Homogeneity in immune features between colorectal liver metastases better identifies patients with good prognosis compared to pathological response to preoperative chemotherapy

ABSTRACTIn colorectal cancer liver metastases (CRLM), the density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy have been associated with oncological outcomes after complete resection. However, the prognostic significance of the heterogeneity of these features in patients with multiple CRLMs remains under investigation. We used a tissue microarray of 220 mismatch repair-gene proficient CRLMs resected in 97 patients followed prospectively to quantify CD3+ T cells and MHC-I by immunohistochemistry. Histopathological response to preoperative chemotherapy was assessed using standard scoring systems. We tested associations between clinical, immunological, and pathological features with oncologic outcomes. Overall, 29 patients (30.2%) had CRLMs homogeneous for CD3+ T cell infiltration and MHC-I. Patients with immune homogeneous compared to heterogeneous CRLMs had longer median time to recurrence (TTR) (30 vs. 12 months, p = .0018) and disease-specific survival (DSS) (not reached vs. 48 months, p = .0009). At 6 years, 80% of the patients with immune homogeneous CRLMs were still alive. Homogeneity of response to preoperative chemotherapy was seen in 60 (61.9%) and 69 (80.2%) patients according to different grading systems and was not associated with TTR or DSS. CD3 and MHC-I heterogeneity was independent of response to pre-operative chemotherapy and of other clinicopathological variables for their association with oncological outcomes. In patients with multiple CRLMs resected with curative intent, similar adaptive immune features seen across metastases could be more informative than pathological response to pre-operative chemotherapy in predicting oncological outcomes

Hypertrophy of the non-embolized liver after chemotherapy

AbstractBackgroundNeoadjuvant chemotherapy (NC+) and portal vein embolization (PVE) enables curative resection in more patients with colorectal-liver metastases (CRLM). However, after NC+, structural alterations have been reported with the risk of post-operative hepatic failure. We undertook to determine if NC+ toxicity limits future remnant liver (FRL) hypertrophy after PVE.MethodsPVE was performed in 20 patients, 13 (65%) of whom previously received a mean FOLFIRI (5-fluorouracil + leucovorin + irinotecan) regimen (NC+) of 6.6 cycles. The seven remaining patients served as the control group without NC (NC−).ResultsCRLM were bilateral in 69% (NC+) and 57% (NC−), and synchronous in 84% (NC+) and 14% (NC−). The FRL hypertrophy rate was 54.1% (NC+) and 43.7% (NC−) (P= 0.3). CRLM were unresectable in four of our 20 patients, i.e. group NC+: one insufficient FRL hypertrophy and one severe steatosis; and group NC−: two tumoral progressions. In both groups, the operative parameters were comparable except for pedicular clamping: 8 (NC+) and 36min (NC−), respectively (P < 0.05). Also, the surgical outcome rate and hospital stay were comparable. No significant pathological difference was observed between the two groups. No mortality occurred in either group.ConclusionIn view of our limited experience, we conclude that hypertrophy of the non-embolized liver (FRL) is not altered after FOLFIRI-based NC

Fully covered self-expanding metal stents for benign biliary stricture after orthotopic liver transplant: 5-year outcomes

Background and Aims: Minimally invasive treatments of anastomotic benign biliary stricture (BBS) after orthotopic liver transplantation (OLT) include endoscopic placement of multiple plastic stents or fully covered self-expandable metal stents (FCSEMSs). No multiyear efficacy data are available on FCSEMS treatment after OLT. Methods: We prospectively studied long-term efficacy and safety of FCSEMS treatment in adults aged ≥18 years with past OLT, cholangiographically confirmed BBS, and an indication for ERCP with stent placement. Stent removal was planned after 4 to 6 months, with subsequent follow-up until 5 years or stricture recurrence. Long-term outcomes were freedom from stricture recurrence, freedom from recurrent stent placement, and stent-related serious adverse events (SAEs). Results: In 41 patients, long-term follow-up began after FCSEMS removal (n = 33) or observation of complete distal migration (CDM) (n = 8). On an intention-to-treat basis, the 5-year probability of remaining stent-free after FCSEMS removal or observation of CDM was 48.9% (95% confidence interval [CI], 33.2%-64.7%) among all patients and 60.9% (95% CI, 43.6%-78.2%) among 31 patients with over 4 months of FCSEMS indwell time. In 28 patients with stricture resolution at FCSEMS removal or observed CDM (median, 5.0 months indwell time), the 5-year probability of no stricture recurrence was 72.6% (95% CI, 55.3%-90%). Sixteen patients (39%) had at least 1 related SAE, most commonly cholangitis (n = 10). Conclusions: By 5 years after temporary FCSEMS treatment of post-OLT BBS, approximately half of all patients remained stent-free on an intention-to-treat basis. Stent-related SAEs (especially cholangitis) were common. FCSEMS placement is a viable long-term treatment option for patients with post-OLT BBS. (Clinical trial registration number: NCT01014390.)SCOPUS: ar.jinfo:eu-repo/semantics/publishe