Three-year outcomes of preoperative chemoradiotherapy plus nivolumab in microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). We reported the short-term outcomes of the VOLTAGE trial that investigated the safety and efficacy of preoperative CRT followed by nivolumab and surgery. Here, we present the 3-year outcomes of this trial. METHODS: Thirty-nine patients with microsatellite stable (MSS) LARC and five patients with microsatellite instability-high (MSI-H) LARC underwent CRT (50.4 Gy) followed by five doses of nivolumab (240 mg) and surgery. The 3-year relapse-free survival (RFS), overall survival (OS), and associations with biomarkers were evaluated. RESULTS: The 3-year RFS rates in patients with MSS and MSI-H were 79.5% and 100%, respectively, and the 3-year OS rates were 97.4% and 100%, respectively. Of the MSS patients, those with pre-CRT PD-L1 positivity, pre-CRT high CD8 + T cell/effector regulatory T cell (eTreg) ratio, pre-CRT high expression of Ki-67, CTLA-4, and PD-1 had a trend toward better 3-year RFS than those without. CONCLUSIONS: Three-year outcomes of patients with MSI-H were better than those of patients with MSS. PD-L1 positivity, elevated CD8/eTreg ratio, and high expression of Ki-67, CTLA-4, and PD-1 could be positive predictors of prognosis in patients with MSS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02948348.

A negative pressure-based visualization technique for abdominal Veress needle insertion.

PURPOSE: Abdominal Veress needle insertion is commonly performed to generate a pneumoperitoneum during laparoscopy. Various safety tests are conducted to confirm accurate needle tip positioning into the abdominal cavity. However, these occasionally yield unclear results and do not help directly visualize the peritoneum puncture. We validated a negative pressure-based technique that helps instantly visualize the moment of the Veress needle entry into the abdominal cavity. METHODS: This study included 761 patients who underwent laparoscopic hernioplasty between 2003 and 2021 that entailed pneumoperitoneum creation using a Veress needle. They were divided into conventional technique (CON) and negative pressure visualization technique (NPV) groups. The patients were propensity score-matched (1:1) to minimize selection bias. To determine whether the technique gave a clear result to the surgeon and precisely informed the moment of entry, failed entry and emphysematous complications were compared between the groups. RESULTS: The propensity score-matching yielded 105 pairs in the matched CON and NPV groups. Failed entry did not occur in the NPV group, whereas it occurred in 8 patients (7.6%) in the CON group (p = 0.004). No patient experienced extraperitoneal emphysema in the matched NPV group, whereas 7 patients (6.7%) in the CON group did (p = 0.007). The groups did not differ in the incidence of omental or mesenteric emphysema. CONCLUSION: The NPV eliminated the incidence of failed entry and decreased the incidence of extraperitoneal emphysema, indicating that it could simply and adequately inform the moment of needle entry into the abdominal cavity.

Sacral neuromodulation for the prevention of a permanent stoma in patients with severe defecation disorder following intersphincteric resection.

PURPOSE: Severe defecation disorder occurs frequently in coloanal anastomosis for low rectal cancer, and may affect quality of life. Sacral neuromodulation (SNM) has been reported to be successful after rectal resection, but there are no results for patients treated with intersphincteric resection (ISR). METHODS: A retrospective single-center study of SNM was performed for patient with defecation disorder following ISR. Pre- and post-treatment bowel frequencies, fecal incontinence episodes, and Wexner, LARS and FIQL scores were assessed to evaluate the efficacy. A good response was defined as ≥ 50% reduction of bowel frequency per day or fecal incontinence episodes per week. RESULTS: 10 patients (7 males, mean age 67.5 years) underwent SNM. All patients had severe fecal incontinence with a median Wexner score of 15 (13-20) and a median LARS score of 41 (36-41). The Wexner score improved after SNM, but not significantly (p = 0.06). LARS and FIQL scores significantly improved after SNM (p = 0.02, p = 0.01). At the end of follow-up, the good response rate was 40%. Three cases without a good response required creation of a permanent stoma. CONCLUSION: Seven out of 10 patients did not require a permanent colostomy after SNM. SNM should be considered before performing a permanent colostomy.

Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) and surgical resection are the standard treatment for locally advanced rectal cancer (LARC). Combining immune checkpoint inhibitors with radiation suggests a promising approach for enhancing efficacy. We investigated the efficacy of CRT followed by nivolumab and surgery in patients with LARC. PATIENTS AND METHODS: In phase I, we investigated the feasibility of sequentially combined CRT, 5 cycles of nivolumab, and radical surgery. In phase II, patients with microsatellite stable (MSS) and microsatellite instability-high (MSI-H) LARC were evaluated. RESULTS: Three patients in phase I received full courses of CRT and nivolumab without dose modification; the schedule was recommended for phase II. A pathologic complete response (pCR) was centrally confirmed in 30% [11/37; 90% confidence interval (CI), 18%-44%] and 60% (3/5) of the MSS and exploratory MSI-H cohorts, respectively. While immune-related severe adverse events were observed in 3 patients, no treatment-related deaths were observed. In 38 patients with MSS who underwent surgery, pCR rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were observed in those with programmed cell death ligand 1 (PD-L1) tumor proportion score ≥1% and <1%, respectively; IHC staining was performed using pre-CRT samples. In 24 patients with MSS, pre-CRT samples were analyzed by flow cytometry; pCR rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) were observed for CD8+ T cell/effector regulatory T cell (CD8/eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating lymphocytes. CONCLUSIONS: CRT followed by consolidation nivolumab could increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio were positive predictors in patients with MSS LARC.

Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer.

Patients with colorectal cancers (CRCs) generally exhibit improved survival through intensive lymph node (LN) dissection. However, recent progress in cancer immunotherapy revisits the potential importance of regional LNs, where T cells are primed to attack tumor cells. To elucidate the role of regional LN, we investigated the immunological status of nonmetastatic regional LN lymphocytes (LNLs) in comparison with those of the tumor microenvironment (tumor-infiltrating lymphocytes; TILs) using flow cytometry and next-generation sequencing. LNLs comprised an intermediate level of the effector T cell population between peripheral blood lymphocytes (PBLs) and TILs. Significant overlap of the T cell receptor (TCR) repertoire was observed in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) CRCs with high tumor mutation burden (TMB), although limited TCRs were shared between nonmetastatic LNs and primary tumors in microsatellite stable/MMR proficient (MSS/pMMR) CRC patients with low TMB. In line with the overlap of the TCR repertoire, an excessive LN dissection did not provide a positive impact on long-term prognosis in our MSI-H/dMMR CRC cohort (n = 130). We propose that regional LNs play an important role in antitumor immunity, particularly in MSI-H/dMMR CRCs with high TMB, requiring care to be taken regarding excessive nonmetastatic LN dissection in MSI-H/dMMR CRC patients.

Asynchronous abdomino-parasacral resection of a giant pelvic lipoma protruding to the left buttock.

INTRODUCTION: Few reports detail adequate surgical management of giant pelvic tumors that traverse the sciatic foramen. PRESENTATION OF CASE: We present a case of a giant retroperitoneal pelvic lipoma that presented with a dumbbell shape on imaging, occupying the entire lesser pelvis and protruding to the gluteus through the sciatic foramen. Surgery was performed for en bloc resection of the tumor. DISCUSSION: A parasacral approach with the patient in the prone position was necessary to dissect the tumor in the buttock, manipulate around the sciatic foramen and preserve collateral blood flow for the gluteal muscle. An abdominal approach was also essential to ligate the internal iliac vessels involved in the tumor. Accordingly changings the position of the patient during the operation were required. Division of the sacrotuberous and sacrospinous ligaments and packing of the soft tumor into a plastic bag were useful to pass the buttock portion through the foramen without the tumor breaking off. CONCLUSION: The asynchronous abdomino-parasacral approach with several turnings of the patient's body and plastic bag packing of the tumor were advantageous to manage en bloc resection of the giant pelvic lipoma presented in this case study.