Pancreatic head cancer - Current surgery techniques.

Pancreatic head cancer is a highly fatal disease. For now, surgery offers the only potential long-term cure albeit with a high risk of complications. However, the progress of surgical technique during the past decade has resulted in 5-year survival approaching 30% after resection and adjuvant chemotherapy. This paper presents current data on the recommended extent of lymphadenectomy, the resection margin, on the definition of resectable and borderline resectable tumors and mesopancreas. Surgical techniques proposed to improve PD are presented: the artery first approach, the uncinate process first, the mesopancreas first approach, the triangle operation, periarterial divestment, and multiorgan resection.

A chronicle of the pancreatoduodenectomy technique development - from the surgeon's hand to the robotic arm.

BACKGROUND: Pancreatoduodenectomy (PD) remains one of the most challenging abdominal surgical procedures. METHODS: A review of the literature regarding the history of PD, starting from the pioneers, Walter Kausch and Alan Whipple, through the great surgeons of the last century, up to the present day. RESULTS: The greatest development of the PD technique took place at the end of the twentieth century. Over the last 40 years, there have been huge technological advances in medicine, which have resulted in the introduction of laparoscopic and robotic techniques for abdominal surgery. However, it turns out that PD is still performed as it used to be "by the surgeon's hand" via laparotomy rather than using the most modern robot or laparoscope and is currently recommended by experts for treatment of pancreatic head cancer (PHC). This is mainly caused by not many data comparing these three PD methods. Moreover, increasingly the results achieved by surgeons advanced in minimally invasive pancreatic resections are comparable to or even better than those achieved by the open method in reference centres. Robot-assisted PD appears to be gaining an advantage over laparoscopic technique in the efficacy of PHC treatment. The obstacles most inhibiting the use of surgical robotics are the high cost of the device and procedure, and the long learning curve. A bright future lies ahead for both methods, with the robotic technique in the forefront. CONCLUSIONS: Despite significant advances in access and surgical technique, PD remains a challenging surgical procedure requiring a big surgeon's experience.

Modifiable and Non-Modifiable Risk Factors for the Development of Non-Hereditary Pancreatic Cancer.

Pancreatic cancer is becoming an increasing healthcare concern. Though it is a 14th most common cancer worldwide, its incidence is steadily rising. Results of currently available therapies are still not satisfactory. Therefore, great attention should be put on the identification and reduction of risk factors for pancreatic cancer. A thorough up-to-date review of available data on the impact of well-established and novel risk factors of pancreatic cancer development have been performed. Several risk factors associated with lifestyle have significant impact on the risk of pancreatic cancer (i.e., smoking, obesity, alcohol consumption). Physicians should also be aware of the novel findings suggesting increasing role of microbiome, including viral and bacterial infections, in the development of pancreatic cancer. A growing body of evidence suggest also an increased risk during certain occupational exposures. In general, lifestyle seems to be a major contributor in the development of pancreatic cancer. Special attention should be given to individuals with a vicious cluster consisting of metabolic syndrome, tobacco smoking and alcohol consumption. Physicians should urge patients to comply to healthy diet, cessation of smoking and moderation of alcohol consumption, which may halve pancreatic cancer incidence. Further studies are warranted to explore the potential use of therapeutic approach on novel risk factors (e.g., microbiome).

Current status of inherited pancreatic cancer.

BACKGROUND: It is estimated that about 10% of pancreatic cancer cases have a genetic background. People with a familial predisposition to pancreatic cancer can be divided into 2 groups. The first is termed hereditary pancreatic cancer, which occurs in individuals with a known hereditary cancer syndrome caused by germline single gene mutations (e.g., BRCA1/2, CDKN2A). The second is considered as familial pancreatic cancer, which is associated with several genetic factors responsible for the more common development of pancreatic cancer in certain families, but the precise single gene mutation has not been found. AIM: This review summarizes the current state of knowledge regarding the risk of pancreatic cancer development in hereditary pancreatic cancer and familial pancreatic cancer patients. Furthermore, it gathers the latest recommendations from the three major organizations dealing with the prevention of pancreatic cancer in high-risk groups and explores recent guidelines of scientific societies on screening for pancreatic cancers in individuals at risk for hereditary or familial pancreatic cancer. CONCLUSIONS: In order to improve patients' outcomes, authors of current guidelines recommend early and intensive screening in patients with pancreatic cancer resulting from genetic background. The screening should be performed in excellence centers. The scope, extent and cost-effectiveness of such interventions requires further studies.

