Background/Aims: Current chemotherapy regimens for cholangiocarcinoma (CCA) yield poor outcomes, with a median overall survival of <12 months. Recent data on the genomic landscape of CCAs have created opportunities for targeted therapy. Yet, data regarding its efficacy are scarce. We aimed to describe the genomic landscape of a CCA patient cohort using next-generation sequencing (NGS), focusing on the ERBB/EFGR pathway and assessing response to anti-HER2 agents. Methods: Tissue samples of intrahepatic CCA (IHCC) and extrahepatic CCA (EHCC) underwent NGS for somatic aberrations. The clinical outcomes for patients treated with anti-HER2 agents were evaluated. Results: A total of 1,863 CCA cases (1,615 IHCCs and 248 EHCCs) underwent NGS, and they revealed a high prevalence of ERBB alterations (IHCC, 4.2%; EHCC, 9.7%). Among these, 23.8% of the IHCCs and 53.6% of the EHCCs had a point mutation in ERBB2, and 66.6% of the IHCCs and 41.2% of the EHCCs had ERBB copy number amplification. Three EHCC patients were diagnosed at our institute with ERBB/EGFR aberrations; 2 patients were treated with neratinib and 1 patient with a chemotherapy-trastuzumab combination. All 3 achieved disease stabilization and a clinical benefit. One patient underwent a liquid biopsy before and after 3 months of treatment, demonstrating disappearance of the ERBB2 clone and emergence of a Myc-mutated clone after treatment. Conclusions: The genomic landscape of CCAs may harbor targetable alterations, especially in the ERBB/EGFR pathway. These alterations may have clinical significance in everyday practice.

(1) Background: We aimed to explore the association between neoadjuvant treatment, tumor-infiltrating immune lymphocyte (TIL), and tumor-associated macrophage (TAM) and survival in patients with esophageal adenocarcinoma. (2) Methods: Patients who underwent esophagectomy were divided into three groups according to their treatment modality and tumor regression grade (TRG): (i) surgery-only group (SG), (ii) good responders (GR) group (TRG 0–1), and (iii) bad responders (BR) group (TRG 2–3). We then carried out statistical correlations of the immunofluorescence analysis of the immune infiltrate in the esophageal surgical specimens with several clinical and pathological parameters. In addition, we analyzed The Cancer Genomic Atlas (TCGA) dataset for differences in TILs, TAMs, and protein expression in immune pathways. (3) Results: Forty-three patients (SG—15, GR—13, and BR—13) were evaluated. The highest enrichment of CD3+ (p < 0.001), CD8+ (p = 0.001) and CD4+ (p = 0.009) was observed in the stroma of GR patients. On multivariate analysis, only CD8+ T cell and signet-ring features were independent prognostic factors for overall survival. In TCGA analysis, we identified overexpression of TAM and colony-stimulating factor 1 receptor (CSF-1R). (4) Conclusions: High enrichment of lymphocyte subpopulations in the microenvironment of esophageal adenocarcinoma is associated with a favorable response to neoadjuvant treatment and an improved patient outcome.

Background: Pancreatic cancer has a high mortality rate worldwide. Most patients progress to advanced stages, often with metastasis, resulting in a low survival rate. Despite advancements in surgical and oncological treatments, early diagnosis and better risk stratification remain critical. Methods: This retrospective cross-sectional study focused on analyzing data from patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, in order to determine whether the neutrophil-to-lymphocyte ratio (NLR) and other immune–inflammatory markers, such as the systemic immune–inflammation index (SII) and prognostic nutritional index (PNI), can predict postoperative complications and survival outcomes. Results: Analysis of 136 patients revealed that a higher NLR (≥2.5) was significantly associated with longer overall survival (39 months, IQR: 17–100 months; p = 0.004), compared to lower NLR (<2.5; 18 months, IQR: 9–39 months). Higher SII (≥600) was also associated with significantly improved survival (34 months, IQR: 17–114 months; p = 0.001) compared to lower SII (<600; 20 months, IQR: 9–45 months). No significant differences were observed in postoperative complications or other clinical outcomes between NLR groups, although a trend toward more complications in the higher NLR group was noted (p = 0.06). PNI showed no significant impact on survival (PNI < 38.8: 22 months, IQR: 14–60 months; PNI ≥ 38.8: 33 months, IQR: 14–115 months; p = 0.1) or complications (p = 0.8). Conclusions: Our study highlights the prognostic utility of NLR and SII in patients with adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy. Regarding complications, there were no significant differences across groups stratified by NLR, SII, or PNI, suggesting that while NLR and SII are valuable for predicting long-term oncological outcomes in patients undergoing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas, they may not be reliable indicators of immediate postoperative morbidity.

Context: The role of the laparoscopic left lateral sectionectomy (LLLS) is debatable, and Level-1 data are lacking. Aims: The aim of the study is to evaluate the feasibility and safety of this approach. Settings and Design: This was a retrospective study. Subjects and Methods: From 2007 to 2014, patients undergoing LLLS were identified from two institutions. Statistical Analysis Used: Continuous variables were compared between groups with Student's t-test or Mann–Whitney test, as appropriate by type of distribution. Categorical variables were compared with Chi-square or Fisher's exact test, depending on the number of observations. Results: Thirty-eight patients were included in the study. The mean age was 63.5 + 13 years (range, 31–89), and the mean number of tumours was 1.7 + 1.5. Eleven (29%) patients underwent LLS combined with an additional liver resection (combined resections group). The mean duration of the operation and the mean estimated blood loss were significantly decreased in the LLS group compared to the combined resection group (101 + 71 min vs. 208 + 98 min and 216 + 217 ml vs. 450 + 223 ml;P < 0.05 for both, respectively). The major complications rate was 8% and no mortality occurred. Conclusions: In a subset of carefully selected cases, LLLS may provide the benefits of laparoscopy. This does not appear to compromise perioperative morbidity rates. We believe that this approach may serve as a training platform for surgical trainees.

(1) Background: Hand-assisted laparoscopic surgery (HALS) has engendered growing attention as a safe procedure for the resection of metastatic liver disease. However, there is little data available regarding the outcomes of HALS for colorectal liver metastasis (CRLM) in patients over the age of 75. (2) Methods: We compare the short- and long-term outcomes of patients >75-years-old (defined in our study as “elderly patients” and referred to as group 1, G1), with patients <75-years-old (defined in our study as “younger patients” and referred to as group 2, G2). (3) Results: Of 145 patients, 28 were in G1 and 117 were in G2. The most common site of the primary tumor was the right colon in G1, and the left colon in G2 (p = 0.05). More patients in G1 underwent laparoscopic anterior segment resection compared with G2 (43% vs. 39% respectively) (p = 0.003). 53% of patients in G1 and 74% of patients in G2 completed neoadjuvant therapy (p = 0.04). The median size of the largest metastasis was 32 (IQR 19–52) mm in G1 and 20 (IQR 13–35) mm in G2 (p = 0.001). The rate of complications (Dindo-Clavien grade ≥ III) was slightly higher in G1 (p = 0.06). The overall 5-year survival was 30% in G1 and 52% in G2 (p = 0.12). (4) Conclusions: Hand-assisted laparoscopic surgery for colorectal liver metastasis is safe and effective in an elderly patient population.