A pathological complete response after nivolumab plus ipilimumab therapy for DNA mismatch repair-deficient/microsatellite instability-high metastatic colon cancer: A case report.

The standard treatment for colorectal cancer has always been surgery and chemotherapy, which may be used in combination to treat patients. Immune checkpoint inhibitors have been a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair. However, little information is available about their use in neoadjuvant and conversion settings with only a few case reports and only one phase 2 trial. The present study reports the case of a large, locally advanced right-sided metastatic deficient mismatch repair/microsatellite instability-high colon cancer, which showed a pathological complete response after combination treatment with nivolumab and ipilimumab. To the best of our knowledge, resected metastatic colon cancer with a pathological complete response after treatment using dual immune checkpoint inhibitors has not been previously reported. Overall, this case report suggests the use of immune checkpoint inhibitors before colorectal surgery.

An anatomical review of various superior mesenteric artery-first approaches during pancreatoduodenectomy for pancreatic cancer.

When pancreatic head cancer invades the superior mesenteric artery (SMA), attempts at curative resection are aborted. Preoperative imaging diagnostics to determine the surgical curability have yet to surpass the intraoperative information acquired via inspection, palpation, and trial dissection. Pancreatoduodenectomy (PD) is a standard measure for treating periampullary cancers. In conventional PD, SMA invasion is usually identified by dissecting the retroportal lamina, which connects the uncinate process and SMA nerve plexus after dividing the neck of the pancreas. During PD for pancreatic head cancer, this retroperitoneal margin frequently vitiates surgical curability. SMA-first approaches during PD are methods where the SMA is dissected first by severing the posterior pancreatic capsule to assess the SMA involvement of pancreatic cancer early in the operation. The first report of such an approach prompted subsequent reports of various maneuvers that are now known collectively as "artery-first" approaches. We herein review those approaches by classifying them according to (1) the side of the mesocolon from where the SMA approach occurs (supracolic or infracolic) and (2) the direction of access (right or left and anterior or posterior). The steps of the reported PD procedures are numbered according to a timeline and summarized using anatomical division of the SMA.

Filiform polyposis with sigmoid colon adenocarcinoma: a case report.

BACKGROUND: Filiform polyposis is a rare form of inflammatory polyposis, which is occasionally formed in the colon of patients with history of inflammatory bowel disease (IBD). It is characterized by presence of several to hundreds of slender, worm-like polyps in the colon lined by histologically normal colonic mucosa and often coalesce, resulting in a tumor-like mass. Filiform polyposis is most frequently associated with a post-inflammatory reparative process in patients with IBD history, and only cases of filiform polyposis occurring in patients without IBD history have been reported. Filiform polyposis has been considered as a benign inflammatory polyposis without any risk of dysplasia, while the possibility of carcinogenesis of inflammatory polyps is not fully excluded. To date, only three cases of filiform polyposis coexisting with dysplasia have been reported. CASE PRESENTATION: A 59-year-old male patient with no past medical history of IBD underwent laparoscopic sigmoidectomy for obstructive filiform polyposis, which was associated with sigmoid colon adenocarcinoma. Based on the histological findings of the resected specimen, invasive sigmoid colon adenocarcinoma was surrounded by filiform polyposis, and adenocarcinoma also scattered uniformly on the surface of filiform polyposis. In immunohistochemistry, abnormal p53 expression was observed in adenocarcinoma, while it was not shown in mucosa on filiform polyposis. CONCLUSIONS: This is the fourth case of filiform polyposis that is closely associated with colon dysplasia or adenocarcinoma based on histological findings. However, immunohistochemical findings did not support the theory that inflammation initiates adenocarcinoma in filiform polyposis like IBD. Hence, further immunohistochemical and genetic analyses are needed to clarify the association between filiform polyposis and carcinogenesis.

A novel RORγt inhibitor is a potential therapeutic agent for the topical treatment of psoriasis with low risk of thymic aberrations.

BACKGROUND: Retinoic acid receptor-related orphan receptor gamma t (RORγt) has critical roles in the development, maintenance and function of interleukin (IL)-17-producing cells and is a highly attractive target for the treatment of IL-17-mediated autoimmune disease, particularly psoriasis. On the other hand, RORγt is also critical for controlling apoptosis during thymopoiesis, and genetic RORγt ablation or systematic RORγt inhibition cause progressive thymic aberrations leading to T cell lymphomas. OBJECTIVE: We investigated whether topical administration of our novel RORγt inhibitor, S18-000003 has therapeutic potential for psoriasis with low risk of thymic aberrations. METHODS: We evaluated the effect of topical S18-000003 on psoriasis-like skin inflammation and influence on the thymus in a 12-O-tetradecanoylphorbol-13-acetate-induced K14.Stat3C mouse psoriasis model. RESULTS: S18-000003 markedly inhibited the development of psoriatic skin inflammation via suppression of the IL-17 pathway. In the skin, S18-000003 suppressed all subsets of IL-17-producing cells that we previously identified in this psoriasis model: Th17 cells, Tc17 cells, dermal γδ T cells, TCR- cells that probably included innate lymphoid cells, and CD4-CD8- double-negative αß T cells. Notably, neither reduction of CD4+CD8+ double-positive thymocytes nor dysregulation of cell cycling was observed in S18-000003-treated mice, even at a high dose. CONCLUSION: Our topically administered RORγt inhibitor is a potential therapeutic agent for psoriasis with low risk of thymic lymphoma.

