miRNAs in Cancer (Review of Literature).

MicroRNAs (miRNAs) are short, noncoding, single-stranded RNA molecules that regulate gene expression at the post-transcriptional level by binding to mRNAs. miRNAs affect the course of processes of fundamental importance for the proper functioning of the organism. These processes include cell division, proliferation, differentiation, cell apoptosis and the formation of blood vessels. Altered expression of individual miRNAs has been shown in numerous cancers, which may indicate the oncogenic or suppressor potential of the molecules in question. This paper discusses the current knowledge about the possibility of using miRNA as a diagnostic marker and a potential target in modern anticancer therapies.

Comparison of clinical usefulness of serum Ca125 and CA19-9 in pancreatic adenocarcinoma diagnosis: meta-analysis and systematic review of literature.

INTRODUCTION: Pancreatic adenocarcinoma remains one of the most lethal cancers. The only recommended biomarker CA19-9 proves to be not accurate enough to establish a certain diagnosis. Therefore, a determination of usefulness of other biomarkers is essential. Our aim was to compare the specificity and sensitivity of Ca125 and CA19-9 by means of meta-analysis. The systematic review of combined tests (CA19-9 + Ca125) was also performed. METHODS: We conducted a systematic search of Medline (via PubMed) and Ovid. After screening of abstracts and the assessment of full-texts, nine studies (number of patients, n = 1599) were included. Hierarchical summary receiver under operator curve (hsROC) model was applied to estimate the diagnostic accuracy. RESULTS: CA19-9 sensitivity and specificity were 0.748 (95%CI 0.676-0.809) and 0.782 (95%CI 0.716-0.836), respectively. These values were estimated on 0.593 (95%CI 0.489-0.69) and 0.754 (95%CI 0.817-0.668) for Ca125. Regarding the heterogeneity of studies, a strong threshold effect for Ca125 and moderate one for CA19-9 were found. CONCLUSIONS: Our meta-analysis did not prove the superiority of Ca125. It should be nevertheless noted that the sparsity of studies precludes accurate analysis of various factors' influence. The review of proposed combined tests shows that CA19-9 + Ca125 models are generally characterized by higher sensitivity.

The concentration of D-dimers in portal blood positively correlates with overall survival in patients with non-resectable pancreatic cancer.

BACKGROUND: Several recent studies provide evidence that D-dimer (DD) concentration in peripheral blood correlates negatively with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). Contrarily, there are recent evidence indicating that preoperative plasma fibrinogen, but not D-dimer might represent a prognostic factor in non-metastatic gastrointestinal cancers. METHODS: In a single-center prospective study, we enrolled 62 patients undergoing surgery for pathologically confirmed PDAC without detectable venous thrombosis. Intraoperatively, the sample of the blood from the portal vein was obtained. DD concentration in these samples was measured. Patients were followed postoperatively until time of death from any cause. RESULTS: We found that OS for patients with portal blood DD values above 2700 (ng/mL) (n = 22 from 62 patients) was higher by 158% than that for the patients (n = 42) with DD values ≤ 2700 (416 days versus 161 days, p = 0.05). On the contrary to the studies investigating DD concentration in peripheral blood, we have found that patients with higher DD level in the portal vein had longer mean OS than patients with lower ones. CONCLUSIONS: Further investigation is necessary both to confirm our results in a larger patient population and to elucidate the mechanism for the correlation between portal blood D-dimer concentrations and survival time. Along with other authors, we conclude that portal circulation is characterized by unique, biological environment that requires further evaluation.

Application of Endoscopic Submucosal Dissection (ESD) in Treatment of Gastrointestinal Lesions-Single Center Experience.

