Chemotherapy versus chemoradiotherapy in borderline resectable and locally advanced pancreatic adenocarcinoma.

The role of radiotherapy in borderline resectable (BRPC) and locally advanced pancreatic carcinoma (LAPC) remains controversial. In our study, we retrospectively evaluated 48 patients with BRPC (14; 29.2%) and LAPC (34; 70. 8%) who underwent 6-8 cycles of induction mFOLFIRINOX chemotherapy alone (23; 47.9%) or 4-6 cycles of mFOLFIRINOX followed by hypofractionated radiotherapy (up to the total dose of 39.9 Gy in 15 fractions) (25; 52.1%). Survival parameters were evaluated using the Gehan-Breslow-Wilcoxon Test and compared by using the long-rank test. The addition of radiotherapy was not associated with better survival (16.9 months for chemotherapy only versus 15.9 months for the combined therapy; p=0.486), as well as for both subgroups (13.5 months vs. 18.3 months; p=0.679) and (20.7 months vs. 13.8 months; p=0.425) for BRPC and LAPC, respectively. A higher resection rate was seen in the BRPC group compared to the LAPC group (43% vs. 17.6%, respectively). Our study revealed a significantly higher rate of lung metastases in patients after the combination therapy compared to those treated by chemotherapy only (19% vs. 0%, respectively; p=0.045). Such a borderline result, however, prevents us from drawing clear conclusions about whether this is an artifact caused by the low number of patients or whether radiotherapy leads to a selection of stem cells with a predilection to the generalization to the lungs.

28 day post-operative persisted hypercoagulability after surgery for benign diseases: a prospective cohort study.

BACKGROUND: Surgery for benign disease is associated with a low-risk of developing venous thromboembolism (VTE). Despite a relatively low incidence of postoperative VTE in patients after elective cholecystectomy and abdominal hernia repair there are data proving hypercoagulability in the early postoperative period. We focused on assessment of the systemic inflammatory response and coagulation status in these surgical patients after hospital discharge. METHODS: Prospectively, patients who underwent surgery for benign disease were included. Two hundred sixteen patients were enrolled - 90 patients in laparoscopic cholecystectomy (LC) group and 126 patients in hernia surgery (HS) group. Risk assessment of VTE according to the Caprini risk assessment model was performed in all patients. Prevalence of VTE in postoperative period was observed. Markers of systemic inflammatory response (IL-6, CRP, α-1-acid glycoprotein, transferrin) and coagulation markers (PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer) were measured before surgery, on 7-10th postoperative day and on 28-30th postoperative day. RESULTS: Clinically apparent deep vein thrombosis was diagnosed in only one patient - 0.46%. Statistically significant elevation of inflammatory markers IL-6, CRP and α-1-acid glycoprotein (p < 0.001; all) were proved in both groups of patients on 7-10th postoperative day. Statistically significant elevation of coagulation markers PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer (p < 0.001; all) were proved in LC and HS groups on 7-10th postoperative day. No statistical difference was observed in IL-6, CRP and α-1-acid glycoprotein levels a month after surgery as compared with preoperative levels within each group. Statistically significant elevation of fibrinogen and prothrombin fragment F1 + 2 levels (p < 0.001; both) persisted on 28-30th postoperative day in both groups. Persisted elevation of D-dimer levels was proved only in HS group (p < 0.001), not in LC group (p = 0.138), a month after surgery. CONCLUSIONS: Activated systemic inflammatory response and hypercoagulable condition were verified in patients after laparoscopic cholecystectomy and hernia surgery after their hospital discharge. Hypercoagulability persisted even a month after surgery. Nevertheless, we observed very low prevalence of clinically apparent VTE in patients with in-hospital postoperative VTE prophylaxis. TRIAL REGISTRATION: Trials of the Czech Ministry of Health No. RVO-VFN64165 and NT 13251-4 .

Pancreatic Cancer Diagnostics and Treatment--Current State.

Pancreatic ductal adenocarcinoma (PDAC) represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60-80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5). In contrast R0 resection shows the survival 18-27 months. Laboratory and imaging screening methods are not indicated on large scale. Risk factors are smoking, alcohol abuse, chronic pancreatitis, diabetes mellitus. Genetic background in most PDAC has not been detected yet. Some genes connected with high risk of PDAC (e.g. BRCA2, PALB2) have been identified as significant and highly penetrative, but link between PDAC and these genes can be seen only in 10-20%. This article surveys perspective oncogenes, tumour suppressor genes, microRNA. Albeit CT is still favoured over other imaging methods, involvement of NMR rises. Surgery prefers the "vessel first" approach, which proves to be justified especially in R0 resection. According to EBM immunotherapy same as radiotherapy are not significant in PDAC treatment. Chemotherapy shows limited importance in conversion treatment of locally advanced or borderline tumours or in case of metastatic spread. Unified procedures cannot be defined due to inhomogenous arrays. Surgical resection is the only chance for curative treatment of PDAC and depends mainly on timely indication for surgery and quality of multidisciplinary team in a high-volume centre.

Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery.

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs.

New methodology of TMB assessment from tissue and liquid biopsy in NSCLC.

Immunotherapy has dramatically influenced and changed therapeutical approach in non-small cell lung cancer (NSCLC) in recent five years. Even though we can reach long-term response to this treatment in approximately 20% of patients with NSCLC, we are still not able to identify this cohort of patients based on predictive biomarkers. In our study we have focused on tumor mutation burden (TMB), one of the potential biomarkers which could predict effectiveness of check-point inhibitors, but has several limitations, especially in multiple approaches to TMB quantification and ununiform threshold. We determined the value of TMB in tumor tissue (tTMB) and blood (bTMB) in 20 patients with early stage NSCLC using original custom gene panel LMB_TMB1. We evaluated various possibilities of TMB calculation and concluded that TMB should be counted from both somatic non-synonymous and synonymous mutations. Considering various factors, we established cut-offs of tTMB in/excluding HLA genes as ≥22 mut/Mb and 12 mut/Mb respectively, and cut-offs of bTMB were defined as ≥21 mut/Mb and ≥5 mut/Mb, respectively. We also observed trend in correlation of somatic mutations in HLA genes with overall survival of patients.

[Current status of pancreatic cancer diagnosis]. / Soucasný stav diagnostiky karcinomu pankreatu.

Pancreatic cancer still remains one of the tumors with the worst prognosis. The five-year survival rate ranges between 0.4 to 2 per cent. In most cases the tumor is diagnosed at an advanced stage, which does not allow a radical surgical treatment. Currently, the diagnosis of pancreatic cancer is based on dynamically developing imaging methods that allow detecting even small lesions. The basic testing method is the contrast computed tomography which is, in most cases, linked up to the endoscopic ultrasonography. In most patients results of the cytopathological and histological examinations are obtained before surgical or oncological therapy. The decisive factor for further therapeutic approach is the tumor staging. Despite the apparent progress in diagnostic techniques, the early diagnosis of pancreatic cancer remains unsatisfactory.

[Our experience with pancreatic cancer and its relation to diabetes mellitus]. / Karcinom pankreatu--nase zkusenosti se vztahem k diabetes mellitus.

BACKGROUND: Despite the introduction of new imaging methods, the prognosis of pancreatic carcinoma (PC) remains hopeless. Therefore, there has been exerted much effort to elucidate the risk factor enabling the diagnosis of PC in the "preclinical state". At the time of PC diagnosis, more than 30% of patients suffer from diabetes mellitus, much more often than in the rest of the population. It is not clear whether DM is a risk factor for PC onset or DM appears secondary to the destruction of the gland by the tumor progression or by the effect of unknown factors produced by the cancer cells. METHODS AND RESULTS: We enrolled 204 individuals into the study, 69 of them were controls, 70 patients had type 2 diabetes mellitus and 65 cases had newly diagnosed PC. The patients with PC had in 68% of cases disturbed glucose homeostasis and significantly higher values of insulin resistance index (HOMA-IR) in comparison with the control group. The presence of glucose homeostasis disturbances does not influence tumor staging and localization. CONCLUSIONS: Results of our pilot study confirmed the so far unsatisfactory state of PC diagnostics (majority of cases fall to stages III and IV) and corroborated the close relation to DM. The early markers for the risk of pancreatic carcinoma development should be searched among the factors participating in the regulation of the glucose homeostasis and insulin sensitivity.

Necrotizing Soft Tissue Infections: A Focused Review of Pathophysiology, Diagnosis, Operative Management, Antimicrobial Therapy, and Pediatrics.

Background: Necrotizing fasciitis is a major health problem throughout the world. The purpose of this review is to assist providers with the care of these patients through a better understanding of the pathophysiology and management options. Methods: This is a collaborative review of the literature between members of the Surgical Infection Society of North America and World Society of Emergency Surgery. Results: Necrotizing fasciitis continues to be difficult to manage with the mainstay being early diagnosis and surgical intervention. Recognition of at-risk populations assists with the initiation of treatment, thereby impacting outcomes. Conclusions: Although there are some additional treatment strategies available, surgical debridement and antimicrobial therapy are central to the successful eradication of the disease process.

Germline mutation in the TP53 gene in uveal melanoma.

