Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs), an investigational cellular therapy, has demonstrated antitumor efficacy in patients with advanced solid tumors, including melanoma. Tumor-infiltrating lymphocyte cell therapy involves surgical resection of a patient's tumor, ex vivo TIL expansion under conditions that overcome immunosuppressive responses elicited by the tumor and the tumor microenvironment, administration of a lymphodepleting regimen, and infusion of the final TIL cell therapy product back into the patient followed by interleukin 2 administration to support T-cell activity. The surgeon plays a central role in patient identification and tumor selection—steps that are critical for successful outcomes of TIL cell therapy. Commercialization of TIL cell therapy and its broader access to patients will require education and collaboration among surgeons, oncologists, and cellular therapists. This review highlights the unique role that surgeons will play in the implementation of TIL cell therapy and serves as a contemporary report of best practices for patient selection and tumor resection methods.

In the 8th edition of the American Joint Committee on Cancer melanoma staging system, the T1b category has been redefined based solely on thickness and ulceration. National Comprehensive Cancer Network guidelines recommend consideration of sentinel lymph node biopsy (SLNB) for all patients with T1b melanomas (0.8 to 1.0 mm thick). We hypothesized that the new staging system would lead to excessive use of SLNB in patients with non-ulcerated T1b melanomas with a low risk of positive sentinel lymph nodes. The National Cancer Database 2015 Melanoma Public Use File was used to select patients undergoing SLNB for thin T1 cutaneous melanoma from 2010 to 2015. Clinicopathologic risk factors for having a positive SLNB were evaluated. Univariable and multivariable logistic regression models and classification and regression tree analysis were performed to identify groups with high and low risk of positive SLNB. We selected patients undergoing SLNB without ulceration with thickness 0.75 to 1.04 mm, staged T1b in the new 8th edition American Joint Committee on Cancer by thickness criteria alone (6,894 patients). Independent risk factors for a positive sentinel lymph node were age 56 years or younger (odds ratio [OR] 1.74; 95% CI 1.38 to 2.17), thickness 1.0 vs 0.8 to 0.9 mm (OR 1.36; 95% CI 1.09 to 1.70), female sex (OR 1.36; 95% CI 1.09 to 1.69), and mitotic rate ≥1/mm2 (OR 2.01; 95% CI 1.54 to 2.64). Classification and regression tree analysis identified 2 groups based on age, mitotic rate, and thickness with a risk of positive SLNB <5%. These 2 groups made up 55% of T1b, nonulcerated melanoma patients who underwent SLNB. The new 8th edition American Joint Committee on Cancer melanoma staging system T1b category should not be used to determine use of SLNB in thin melanoma, as more than one half of T1b lesions without ulceration have a low risk of positive sentinel lymph nodes.

More than 50% of metastatic melanoma patients have a specific mutation in the serine/threonine kinase BRAF. This results in constitutive activation of the RAS-RAF-MEK-ERK-MAP kinase pathway, which causes uncontrolled cell growth. Vemurafenib (PLX4032) is an oral chemotherapeutic agent that targets the specific mutation V600E in the BRAF protein. Initial response rates are high in patients with BRAF mutant melanoma treated with a BRAF inhibitor such as vemurafenib, but resistance nearly always develops and disease progression ensues. There are several different mechanisms by which melanoma develops BRAF inhibitor resistance. One potential component of resistance is increased drug efflux. Overexpressed ABCB5 (ATP-binding cassette transporter, subfamily B, member 5) has been shown to efflux anti-cancer drugs from cancer cells. The purpose of this study is to determine whether ABCB5 is highly expressed in BRAF inhibitor-resistant melanoma cells and to evaluate whether ABCB5 is involved in the development of resistance to BRAF inhibitors in cutaneous melanoma. We established three BRAF inhibitor-resistant melanoma cell lines with BRAF mutation. The expression level of ABCB5 in PLX-resistant cell lines was checked by real-time PCR and Western blot analysis. SK-MEL-2 melanoma cells with wild-type BRAF were used for comparison. The association of different levels of ABCB5 with the changes of ERK, p-ERK, Akt and p-Akt was also assessed by Western blotting. Re-sensitization of melanoma cells to PLX was tested by p-ERK inhibitor PD58059 and ABCB5 knockdown by ABCB5 siRNA, respectively. We showed that ABCB5 was overexpressed in SK-MEL-28PLXr and A2058PLXr cells but not in A375PLXr cells. ABCB5 overexpression is associated with activation of p-ERK status but not Akt. Inhibition of p-ERK re-sensitized SK-MEL-28PLXr and A2058PLXr cells to PLX treatment, but knockdown of ABCB5 did not re-sensitize A2058 PLXr and SK-MEL-28 PLXr cells to PLX treatment. These results confirm that, even though ABCB5 was overexpressed in SK-MEL-28 and A2058 melanoma cells that develop resistance to BRAF inhibitors, ABCB5 may not be a major targetable contributor to BRAF resistance. p-ERK inhibition may play important roles in BRAF resistance in these two melanoma cell lines.