Giant pseudocyst of the retroperitoneal space mimicking a lesion arising from the left adrenal gland.

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Treatment of type 2 diabetes mellitus and risk of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer of the exocrine part of the pancreas with poor prognosis. Up to 85% of PDAC patients are diagnosed with diabetes or hyperglycaemia at the time of diagnosis indicating that impaired glucose homeostasis is a common event in this cancer. A mechanism of association between PDAC and diabetes is very complex and still not fully understood. Currently, the various classes of anti-diabetic drugs are used in diabetes treatment. It is possible that specific types of anti-diabetic drugs for diabetes may have different impacts on pancreatic cancer development. Moreover, the intriguing question of whether diabetes can facilitate PDAC development remains unanswered. This paper presents the results of recent studies on the effect of the anti-diabetic treatment used on pancreatic cancer risk in diabetic patients.

Association between acute pancreatitis and COVID-19 infection: What do we know?

The disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called coronavirus disease 2019 (COVID-19), first originated in Wuhan, China, displaying atypical pneumonia-like respiratory symptoms in affected patients. SARS-CoV-2 primarily attacks the respiratory system, and the most common symptoms include cough, shortness of breath, and fever. However, its impact on the digestive system has been shown, and various clinical gastrointestinal manifestations of this disease have been recognized. Some reports have shown acute pancreatitis (AP) as the initial symptom in patients with COVID-19. AP may be a consequence of direct pancreatic damage by the virus because pancreatic acinar cells contain angiotensin-converting enzyme 2 receptor proteins, and SARS-CoV-2 can bind to these receptors, causing pancreatic injury. Moreover, AP may be a secondary indicator of cytokine storms and altered inflammatory responses. Our review of the literature shows that SARS-CoV-2 appears to be a new etiological infectious factor related to AP. In this manuscript, a comprehensive review of case reports and case series of patients with AP and COVID-19 is presented. All reports on COVID-19-associated AP are summarized. All cases are thoroughly analyzed and discussed in-depth.

Fluid Therapy in Patients Undergoing Abdominal Surgery: A Bumpy Road Towards Individualized Management.

Prudent intraoperative fluid replacement therapy, inotropes, and vasoactive drugs should be guided by adequate hemodynamic monitoring. The study aimed to evaluate the single-centre practice on intraoperative fluid therapy in abdominal surgery (AS). The evaluation, based on a review of medical files, included 235 patients (103 men), aged 60 ± 15 years who underwent AS between September and November 2017. Fluid therapy was analyzed in terms of quality and quantity. There were 124 high-risk patients according to the American Society of Anaesthesiologists Classification (ASA Class 3+) and 89 high-risk procedures performed. The median duration of procedures was 175 (IQR 106-284) min. Eleven patients died post-operatively. The median fluids volume was 10.4 mL/kg/h of anaesthesia, including 9.1 mL/kg/h of crystalloids and 2.7 mL/kg/h of synthetic colloids. Patients undergoing longer than the median procedures received significantly fewer fluids than those who underwent shorter procedures. The volume of fluids in the longer procedures depended on the procedural risk classification and was significantly greater in high-risk patients undergoing high-risk surgery. Patients who died received significantly more fluids than survivors. In all patients, a non-invasive blood pressure monitoring was used and only six patients had therapy guided by metabolic equilibrium. The fluid therapy used was liberal but complied with the recommendations regarding the type of fluid and risk-adjusted dosing. Hemodynamic monitoring was suboptimal and requires modifications. In conclusion, the optimization of intraoperative fluid therapy requires a balanced and standardized approach consistent with treatment procedures.

Procoagulant Disorders in Patients with Newly Diagnosed Pancreatic Adenocarcinoma.

Background and objectives: Cancer coagulopathy is thought to be partially due to the up-regulation of tissue factor (TF), thrombin-antithrombin complex (TAT) and soluble P-selectin (sP-selectin). The purpose of this study was to evaluate the clinical significance of TF, TAT and sP-selectin in patients with pancreatic cancer. Materials and methods: The study included 93 subjects: 73 newly diagnosed patients with pancreatic adenocarcinoma (42 with stage I-III and 31 with metastatic cancer (stage IV)) and a control group of 20 healthy subjects. Analyzed patients were hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz or in the Department of Digestive Tract Surgery, Silesian University, Katowice, Poland. All laboratory parameters were measured using ELISA procedures. Results: TF plasma levels were detectable in all patients and were significantly higher in metastatic cancer compared to stage I-III patients and the control group (p < 0.05). In patients with pancreatic adenocarcinoma, the median levels of TAT were also elevated compared to the control group. Moreover, patients with metastases had significantly higher TAT concentration compared to the I-III cancer group. On the other hand, only the metastatic patients group showed significantly higher plasma sP-selectin levels compared to the controls (p = 0.009), whereas there was no difference between localized and metastatic cancer patients. Conclusions: The coagulation disorders are present in the majority of patients with pancreatic adenocarcinoma already at the diagnosis stage and reflect cancer progression and spread.

