Tumor-Infiltrating Lymphocyte Function Predicts Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

PURPOSE: The presence of tumor-infiltrating lymphocytes (TILs) in tumors is superior to conventional pathologic staging in predicting patient outcome. However, their presence does not define TIL functionality. Here we developed an assay that tests TIL cytotoxicity in patients with locally advanced rectal cancer before definitive treatment, identifying those who will obtain a pathologic complete response (pCR). We also used the assay to demonstrate the rescue of TIL function after checkpoint inhibition blockade (CIB). PATIENTS AND METHODS: Thirty-four consecutive patients were identified initially, with successful completion of the assay before surgery in those 17 patients who underwent full treatment. An in vitro cytotoxic assay of rectal cancer tumoroids cocultured with patient-matched TILs was established and validated. Newly diagnosed patients were recruited with pretreatment biopsy specimens processed within 1 month. Evaluation of TIL-mediated tumoroid lysis was performed by measuring the mean fluorescence intensity of cell death marker, propidium iodide. CIB (anti-programmed cell death protein 1 [anti-PD-1] antibody) response was also assessed in a subset of patient specimens. RESULTS: Six of the 17 patients achieved an objective pCR on final evaluation of the resected specimen after neoadjuvant chemoradiotherapy. Cytotoxic killing identified the pCR group with a higher mean fluorescence intensity (27,982 [95% CI, 25,340 to 30,625]) compared with the non-pCR cohort (12,428 [95% CI, 9,434 to 15,423]; p < .001). Assessment of the effectiveness of CIB revealed partial restoration of cytotoxicity in TILs with increased PD-1 expression with anti-PD-1 antibody exposure. CONCLUSION: Evaluating TIL function can be undertaken within weeks of the diagnostic biopsy, affording the potential to alter patient management decisions and refine selection for a watch-and-wait protocol. This cytotoxic assay also has the potential to serve as a platform to assist in the additional development of CIB.

Prophylactic mesh reinforcement reduces stomal site incisional hernia after ileostomy closure.

BACKGROUND: Stomal site incisional hernia is a common complication following ileostomy closure. The effectiveness of prophylactic mesh placement at the time of stomal closure is unknown because of fear of mesh infection and subsequent wound complications. The present study investigated whether prophylactic mesh placement reduces the rate of incisional hernia after ileostomy closure without increasing wound complications. The study was based on retrospective review of consecutive ileostomy closures undertaken at a tertiary referral center between January 2007 and December 2011. Hernias were identified through clinical examination and computed tomography. RESULTS: Eighty-three cases of ileostomy closure were reviewed; 47 patients received mesh reinforcement, and 36 underwent non-mesh closure (controls). In total, 16 (19.3 %) patients developed incisional hernia, 13 (36.1 %) of which occurred in the control group; 3 (6.4 %), in the mesh group [odds ratio (OR): 8.29; 95 % confidence interval (CI) 2.14-32.08; p = 0.001]. Incisional hernia repair was performed in 3 (23 %) patients in the control group; no hernias in the mesh group required surgery. There was no significant difference in wound infection rates between mesh (2 patients, 4.3 %) and control (1 patient, 2.8 %) groups. No mesh infection was found. Multivariate analysis demonstrated that malignancy (OR: 21.93, 95 % CI 1.58-303.95; p = 0.021) and diabetes (OR: 20.98, 95 % CI 3.23-136.31; p = 0.001) independently predicted incisional herniation, while mesh reinforcement prevented hernia development (OR: 0.06, 95 % CI 0.01-0.36; p = 0.002). CONCLUSIONS: Mesh placement significantly reduced the incidence of incisional hernia following ileostomy closure, but without increasing complication rates. This technique should be strongly considered in patients at high risk of hernia development.

Lumbar plexus schwannoma causing recurrent syncope.

Retroperitoneal schwannomas are rare and present non-specifically. They usually manifest secondary to their compressive effects on adjacent structures. We describe a patient who presented with recurrent syncope resulting from a large retroperitoneal schwannoma stretching the inferior vena cava and compromising venous return. We also discuss the salient aspects of preoperative investigations leading to definitive diagnosis and surgery.

Early soft tissue coverage and negative pressure wound therapy optimises patient outcomes in lower limb trauma.

BACKGROUND: The timing of soft tissue reconstruction for severe open lower limb trauma is critical to its successful outcome, particularly in the setting of exposed metalware and pre-existing wound infection. The use of negative pressure wound therapy (NPWT) may allow a delay in soft tissue coverage without adverse effects. This study evaluated the impact of delayed free-flap reconstruction, prolonged metalware exposure, pre-flap wound infection, and the efficacy of NPWT on the success of soft tissue coverage after open lower limb injury. METHODS: Retrospective review of all free-flap reconstructions for lower limb trauma undertaken at a tertiary trauma centre between June 2002 and July 2009. RESULTS: 103 patients underwent 105 free-flap reconstructions. Compared with patients who were reconstructed within 3 days of injury, the cohort with delayed reconstruction beyond 7 days had significantly increased rates of pre-flap wound infection, flap re-operation, deep metal infection and osteomyelitis. Pre-flap wound infection independently predicted adverse surgical outcomes. In the setting of exposed metalware, free-flap transfer beyond one day significantly increased the flap failure rate. These patients required more surgical procedures and a longer hospital stay. The use of NPWT significantly lowered the rate of flap re-operations and venous thrombosis, but did not allow a delay in reconstruction beyond 7 days from injury without a concomitant rise in skeletal and flap complications. CONCLUSIONS: Following open lower limb trauma, soft tissue coverage within 3 days of injury and immediately following fracture fixation with exposed metalware minimises pre-flap wound infection and optimises surgical outcomes. NPWT provides effective temporary wound coverage, but does not allow a delay in definitive free-flap reconstruction.