[Organ preservation in locally advanced colorectal cancer with microsatellite instability-high after immunotherapy].

Neoadjuvant immunotherapy has achieved exciting efficacy with high clinical complete response (cCR) and pathologic complete response (pCR) rates and durable long-term effects. PD-1 checkpoint blockade-based immunotherapy has been highly successful in microsatellite instability high (MSI-H)/mismatch repair deficiency (dMMR) colorectal cancer and has been recommended as the first-line treatment for metastatic colorectal cancer by domestic and international guidelines. Several studies have shown that immunotherapy can be a potentially curable treatment for MSI-H rectal cancer and has even shown promise in organ preservation in colon cancer. In this study, we first clarified the feasibility of the watch-and-wait strategy after PD-1 checkpoint blockade treatment by indirect and direct evidence. Then from the assessment tools (including digital rectal examination, endoscopy, radiology, and lymph node assessment), the viable assessment methods of cCR for immunotherapy and related difficulties are proposed. Finally, the medication choices of immunotherapy, the treatment regimen, and the follow-up strategy are further discussed. We hope that neoadjuvant immunotherapy could be appropriately applied in MSI-H/dMMR colorectal cancer so that more patients can achieve organ preservation.

[Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer].

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.

Syndrome of endemic arsenism and fluorosis. A clinical study.

Sixty-five patients in Xinjiang with syndrome of endemic arsenism and fluorosis (SEAF) were investigated clinically from March 1982 to August 1989. SEAF is a kind of chronic syndrome resulting from the combined, harmful effects of two trace elements, arsenic and fluorine. Peripheral neuritis and cardiovascular changes were observed in this syndrome more often than in simple arsenism or simple fluorosis. The excessive quantities of these two trace elements in blood might have a synergic, harmful effect on the nervous and circulatory systems. No definite conclusion could be reached with regard to the morbidity of skin and visceral tumors in this series. The incidence of associated skin cancer was found to be 7.7% and an associated Grade II squamous cell carcinoma of the esophagus was encountered in one patient.