Pancreaticojejunostomy-a review of modern techniques.

BACKGROUND: Pancreaticojejunal anastomosis is one of the most demanding procedures in surgery. Up to now, no technique has been proven to reduce the incidence of POPF when compared to the other methods. PURPOSE: The aim of this review was to provide a concise and illustrated description of the most recent methods of pancreaticojejunostomy. Their development was directly related to the still ongoing search by surgeons for such a technique of anastomosis that would eliminate the problem of POPF. CONCLUSIONS: Knowledge of various techniques of anastomosis may help the surgeon to find the most suitable and optimal method of pancreatic-intestinal anastomosis for the patient.

Roux-en-Y duodenojejunostomy improves gastric emptying in experimental obstruction of the distal duodenum.

INTRODUCTION: We undertook a comparative survey of gastric emptying (GE) kinetics after two variants of bypass surgery for upper bowel obstruction. MATERIAL & METHODS: In 10 dogs with experimental upper bowel obstruction, five were randomized to obtain gastrojejunal anastomosis (GA), and the other five received Roux-en-Y duodenojejunal anastomosis (DA). Duplicate scintigraphic measurements of GE of a solid meal were accomplished in every animal before surgery and during the early (2-3 weeks), medium (3 months), and late (6 months) post-operative period. The GE curves were fitted with a power-exponential function to derive the GE half time T½, and the curve shape parameter S. RESULTS: Early after surgery T½ slightly decreased by -18±21 min in the DA group and lengthened by 91±37 min in the GA group (p = 0.042). In both groups an increase in the S parameter was found then. In either group T½ gradually declined towards the basal value during the medium and late post-operative period. On the other hand, net differences relative to the basal situation in the S values appeared to be positive in the GA group (0.32±0.11 at 3 months; 0.64±0.19 at six months), and negative in the DA group (-0.30±0.09 at 3 months; -0.01±0.20 at six months). Hence a statistically significant contrast was found between those differences: p = 0.0022 at 3 months, and p = 0.045 at six months after the surgery. CONCLUSION: Roux-en-Y duodenojejunal anastomosis appears to be superior to the classical gastrojejunal anastomosis while restoring patency of the gastrointestinal passage in the case of upper bowel obstruction.

Patients' Opinions about Polish Surgeons and Surgical Treatment.

In Polish society Stereotypes about the surgeons are deeply rooted, which could really affect their relationship with the patient and the entire treatment process. The aim of the study was to evaluate the results of an opinion survey on the image of the surgeon and operative treatment. MATERIAL AND METHODS: Between 1 January and 30 October 2012, 1000 patients were examined by use of a original questionnaire containing 25 questions. Results were analyzed statistically by STATISTICA test. Differences between groups were tested using Chi-square test (X2) with Yates modification, adopting the significance level α = 0.05. RESULTS: The study group consisted of 1000 patients, including 56% of women (n = 560) and 44% of men (n = 440). The media image of Polish surgeon was identified as positive by 78% of respondents. A majority of patients (74%) considered that the Polish surgeons had equal level of competence and skills as foreign specialists. The greatest trust of the respondents (n = 537) had surgeons in middle age (40-60 years). For the majority of patients (n = 649) a sex of the surgeon had no significance. Respondents clearly stated that a surgeon performing the operation should not have additional financial rewards. Almost all respondents in medical emergencies without hesitation declared their agreement to surgery (n = 974). CONCLUSIONS: Present knowledge of Polish patients about surgeons and surgical treatment is high. The surgeon has a high social prestige, respect and appreciation, and his image in the opinion of the vast majority of respondents is positive.

Analysis of XRCC2 and XRCC3 gene polymorphisms in pancreatic cancer.

