ABSTRACT
Background: Single-agent immunotherapy is less effective in patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). Whether pMMR/MSS mCRC patients benefit from combination immunotherapy remains unclear. This study aimed to evaluate the efficacy and safety of anti-programmed cell death protein 1 (PD-1) therapy combined with chemotherapy and bevacizumab in pMMR/MSS colorectal liver metastases (CRLM) patients. Methods: A total of 12 patients with pMMR/MSS CRLM treated at The Sixth Affiliated Hospital of Sun Yat-sen University were enrolled. All patients were treated with at least 4 doses of PD-1 monoclonal antibody combined with chemotherapy and bevacizumab as neoadjuvant/adjuvant therapy. Results: A total of 10 of the 12 patients received the combined therapies before primary tumor resection; the disease control rate (DCR) was 100% (10/10), and the objective response rate (ORR) was 70% (7/10). The ORR of liver metastases was 75% (9/12). Pathological complete response (pCR) was achieved in 1 primary tumor patient and 2 patients with hepatic lesions. A total of 5 patients underwent simultaneous resection of the primary tumor and liver metastases; 9 patients underwent microwave ablation for liver metastases. A total of 7 patients were assessed as having no evidence of disease (NED) with a median progression-free survival (PFS) interval of 9.2 (1.5-15.8) months after multimodality treatments for both primary and metastatic lesions. No severe immune-related adverse events (irAEs) and operational complications were observed. Conclusions: PD-1 blockade combined with chemotherapy and bevacizumab might be safe and effective for patients with pMMR/MSS CRLM. This treatment strategy might lead to better tumor regression and a higher chance of achieving NED.
ABSTRACT
In differentiated thyroid cancer (DTC), the association between thyroid-stimulating hormone receptor (TSHR) and metastasis, and the underlying molecular mechanisms remain unclear. The role of TSHR in the epithelial-mesenchymal transition (EMT) has not yet been reported, to the best of our knowledge. In the present study, the role of TSHR in the distant metastasis of DTC was investigated. TSHR was significantly downregulated in well-differentiated thyroid cancer cells and tissues, and a lack of TSHR promoted thyroid cancer cell invasion and metastasis by inhibiting the EMT of thyroid cancer cells. In addition, the prognostic value of TSHR in thyroid cancer was analyzed. Immunohistochemical analysis of 172 DTC tissues revealed that a lack of expression of TSHR was associated with distant metastasis and a poor survival rate. Multivariate analyses demonstrated that TSHR expression was a significant prognostic factor for distant metastasis and survival time. The results from the present study demonstrated that TSHR inhibits metastasis through regulating EMT in vitro, and that a lack of expression of TSHR is a significant independent factor affecting distant metastasis and poor prognosis in DTC.
ABSTRACT
Skin paddle necrosis and neck function damage, particularly rotation, are two problems associated with the infrahyoid myocutaneous flap clinical application. The aim of this study was to investigate vessel supply and drainage of the skin paddle and to report our modified flap incision technique. In this work, we conducted a cadaveric study and reviewed our experience with the modified incision and describe the surgical procedure. We confirmed the platysma muscle branch feeds the skin paddle overlying the infrahyoid myocutaneous flap. The length between the platysma muscle branch entry point and its originating point measured 3.38 (min 2.51, max 4.52) cm. The flap has two drainage systems. The skin paddle of the flap was drained by the anterior jugular vein and external jugular vein, respectively, or both. The infrahyoid muscles were drained by the superior thyroid vein. In the early four cases, where the platysma muscle branch was not protected, skin paddle necrosis appeared in two cases. In the later seven cases, which involved preservation of the platysma muscle branch, all flaps successfully survived. Patients in whom a modified incision was used all achieved both satisfactory rehabilitation of neck function and an adequate esthetic result. We conclude that the necrosis rate of the skin paddle of the flap can be reduced by carefully protecting its supply and drainage vessels. The modified incision can improve neck function postoperatively.