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Background
Postoperative pancreatic fistula (POPF) is the most critical complication after pancreatoduodenectomy (PD). Preoperative identification of high-risk patients and optimal pancreatic reconstruction technique can be a way to reduce postoperative complications.
Methods
A series of 386 patients underwent PD over a 10-year period (2009–2019). On routinely performed preoperative computed tomography (CT) images, the ventro-dorsal diameters of duct (D) and parenchyma (P) were measured in the cutting plane at the superior mesenteric vein. Then, the ratio of both values was calculated (D/P ratio) Double-layer pancreatojejunostomy with alignment of duct and mucosa (ADAM) by two monofilament threads (MFT) was performed in 359 patients and pancreatogastrostomy (PG) in 27 patients. The incidence of POPF was diagnosed according to the International Study Group for Pancreatic Fistula criteria.
Results
The overall rate of POPF was 21% (n = 80), and the rate of clinically relevant type B/C fistulas 6.5% (n = 25). A D/P ratio of <0.2 was significantly associated with type B/C fistula (11%, p < 0.01). In low-risk patients (D/P ratio >0.2), type B/C fistula occurred only in 2%, and in high-risk patients (D/P ratio <0.2) in 9%. ADAM anastomosis was performed safely by two different surgeons. A PG anastomosis had double-digit POPF rates in all groups.
Conclusion
Preoperative CT imaging with D/P measurement may predict the risk of POPF development. A cut off D/P ratio of <0.2 was significantly associated with clinical relevant POPF. ADAM anastomosis may be an option for pancreatojejunostomy. However, preoperative knowledge of the D/P ratio could guide decision-making for primary pancreatectomy when pancreatic reconstruction is critical.
Sphingosine-1-phosphate (S1P) regulates the migration of follicular B cells
(B2 cells) and directs the positioning of Marginal zone B cells (MZ B cells) within the spleen. The
function of S1P signalling in the third B cell lineage, B1 B cells, mainly present in the pleural and
peritoneal cavity, has not yet been determined. Methods: S1P receptor expression was analysed
in peritoneal B cells by real-time polymerase chain reaction (qPCR). The chemotactic response to
S1P was studied in vitro. The role of S1P signalling was further explored in a s1p4
−/− mouse
strain. Results: Peritoneal B cells expressed considerable amounts of the S1P receptors 1 and 4
(S1P1 and S1P4, respectively). S1P1 showed differential expression between the distinct peritoneal B
cell lineages. While B2 cells showed no chemotactic response to S1P, B1 B cells showed a migration
response to S1P. s1p4
−/− mice displayed significant alterations in the composition of peritoneal
B cell populations, as well as a significant reduction of mucosal immunoglobulin A (IgA) in the
gut. Discussion: S1P signalling influences peritoneal B1 B cell migration. S1P4 deficiency alters the
composition of peritoneal B cell populations and reduces secretory IgA levels. These findings suggest
that S1P signalling may be a target to modulate B cell function in inflammatory intestinal pathologies.
Despite continuous advances in therapy, malignant melanoma is still among the deadliest
types of cancer. At the same time, owing to its high plasticity and immunogenicity, melanoma is
regarded as a model tumor entity when testing new treatment approaches. Cold physical plasma is a
novel anticancer tool that utilizes a plethora of reactive oxygen species (ROS) being deposited on the
target cells and tissues. To test whether plasma treatment would enhance the toxicity of an established
antitumor therapy, ionizing radiation, we combined both physical treatment modalities targeting
B16F10 murine melanoma cell in vitro. Repeated rather than single radiotherapy, in combination
with gas plasma-introduced ROS, induced apoptosis and cell cycle arrest in an additive fashion. In
tendency, gas plasma treatment sensitized the cells to subsequent radiotherapy rather than the other
way around. This was concomitant with increased levels of TNFα, IL6, and GM-CSF in supernatants.
Murine JAWS dendritic cells cultured in these supernatants showed an increased expression of cell
surface activation markers, such as MHCII and CD83. For PD-L1 and PD-L2, increased expression
was observed. Our results are the first to suggest an additive therapeutic effect of gas plasma and
radiotherapy, and translational tumor models are needed to develop this concept further.
Medical gas plasmas are of emerging interest in pre-clinical oncological research. Similar to an array of first-line chemotherapeutics and physics-based therapies already approved for clinical application, plasmas target the tumor redox state by generating a variety of highly reactive species eligible for local tumor treatments. Considering internal tumors with limited accessibility, medical gas plasmas help to enrich liquids with stable, low-dose oxidants ideal for intratumoral injection and lavage. Pre-clinical investigation of such liquids in numerous tumor entities and models in vitro and in vivo provided evidence of their clinical relevance, broadening the range of patients that could benefit from medical gas plasma therapy in the future. Likewise, the application of such liquids might be promising for recurrent BRAF(V600E) papillary thyroid carcinomas, resistant to adjuvant administration of radioiodine. From a redox biology point of view, studying redox-based approaches in thyroid carcinomas is particularly interesting, as they evolve in a highly oxidative environment requiring the capability to cope with large amounts of ROS/RNS. Knowledge on their behavior under different redox conditions is scarce. The present study aimed to clarify resistance, proliferative activity, and the oxidative stress response of human papillary thyroid cancer cells K1 after exposure to plasma-oxidized DMEM (oxDMEM). Cellular responses were also evaluated when treated with different dosages of hydrogen peroxide and the RNS donor sodium nitroprusside (SNP). Our findings outline plasma-oxidized liquids as a promising approach targeting BRAF(V600E) papillary thyroid carcinomas and extend current knowledge on the susceptibility of cells to undergo ROS/RNS-induced cell death.