The double-strand break DNA repair pathway, including XRCC2 and XRCC3 genes, is implicated in maintaining genomic stability and therefore could affect the pancreatic cancer risk. The aim of the present study was to evaluate the clinical significance of the XRCC2 and XRCC3 gene polymorphisms in patients with pancreatic cancer. The present study included 203 patients: 101 with pancreatic cancer and 102 healthy controls. The Arg188His XRCC2 and the Thr241Met XRCC3 gene polymorphisms have been studied in DNA isolated from blood samples. The associations of the analysed genotypes and clinical data at diagnosis have been evaluated. The frequencies of the genotypes of the Arg188His XRCC2 and Thr241Met XRCC3 polymorphisms did not differ significantly between patients and controls. The study did not identify a correlation between the XRCC2 and XRCC3 genes polymorphisms and tumor size or localisation. Analysed polymorphisms were also not associated with the gender and age of the patient, or the presence of regional or distant metastases. In conclusion, the present study did not suggest an association between the Arg188His XRCC2 and the Thr241Met XRCC3 polymorphisms and the clinical data of patients with pancreatic cancer.

Utility of serum IgG, IgG4 and carbonic anhydrase II antibodies in distinguishing autoimmune pancreatitis from pancreatic cancer and chronic pancreatitis.

PURPOSE: Autoimmune pancreatitis (AIP) can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. The aim of our study was to compare IgG, IgG4 and anti-CAIIAb serum levels in patients with AIP, pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) and to assess their clinical significance and utility in differential diagnosis of pancreatic diseases. PATIENT/METHODS: The study included 124 patients: 45 with PA, 24 with AIP and 55 with CP. Peripheral venous blood samples were obtained from all analyzed patients at the time of hospital admission and total IgG, IgG4 and anti-CAIIAB serum levels were measured using ELISA tests. RESULTS: Serum levels of IgG, IgG4 and anti-CAIIAb were significantly higher in patients with AIP compared to PA and CP patients (p<0.001). In AIP patients the median IgG levels were 19.7 g/l, IgG4 levels - 301.9 mg/dl and anti-CAIIAb - 81.82 ng/ml, compared to 10.61 g/l, 123.2mg/dl and 28.6 ng/ml, respectively, in PA patients. IgG4 for the cut-off 210 mg/dl showed the best sensitivity and specificity (83.8% and 89.5%) in AIP diagnosis compared to IgG (69.3% and 87.3%, respectively) and anti-CAIIAb (45.3% and 74.3%). However, 16 (35.5%) patients with PA and 14 (25.4%) patients with CP had IgG4 levels greater than 140 mg/dl. Moreover, in 3 (6.67%) patients with pancreatic cancer those values were greater than 280 mg/dl. No patients with CP had IgG4 more than 280 mg/dl. CONCLUSIONS: IgG4 at cut-off 210 mg/dl showed the best sensitivity and specificity in AIP diagnosis compared to IgG and anti-CAIIAb, however elevations of serum IgG4 may be seen in subjects without AIP, including pancreatic cancer.

Concentration of gelatinases and their tissue inhibitors in pancreatic inflammatory and neoplastic tumors and their influence on the early postoperative course.

UNLABELLED: Pancreatic cancer (PC) is the fourth leading cause of death in the world, due to neoplastic disease. Chronic pancreatitis (CP) is a progressive disease leading towards pancreatic fibrosis. The aim of the study was to assess the impact of matrix metalloproteinases 2 and 9 (MMP2 and 9) and their tissue inhibitor (TIMP 1 and 2) concentrations in case of PC and CP tissue homogenates on early treatment results of patients subject to pancreatic resections. MATERIAL AND METHODS: The study group comprised 63 patients, including 25 (39.68%) female and 38 (60.32%) male patients. Group 1 (CP) consisted of 31 patients with CP (F: M = 10/21). Group 2 (PC) consisted of 32 patients with PC (F: M = 15:17). The pancreatic tumor samples were collected from the resected pancreas, being subject to electrophoresis and immunoenzymatic studies. After confirming their activity, MMP2, MMP9, TIMP1, TIMP2 concentrations were determined. Correlation analysis of MMPs and TIMPs concentrations was performed in relation to the following: tumor diameter, age, BMI, hospitalization, duration of symptoms and surgery, blood loss, incidence of perioperative complications. RESULTS: Group differences were presented in terms of: age, BMI, ASA, duration of symptoms, jaundice, tumor diameter, time of operation. There were no differences considering weight loss, blood loss, extent of resection, and hospitalization. Significant MMPs and TIMPs concentration differences between groups were demonstrated. CONCLUSIONS: Comparison of PC to CP tissue samples showed significantly higher levels of metalloproteinases and TIMPs in the former. Positive correlations of MMP1, TIMP1 and 2 with tumor diameter (CP) were observed, and MMP2 with the duration of surgery and blood loss (PC). There was no MMPs and TIMPs concentration levels influence on the incidence of postoperative complications.