Background and Objectives: Endoscopic resection of gastrointestinal (GI) tract lesions, originating from Japan, is becoming more frequently used in European countries. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) ensure minimally invasive removal of benign, premalignant, and early neoplastic tumors of esophagus, stomach, and intestine in selected group of patients. Aim of this study was to determine the outcomes, radical resection rate (R0), and complication rate of ESD procedures performed in our department. Methods: The data from 100 ESD procedures of esophageal, gastric, duodenal, and colorectal lesions performed in out unit between 02.01.2020 and 30.06.2023 were collected and analyzed retrospectively. Results: A total of 42 male and 58 female patients in the median age of 64 years (range, 31-89 years) underwent ESD. Mean duration of the procedure was 66 minutes (ranging 25-185 minutes). Tumors were located in the esophagus in 8 cases (8%), stomach in 25 cases (25%), duodenum in 1 case (1%), and colon in 66 cases (66%). Radical resection was achieved in 98 cases (98%); 2 patients were qualified for surgical treatment. Average size of dissection lesions was 26 × 19 mm. The biggest one was 60 × 60 mm (sigmoid adenoma), and the smallest one was 5 × 5 mm (gastrointestinal neuroectodermal tumors). Complication occurred in 10 patients (10%)-9 perforations of the wall of intestine (9%) and 1 hemorrhage, which required endoscopic intervention (1%). Conclusions: Implementation of ESD to clinical practice gives the opportunity for minimally invasive, radical treatment of benign, premalignant, and early neoplastic lesions of gastrointestinal tract in selected group of patients. Experienced endoscopists, following current guidelines and standardized process of qualification, are crucial to minimize the risk of severe complications.

A Comparison of Miller Straight Blade and Macintosh Blade Laryngoscopes for Intubation in Morbidly Obese Patients.

The primary objective of this study was to demonstrate whether the Miller blade laryngoscope could provide better visualization of the vocal cords in morbidly obese patients than the Macintosh blade laryngoscope. The secondary objective was to identify the patient-measured factors associated with better visualization of the vocal cords when using the Miller vs. Macintosh blade, as well as whether the application of external pressure might improve the visibility of the glottis during intubation. A prospective, observational study encompassing 110 patients with a BMI > 40 undergoing elective bariatric surgery and intubation procedure was performed. The evaluation of the vocal cords was performed according to the Cormack-Lehane scale and POGO scale in the same patient during intubation, performed with a Miller and a Macintosh blade laryngoscope, in a random matter. The following parameters were assessed: body weight, height, BMI, neck circumference, thyromental distance, sternomental distance, mouth opening, and Mallampati scale and their impact on visualization of the vocal cords using the Miller blade without the application of external pressure. The Miller blade provides an improved view of the glottis compared to the Macintosh blade measured with both the Cormac-Lehane scale (45 (40.91%) without external pressure application on the larynx, and 18 (16.36%) with external pressure application on the larynx) and the POGO scale (45 (40.91%) without external pressure application on the larynx, and 19 (17.27%) with external pressure application on the larynx). The application of laryngeal pressure improved the view of the glottis. Among the measured features, a significant improvement in the visibility of the glottis could be found in patients with a BMI over 44.244 kg/m2 and a neck circumference over 46 cm. To conclude, the usage of the Miller blade improves the visibility of the glottis compared to the Macintosh blade in morbidly obese patients. The recommendation to use the Miller blade in this group of patients requires further investigation, taking into account the effectiveness of the intubation. Trial Registration: NCT05494463.

Comparison of UESCOPE VL 400, I-View, Non-Channeled Airtraq Videolaryngoscopes and Macintosh Laryngoscope for Tracheal Intubation in Simulated Out-of-Hospital Conditions: A Randomized Crossover Manikin Study.

