Gender-Specific Coagulation Profiles of Peripheral and Portal Blood May Help to Differentiate Malignant from Benign Pancreatic Tumour-Pilot Study.

Objective: Pancreatic adenocarcinoma (PDAC) and mass forming chronic pancreatitis (CP) can be easily misdiagnosed due to their resemblances in clinical, radiological, and biochemical criteria. In our previous study, we reported a very high concentration of D-Dimers in portal blood in patients with pancreatic cancer which may help to differentiate malignant from benign pancreatic tumours. In this study, we aim to describe other portal and peripheral coagulation profiles of PDAC in comparison to CP patients, as well to test the hypothesis; thus, it is possible to distinguish pancreatic malignancy and benign tumour based on these parameters. Methods: We included retrospectively 115 patients with the absence of venous thromboembolism (VTE), qualified to surgical treatment due to pancreatic tumours, both PDAC and CP. Patients underwent surgery in General and Transplant Surgery Unit of Medical University of Lodz between December 2011 and February 2014. Patients with distant metastases diagnosed before or during the surgery were excluded. The coagulation profile, which includes fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT), was determined in blood samples from the portal and peripheral vein taken intraoperatively. Results: The fibrinogen level was higher and the aPTT index shortened in the peripheral and portal blood of the PDAC group, which reflects the well-known link between PDAC and general hypercoagulability. Furthermore, these effects are sex-specific. The mean age in the CP group was lower than in the PDAC group (54.63 ± 12.37 vs. 63.77 ± 3.23, p < 0.001) and correlated with the fibrinogen distribution in male patients with CP (portal r = 0.34; p = 0.07; peripheral r = 0.39; p = 0.04). We calculated sex-specific logistic regression models (male: peripheral aPTT and age, AUC: 0.795, female: portal fibrinogen and age, AUC: 0.805), both maintaining the good discrimination properties after V-fold cross validation (0.759, 0.742). Conclusions: Our study shows that the differences between coagulation profiles in PDAC and CP patients not only seems to be a reflection of gender-specific biological features, but also helps to discriminate between them. The main goal of the study was to explore the biology of pancreatic cancer and lay a solid base for further investigations of PDAC biomarkers. This paper is the first to describe the detailed coagulation profile in portal blood in patients with pancreatic solid tumors. At present, the clinical application of our results is not clear; however, we hope that it may improve our understanding of this complex disease.

Port site metastases a year after initial laparoscopic cholecystectomy. Should the use of retrieval bags during laparoscopic cholecystectomy be the new gold standard?