SN-38 Acts as a Radiosensitizer for Colorectal Cancer by Inhibiting the Radiation-induced Up-regulation of HIF-1α.

BACKGROUND/AIM: Hypoxia offers resistance to therapy in human solid tumors. The aim of the study was to investigate whether SN-38, the active metabolite of irinotecan, acts as a radiosensitizer through inhibition of hypoxia-inducible factor (HIF)-1α in the human colorectal cancer (CRC) cells. MATERIALS AND METHODS: HT29 and SW480 cells were cultured with SN-38 (0-4 µM) immediately after irradiation (0-8 Gy). HIF-1α expression was assessed using flow-cytometry and western blot analysis. Cell proliferation was evaluated by the calcein assay. Apoptosis and cell cycle were determined by flow-cytometry. RESULTS: Radiation up-regulated HIF-1α, and SN-38 inhibited the radiation-induced HIF-1α. The combination of radiation and SN-38 inhibited cell proliferation more than radiation alone; treatment with SN-38 after radiation exposure did not increase the number of apoptotic cells, whereas, it enhanced the S and G2/M cell-cycle arrest and decreased the population of cells in G1 Conclusion: SN-38 inhibits the radiation-induced up-regulation of HIF-1α and acts as a radiosensitizer by inducing cell-cycle arrest in CRC cells.

Value of FDG-PET/CT Volumetry After Chemoradiotherapy in Rectal Cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by an optimal surgery is the standard treatment for patients with locally advanced rectal cancer. FDG-PET/CT is commonly used as the modality for assessing the effect of chemoradiotherapy. OBJECTIVE: The purpose of this study was to investigate whether PET/CT-based volumetry could contribute to the prediction of pathological complete response or prognosis after neoadjuvant chemoradiotherapy. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at a single research center. PATIENTS: Ninety-one consecutive patients with locally advanced rectal cancer were enrolled between January 2005 and December 2015. INTERVENTION: Patients underwent PET/CT before and after neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURES: Maximum standardized uptake value and total lesion glycolysis on PET/CT before and after neoadjuvant chemoradiotherapy were calculated using isocontour methods. Correlations between these variables and clinicopathological factors and prognosis were assessed. RESULTS: PET/CT-associated variables before chemoradiotherapy were not correlated with either clinicopathological factors or prognosis. Maximum standardized uptake value was associated with pathological complete response, but total lesion glycolysis was not. Maximum standardized uptake value correlated with ypT, whereas total lesion glycolysis correlated with both ypT and ypN. High total lesion glycolysis was associated with a considerably poorer prognosis; the 5-year recurrence rate was 65% and the 5-year mortality rate 42%, whereas in lesions with low total lesion glycolysis, these were 6% and 2%. On multivariate analysis, high total lesion glycolysis was an independent risk factor for recurrence (HR = 4.718; p = 0.04). LIMITATIONS: The gain in fluoro-2-deoxy-D-glucose uptake may differ between scanners, thus the general applicability of this threshold should be validated. CONCLUSIONS: In patients with locally advanced rectal cancer, high total lesion glycolysis after neoadjuvant chemoradiotherapy is strongly associated with a worse prognosis. Total lesion glycolysis after chemoradiotherapy may be a promising preoperative predictor of recurrence and death. See Video Abstract at http://links.lww.com/DCR/A464.

A case of disseminated carcinomatosis of the bone marrow originating from gastric cancer 3 years after intraperitoneal chemotherapy against peritoneal carcinomatosis.

BACKGROUND: Clinical studies of intraperitoneal chemotherapy with paclitaxel in patients of gastric cancer with peritoneal carcinomatosis is well tolerated and effective, and rare cases of metastasis and recurrence have experienced during the treatment. Disseminated carcinomatosis of the bone marrow is highly rare in gastric cancer and associated with a poor prognosis. CASE PRESENTATION: A 59-year-old woman of gastric cancer with peritoneal carcinomatosis received five courses of chemotherapy with intraperitoneal administration of paclitaxel, and laparoscopy showed disappearance of the peritoneal carcinomatosis. She subsequently underwent total gastrectomy, and the histopathological findings showed a complete response to the chemotherapy. Postoperatively, chemotherapy with intraperitoneal administration of paclitaxel was continued for 30 months, without apparent recurrence. However, the gastric cancer recurred as disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation, and we hence changed the chemotherapy regimen to weekly irinotecan. Remission was achieved, and she did not experience any major symptoms; however, she died 6 months after the diagnosis of disseminated carcinomatosis of the bone marrow. CONCLUSIONS: Since intraperitoneal paclitaxel administration can strongly suppress peritoneal carcinomatosis of gastric cancer, careful attention should be paid not only to peritoneal recurrence but also for rare site metastases, such as bone marrow metastases.