The aim of the study was to test the hypothesis that the results obtained with three different types of video laryngoscopes (UESCOPE VL-400, I-View, Non-Channeled Aitraq) with and without an endotracheal stylet should be better than the results obtained with a Macintosh laryngoscope in a simulated out-of-hospital scenario by a person without clinical experience. Primary outcome measures were the time taken to successfully achieve tracheal intubation (TI). Secondary outcomes included the grade of glottic view (Cormack and Lehane grades 1-4), the incidence of successful TI, the number of audible dental clicks indicating potential dental damage, the level of effort required to perform TI, and the operator's comfort during the procedure. The time required to achieve tracheal intubation successfully was significantly longer with the Macintosh laryngoscope and Airtraq than with the other video laryngoscopes. The use of the stylet significantly reduced the time required for tracheal intubation with the Macintosh laryngoscope (21.8 sec. vs. 24.0 sec., p = 0.026), UESCOPE VL 400 (18.1 sec. vs. 23.4 sec., p = 0.013), and Airtraq (22.7 sec. vs. 34.5 sec., p < 0.001). There were no significant differences in intubation time when using the I-View with or without stylets. No differences were observed in the Cormack-Lehane grading. The success rate of intubation was 100% for the Macintosh and I-View laryngoscopes used with or without stylets and for the UESCOPE VL 400 and Airtraq laryngoscopes used with stylets. Without stylets, the success rate of intubation was 96.6% for the UESCOPE VL 400 and 86.6% for the Airtraq. There were no significant differences in the risk of dental damage between the Macintosh, UESCOPE VL 400, I-View, and Airtraq laryngoscopes, regardless of the use of stylets (without and with stylets). The use of stylets significantly reduced dental damage only for the Airtraq laryngoscope: 8 (26.6%) vs. 2 (6.6%). Statistically significant differences in perceived exertion were observed between the mentioned laryngoscopes, both with and without stylets. However, there were no differences in the comfort of use between the laryngoscopes, regardless of the use of stylets (without and with stylets. The use of stylets led to better comfort in the case of the Macintosh (2.5 vs. 3, p = 0.043) and UESCOPE VL 400 (2 vs. 3, p = 0.008) laryngoscopes. In our study, the I-View and UESCOPE VL-400 video laryngoscopes provided better intubation results than the Macintosh laryngoscope in terms of time needed to intubate, glottis visibility, and reduction in dental damage. The use of the stylet did not significantly improve the intubation results compared to the results obtained in direct laryngoscopy. Due to the small study group and the manikin model, additional studies should be performed on a larger study group.

Early adoption of laparoscopic liver surgery in Poland: a national retrospective cohort study.

BACKGROUND: The need for safe and efficient dissemination of minimally invasive approach in liver surgery is among the current challenges for hepatobiliary surgeons. After the stage of innovators and pioneers, the following countries should adopt a laparoscopic approach. The aim of this study was to assess the national experience and trend in implementing laparoscopic liver resection (LLR) in Poland. MATERIALS AND METHODS: A national registry of LLR performed in Poland was established in June 2020. All LLR cases performed before were included retrospectively, followed by prospectively collected new cases. Baseline characteristics, preoperative and intraoperative data, short-term results and long-term follow-up were recorded. RESULTS: Since 2010 up to the end of 2022 there were 718 LLRs performed in Poland. The national rate of laparoscopic approach has gradually increased since 2017 ( P <0.001), reaching the rate of 11.7% in 2022. There were 443 (61.7%), 107 (14.9%), and 168 (23.4%) LLRs performed in accordance to increasing grades of difficulty. The move towards more demanding cases had an increasing trend over the years ( P <0.001). Total intraoperative adverse event and postoperative severe complications rates were estimated for 13.5% ( n =97) and 6.7% ( n =48), respectively. 30-day reoperation, readmission and postoperative mortality rates were 3.6% ( n =26), 2.8% ( n =20), and 0.8% ( n =6), respectively. While the R0 resection margin was assessed in 643 (89.6%) cases, the total textbook outcomes (TO) were achieved in 525 (74.5%) cases. Overcoming the learning curve of 60 LLRs, resulted in an increasing TO rate from 72.3 to 80.6% ( P =0.024). CONCLUSIONS: It is the first national analysis of a laparoscopic approach in liver surgery in Poland. An increasing trend of minimizing invasiveness in liver resection has been observed. Responsible selection of cases in accordance with difficulty may provide results within global benchmark values and textbook outcomes already during the learning curve.

Major liver resection results in early exacerbation of insulin resistance, and may be a risk factor of developing overt diabetes in the future.

