BackgroundSurgical resection is the only potentially curative treatment for pancreatic neuroendocrine tumors. The choice for the type of procedure is influenced by the expected oncological benefit and the anticipated risk of procedure-specific complications. Few studies have focused on complications in these patients. This cohort study aimed to assess complications and risk factors after resections of pancreatic neuroendocrine tumors.MethodsPatients undergoing resection of a pancreatic neuroendocrine tumor were identified within 2 centers of excellence. Complications were assessed according to the Clavien-Dindo classification and the comprehensive complication index. Logistic regression was performed to compare surgical procedures with adjustment for potential confounders (Clavien-Dindo ≥3).ResultsThe cohort comprised 123 patients, including 12 enucleations, 50 distal pancreatectomies, 51 pancreatoduodenectomies, and 10 total/combined pancreatectomies. Mortality was 0.8%, a severe complication occurred in 41.5%, and the failure-to-rescue rate was 2.0%. The median comprehensive complication index was 22.6 (0–100); the comprehensive complication index increased after more extensive resections. After adjustment, a pancreatoduodenectomy, as compared to a distal pancreatectomy, increased the risk for a severe complication (odds ratio 3.13 [95% confidence interval 1.32–7.41]). Of the patients with multiple endocrine neoplasia type 1 or von Hippel-Lindau, 51.9% developed a severe complication vs 38.5% with sporadic disease. After major resections, morbidity was significantly higher in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau (comprehensive complication index 45.1 vs 28.9, P = .029).ConclusionSurgery for pancreatic neuroendocrine tumors is associated with a high rate of complications but low failure-to-rescue in centers of excellence. Complications are procedure-specific. Major resections in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau appear to increase the risk of complications.
The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic.An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave.Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37).The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making.The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.
This prospective nationwide cohort study examined the feasibility of a watchful-waiting protocol for non-functional pancreatic neuroendocrine tumours (NF-pNET) of 2 cm or smaller. In total, 8 of 76 patients (11 per cent) with a NF-pNET no larger than 2 cm showed significant tumour progression (more than 0.5 cm/year) during 17 months of follow-up, of whom two opted for resection. No patient developed metastases. Quality of life was poorer than in the reference population. Watchful waiting seems a safe alternative to upfront surgery in patients with a NF-pNET no larger than 2 cm, although longer follow-up is necessary.
Death receptors are a unique class of cell-surface receptors which are best known for their ability to induce apoptosis upon binding their respective ligands. Among the best studied death receptors are CD95 and TNF-related apoptosis-inducing ligand (TRAIL) receptors. Apoptosis has long been thought to be the primary outcome of death receptor activation and this has lead to the development of death receptor-stimulating agents as anti-tumor therapeutics. However, more recent data suggest that CD95 and TRAIL receptors can also act in a pro-tumorigenic fashion by stimulating tumor cell proliferation, survival and invasion. Identification of the factors and molecular mechanisms that determine these various outcomes in death receptor signaling may lead to new therapeutic strategies targeting death receptors in (surgical) cancer therapy. Colorectal carcinoma (CRC) poses a serious threat to public health as it is one of the most common malignancies in the Western world with over one million new cases each year. The KRAS oncogene is one of the most frequently mutated oncogenes in human cancer with a prevalence of approximately 35-45% in colorectal cancer. It is known that a mutation in the KRAS oncogene contributes to the formation of colorectal tumors, however the role of KRAS in metastasis formation is less known. The presence of liver metastases is the major determinant of survival in patients with colorectal cancer. Approximately 25% of the patients with colorectal cancer already have liver metastases at diagnosis. Only a subgroup of patients with these synchronous colorectal liver metastases benefits from liver surgery. Currently, there are no reliable tools to identify such patients. This thesis describes the role of death receptors in the development and outgrowth of colorectal liver metastases. The key findings in this thesis are that (1) death receptors can be switched into metastasis-promoting receptors by the single common oncogene K-Ras and this is important for survival of metastatic tumor cells and their outgrowth in the liver. An immediate implication of the finding that oncogenic K-Ras alters CD95 signaling output is that therapeutic targeting of death receptors by CD95/TRAIL could have adverse effects on disease progression by promoting invasion and dissemination of micrometastases instead of clearing them. This is a major concern, at least when considering such compounds in the treatment of tumors harboring activating mutations in the K-Ras gene. In addition, (2) CD95 plays an important role in surgery-stimulated outgrowth of colorectal micrometastases in the liver. Therapy antagonizing death receptor signaling could therefore be of interest in the reduction of accelerated outgrowth. Furthermore, (3) preliminary results indicate that circulating CD95L might be usefull as a prognostic factor contributing to the selection of patients for liver surgery
The aim of this study was to evaluate the introduction of diagnostic laparoscopy (DLS) in patients with colorectal peritoneal metastases (PM) to prevent non-therapeutic laparotomies during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC).Patients with histologically proven colorectal PM who underwent a laparotomy for potential CRS + HIPEC from January 2006 to January 2019 were retrospectively identified from a prospectively maintained database. In 2012, DLS was introduced in the preoperative work-up for CRS + HIPEC in our academic center. The rates of non-therapeutic laparotomies, major postoperative complications (Clavien-Dindo grade III or higher), and survival outcomes were investigated for patients who underwent a laparotomy before (cohort A) and after (cohort B) the introduction of DLS. In cohort B, the reasons to refrain from DLS were retrospectively explored from medical records.Overall, 172 patients were included [cohort A: 48 patients (27.9%); cohort B: 124 patients (72.1%)]. A significant drop in the rate of non-therapeutic laparotomies occurred in cohort B compared with cohort A (21.0 vs. 35.4%: p = 0.044), despite only 85 patients (68.5%) from cohort B undergoing DLS in our academic center. The most important reason to refrain from DLS was a recently performed DLS or laparotomy in the referring hospital (48.7%). Major postoperative complications, in-hospital mortality, and survival outcomes were similar for both cohorts.Performing DLS during the preoperative work-up for CRS + HIPEC prevents non-therapeutic laparotomies in patients with colorectal PM. We recommend performing this laparoscopic screening in an experienced HIPEC center.
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