Cold medical gas plasmas are under pre-clinical investigation concerning their hemostatic activity and could be applied for intra-operative bleeding control in the future. The technological leap innovation was their generation at body temperature, thereby causing no thermal harm to the tissue and ensuring tissue integrity. This directly contrasts with current techniques such as electrocautery, which induces hemostasis by carbonizing the tissue using a heated electrode. However, the necrotized tissue is prone to fall, raising the risk of post-operative complications such as secondary bleedings or infection. In recent years, various studies have reported on the ability of medical gas plasmas to induce blood coagulation, including several suggestions concerning their mode of action. As non-invasive and gentle hemostatic agents, medical gas plasmas could be particularly eligible for vulnerable tissues, e.g., colorectal surgery and neurosurgery. Further, their usage could be beneficial regarding the prevention of post-operative bleedings due to the absence or sloughing of eschar. However, no clinical trials or individual healing attempts for medical gas plasmas have been reported to pave the way for clinical approvement until now, despite promising results in experimental animal models. In this light, the present mini-review aims to emphasize the potential of medical gas plasmas to serve as a hemostatic agent in clinical procedures. Providing a detailed overview of the current state of knowledge, feasible application fields are discussed, and possible obstacles are addressed.
Simple Summary
Pancreatic neuroendocrine tumors (pNET) are a heterogeneous and challenging entity, and today’s guidelines offer a variety of treatment modalities, while surgery has a clear role for patients with resectable tumors and early stages, advanced, or metastatic pNET may benefit from treatments that were evaluated in randomized controlled studies during the last year. With this review, we aim to provide an updated view on treatment options for metastatic pNET.
Background: Despite the growing concern over its potentially severe side effects and considerable economic burden, stress ulcer prophylaxis (SUP) is still frequently prescribed to patients in medical non-intensive care units. Recent data indicate that the situation is similar in surgical departments. Currently, data on the concepts within and regulation of routine SUP practice in surgical departments are sparse. The present study was designed to examine the current practice of SUP in Mecklenburg West Pomerania, Germany, and to identify possible reasons for the dissociation of medical literature and clinical practice. Methods: A questionnaire-based survey was conducted to elucidate current SUP practices in surgical departments of acute care hospitals in Mecklenburg Western Pomerania, Germany. Results: In most surgical departments (68%), a standard operating procedure (SOP) for SUP had not been developed. In departments with an existing SOP, 47.6% of responding medical staff members (MSM) with prescribing authority did not know of its existence. Of the MSMs aware of the existence of an SUP-SOP, only 42.9% indicated that they were familiar with its content. Critical re-evaluation of SUP indications upon transfer from the intensive care unit (ICU) to the general hospital ward (GHW) and before hospital discharge was performed frequently or systematically by only about half of the responding MSMs. Discussion: In the face of continued massive over-prescription of SUP in the perioperative routine, the development of easy-to-use local guidelines and their strict implementation in the clinical routine, as well as intensified medial education on this subject, may be effective tools to reduce acid-suppressive medication (ASM) associated side effects and economic burden.
The requirements for new technologies to serve as anticancer agents go far beyond their toxicity potential. Novel applications also need to be safe on a molecular and patient level. In a broader sense, this also relates to cancer metastasis and inflammation. In a previous study, the toxicity of an atmospheric pressure argon plasma jet in four human pancreatic cancer cell lines was confirmed and plasma treatment did not promote metastasis in vitro and in ovo. Here, these results are extended by additional types of analysis and new models to validate and define on a molecular level the changes related to metastatic processes in pancreatic cancer cells following plasma treatment in vitro and in ovo. In solid tumors that were grown on the chorion-allantois membrane of fertilized chicken eggs (TUM-CAM), plasma treatment induced modest to profound apoptosis in the tissues. This, however, was not associated with a change in the expression levels of adhesion molecules, as shown using immunofluorescence of ultrathin tissue sections. Culturing of the cells detached from these solid tumors for 6d revealed a similar or smaller total growth area and expression of ZEB1, a transcription factor associated with cancer metastasis, in the plasma-treated pancreatic cancer tissues. Analysis of in vitro and in ovo supernatants of 13 different cytokines and chemokines revealed cell line-specific effects of the plasma treatment but a noticeable increase of, e.g., growth-promoting interleukin 10 was not observed. Moreover, markers of epithelial-to-mesenchymal transition (EMT), a metastasis-promoting cellular program, were investigated. Plasma-treated pancreatic cancer cells did not present an EMT-profile. Finally, a realistic 3D tumor spheroid co-culture model with pancreatic stellate cells was employed, and the invasive properties in a gel-like cellular matrix were investigated. Tumor outgrowth and spread was similar or decreased in the plasma conditions. Altogether, these results provide valuable insights into the effect of plasma treatment on metastasis-related properties of cancer cells and did not suggest EMT-promoting effects of this novel cancer therapy.