Introduction
Guidelines for perioperative systemic therapy administration in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are ...evolving. Decisions regarding adjuvant therapy are influenced by postoperative morbidity, which is common after pancreatoduodenectomy. We evaluated whether postoperative complications are associated with receipt of adjuvant therapy after pancreatoduodenectomy.
Methods
A retrospective analysis of patients undergoing pancreatoduodenectomy for PDAC or dCCA from 2015 to 2020 was conducted. Demographic, clinicopathologic, and postoperative variables were analyzed.
Results
Overall, 186 patients were included—145 with PDAC and 41 with dCCA. Postoperative complication rates were similar for both pathologies (61% and 66% for PDAC and dCCA, respectively). Major postoperative complications (MPCs), defined as Clavien–Dindo >3, occurred in 15% and 24% of PDAC and dCCA patients, respectively. Patients with MPCs received lower rates of adjuvant therapy administration, irrespective of primary tumor (PDAC: 21 vs. 72%,
p
= 0.008; dCCA: 20 vs. 58%,
p
= 0.065). Recurrence-free survival (RFS) was worse for patients with PDAC who experienced an MPC 8 months (interquartile range IQR 1–15) vs. 23 months (IQR 19–27),
p
< 0.001 or who did not receive any perioperative systemic therapy 11 months (IQR 7–15) vs. 23 months (IQR 18–29),
p
= 0.038. In patients with dCCA, 1-year RFS was worse for patients who did not receive adjuvant therapy (55 vs. 77%,
p
= 0.038).
Conclusion
Patients who underwent pancreatoduodenectomy for either PDAC or dCCA and who experienced an MPC had lower rates of adjuvant therapy and worse RFS, suggesting that clinicians adopt a standard neoadjuvant systemic therapy strategy in patients with PDAC. Our results propose a paradigm shift towards preoperative systemic therapy in patients with dCCA.
Tumor-associated macrophages (TAMs) are a major component of the cancer microenvironment. Modulation of TAMs is under intense investigation because they are thought to be nearly always of the M2 ...subtype, which supports tumor growth. Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and typically results from an activating mutation in the KIT oncogene. Using a spontaneous mouse model of GIST and 57 freshly procured human GISTs, we discovered that TAMs displayed an M1-like phenotype and function at baseline. In both mice and humans, the KIT oncoprotein inhibitor imatinib polarized TAMs to become M2-like, a process which involved TAM interaction with apoptotic tumor cells leading to the induction of CCAAT/enhancer binding protein (C/EBP) transcription factors. In human GISTs that eventually developed resistance to imatinib, TAMs reverted to an M1-like phenotype and had a similar gene expression profile as TAMs from untreated human GISTs. Therefore, TAM polarization depends on tumor cell oncogene activity and has important implications for immunotherapeutic strategies in human cancers.
Background
Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal ...(CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival.
Methods
We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up.
Results
A total of 103 patients met inclusion criteria and were analyzed. CC score 0–1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range IQR 5–17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14–20, hazard ratio HR 3.1,
p
= 0.007, and PCI > 20, HR 5.3,
p
≤ 0.001) and incomplete CRS (CC score-2, HR 2.96,
p
= 0.02). Patients with low PCI (0–6) had 5-year OS 60.7%.
Conclusions
Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.
Checkpoint blockade in esophagogastric cancer Cohen, Noah A.; Strong, Vivian E.; Janjigian, Yelena Y.
Journal of surgical oncology,
July 1, 2018, Letnik:
118, Številka:
1
Journal Article
Recenzirano
Odprti dostop
There are few effective treatment options for metastatic esophagogastric adenocarcinomas after progression on second‐line chemotherapy. Immune checkpoint blockade therapy is a promising treatment ...strategy for selected advanced esophagogastric cancer, and the PD‐1 inhibitor pembrolizumab has recently been approved for metastatic or recurrent gastric or gastroesophageal junction cancer that has progressed beyond second‐line systemic therapy. We review the current data supporting immune checkpoint blockade therapy in advanced esophagogastric adenocarcinoma.
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