Andrew M. Blakely

Surgical Considerations in the Treatment of Gastric Cancer

Gastric cancer is one of the most common malignancies in the world and is a leading cause of cancer death. Surgical treatment remains the best treatment option for potential cure and can be beneficial in the palliation of advanced disease. Several neoadjuvant chemotherapy regimens have been recently evaluated as potential adjuncts to surgery. This review describes the current role of surgical therapy in staging, resection, and palliation of gastric cancer.

Elevated C-reactive protein as a predictor of patient outcomes following palliative surgery

Optimal surgical decision‐making and informed consent for palliative procedures is limited by a lack of appropriate outcomes data. Elevated C‐reactive protein (CRP) may help guide patient selection for palliative surgery.

Suboptimal Compliance With National Comprehensive Cancer Network Melanoma Guidelines: Who Is at Risk?

Background: National Comprehensive Cancer Network (NCCN) melanoma treatment guidelines are based on best available literature. We evaluated NCCN excision margin and sentinel lymph node biopsy (SLNB) guideline adherence to identify patient populations at risk for suboptimal care. Methods: Retrospective review of prospectively maintained database of all patients who underwent operation for invasive melanoma from January 2005 to 2015. Results: In total, 865 patients underwent operation for 522 thin (60.3%), 268 intermediate-thickness (31.0%), and 75 thick (8.7%) melanomas. Tumor location was 349 extremity (40.4%), 348 trunk (40.2%), and 168 head/neck (19.4%). SLNB was performed in 422 patients (48.8%); 75 (17.8%) were positive, and 67 (15.9%) underwent therapeutic lymphadenectomy. A total of 154 lesions (17.8%) were ulcerated; 444 had mitotic rate ≥1 (51.3%). In total, 788 patients (91.1%) fulfilled both NCCN guidelines. Recommended surgical margins were achieved in 837 patients (96.8%) and SLNB was performed as appropriate in 806 patients (93.2%); 10 patients (1.2%) were deficient for both. Deficient margins and lack of SLNB were associated with increased invasion depth and head/neck location; deficient SLNB was associated with age 80 and above (P<0.0001). Overall recurrence was 7.1%: 15 local (1.7%), 23 regional (2.7%), and 23 distant (2.7%) failures. Local recurrence was associated with head/neck location (P=0.031); all recurrence types were associated with increased tumor thickness. Conclusions: NCCN excision and SLNB guidelines were almost always met. Patients at risk for not meeting criteria included the elderly and those with head/neck tumors. Failure to meet NCCN criteria was not associated with increased disease recurrence. Surgeons must carefully balance the risks of not pursuing NCCN guidelines with treatment goals.

Role of immune microenvironment in gastrointestinal stromal tumours

The immune microenvironment is a prognostic factor for various malignancies. The significance of key players of this immune microenvironment, including tumour‐infiltrating lymphocytes (TILs) and expression of programmed death‐ligand 1 (PD‐L1), indoleamine 2,3‐dioxygenase (IDO) and tryptophanyl‐tRNA synthetase (WARS) in gastrointestinal stromal tumours (GISTs) is largely unknown.

Surgical palliation for malignant disease requiring locoregional control

BACKGROUND Surgical palliation of cancer is best defined as procedures performed with non-curative intent to improve quality of life or control symptoms of advanced malignancy. Soft tissue involvement of advanced malignancies may produce symptoms such as pain, bleeding, or odor that significantly reduce quality of life. Literature on outcomes of palliative resection of soft tissue malignancy for local or regional control is lacking. METHODS Soft tissue resections performed with palliative intent for locoregional control were identified from a prospectively maintained palliative surgery database at a tertiary care center from January 2004 to July 2013. Tumor type, presenting symptom, procedure performed, and symptom recurrence were recorded. Patients were followed for at least 60 days or until death. RESULTS Thirty-one patients who underwent palliative soft tissue resection for local control were identified. Primary tumor types included melanoma (n=9, 29.0%), squamous cell carcinoma (n=9, 29.0%), sarcoma (n=5, 16.1%), breast (n=3, 9.7%), and other (n=5, 16.1%). Eighteen of 31 patients (58.1%) underwent resection for pain, two (6.5%) for bleeding, and eleven (35.5%) for local control or other symptoms. Procedures were performed on the trunk (n=17, 54.8%), extremities (n=7, 22.6%), head/neck (n=5, 16.1%), or multiple areas (n=2, 6.5%). Eleven of 31 patients (35.5%) underwent axillary, inguinal, or neck lymph node dissection, seventeen (54.8%) radical resection, and three (9.7%) wound excision. Split-thickness skin graft was performed in 6 of 17 radical resections (35.3%). Five patients (16.1%) had symptom recurrence at the site of the initial palliative procedure, of whom four (12.9%) underwent a second palliative procedure. Seven patients (22.6%) had new disease-related symptoms develop during follow-up. Thirty-day morbidity was 29.0%; mortality was 3.2%, which was associated with progression of disease. CONCLUSIONS Palliative surgery for local control of advanced soft tissue malignancy can provide durable symptom relief and improved quality of life. These procedures positively impact patients regardless of primary tumor type or tumor extent. Careful patient selection is important in order to maximize benefit of surgical palliation and minimize morbidity and mortality.

