PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.

Introduction: This timely study assesses the immunosuppressive effects of surgery on cytotoxic Th1-like immunity and investigates if immune checkpoint blockade (ICB) can boost Th1-like immunity in the perioperative window in upper gastrointestinal cancer (UGI) patients. Methods: PBMCs were isolated from 11 UGI patients undergoing tumour resection on post-operative days (POD) 0, 1, 7 and 42 and expanded ex vivo using anti-CD3/28 and IL-2 for 5 days in the absence/presence of nivolumab or ipilimumab. T cells were subsequently immunophenotyped via flow cytometry to determine the frequency of T helper (Th)1-like, Th1/17-like, Th17-like and regulatory T cell (Tregs) subsets and their immune checkpoint expression profile. Lymphocyte secretions were also assessed via multiplex ELISA (IFN-γ, granzyme B, IL-17 and IL-10). The 48h cytotoxic ability of vehicle-, nivolumab- and ipilimumab-expanded PBMCs isolated on POD 0, 1, 7 and 42 against radiosensitive and radioresistant oesophageal adenocarcinoma tumour cells (OE33 P and OE33 R) was also examined using a cell counting kit-8 (CCK-8) assay to determine if surgery affected the killing ability of lymphocytes and whether the use of ICB could enhance cytotoxicity. Results: Th1-like immunity was suppressed in expanded PBMCs in the immediate post-operative setting. The frequency of expanded circulating Th1-like cells was significantly decreased post-operatively accompanied by a decrease in IFN-γ production and a concomitant increase in the frequency of expanded regulatory T cells with an increase in circulating levels of IL-10. Interestingly, PD-L1 and CTLA-4 immune checkpoint proteins were also upregulated on expanded Th1-like cells post-operatively. Additionally, the cytotoxic ability of expanded lymphocytes against oesophageal adenocarcinoma tumour cells was abrogated post-surgery. Of note, the addition of nivolumab or ipilimumab attenuated the surgery-mediated suppression of lymphocyte cytotoxicity, demonstrated by a significant increase in tumour cell killing and an increase in the frequency of Th1-like cells and Th1 cytokine production. Conclusion: These findings support the hypothesis of a surgery-mediated suppression in Th1-like cytotoxic immunity and highlights a rationale for the use of ICB within the perioperative setting to abrogate tumour-promoting effects of surgery and ameliorate the risk of recurrence.

Splenectomy for isolated splenic metastasis from primary lung adenocarcinoma.

A 73-year-old woman was referred to a tertiary centre with isolated splenic metastasis from previous pT1aNo stage 1a lung adenocarcinoma. The patient underwent a right lower lobe lobectomy and mediastinal lymph node dissection 2 years ago for invasive adenocarcinoma with no adjuvant therapy. An incidental finding of new splenic cyst was noted on surveillance imaging, which was fluorodeoxyglucose positive on positron emission tomography, and confirmed on cytology to be metastatic lung adenocarcinoma. After multi-disciplinary team's review, the patient underwent splenectomy, with partial excision of diaphragm due to local infiltration. Her postoperative course was eventful, and was complicated by a simple fluid collection in the surgical bed (amylase negative), a left sided pneumonia and atelectasis and left sided pleural effusion, requiring antibiotics and radiological drainage of the abdominal and pleural collection. The patient recovered well and is currently doing well 9 months postoperatively with no evidence of recurrence or metastatic disease.

Strictureplasty versus bowel resection for the surgical management of fibrostenotic Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Strictureplasty (SPX) conserves bowel length and minimizes the risk of developing short bowel syndrome in patients undergoing surgery for Crohn's disease (CD). However, SPX may be associated with a higher risk of recurrence compared with bowel resection (BR). AIM: We sought to compare morbidity and recurrence following SPX and BR in patients with fibrostenotic CD. METHODS: A systematic review was performed according to PRISMA and MOOSE guidelines. Observational studies that compared outcomes of CD patients undergoing either SPX or BR were identified. Log hazard ratios (InHR) for recurrence-free survival (RFS) and their standard errors were calculated from Kaplan-Meier plots or Cox regression models and pooled using the inverse variance method. Dichotomous variables were pooled as odds ratios (OR) using the Mantel-Haenszel method. Continuous variables were pooled as weighted mean differences. RESULTS: Twelve studies of 1026 CD patients (SPX n = 444, 43.27%; BR with or without SPX n = 582, 56.72%) were eligible for inclusion. There was an increased likelihood of disease recurrence with SPX than with BR (OR 1.61; 95% CI, 1.03, 2.52; p = 0.04; I2 = 0%). Patients who had a SPX alone had a significantly reduced RFS than those who underwent BR (HR 1.47; 95% CI, 1.08, 2.01; p = 0.02; I2 = 0%). There was no difference in morbidity between the groups (OR 0.58; 95% CI, 0.26, 1.28; p = 0.18; I2 = 0%). CONCLUSION: SPX should only be performed in those patients with Crohn's strictures that are at high risk for short bowel syndrome and intestinal failure; otherwise, BR is the favored surgical technique for the management of fibrostenotic CD.