PURPOSE: This single center prospective cohort study evaluated the influence of hemihepatectomy on glucose homeostasis. METHODS: The study included 30 patients undergoing hemihepatectomy. All patients underwent an oral 75 g glucose tolerance test before (baseline), 1 week and 1 month after the surgery. Plasma glucose, insulin and glucagon were measured in the OGTT samples, and the HOMA index was calculated. The fasting levels of interleukin 6 and 1ß, tumor necrosis factor and adiponectin were assessed. RESULTS: The fasting plasma and 120-min post-challenge mean glucose level increased during the study from 89.6 to 103.5 mg/dl (by 15.5 %) and from 136.4 to 162.2 (by 18.9 %; p = 0.51), respectively, accompanied by an increase in fasting glucagon (from 3.2 to 5.9 ng/mL; p = 0.043) and insulin (from 14.6 to 19.3 IU/mL) and by a decrease in plasma insulin at 60 min of OGTT (p = 0.34). An increase of IL-6 (p = 0.015) and TNF (from 49.7 to 53 pg/mL), and decrease of plasma APO (7658 to 5152 ng/mL) and exacerbation of insulin resistance (p = 0.007) were noted. CONCLUSION: Hemihepatectomy resulted in moderate disturbances in glucose homeostasis, in a majority of patients that was likely to be of minor clinical relevance. However, the patients might be at higher risk of developing overt diabetes following long-term survival.

Increased GPR35 expression in human colorectal and pancreatic cancer samples: A preliminary clinical validation of a new biomarker.

BACKGROUND: G protein-coupled receptor 35 (GPR35) is involved in carcinogenesis; however, limited experimental data are available on its actual expression in patients with colorectal cancer (CRC) and pancreatic adenocarcinoma (PDAC). OBJECTIVES: We aimed to measure the relative expression of GPR35 in samples from patients with CRC or PDAC. MATERIAL AND METHODS: Using real-time polymerase chain reaction (RT-PCR), we have examined GPR35 expression in surgery samples from 40 CRC and 17 PDAC patients, and performed analysis of the results. RESULTS: The analysis of GPR35 expression in patients with CRC revealed correlations between relative GPR35 mRNA expression and several tumor characteristics, with statistical significance for higher American Joint Committee on Cancer (AJCC) stages, T stages and histological grades. GPR35 expression was significantly higher in tumor samples compared to the paired healthy samples collected from the same patient. Similar, although not statistically significant trends were found in PDAC tumor samples for sex (lower expression in women) and for samples with no nodal involvement (lower expression). Samples with higher tumor T stages and higher histological grades or considered inoperable had higher GPR35 expression. CONCLUSIONS: We have identified correlations which confirm our expectation of high GPR35 expression in CRC and PDAC. Our findings suggest the prognostic value of GPR35 testing in patients with an increased risk of CRC or PDAC development, and warrant further clinical confirmation.

Principles of minimize bleeding and the transfusion of blood and its components in operated patients - surgical aspects.

One of the target of perioperative tratment in surgery is decreasing intraoperative bleeding, which increases the number of perioperative procedures, mortality and treatment costs, and also causes the risk of transfusion of blood and its components. Trying to minimize the blood loss(mainly during the operation) as well as the need to transfuse blood and its components (broadly understood perioperative period) should be standard treatment for a patient undergoing a procedure. In the case of this method, the following steps should be taken: 1) in the preoperative period: identyfication of risk groups as quickly as possible, detecting and treating anemia, applying prehabilitation, modyfying anticoagulant treatment, considering donating one's own blood in some patients and in selected cases erythropoietin preparations; 2) in the perioperative period: aim for normothermia, normovolemia and normoglycemia, use of surgical methods that reduce bleeding, such as minimally invasive surgery, high-energy coagulation, local hemostatics, prevention of surgical site infection, proper transfusion of blood and its components if it occurs; 3) in the postoperative period: monitor the condition of patients, primarily for the detection of bleeding, rapid reoperation if required, suplementation (oral administration preferred) nutrition with microelements (iron) and vitamins, updating its general condition. All these activities, comprehensively and in surgical cooperation with the anesthesiologist, should reduce the blood loss and transfusion of blood and its components.

Sentinel lymph node mapping in tumors of the pancreatic body: preliminary report.