As a result of gallbladder cancer being rare, it is often an understudied disease. There is lack of information particularly about long-term outcomes after resection during either laparoscopic or open surgery techniques [4]. There is also little data on the ways in which surgical techniques can be improved to further aid patients diagnosed with gallstones or other indications for cholecystectomy, and resulting positive histopathology. Furthermore, there is a lack of general acknowledgement on the vitality of using plastic retrieval bags during cholecystectomy regardless of the histopathology. The case study at hand shows how critical a plastic bag can be during cholecystectomy in further preventing the risk of local or distant metastasis originating from the gallbladder. This is especially important as it is estimated that almost one third of patients who undergo curative intent surgery for gallbladder cancer develop a tumor recurrence. Specifically, our patient was found to have a distant recurrence occurring a year after the elective surgery, which is in range with the usual median recurrence of 9.5 months or within the first 12 months [5]. </br> </br> Laparoscopic cholecystectomy is a common surgical procedure, and remains the gold standard for the management of benign gallbladder and biliary disease. While this procedure can be technically straightforward, there are some key factors that surgeons must take into consideration with one of them being whether to use a retrieval bag or not. According to the "Guidelines for the Clinical Application of Laparoscopic Biliary Tract Surgery" of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), the use of a retrieval bag for gallbladder extractions is purely at the discretion of the surgeon [6]. Generally, plastic bags should be used when gallbladder cancer is suspected to minimize disseminating tumor cells, or in the case of acute cholecystitis, to avoid spillage of gallbladder contents including possible infected bile, stones or pus. While one study states that when a cholecystectomy is performed due to gallstones, generally, surgeons will only opt for a plastic bag if there are large gallstones, great inflammation or an edematous gallbladder [7, 8]. However, another article claims the adverse, with endoscopic bags being in fact used commonly in elective cholecystectomy, despite the increased cost and apparent benefit [7]. A major drawback, and possible reason why some surgeons may decide not to use retrieval bags could be due to the extra skills needed, or increased difficulty to the surgery. This could be due to the need for enlargement of port site incision, placement of the bag around the gallbladder, as well as the potential risk to abdominal organ damage during the insertion and retrieval of the bag [7]. Sometimes the decision not to use the bag is purely economic, especially in developing countries. Fortunately nowadays commercially available endobags become more inexpensive, and to the very little extent, increase final costs of laparoscopic cholecystectomy. However, in order to reduce these costs several studies have shown that sterile male condoms or surgical non-powdered gloves can be used [9]. </br> </br> Umbilical port site recurrence is traditionally a major concern, however there is still little research around the exact mechanism responsible for port site recurrence. Port site metastasis is the most common form of parietal recurrence with all stages of gallbladder carcinoma being reported at any of the trocar sites. Historically it was proved that the risk of port site metastasis after laparoscopic removal of incidental gallbladder cancer remained at the level of 14-30% of all cases. Recent study conducted to assess the incidence of port site metastasis in incidental gallbladder cancer in the modern era (2000-2014) versus the historic era (1991-1999) proved that this incidence has decreased but is still relatively high to other primary tumors [10]. </br> </br>It generally presents after latency, ranging from a few months to 3-4 years. Many factors can contribute to port site metastasis [9]. One of the most important is intraoperative spillage of bile from gallbladder wall perforation, which has been described in 30% of laparoscopic cholecystectomy cases, and it has been linked to port site metastasis [11]. Interestingly, local recurrence was noted only in a minority of patients, with distant sites such as the liver and peritoneum being the most common sites for disease recurrence [4]. </br> </br> Some hypotheses suggest to elucidate the cause of port site metastasis, including direct "chimney stack effect" in which the cancer cells may spread along trocar wound [12]. However, recent studies indicated that the chimney effect may not be the key reason for port site metastasis after laparoscopy and other factors may play crucial role in the development of this phenomenon, such as biological invasiveness of cancer, local traumatic factors, as well as host immune response [13]. Current evidence suggests that carbon dioxide pneumoperitoneum does not enhance wound metastases following laparoscopic abdominal tumour surgery. Animal studies indicated that overall postoperative wound recurrence of cancer is not significantly different between routine and gasless laparoscopic surgery [14]. null Tissue specimens removed during surgery are examined both macroscopically and microscopically, and despite this, false negatives can still persist. While there is clear data pertaining to false negatives associated with biopsies done with FNA occurring in a staggering 11-41% to detect malignancy before surgery [15], there is little data for false negatives in the postsurgical setting. Although histopathological analysis is usually very reliable to exclude malignancy, it may fail. This is clearly evident with our case, where the result was false negative. The cause for false negativity could be due to, for example, improper sampling despite guidelines indicating that three samples ought to be taken from high-risk areas of the specimen [16]. With false positives being possible both in pre- and postsurgery biopsies, surgeons must be cautious and take this factor into account in their surgical approach [17]. </br></br> At present, the only method that is universally used to reduce the recurrence of gallbladder cancer is cholecystectomy as incision of port sites and the use of endoscopic bags have been variably used among surgeons. Moreover, the use of adjuvant therapy after cholecystectomy has not shown to decrease the rate of recurrence, however, patients who underwent chemotherapy treatment often did slightly better [4]. Port site metastases are independently associated with a worse prognosis. Resection of previous laparoscopy port sites is advised in patients with peritoneal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) to ensure complete cytoreduction [18]. </br></br> It is clear from this standpoint that other solutions and ideas are needed. One of these could be permanent implementation of retrieval bags during cholecystectomies, especially due to the fact that it is not always possible to foresee the problems of retraction or to show a positive histopathological result in case of gallbladder rupture [4, 17]. In every cholecystectomy there is a risk of gallbladder perforation and spread of malignant cells. Perforation of the gallbladder is in fact a frequent complication during laparoscopic cholecystectomy, with a much higher risk of perforation in acute conditions like acute cholecystitis or gallbladder empyema. Some other methods that could be used to prevent dissemination of either gallbladder contents or malignant cells include clip application, rubber band ligation or endoscopic loop application. Rubber band ligation is especially good because it is considered as a safe, simple, inexpensive method, not increasing the duration of surgery [19]. Regardless of what method a surgeon decides to use to prevent cell dissemination during cholecystectomy, it is vital that one is used, and that the guidelines are amended. This case study provides the means for this, especially since a negative histopathological biopsy still does not exclude the possibility of traces of cancerous cells being undisclosed, allowing for a potential risk of port site metastases.

Beger procedure in a 20-year-old female with solid pseudopapillary tumour of the pancreas.

UNLABELLED: Solid pseudopapillary tumour is a rare indolent neoplasm of the pancreas (< 2% of exocrine pancreatic tumours), which predominantly affects young women at reproductive age, without significant clinical symptoms. We report a case of a 20-year-old Caucasian female who presented with upper abdominal pain of one-year duration. Ultrasound scans of the abdomen demonstrated enlarged pancreatic head and body containing a poorly separated mass (52 × 41 × 36 mm) with a multi-cystic component 20-24 mm in diameter. Laboratory tests including, tumour markers levels, were normal. She underwent complete resection of the tumour using a Beger procedure. By immunohistochemistry, the case stained strongly for CD10 and CD56 and was negative for cytokeratin-7 (CK-7), synaptophysin and chromogranin A. The proliferation index (Ki-67) was < 1%. The patient is being followed-up and remains healthy. CONCLUSIONS: Solid pseudopapillary tumour is a tumour with low potential of malignancy and with generally favourable prognosis; surgical resection is usually curative.

