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Background and Objectives: Lymphatic mapping (LM) and blue dye injections are essential to identification of sentinel lymph nodes (SLN) for melanoma. LM is performed the day before (DB) or the same day (SD) of surgery, but the optimal timing is unknown. Similarly, methylene blue (MB), used during SLN biopsy (SLNB), is administered diluted (dMB) or undiluted (uMB), but the relative efficacies are unknown., Methods: Patients who underwent SLNB for melanoma from 2009 to 2013 at our institution were evaluated. Outcomes included operative correlation with LM, SLN identification, and postoperative complications., Results: One hundred seventy-one patients underwent SLNB. Sixty-seven (39%) had DB LM. Sixty-seven (39%) received uMB. Operative findings correlated with both LM groups, though the DB patients had lower background count (P = 0.018) and lower highest SLN radioactive signal count (P = 0.046). More uMB patients had blue SLNs (90% vs. 68%, P = 0.001). There was no difference in the total number of SLNs or complication rates in the LM and MB groups., Conclusions: This is the first study to compare the use of DB LM with SD LM and the efficacy of uMB versus dMB. DB LM and uMB offer advantageous alternatives for patients and their surgeons without loss of accuracy or increased morbidity. J. Surg. Oncol. 2016;114:947-950. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background/objectives: Heated intraperitoneal chemotherapy (HIPEC) kills cancer cells via thermal injury and improved chemotherapeutic cytotoxicity. We hypothesize that higher HIPEC flow rates improve peritoneal heating and HIPEC efficacy., Methods: (1) A HIPEC-model (30.8 L cooler with attached extracorporeal pump) was filled with 37°C water containing a suspended 1 L saline bag (SB) wrapped in a cooling sleeve, creating a constant heat sink. (2) HIPECs were performed in a swine model. Inflow, outflow, and peritoneal temperatures were monitored as flow rates varied. (3) Flow rates and temperatures during 20 HIPECs were reviewed., Results: Higher flow rates decreased time required to increase water bath (WB) and SB temperature to 43°C. With a constant heat sink, the minimum flow rate required to reach 43°C in the WB was 1.75 L/min. Higher flow rates lead to greater temperature gradients between the WB and SB. In the swine model, the minimum flow rate required to reach 43°C outflow was 2.5-3.0 L/min. Higher flows led to more rapid heating of the peritoneum and greater peritoneal/outflow temperature gradients. Increased flow during clinical HIPEC suggested improved peritoneal heating with lower average visceral temperatures., Conclusions: There is a minimum flow rate required to reach goal temperature during HIPEC. Flow rate is an important variable in achieving and maintaining goal temperatures during HIPEC., (© 2014 Wiley Periodicals, Inc.)

Lymph nodes are the most common and earliest site of malignancies arising in epithelia. However, the reason for this pattern of preferential metastasis is not clear. This article reviews features of the metastatic process and lymph node microenvironment which might potentiate lymph node metastases. There is intriguing evidence that preferential lymph node metastasis is due to (1) the efficiency of lymph nodes as filters of the tumor cells which arrive there, and (2) the probability that adhesive interactions, normally governing the generation of different T-cell immune responses, are responsible for this efficiency and may also promote invasion and proliferation of tumor cells in the lymph node. Manipulation of the cytokine environment in a lymph node draining a primary epithelial tumor may alter both the expression of cell adhesion molecules within the node and the subsequent metastatic ability of the tumor cells arriving at it.

Background and Objectives: Angiogenesis in malignant neoplasms, as measured by microvessel density, has been shown to correlate with survival or stage in some studies of breast, gastric, and colorectal cancer. We hypothesized that aggressive cancers promote angiogenesis in normal tissue adjacent to the invading neoplasm., Methods: To test this hypothesis, 36 specimens of colon adenocarcinoma curatively resected between 1986 and 1990 were sectioned and stained for factor VIII-related antigen, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8). Microvessel density was measured within the colon cancer and in adjacent, histologically normal tissue. Clinical/pathological variables were examined using multivariate analysis and Student t-test., Results: Microvessel density was higher in the neoplasms (26.0+/-1.66/ 0.25 mm2) than in the surrounding normal tissue (22.3+/-1.88/0.25 mm2) (P=0.03). The difference was primarily due to smaller neoplasms (T1 and T2) which had vessel counts of 10.6+/-0.74/0.25 mm2 in the adjacent normal tissue compared to vessel counts of 18.9+/-3.02/0.25 mm2 within these tumors (P=0.02). T3 and T4 neoplasms had equivalent amounts of angiogenesis within the lesion (26.9+/-1.81/0.25 mm2) and in the histologically normal margin (24.2+/-1.98/0.25 mm2) (P=0.12). VEGF was present in the tumor microenvironment in 100% and IL-8 in 45% of specimens stained for these angiogenic cytokines. Microvessel density did not correlate with 5-year survival., Conclusions: Our data suggest that colon cancers that invade through the muscularis propria may have a greater ability to induce angiogenesis in adjacent normal tissue.

The ability to metastasize requires that tumor cells be able to degrade matrix. Nontoxic compounds that inhibit matrix digestion might be useful as anti-metastatic agents. We have investigated whether phenytoin, a drug commonly used in clinical practice that inhibits the production of collagenase by some cells, inhibits metastases in a standard animal model of metastasis: In vitro, phenytoin inhibited the proliferative response of B16 F10 melanoma cells to serum-containing media (75% inhibition at 25 micrograms/ml) but had no effect on their ability to degrade a type I collagen gel (1-100 micrograms/ml). Treatment of these cells with phenytoin prior to inoculation in vivo did not inhibit tumor growth, implantation in a surgical wound, or incidence of spontaneous metastases from a primary tumor growing in the foot. Pretreatment of mice with phenytoin (15, 40, and 75 mg/kg/day) diminished pulmonary metastases following tail vein injection in a minimal but dose dependent fashion; mean number of pulmonary colonies 4.6 +/- 3.1 (75/mg/kg/day) vs. 10.2 +/- 9.9 (control). However, tumor growth, implantation, and spontaneous metastases were not inhibited by pretreating the mice with the same doses of phenytoin. It is concluded that phenytoin has an insignificant inhibitory effect on tumor growth and metastasis.