To investigate prognostic impact of parenchymal-sparing hepatectomy (PSH) for solitary small colorectal liver metastasis (CLM).
It is unclear whether PSH confers an oncologic benefit through ...increased salvageability or is a detriment through increasing recurrence rate.
Database of 300 CLM patients with a solitary tumor (≤ 30 mm in size) was reviewed from 1993 to 2013. A total of 156 patients underwent PSH and 144 patients underwent right hepatectomy, left hepatectomy, or left lateral sectionectomy (non-PSH group).
The rate of PSH increased over the study period (P < 0.01). PSH did not impact negatively on overall (OS), recurrence-free, and liver-only recurrence-free survival, compared with non-PSH (P = 0.53, P = 0.97, and P = 0.69, respectively). Liver-only recurrence was observed in 22 patients (14%) in the PSH and 25 (17%) in the non-PSH group (P = 0.44). Repeat hepatectomy was more frequently performed in the PSH group (68% vs 24%, P < 0.01). Subanalysis of patients with liver-only recurrence revealed better 5-year overall survival from initial hepatectomy and from liver recurrence in the PSH than in the non-PSH group 72.4% vs 47.2% (P = 0.047) and 73.6% vs 30.1% (P = 0.018), respectively. Multivariate analysis revealed that non-PSH was a risk of noncandidacy for repeat hepatectomy (hazard ratio: 8.18, confidence interval: 1.89-45.7, P < 0.01).
PSH did not increase recurrence in the liver remnant but more importantly improved 5-year survival in case of recurrence (salvageability). PSH should be the standard approach to CLM to allow for salvage surgery in case of liver recurrence.
While clinical outcomes of minimally invasive pancreatic resection (MIPR) compared to open surgery are well examined, only few studies focus on its associated cost. The aim of this study is to ...evaluate cost analyses comparing MIPR to open pancreatic resection (OPR). A systematic review of the literature using PubMed of all published studies between 2000 and 2017 was performed. Studies reporting on cost of laparoscopic distal pancreatectomy (LDP) and laparoscopic pancreatoduodenectomy (LPD) compared to open surgery were identified. Fourteen studies were included, eight that reported a cost comparison between LDP and open surgery and six that compared costs between LPD and open surgery. For both, LDP and LPD, operative costs were higher due to higher costs for surgical equipment. Reports suggest that lower postoperative costs for LDP and LPD could balance out the operative costs resulting in overall decreased costs for the laparoscopic compared to the open approach. Recent results show a positive trend towards cost savings for MIPR. To assess the overall benefit of MIPR compared to OPR comprehensive cost analyses and long-term quality outcomes need to be investigated.
About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of ...viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.
This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The ...group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.
To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM).
The t-CS relies on the following ...factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS.
Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients.
A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not.
Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.
The STAT3 transcription factor is an important regulator of stem cell self-renewal, cancer cell survival, and inflammation. In the pancreas, STAT3 is dispensable for normal development, whereas the ...majority of pancreatic ductal adenocarcinomas (PDAC) show constitutive activation of STAT3, suggesting its potential as a therapeutic target in this cancer. Here, we sought to define the mechanisms of STAT3 activation and its functional importance in PDAC pathogenesis. Large-scale screening of cancer cell lines with a JAK2 inhibitor that blocks STAT3 function revealed a more than 30-fold range in sensitivity in PDAC, and showed a close correlation of sensitivity with levels of tyrosine-phosphorylated STAT3 and of the gp130 receptor, an upstream signaling component. Correspondingly, upregulation of the IL6/LIF-gp130 pathway accounted for the strong STAT3 activation in PDAC subsets. To define functions of STAT3 in vivo, we developed mouse models that test the impact of conditional inactivation of STAT3 in KRAS-driven PDAC. We showed that STAT3 is required for the development of the earliest premalignant pancreatic lesions, acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Moreover, acute STAT3 inactivation blocked PDAC initiation in a second in vivo model. Our results show that STAT3 has critical roles throughout the course of PDAC pathogenesis, supporting the development of therapeutic approaches targeting this pathway. Moreover, our work suggests that gp130 and phospho-STAT3 expression may be effective biomarkers for predicting response to JAK2 inhibitors.