Roux-en-Y biliary by-pass - a new approach in the treatment of hypertriglyceridemia induced recurrent acute pancreatitis. Clinical case study.

Acute pancreatitis is a disease with significant mortality. Hypertriglyceridemia (HTG) is the third most common etiological factor of this disorder after alcohol and gall-stones. The authors presented a case of 42-years old caucasian female who was hospitalized due to recurrence of acute pancreatitis. She had been diagnosed with HTG. She had earlier seven episodes of acute pancreatitis. Endoscopic papillotomy and conservatory treatment didn't change her complaints and she was consented for surgery. Exclusion of distal part of bile duct was performed. The common bile duct was anastomosed side-to-side to the 70 cm long Roux loop of the jejunum with the ligation of the distal part of the common bile duct. Following the surgery authors observed normalization of amylase, lipase, leukocytosis and CRP levels. During six months after procedure patient didn't have any new episode of pancreatitis. Exclusion of distal part of bile duct may be a useful tool in surgical treatment of recurrent acute hypertriglyceridemia-induced pancreatitis.

CA 19-9 concentration in peripheral and portal blood of patients operated on for pancreatic tumor.

UNLABELLED: Pancreatic cancer is one of the most common malignant diseases in the world. Morbidity rate increases and now reaches around 200 000 new cases yearly. Poor prognosis mainly results from usually late diagnosis and non-specific symptoms. Despite of advances in radiological diagnosis of pancreatic diseases, differentiation between malignant and inflammatory pancreatic tumors still remains difficult. The aim of the study was the assessment of clinical utility of CA 19-9 in peripheral and portal blood of patients with pancreatic tumor. MATERIAL AND METHODS: 66 patients were hospitalized at the Department of General and Transplant Surgery between October 2010 nad July 2012 due to pancreatic tumor. Blood samples were collected from peripheral vein before surgery and intraoperatively from the portal vein to measure CA 19-9 concentration. 57 patients were diagnosed with malignant tumor and 9 with inflammatory lesion. Metastases to the liver were present in 7 of all patients. Radical surgery (Whipple's procedure in 27 cases) were performed in 34 patients. RESULTS: Significantly higher CA 19-9 concentration in the peripheral blood and in the portal blood as well was found in the pancreatic cancer group than in the inflammatory lesions group (51.2 vs <3 and 52.1 vs 6.3 respectively). Marker concentration in case of malignant lesions was significantly higher in the portal blood than in the peripheral blood (52.1 vs 51.2; p<0.05). CA 19-9 concentration of patients with malignant pancreatic tumors but without metastases to the liver was significanlty higher in the portal blood than in the peripheral blood (19.32 vs 18.65; p<0.01). CONCLUSIONS: Determination of the CA 19-9 concentration not only in the peripheral blood but in the portal blood as well might be a useful diagnostic tool in order to differentiate between the malignant and inflammatory pancreatic tumors. We did not see any statistically significant dependency between the CA 19-9 concentrations in the peripheral blood and portal blood and if the surgery was radical or not, but significantly higher concentrations of CA 19-9 in the portal blood than the peripheral blood among the patients suffering from the malignant pancreatic tumor without metastases to the liver might be useful tool when decisions on performing pancreatoduodenectomy are being made since this surgery is forborne from when metastases are present.

CA 125 concentration in portal blood as a predictor of resectability in pancreatic tumor.

AIM OF THE STUDY: Pancreatic cancer is one of the most frequent cancers in the world. Only 20% of patients seem to have disease confined to the pancreas, but in only every second case the tumor turns out to be resectable during surgery. Tumor markers may be a useful tool in differentiating benign from malignant pancreatic tumors and in clinical staging. The purpose of the study is to assess CA 125 utility as a predictor of resectability in pancreatic tumor. MATERIAL AND METHODS: 66 patients were operated on for pancreatic tumor between October 2010 and July 2012. CA 125 concentration was measured in peripheral and portal blood. 57 patients were diagnosed with malignant and 9 with inflammatory tumor. Seven patients had metastases to the liver. Radical surgery was performed in 34 patients. RESULTS: Significantly higher CA 125 concentration in portal blood was found in the pancreatic cancer than in the inflammatory tumor group (36.5 ±99.6 vs. 16.4 ±26.5; p < 0.05). CA 125 concentration in peripheral blood and in portal blood as well of patients with malignant pancreatic tumors and with metastases to the liver was significantly higher than in the group without metastases (146.15 ±256.1 vs. 18.5 ±17.5; p < 0.01 and 147.5 ±261.2 vs. 19.7 ±24.3; p < 0.05, respectively). CA 125 values in the group without metastases to the liver and in the case of radical surgery were significantly higher in portal than in peripheral blood (19.7 ±24.3 vs. 18.5 ±17.5; p < 0.001 and 13.2 ±15.0 vs. 13.0 ±15.2; p < 0.001, respectively). CONCLUSIONS: Determination of CA 125 concentration in peripheral blood and in portal blood as well might be a useful tool in differentiating between malignant and inflammatory pancreatic tumors and when decisions on surgery extensiveness are being made.