The impact of preoperative nutritional screening, ERAS protocol, and mini-invasive surgery in surgical oncology: A multi-institutional SEM analysis of patients with digestive cancer.

Background: Mini-invasive surgery (MIS), ERAS, and preoperative nutritional screening are currently used to reduce complications and the length of hospital stay (LOS); however, inter-variable correlations have seldom been explored. This research aimed to define inter-variable correlations in a large series of patients with gastrointestinal cancer and their impact on outcomes. Methods: Patients with consecutive cancer who underwent radical gastrointestinal surgery between 2019 and 2020 were analyzed. Age, BMI, comorbidities, ERAS, nutritional screening, and MIS were evaluated to determine their impact on 30-day complications and LOS. Inter-variable correlations were measured, and a latent variable was computed to define the patients' performance status using nutritional screening and comorbidity. Analyses were conducted using structural equation modeling (SEM). Results: Of the 1,968 eligible patients, 1,648 were analyzed. Univariable analyses documented the benefit of nutritional screening for LOS and MIS and ERAS (≥7 items) for LOS and complications; conversely, being male and comorbidities correlated with complications, while increased age and BMI correlated with worse outcomes. SEM analysis revealed that (a) the latent variable is explained by the use of nutritional screening (p0·004); (b) the variables were correlated (age-comorbidity, ERAS-MIS, and ERAS-nutritional screening, p < 0·001); and (c) their impact on the outcomes was based on direct effects (complications: sex, p0·001), indirect effects (LOS: MIS-ERAS-nutritional screening, p < 0·001; complications: MIS-ERAS, p0·001), and regression-based effects (LOS: ERAS, MIS, p < 0·001, nutritional screening, p0·021; complications: ERAS, MIS, p < 0·001, sex, p0·001). Finally, LOS and complications were correlated (p < 0·001). Conclusion: Enhanced recovery after surgery (ERAS), MIS, and nutritional screening are beneficial in surgical oncology; however, the inter-variable correlation is reliable, underlying the importance of the multidisciplinary approach.

Improvement of Metastatic Colorectal Cancer Patient Survival: Single Institution Experience.

The survival rates of patients with metastatic colorectal cancer (mCRC) have improved in recent years. We analysed the survival of mCRC patients followed at a single institution over the last 17 years. We retrospectively collected data from 899 mCRC patients treated from 2001 to 2016. Patients were divided into two groups based on the year of diagnosis: Cohort A (2001⁻2006) and Cohort B (2007⁻2014). A total of 788 patients were analysed. The median survival of the whole population was 32.0 months with a significant difference between Cohort A and B (29.2 vs. 33.5 months; p = 0.041). Surgical procedures significantly increased in Cohort B, however, no significant changes in survival were observed in patients undergoing surgery (58.9 months Cohort A vs. 58.2 months Cohort B, p = 0.822). Similarly, we did not demonstrate survival improvement in patients treated with systemic therapy alone (18.9 months Cohort A vs. 20.7 months Cohort B; p = 0.948). At the multivariate analysis, right-sided primary and synchronous metastatic tumour were found to be independent unfavorable prognostic factors. Improvements of mCRC patient survival might relate to integrated approach, with more patients undergoing extra-hepatic surgery. The medical approach seems to have had a more favourable impact on subgroups characterized by a worse prognosis.

Outcome of metastatic colorectal cancer: analysis of a consecutive series of 229 patients. The impact of a multidisciplinary approach.