Pancreatic cyst fluid analysis for differential diagnosis between benign and malignant lesions.

The majority of pancreatic cysts are detected incidentally when abdominal imaging is performed during unrelated procedures. The aim of the present study was to assess the diagnostic utility and clinical value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and amylase analysis in pancreatic cyst fluid. The study included 52 patients with pancreatic cystic lesions, who underwent fine-needle aspiration biopsy to collect cystic fluid for cytological and biochemical analysis. Cysts were classified as benign (simple cysts, pseudocysts and serous cystadenomas) in 36 patients or premalignant/malignant (mucinous cyst-adenomas, intraductal papillary mucinous neoplasm and cystadenocarcinomas) in 16 patients. CEA and CA 19-9 were elevated in patients with malignant cysts (238±12.5 ng/ml and 222±31.5 U/ml, respectively) compared with benign lesions (34.5±3.7 ng/ml and 18.5±1.9 U/ml, respectively; P<0.001). Based on these results, the sensitivity and specificity of CEA were 91.8 and 63.9% and of CA 19-9 were 81.3 and 69.4%, respectively. Mean amylase levels in benign lesions (27825.7±91.9 U/l) were higher compared with malignant pancreatic cysts (8359.2±32.7 U/l; P<0.05). Cyst fluid analysis may prove a safe and useful adjunct for the differential diagnosis of pancreatic cystic lesions. In the present study, promising results for CEA and CA 19-9 have been demonstrated, however, the clinical value of these molecules must be confirmed.

A comparative analysis of K-ras mutation and carcinoembryonic antigen in pancreatic cyst fluid.

BACKGROUND/AIMS: Analysis of cystic fluid may be useful in distinguishing between benign and malignant cysts which has significant impact on their management. The aim of our study was to assess the diagnostic utility of carcinoembryonic antigen (CEA) and K-ras gene mutation in pancreatic cysts fluid. METHODS: The study included 56 patients with pancreatic cystic fluid collected for analysis. The cysts were classified as benign (simple cysts, pseudocysts, serous cystadenoma) - 39 patients or premalignant/malignant (mucinous cystadenoma, IPMN, cystadenocarcinoma) - 17 patients. The patients history, CEA fluid concentrations and presence of K-ras mutation were analyzed. RESULTS: CEA were higher in patients with malignant cysts (mean levels 238 ± 12.5 ng/ml; range 32.8-4985 ng/ml) compared to benign lesions (mean levels 34.5 ± 3.7 ng/ml; range 3.9-693 ng/ml; p < 0.001). K-ras mutation correctly classified 11 of 17 patients with premalignant/malignant lesions. It was also detected in 1 patient with final diagnosis of benign cyst (the sensitivity 64.7% and the specificity 97.4%; p < 0.01). If CEA and molecular analysis were combined in that cysts with either CEA level>45 ng/ml or presence of K-ras mutation, than 16 of 17 premalignant/malignant cysts were correctly identified (94.1%). CONCLUSION: Molecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis and should be considered when cyst cytologic examination is negative for malignancy.

Quality-of-life assessment in the treatment of iatrogenic bile duct injuries: hepaticojejunostomy versus end-to-end biliary reconstructions.

BACKGROUND: Assessment and comparison of quality of life (QOL) in patients treated for iatrogenic bile duct injuries (IBDI) with Roux-en-Y hepaticojejunostomy (HJ) or end-to-end ductal anastomosis (EE). METHODS: The Medical Outcomes Study Short Form 36v2 (SF-36v2) Health Survey and the Karnofsky score were used. Comparative analysis of QOL was performed in 41 patients following reconstructive surgery for IBDI between 1990 and 2005: 22 - HJ and 21 - EE. RESULTS: Seven of eight values were comparable in both analysed groups: role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health index. Physical functioning was significantly better in patients following EE (P = 0.04). Physical component summary (P = 0.11) and mental component summary (P = 0.92) in both groups were comparable. QOL according to the Karnofsky scale was comparable in both groups (P = 0.294). CONCLUSIONS: Physical functioning was significantly better in patients after EE. Other values of QOF according to the SF-36v2 and the Karnofsky score were comparable in both groups.