AIM OF THE STUDY: Actual lymphatic drainage of pancreatic body neoplasms and the proper extent of lymphadenectomy remain unknown. The aim of the study was to define the exact lymphatic draining pattern using the dye mapping method. MATERIAL AND METHODS: The study enrolled patients who were operated on for tumor of the pancreatic body in the Department of General and Transplant Surgery of the Medical University of Lodz during 2010, with injection of 1 ml of blue dye (Patent Blue, Guerbet) in the centre of the neoplasm and sentinel node identification. Radical surgical management included distal pancreatectomy, whereas gastrojejunal or triple bypass anastomoses were performed in irresectable cases. RESULTS: The study group consisted of 13 patients with locally advanced tumors of the pancreatic body (T3 and T4, mean tumor size 4.9 cm). Lymphatic mapping was able to identify sentinel nodes in 5 of 13 cases (38.46%). A sentinel node was found in station 11p (3 cases) and 9 (1 case). Skip metastasis to the left gastric artery node (group 7) was noted. All identified sentinel nodes were metastatic; tumor deposits were confirmed in non-sentinel nodes as well. CONCLUSIONS: In advanced pancreatic body tumors feasibility of sentinel node navigation is considerably restricted. Further studies in smaller tumors using optimized newer markers may define the exact lymphatic draining pattern.

Tension-Free Hiatal Hernia Repair Using Ligamentum Teres in Paraoesophageal Hernia Treatment.

AbstractIntroductionType II and III (paraoesophageal and mixed) hiatal hernia treatment remains a technically difficult procedure carrying a risk of complications and recurrence as high as 40%. Using synthetic meshes entails possible serious complications; efficacy of biologic materials remains unclear and requires further research.AimThe aim of the article was to present the centres experience of type II and III large hiatal hernia treatment using the ligamentum teres and to draw attention to potential benefits of conducted procedures.Material and MethodsThe study enrolled 6 patients: 3 women and 3 men aged 37-58 with radiologically and endoscopically confirmed large paraoesophageal hernias. The patients underwent Nissen fundoplication and hiatal hernia repair using the ligamentum teres. The patients were followed up for six months with subsequent radiological and endoscopic assessment.ResultsDuring the six-month follow-up no clinical or radiological characteristics of hiatal hernia recurrence were observed in the patients. Two patients reported symptoms of dysphagia; mortality was 0%.ConclusionsHiatal hernia repair using the vascularized ligamentum teres may constitute an effective and safe method of large hiatal hernia repair.

Analysis of miR-143, miR-1, miR-210 and let-7e Expression in Colorectal Cancer in Relation to Histopathological Features.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules involved in the control of the expression of many genes and are responsible for, among other things, cell death, differentiation and the control of their division. Changes in miRNA expression profiles have been observed in colorectal cancer. This discovery significantly enriches our knowledge of the pathogenesis of colorectal cancer and offers new goals in diagnostics and therapy. AIM: The aim of this study was to analyze the expression of four miRNA sequences-miR-143, miR-1, miR-210 and let-7e-and to investigate their significance in the risk of developing colorectal cancer. MATERIALS AND METHODS: miRNA sequences were investigated in formalin-fixed, paraffin-embedded (FFPE) tissue in colorectal cancer patients (n = 150) and in cancer-free controls (n = 150). The real-time PCR method was used. RESULTS: This study revealed a lower expression of miR-143 in colorectal cancer patients than in the controls. miR-143 was positively correlated with the degree of tumor differentiation (grading). Three out of four analyzed miRNA (miR-1, miR-210 and let-7e) were found to be statistically insignificant in terms of colorectal carcinoma risk. CONCLUSIONS: miR-143 may be associated with the development of colorectal cancer.

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.

FT3 to FT4 Conversion Ratio May Be an Independent Prognostic Factor in Pancreatic Cancer Patients.

