Preoperatively, all patients should be assessed for the presence of cardiac, pulmonary, hepatic, renal, or vascular comorbidity. Presupposing appropriate perioperative measures and surgical technique, there is no reason to contraindicate pneumoperitoneum in patients with peritonitis or intraabdominal malignancy. During laparoscopy, monitoring of end tidal CO2 concentration is mandatory. The available data on closed- (Veress needle) and open-access techniques do not allow us to principally favor the use of either technique. Using 2 to 5-mm instead of 5 to 10-mm trocars improves cosmetic result and postoperative pain marginally. It is recommended to use the lowest intraabdominal pressure allowing adequate exposure of the operative field, rather than using a routine pressure. In patients with limited cardiac, pulmonary, or renal function, abdominal wall lifting combined with low-pressure pneumoperitoneum might be an alternative. Abdominal wall lifting devices have no clinically relevant advantages compared to low-pressure (5-7 mmHg) pneumoperitoneum. In patients with cardiopulmonary diseases, intra- and postoperative arterial blood gas monitoring is recommended. The clinical benefits of warmed, humidified insufflation gas are minor and contradictory. Intraoperative sequential intermittent pneumatic compression of the lower extremities is recommended for all prolonged laparoscopic procedures. For the prevention of postoperative pain a wide range of treatment options exists. Although all these options seem to reduce pain, the data currently do not justify a general recommendation.
LSR was associated with a 15.4% reduction in major complication rates, less pain, improved quality of life, and shorter hospitalization at the cost of a longer operating time.
We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.
No conclusions may be drawn on preference of one treatment over another from this RCT because it was prematurely terminated following accrual of 15% of its sample size.
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