Estrogen Receptor Expression in Pancreatic Adenocarcinoma: Time to Reconsider Evidence

Pancreatic adenocarcinoma remains a chemotherapy-resistant and refractory malignancy with high mortality, unaffected by recent progress in anticancer treatment. Expression of estrogen receptors was detected almost 50 years ago, in both benign and malignant pancreatic cells. However, early preclinical studies in pancreatic cancer led to contradictory findings, and most clinical studies failed to demonstrate an effect with tamoxifen treatment. The identification of a second form of estrogen receptor seems to provide some explanation for these discrepancies. Predominantly expressed in malignant cells and structurally different from what was considered the only estrogen receptor, estrogen receptor β was recognized as a negative prognostic factor and a possible therapeutic target in pancreatic ductal adenocarcinoma. Therefore, findings of research before the identification of estrogen receptor β should be reconsidered, and further studies should be designed to reassess the expression and effect of this specific estrogen receptor type in pancreatic cancer

Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network

Bilirubin is a specific marker for the diagnosis of acute appendicitis

Total serum bilirubin and other biochemical parameters have been associated with acute appendicitis, mainly in complicated cases. The present study aimed to evaluate the role of biochemical parameters in the diagnosis of acute appendicitis, and to further investigate the role of bilirubin as a diagnostic marker irrespective of the severity of the pathology. All recorded cases of appendicectomies in a 1-year period in a single institution were reviewed. The median values of white cell count, C-reactive protein and total serum bilirubin on admission were associated with final histology, and their respective rates of abnormal and normal values were compared between patients who were proven to have negative histology and patients who were proven to have acute appendicitis. A total of 300 patients were studied. Median total serum bilirubin, white cell count and C-reactive protein on admission were significantly associated with acute appendicitis (P<0.001). Respective rates of normal and abnormal values were significantly associated with final histology (P<0.001). Total serum bilirubin demonstrated higher specificity (0.88) but lower sensitivity (0.26) and diagnostic accuracy (0.40) for acute appendicitis. In conclusion, total serum bilirubin on admission should be considered in the diagnostic workup to confirm rather than exclude appendicitis, without focusing on subgroups of specific severity of the disease. White cell count and C-reactive protein may also contribute to the diagnostic work-up, although with limited accuracy

Current evidence on laparoscopic vs. open resection for gastric stromal tumours

Although the use of laparoscopic surgery is increasing, controversy still surrounds its application for malignant conditions. Gastrointestinal stromal tumours (GISTs) are less demanding in terms of lymphadenectomy, meaning that laparoscopic resection might have a more defined benefit when compared with open resection. To the best of our knowledge, no randomized study exists that compares the laparoscopic and open resection of GISTs. The current study aimed to examine the relevant literature by means of a systematic review. A systematic literature search was performed individually by two authors, in which three independent databases were searched using specific search-terms. Titles, abstracts and full texts were screened, as well as references to relevant articles, in order to comprise a comprehensive list of studies. Data were extracted using a detailed pre-agreed spreadsheet. Studies were evaluated according to the modified MINORS criteria. A total of 10 studies were included in the present review, yielding a total of 14 entries. The majority of studies reported significantly improved perioperative outcomes for the laparoscopic approach, including improved duration of operation, blood loss and length of hospital stay. Only four studies reported long-term outcomes and findings that were controversial, with some studies detecting no statistically significant differences, one reporting improved and one reporting worse disease-free and overall survival for the laparoscopic group. Three studies were deemed to be good quality, two of which had not reported significantly different long-term outcomes, while the third had reported significantly improved outcomes in the open resection group. While there is a clear benefit for performing laparoscopic surgery in patients with GIST with regards to perioperative outcomes, when it comes to long-term oncological outcomes, uncertainty over its application remains. The lack of randomized trials, as well as the poor reporting of retrospective studies, limits the amount of evidence that is currently available. Laparoscopic surgery for GIST is certainly safe, feasible and likely cost-effective; however, further studies are required to inform on whether this technique is superior to open resection

Global Consequences of Liver Ischemia/Reperfusion Injury

Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organ’s post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion

Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study

BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C). RESULTS: We included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18 months (CI 10-37). We observed no impact of PHAE on ischemic complications. CONCLUSIONS: DP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes

IL-22BP controls the progression of liver metastasis in colorectal cancer

BackgroundThe immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown.MethodsWe used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages.ResultsOur data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice.ConclusionsWe here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC

Estrogen Receptor Expression in Pancreatic Adenocarcinoma Time to Reconsider Evidence

Pancreatic adenocarcinoma remains a chemotherapy-resistant and refractory malignancy with high mortality, unaffected by recent progress in anticancer treatment. Expression of estrogen receptors was detected almost 50 years ago, in both benign and malignant pancreatic cells. However, early preclinical studies in pancreatic cancer led to contradictory findings, and most clinical studies failed to demonstrate an effect with tamoxifen treatment. The identification of a second form of estrogen receptor seems to provide some explanation for these discrepancies. Predominantly expressed in malignant cells and structurally different from what was considered the only estrogen receptor, estrogen receptor beta was recognized as a negative prognostic factor and a possible therapeutic target in pancreatic ductal adenocarcinoma. Therefore, findings of research before the identification of estrogen receptor beta should be reconsidered, and further studies should be designed to reassess the expression and effect of this specific estrogen receptor type in pancreatic cancer

Clinical Effects and Adverse Events Associated With Desflurane Use in Adult Patients Undergoing Supratentorial Craniotomy: A Systematic Review

Desflurane is an inhalational anesthetic agent with an appealing recovery profile. The present systematic review investigates the clinical effects and adverse events associated with desflurane use during supratentorial craniotomy for brain tumor resection in adults in comparison with other inhalational and intravenous anesthetic agents. A literature search was conducted across the MEDLINE, Library of Congress and LISTA (EBSCO) databases from January 2001 to January 2021. Twelve studies published between 2003 and 2020 were included in this systematic review. Desflurane was compared with either isoflurane, sevoflurane, or propofol for anesthesia maintenance. Brain relaxation scores showed no statistically significant difference between desflurane and the other anesthetic agents. Recovery timepoints, such as time to recovery, time to eye opening, time to extubation, time to follow commands, and time to reach a modified Aldrete score ≥9 were significantly shorter with desflurane in the majority of studies. Systemic hemodynamic variables (mean arterial pressure and heart rate) and cerebral hemodynamics (intracranial pressure and cerebrospinal fluid pressure) were comparable between desflurane and other anesthetic agents in each study. The results of this systematic review demonstrate that desflurane is associated with few adverse events when used for anesthesia maintenance in adult patients undergoing supratentorial brain tumor surgery. Large, prospective, comprehensive studies, utilizing standardized parameter evaluation could provide higher levels of evidence to support these findings