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The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating. However, Vδ2 T cells were present at higher frequencies in circulation than in the tissue of either cancer patients or healthy donors. Tregs were decreased in the peripheral blood of SCC patients, but were significantly increased in the tumor compartment of these patients. Tumor-infiltrating γδ T cells preferentially showed an effector memory phenotype and made either IL17 or IFNγ depending on the tumor stage, whereas circulating γδ T cells of SCC patients preferentially made IFNγ. Different cell types in the tumor microenvironment produced chemokines that could recruit circulating γδ T cells to the tumor site and other cytokines that could reprogram γδ T cells to produce IL17. These findings suggest the possibility that γδ T cells in SCC are recruited from the periphery and their features are then affected by the tumor microenvironment. Elevated frequencies of infiltrating Vδ2 T cells and Tregs differently correlated with early and advanced tumor stages, respectively. Our results provide insights into the functions of tumor-infiltrating γδ T cells and define potential tools for tumor immunotherapy. Cancer Immunol Res; 5(5); 397–407. ©2017 AACR.

Background/aim Upper limb breast cancer-related lymphedema (BCRL) is a chronic and severe condition affecting a significant percentage of breast cancer survivors. Even though its physiopathology is well-known, there is no worldwide consensus on BCRL evaluation and a gold-standard treatment. This narrative review aims at providing a brief descriptive overview with regard to BCRL treatment modalities. Materials and methods We conducted a literature search within the PubMed database, and 33 articles out of 56 were selected, including reviews, systematic reviews, and meta-analyses aiming find the most updated evidence regarding BCRL treatment modalities. Results Physical exercise (aerobic exercise, resistance exercise, aquatic therapy), bandages, and intermittent pneumatic compression were shown to be most effective in BCRL patients, in terms of swelling reduction in the acute-intensive phase. Furthermore, physical exercise was beneficial also as a maintenance tool. Manual lymphatic drainage demonstrated efficacy in preventing secondary lymphedema if applied immediately after breast cancer surgery or in early phases of BCRL or as a maintenance tool. Complementary procedures such as acupuncture, reflexology, yoga and photo-biomodulation therapy did not show conclusive results in BCRL treatment. Surgery was shown effective in managing symptoms (liposuction), preventing (lymphaticovenular anastomosis) and treating BCRL (vascularized lymph node transfer). Conclusion BCRL is still a challenging condition either for breast cancer survivors and clinicians, deeply impacting patient functioning and quality of life. Due to the lack of globally accepted criteria in evaluating BCRL, to date a gold standard treatment for this widespread issue is still needed.

The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating. However, Vδ2 T cells were present at higher frequencies in circulation than in the tissue of either cancer patients or healthy donors. Tregs were decreased in the peripheral blood of SCC patients, but were significantly increased in the tumor compartment of these patients. Tumor-infiltrating γδ T cells preferentially showed an effector memory phenotype and made either IL17 or IFNγ depending on the tumor stage, whereas circulating γδ T cells of SCC patients preferentially made IFNγ. Different cell types in the tumor microenvironment produced chemokines that could recruit circulating γδ T cells to the tumor site and other cytokines that could reprogram γδ T cells to produce IL17. These findings suggest the possibility that γδ T cells in SCC are recruited from the periphery and their features are then affected by the tumor microenvironment. Elevated frequencies of infiltrating Vδ2 T cells and Tregs differently correlated with early and advanced tumor stages, respectively. Our results provide insights into the functions of tumor-infiltrating γδ T cells and define potential tools for tumor immunotherapy. Cancer Immunol Res; 5(5); 397–407. ©2017 AACR.

Background: Post Surgical Pyoderma Gangrenosum (PSPG) is a neutrophilic dermatosis causing aseptic necrotic ulcerations within surgical sites. It is often misdiagnosed as infection or ischemia and worsened by the inappropriate treatment. Therefore diagnostic clues must be identified and awareness for PSPG raised.Methods: We present two cases of PSPG after flap surgery and a review of the literature.Results: Seventeen cases of PSPG after flap surgery were found. Fever, pain and redness are the most common initial symptoms. In 63%, lesions were on the flap and the adjacent skin. In 63%, the donor site is also involved. Time to diagnosis was nine days to four years. Frequent debridement (89%) and administration of antibiotics (74%) illustrate the misdiagnosis of infection or ischemia. PSPG in flap surgery seems to be less associated with underlying diseases, than other forms of Pyoderma Gangrenosum. Corticoids are the most commonly used treatment. Of the 19 cases, 10 experienced partial or total flap loss.Conclusion: PSPG must be included in the differential diagnosis of postoperative wound problems. Recognizing the diagnostic clues can lead to early diagnosis and treatment with systemic immunotherapy. Associated diseases should be investigated and additional surgery can only be successful when associated with immunotherapy.

BACKGROUND: Urethral reconstruction in anterolateral thigh flap phalloplasty cannot always be accomplished with one flap, and the ideal technique has not been established yet. In this article, the authors' experience with urethral reconstruction in 93 anterolateral thigh flap phalloplasties is reported. METHODS: Ninety-three anterolateral thigh phalloplasties performed over 13 years at a single center were retrospectively reviewed to evaluate outcomes of the different urethral reconstruction techniques used: anterolateral thigh alone without urethral reconstruction (n = 7), tube-in-tube anterolateral thigh flap (n = 5), prelaminated anterolateral thigh flap with a skin graft (n = 8), anterolateral thigh flap combined with a free radial forearm flap (n = 29), anterolateral thigh flap combined with a pedicled superficial circumflex iliac artery perforator flap (n = 38), and anterolateral thigh flap combined with a skin flap from a previous phalloplasty (n = 6). Seventy-nine phalloplasties were performed for female-to-male sex reassignment surgery. The others were performed in male patients with severe penile insufficiency. RESULTS: Urethral complication rates (fistulas and strictures) were as follows: tube-in-tube anterolateral thigh flap, 20 percent; prelaminated anterolateral thigh flap, 87.5 percent; free radial forearm flap urethra, 37.9 percent; superficial circumflex iliac artery perforator urethral reconstruction, 26.3 percent; and skin flap from previous phalloplasty, 16.7 percent. CONCLUSIONS: When tube-in-tube urethra reconstruction is not possible (94.2 percent of cases), a skin flap such as the superficial circumflex iliac artery perforator flap or the radial forearm flap is used for urethral reconstruction in anterolateral thigh phalloplasties. Flap prelamination is a second choice that gives high stricture rates. If a penis is present, its skin should be used for urethral reconstruction and covered with an anterolateral thigh flap. With these techniques, 91.86 percent of patients are eventually able to void while standing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

We report a case of a woman affected by covered exstrophy, uterus didelphys and external genital malformation presenting with advanced bladder cancer. After neoadjuvant therapy and anterior pelvic exenteration, the abdominal wall was reconstructed with a pedicled myocutaneous muscle-sparing vastus lateralis flap.