database of Systematic Reviews, SciELO, and Korean Journal databases from their inception until May 2017. We considered randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that included patients with colonic cancer comparing L-CME and O-CME. Primary outcomes included the quality of the resected specimen (lymph nodes retrieved, complete mesocolic plane excision, tumor to arterial high tie, resected mesocolon surface). Secondary outcomes included the three-year and five-year overall and disease-free survival rates, recurrence of the disease, surgical data, and postoperative morbidity and mortality. Two authors of the review screened the methodological quality of the eligible trials and independently extracted data from individual studies. RESULTS A total of one RCT and eleven CCTs (four from Europe and seven from Asia) met the inclusion criteria for the current meta-analysis. These studies involved 1619 patients in L-CME and 1477 patients in O-CME. The L-CME was associated with the same quality of the resected specimen, with no differences regarding the retrieved lymphnodes (MD = -1.06, 95%CI: -3.65 to 1.53, P = 0.42), and tumor to high tie distance (MD = 14.26 cm, 95%CI: -4.30 to 32.82, P = 0.13); the surface of the resected mesocolon was higher in the L-CME group (MD = 11.75 cm2, 95%CI: 9.50 to 13.99, P < 0.001). The L-CME was associated with a lower rate of blood transfusions (OR = 0.45, 95%CI: 0.27 to 0.75, P = 0.002), faster recovery of gastrointestinal function, and less postoperative overall complication rate. The L-CME approach was associated with a statistical significant better three-year overall (OR = 2.02, 95%CI: 1.31 to 3.12, P = 0.001, I2 = 28%) and disease-free (OR = 1.45, 95% CI: 1.00 to 2.10, P = 0.05, I2 = 0%) survival. CONCLUSION The laparoscopic approach offers the same quality of the resected specimen as the open approach in complete mesocolic excision with central vascular ligation for colon cancer. The laparoscopic complete mesocolic excision with central vascular ligation is superior in all perioperative results and at least non-inferior in long-term oncological outcomes.

Primary Aortoduodenal Fistula: First you Should Suspect it

A 59 year-old patient was admitted with upper gastrointestinal bleeding. The clinical exam showed mild hypotension and blood samples revealed acute anemia (hemoglobin = 7.5 g/dl). Emergency computed tomography showed an infrarenal abdominal aortic aneurysm and extravasation of the arterial contrast material toward the digestive tract. The patient was transported to the operating room for emergency laparotomy, which showed an aortoduodenal fistula. After proximal and distal aortic vascular control, the two anatomical structures were dissected with duodenorrhaphy, patch repair of the aortic tear and omentum interposition. The postoperative recovery was uneventful, with discharge after 12 days.