Preclinical evidence suggests that T4 can promote tumor growth while T3 can act conversely; therefore, the fT3 and fT4 concentrations should affect overall survival (OS) in cancer patients. The objective of the study was to look for an association between thyroid hormone concentrations in peripheral blood and OS in the pancreatic adenocarcinoma (PDAC) patients group. We included, retrospectively, 15 PDAC patients, without thyroid dysfunction under treatment, who underwent radical surgery, with no prior history of anticancer therapy. TSH, fT3, and fT4 concentrations were determined in blood samples taken preoperatively. We found that the fT3/fT4 ratio categorized into two groups (<0.22 vs. ≥0.22) dichotomized the study population into poor and good prognosis subgroups (log-rank p = 0.03; OS medians, respectively: 3 and 14 months), being a statistically significant predictor both in uni- and multivariate Cox regression analysis. We conclude that the importance of fT4 into fT3 conversion means not just its standard metabolic effects as the final products of thyroid gland activity. We hypothesize that it is linked to the progression of pancreatic malignancies, either via thyroid hormone receptors or indirectly, by interaction with cancer cells product.

[Two-stage liver resections with portal branch ligation--a novel treatment strategy for patients with initially irresectable, bilobar colorectal liver metastases]. / Dwuetapowe resekcje watroby z podwiazaniem galezi zyly wrotnej--nowa strategia leczenia chorych z pierwotnie nieresekcyjnymi, obustronnymi przerzutami raka jelita grubego.

Liver resection is the only potentially curative treatment option of patients with colorectal cancer metastases. However, at the time of diagnosis, most patients have irresectable tumors. Preoperative chemotherapy and portal vein embolization may lead to downsizing of initially irresectable colorectal cancer metastases, located in one lobe of the liver. Although, in group of patients with bilobar involvement such neoadjuvant therapy does not enable performance of radical operation. Irresectability of these tumors is mainly due to a functionally insufficient amount of future, postoperative remnant liver volume. Hereby, we present a novel treatment strategy of two-stage liver resection with portal branch ligation and inter and postoperative chemotherapy, we discuss the indications for this procedure in view of the presented cases and we review the literature on the treatment of patients with initially irresectable, bilobar liver metastases from colorectal cancer.

The Role of microRNA in Pancreatic Cancer.

MicroRNAs (miRNAs) are small ribonucleic acid molecules that play a key role in regulating gene expression. The increasing number of studies undertaken on the functioning of microRNAs in the tumor formation clearly indicates their important potential in oncological therapy. Pancreatic cancer is one of the deadliest cancers. The expression of miRNAs released into the bloodstream appears to be a good indicator of progression and evaluation of the aggressiveness of pancreatic cancer, as indicated by studies. The work reviewed the latest literature on the importance of miRNAs for pancreatic cancer development.

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.

The Pancreatitis, Panniculitis, and Polyarthritis (PPP) Syndrome: Subcutaneous Nodular Fat Necrosis, a Cutaneous Marker of Pancreatic Neoplasia.

The pancreatitis, panniculitis, polyarthritis (PPP) syndrome is a rare skin, joint, and pancreatic disorder, also known as subcutaneous nodular fat necrosis. It results from obstruction of pancreatic ducts with direct secretion of pancreatic enzymes into the bloodstream, causing extra pancreatic fat necrosis with subcutaneous tissue and joint inflammation. It is usually a cutaneous sign of pancreatic cancer or pancreatitis. To our knowledge, this is the first case associated with a pancreatic pseudotumor. We describe a 59-year-old man initially presenting with numerous painful erythematous subcutaneous nodules due to a fibrous pancreatic pseudotumor and its extreme dermatologic disease, resulting in necrosis of the shin and foot so severe that an amputation of the lower leg above the knee was required, a complication not previously described, to our knowledge. We emphasize that PPP syndrome is a cutaneous marker of internal malignancy, most often of pancreatic cancer or pancreatitis, but in this case of a rare pancreatic pseudotumor.

Mucinous cystadenocarcinoma of the spleen - a very rare case of a primary splenic MCN.

INTRODUCTION: We present the case of a primary spleen mucinous cystadenocarcinoma. Several cases of this primary tumor of the spleen have been described worldwide so far. These tumors are classified as mucinous cystic neoplasms (MCN) and occur mainly in the ovaries and pancreas. <br/><br/>Case report: The case concerns a 45-year-old female patient with an accidentally diagnosed splenic tumor with approximately 20 cm in size. Histopathological examinations, following a splenectomy, confirmed the presence of mucinous cystadenocarcinoma.