PURPOSE: New chemotherapy agents and integrated treatments have improved the prognosis of patients with metastatic colorectal cancer. METHODS: From January 2000 to December 2002, 229 consecutive metastatic patients were prospectively followed and their outcomes were analyzed. They were divided initially into four treatment groups: A, palliative chemotherapy for extensive extrahepatic disease with or without hepatic disease (97 patients); B, palliative chemotherapy as in Group A for extensive hepatic disease unlikely to become resectable (36 patients); C, neoadjuvant chemotherapy for potentially resectable liver metastases if responsive to therapy (33 patients); D, immediate surgery for liver metastases (63 patients). RESULTS: The series was analyzed after a median follow-up of 22.6 months. The median progression-free survival was 9, 7.3, 11.5, and 26 months in Groups A, B, C, and D, respectively. The median overall survival was 20.1, 17.2, 24.8, and >48 months in Groups A, B, C, and D, respectively. The outcome was considered for the 69 patients with metastases confined to the liver (Groups B and C), who were treated initially with chemotherapy. Surgery was performed in 21 patients (5 from Group B, and 16 from Group C) and was R0 in 16. In resected patients, the median progression-free survival was 14.7 months and the median overall survival was 40.5 months. In unresected patients, the median progression-free survival was 7.6 months and the median overall survival was 17.5 months. CONCLUSIONS: Neoadjuvant therapy may prolong overall survival in a subset of patients with multiple hepatic metastases. The global impact on progression-free survival is low; less than one-half of the patients resected after chemotherapy are disease-free at three years. However, patients resected after chemotherapy obtained overall survival similar to that of primary surgery, suggesting a positive role for integrated approaches.

Somatic mutations of epidermal growth factor receptor in bile duct and gallbladder carcinoma.

OBJECTIVE: Conventional therapies are still unsuccessful in patients with carcinoma arising from the biliary tract. Somatic mutations of the epidermal growth factor receptor (EGFR) gene and the activation of its downstream pathways predict the sensitivity to small-molecule inhibitors in non-small cell lung carcinoma. Therefore, we analyzed EGFR mutations and related pathways in gallbladder and bile duct carcinomas to consider the possible application of these alternative therapeutic strategies. EXPERIMENTAL DESIGN: Forty paraffin-embedded samples, including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder carcinoma, were studied after tumor cell isolation by laser microdissection and sequencing of EGFR tyrosine kinase domain (exons 18-21). Activation of EGFR pathway was studied by evaluating phosphorylation of mitogen-activated protein kinase and Akt. RESULTS: None of the 40 specimens had mutations in exon 18; one had one missense point mutation in exon 19, two in exon 20, and three in exon 21. In addition, 36 of 40 specimens had the same silent mutation at codon 787 in exon 20, which was also found in peripheral blood cells from healthy donors. Tumor samples harboring EGFR mutation had phosphorylation of one or both downstream transducers analyzed. CONCLUSIONS: This is the first evidence of somatic mutations of the EGFR gene in bile duct carcinoma. Our findings suggest that a subgroup of patients with cholangiocarcinoma or gallbladder carcinoma exhibits somatic mutations of EGFR in the tyrosine kinase domain that can elicit cell signals sustaining survival and proliferation. These tumors might be further evaluated for their susceptibility to small-molecule inhibitor treatment.

Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD.

A pilot study was conducted to evaluate safety and activity of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC) and to determine whether a T-cell response to a tumor-associated antigen (TAA) was induced. Fifteen patients with metastatic CRC underwent HCT from human leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% at day +56. Eight patients experienced grades II to IV acute graft-versus-host disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization longer than 90 days were observed in 1 and 3 patients, respectively. Induction of TAA-specific T cells was evaluated with a carcinoembryonic antigen (CEA)-specific HLA-A(*)0201 pentamer in 6 patients with CRC. CEA-specific CD8(+) T cells were detected in 3 of 3 patients concomitant with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not detected in 9 of 9 control patients with GVHD who received transplants for diagnoses other than CRC. Antitumor activity of CEA-specific T cells was also validated in vitro. In one patient, the induction of CEA-specific T cells was associated with a decrease of serum CEA levels and a partial response. Thus, graft-versus-host reactions associated with allogeneic HCT can trigger the generation of T cells specific for CEA, and this may be associated with a clinical response.