Controversy exists regarding the value and indications for inguinal dissection alone or in combination with an iliac/obturator lymph node dissection for melanoma. We reviewed patients from a multicenter prospective clinical trial and a single center who underwent inguinal dissection alone or combined with an iliac/obturator dissection for cutaneous melanoma. Analyses were stratified and compared by microscopic or macroscopic (palpable or detected by imaging) disease. The study was composed of 134 patients with a median follow-up of 39 months. Indications for inguinal dissection were microscopic disease in 94 (70%) patients and macroscopic nodal disease in 40 (30%) patients. An iliac/obturator dissection yielded tumor-positive pelvic nodes in 25% vs 55% in the microscopic vs macroscopic groups, respectively (p = 0.10). No risk factors for positive pelvic nodes were identified. For both microscopic and macroscopic disease, addition of an iliac/obturator dissection to an inguinal dissection did not significantly reduce the risk of pelvic nodal recurrence. Five-year overall survival rates for 4 groups were compared: microscopic disease, inguinal dissection alone (72%); microscopic disease, iliac/obturator dissection (68%); macroscopic disease, inguinal dissection alone (51%); and macroscopic disease, iliac/obturator dissection (44%) (p = 0.0163). On survival analysis, addition of an iliac/obturator dissection in either microscopic or macroscopic disease did not affect disease-free survival or regional lymph node recurrence-free survival. The addition of an iliac/obturator dissection to an inguinal dissection for both microscopic and macroscopic nodal disease did not significantly affect lymph node recurrence rates, disease-free survival, or overall survival.

Hospital readmission is becoming a quality measure, despite poor understanding of the risks of readmission. This study examines readmission risk factors after major hepatectomy and develops a predictive model. A retrospective review was performed on patients who had undergone major hepatectomy at 1 of 3 academic centers between the years 2000 and 2012. Clinicopathologic and perioperative data were analyzed for risk factors of 90-day readmission using logistic regression. A readmission risk score was developed and validated in a separate validation set to determine its predictive value. Of 1,184 hepatectomies performed, 17.3% of patients were readmitted within 90 days. Factors associated with readmission include operative blood loss (odds ratio [OR] = 1.00; 95% CI, 1.000–1.001), any postoperative complication (OR = 4.3; 95% CI, 1.8–10.4), a major postoperative complication (OR = 5.7; 95% CI, 3.2–10.2), postoperative pulmonary embolism (OR = 12.2; 95% CI, 1.9–78.4), no postoperative blood transfusion (OR = 3.3; 95% CI, 1.7–6.2), surgical site infection (OR = 5.3; 95% CI, 2.9–10.0), and post-hepatectomy hyperbilirubinemia (OR = 1.1; 95% CI, 1.1–1.2). A scoring system based on these risk factors accurately predicted readmission in the validation cohort. A score of >20 points had a positive predictive value of 30.8% and negative predictive value of 95.6%, and a score >50 had a positive predictive value of 50.9% and negative predictive value of 87.7%. This risk score accurately stratifies readmission risk. The risk of hospital readmission within 90 days after major hepatectomy is high and is reliably predicted with a novel scoring system.