Critical analysis of feeding jejunostomy following resection of upper gastrointestinal malignancies

AIM To assess nutritional recovery, particularly regarding feeding jejunostomy tube (FJT) utilization, following upper gastrointestinal resection for malignancy. METHODS A retrospective review was performed of a prospectively-maintained database of adult patients who underwent esophagectomy or gastrectomy (subtotal or total) for cancer with curative intent, from January 2001 to June 2014. Patient demographics, the approach to esophagectomy, the extent of gastrectomy, FJT placement and utilization at discharge, administration of parenteral nutrition (PN), and complications were evaluated. All patients were followed for at least ninety days or until death. RESULTS The 287 patients underwent upper GI resection, comprised of 182 esophagectomy (n = 107 transhiatal, 58.7%; n = 56 Ivor-Lewis, 30.7%) and 105 gastrectomy [n = 63 subtotal (SG), 60.0%; n = 42 total (TG), 40.0%]. 181 of 182 esophagectomy patients underwent FJT, compared with 47 of 105 gastrectomy patients (99.5% vs 44.8%, P < 0.0001), of whom most had undergone TG (n = 39, 92.9% vs n = 8 SG, 12.9%, P < 0.0001). Median length of stay was similar between esophagectomy and gastrectomy groups (14.7 d vs 17.1 d, P = 0.076). Upon discharge, 87 esophagectomy patients (48.1%) were taking enteral feeds, with 53 (29.3%) fully and 34 (18.8%) partially dependent. Meanwhile, 20 of 39 TG patients (51.3%) were either fully (n = 3, 7.7%) or partially (n = 17, 43.6%) dependent on tube feeds, compared with 5 of 8 SG patients (10.6%), all of whom were partially dependent. Gastrectomy patients were significantly less likely to be fully dependent on tube feeds at discharge compared to esophagectomy patients (6.4% vs 29.3%, P = 0.0006). PN was administered despite FJT placement more often following gastrectomy than esophagectomy (n = 11, 23.4% vs n = 7, 3.9%, P = 0.0001). FJT-specific complications requiring reoperation within 30 d of resection occurred more commonly in the gastrectomy group (n = 6), all after TG, compared to 1 esophagectomy patient (12.8% vs 0.6%, P = 0.0003). Six of 7 patients (85.7%) who experienced tube-related complications required PN. CONCLUSION Nutritional recovery following esophagectomy and gastrectomy is distinct. Operations are associated with unique complication profiles. Nutritional supplementation alternative to jejunostomy should be considered in particular scenarios.

Late gastric conduit ischemia from celiac artery stenosis salvaged by stent therapy

Gastric conduit necrosis after esophagectomy usually presents early in the postoperative phase. The etiology of this ischemia most often lies in the inability of the isolated right gastroepiploic artery to provide adequate blood supply to the entire conduit. Here we describe an unusual presentation of late gastric conduit ischemia, occurring many years after surgery as a result of atherosclerosis and stenosis of the celiac artery. Successful salvage of the gastric conduit was achieved with stenting of the celiac artery.

Chapter 8 – Formation of Multicellular Microtissues and Applications in Biofabrication

Scaffold-free tissue engineering approaches take advantage of cell–cell interactions, specifically the phenomena of self-assembly and self-sorting. By using micro-molded nonadhesive hydrogels, mono-dispersed cells can be seeded and directed to form spheroids as well as more complex shapes. These complex structures, including toroids, honeycombs, and loop-ended dogbones, bypass the critical diffusion distance required to maintain cell viability in culture over time. In addition, the formed microtissues are amenable to assays that analyze the self-assembly dynamics, the sorting of two different cell types, the fusion of two individual tissues, and the power produced by cell aggregates as they contract around molded gel pegs. The biofabrication of multiple microtissues into a larger macrotissue with a patent network of lumens for perfusion is an active area of research for eventual translation of tissue engineering products to the operating room.

Expression of PD-L1, indoleamine 2,3-dioxygenase and the immune microenvironment in gastric adenocarcinoma

The tumour microenvironment is increasingly important in several tumours. We studied the relationship of key players of immune microenvironment with clinicopathological parameters in gastric adenocarcinomas.