Hippo-Lats-Yorkie signaling regulates tissue overgrowth and tumorigenesis in
Drosophila. We show that the Mst1 and Mst2 protein kinases, the mammalian Hippo orthologs, are cleaved and constitutively ...activated in the mouse liver. Combined Mst1/2 deficiency in the liver results in loss of inhibitory Ser127 phosphorylation of the Yorkie ortholog, Yap1, massive overgrowth, and hepatocellular carcinoma (HCC). Reexpression of Mst1 in HCC-derived cell lines promotes Yap1 Ser127 phosphorylation and inactivation and abrogates their tumorigenicity. Notably, Mst1/2 inactivates Yap1 in liver through an intermediary kinase distinct from Lats1/2. Approximately 30% of human HCCs show low Yap1(Ser127) phosphorylation and a majority exhibit loss of cleaved, activated Mst1. Mst1/2 inhibition of Yap1 is an important pathway for tumor suppression in liver relevant to human HCC.
Background
In patients undergoing resection of colorectal liver metastases (CLM), resection margin status is a significant predictor of survival, particularly in patients with suboptimal response to ...preoperative therapy.
RAS
mutations have been linked to more invasive and migratory tumor biology and poor response to modern chemotherapy.
Objective
The aim of this study was to evaluate the relationship between
RAS
mutation and resection margin status in patients undergoing resection of CLM.
Methods
Patients who underwent curative resection of CLM from 2005 to 2013 with known
RAS
mutation status were identified from a prospectively maintained database. A positive margin was defined as tumor cells <1 mm from the parenchymal transection line.
Results
The study included 633 patients, of whom 229 (36.2 %) had mutant
RAS
. The positive margin rate was 11.4 % (26/229) for mutant
RAS
and 5.4 % (22/404) for wild-type
RAS
(
p
= 0.007). In multivariate analysis, the only factors associated with a positive margin were
RAS
mutation (hazard ratio HR 2.439;
p
= 0.005) and carcinoembryonic antigen level 4.5 ng/mL or greater (HR 2.060;
p
= 0.026). Among patients presenting with liver-first recurrence during follow-up, those with mutant
RAS
had narrower margins at initial CLM resection (median 4 mm vs. 7 mm;
p
= 0.031). A positive margin (HR 3.360;
p
< 0.001) and
RAS
mutation (HR 1.629;
p
= 0.044) were independently associated with worse overall survival.
Conclusion
RAS
mutations are associated with positive margins in patients undergoing resection of CLM. Tumors with
RAS
mutation should prompt careful efforts to achieve negative resection margins.
To investigate the legitimacy of 90-day mortality as a measure of hepatopancreatobiliary quality.
The 90-day mortality rate has been increasingly but not universally reported after ...hepatopancreatobiliary surgery. The legitimacy of this definition as a measure of surgical quality has not been evaluated.
We retrospectively reviewed the causes of all deaths that occurred within 365 postoperative days in patients undergoing hepatectomy (n = 2811) and/or pancreatectomy (n = 1092) from January 1997 to December 2012. The rates of surgery-related, disease-related, and overall mortality within 30 days, within 30 days or during the index hospitalization, within 90 days, and within 180 days after surgery were calculated.
Seventy-nine (3%) surgery-related deaths and 92 (3%) disease-related deaths occurred within 365 days after hepatectomy. Twenty (2%) surgery-related deaths and 112 (10%) disease-related deaths occurred within 365 days after pancreatectomy. The overall mortality rates at 99 and 118 days optimally reflected surgery-related mortality after hepatobiliary and pancreatic operations, respectively. The 90-day overall mortality rate was a less sensitive but equivalently specific measure of surgery-related death.
The 99- and 118-day definitions of postoperative mortality optimally reflected surgery-related mortality after hepatobiliary and pancreatic operations, respectively. However, among commonly reported metrics, the 90-day overall mortality rate represents a legitimate measure of surgical quality.
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