We performed comprehensive molecular analysis of five cases of metastasizing uveal malignant melanoma (UM) (fresh-frozen samples) with an NGS panel of 73 genes. A likely pathogenic germline TP53 mutation c.760A > G (p.I254V) was found in two tumor samples and matched nontumor tissue. In three cases, pathogenic BAP1 mutation was detected together with germline missense variants of uncertain significance in ATM. All cases carried recurrent activating GNAQ or GNA11 mutation. Moreover, we analyzed samples from another 16 patients with primary UM by direct Sanger sequencing focusing only on TP53 coding region. No other germline TP53 mutation was detected in these samples. Germline TP53 mutation, usually associated with Li-Fraumeni syndrome, is a rare event in UM. To the best of our knowledge, only one family with germline TP53 mutation has previously been described. In our study, we detected TP53 mutation in two patients without known family relationship. The identification of germline aberrations in TP53 or BAP1 is important to identify patients with Li-Fraumeni syndrome or BAP1 cancer syndrome, which is also crucial for proper genetic counseling.

2018 WSES/SIS-E consensus conference: recommendations for the management of skin and soft-tissue infections.

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. SSTIs are a frequent clinical problem in surgical departments. In order to clarify key issues in the management of SSTIs, a task force of experts met in Bertinoro, Italy, on June 28, 2018, for a specialist multidisciplinary consensus conference under the auspices of the World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E). The multifaceted nature of these infections has led to a collaboration among general and emergency surgeons, intensivists, and infectious disease specialists, who have shared these clinical practice recommendations.

Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions.

BACKGROUND: Rivaroxaban represents a selective direct inhibitor of activated coagulation factor X (FXa) having peroral bioavailability and prompt onset of action. OBJECTIVE: The absorbtion of rivaroxaban is quick, reaching maximum plasma concentration 2-4 hours following its administration. Peroral bioavailability is high (80-100 %) and pharmacokinetic variability is considered to be moderate (coefficient of variation 30-40 %). This review discusses the properties, drug interactions, pharmacokinetics and clinical indications of rivaroxaban. METHOD: Dosing regimen of rivaroxaban was derived from pharmacologic data of the development program aimed to gain strong antithrombotic drug and balance between efficacy and risk of bleeding in patients. Results of doseranging trials, pharmacokinetic models and randomised studies of phase III advocate the use of such schemes in everyday practice. RESULTS: The drug has been manufactured to fulfill clinical requirements in a variety of indications in adults: prophylaxis of venous thromboembolism (VTE) following elective knee or hip replacement surgical intervention, therapy and secondary prophylaxis of VTE, prophylaxis of ischemic stroke and embolism in individuals diagnosed with nonvalvular atrial fibrillation (NVAF) with risky characteristics, and in Europe the prophylaxis of atherothrombotic episodes following an acute coronary syndrome in subjects with increased levels of cardiac biomarkers. CONCLUSION: Rivaroxaban may offer benefit in many clinical situations. In comparison with low molecular weight heparin and fondaparinux requiring subcutaneous way of administration, and with vitamin K antagonists (VKAs), which require regular monitoring of international normalized ratio, rivaroxaban is relatively easy to use. However, adjustments of dose are needed in individuals with impaired renal functions.

Management of intra-abdominal infections: recommendations by the WSES 2016 consensus conference.

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.

WSES Guidelines for the management of acute left sided colonic diverticulitis in the emergency setting.

Acute left sided colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in acute setting. A World Society of Emergency Surgery (WSES) Consensus Conference on acute diverticulitis was held during the 3rd World Congress of the WSES in Jerusalem, Israel, on July 7th, 2015. During this consensus conference the guidelines for the management of acute left sided colonic diverticulitis in the emergency setting were presented and discussed. This document represents the executive summary of the final guidelines approved by the consensus conference.

Premalignant and malignant lesions of the heterotopic pancreas in the esophagus: a case report and review of the literature.

Heterotopic pancreas is a congenital pathology of the gastrointestinal tract, particularly rare in the esophagus. Both symptomatology and findings during preoperative examinations are non-specific and therefore do not often lead to an accurate diagnosis, which is usually revealed only by histopathological assessment of a resected specimen. We report an unusual case of a patient suffering from severe dysphagia caused by heterotopic pancreas in the distal esophagus with chronic inflammation and foci of premalignant changes. This article also reviews 14 adult cases of heterotopic pancreas in the esophagus previously reported in the literature, with the aim of determining the clinical features of this disease and possible complications including rare premalignant lesions and malignant transformation. Especially with regard to those complications, we suggest that both symptomatic and incidentally found asymptomatic lesions should be resected.

The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper.

The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear. In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal. However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias. Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time.

A proposal for a CT driven classification of left colon acute diverticulitis.

Computed tomography (CT) imaging is the most appropriate diagnostic tool to confirm suspected left colonic diverticulitis. However, the utility of CT imaging goes beyond accurate diagnosis of diverticulitis; the grade of severity on CT imaging may drive treatment planning of patients presenting with acute diverticulitis. The appropriate management of left colon acute diverticulitis remains still debated because of the vast spectrum of clinical presentations and different approaches to treatment proposed. The authors present a new simple classification system based on both CT scan results driving decisions making management of acute diverticulitis that may be universally accepted for day to day practice.