Complete pathologic response after laparoscopic hepatectomy following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high colon cancer liver metastasis consisting of poorly differentiated adenocarcinoma with squamous differentiation: A case report.

A 56-year-old man referred to our hospital for cecum cancer. Enhanced computed tomography (CT) found swollen reginal lymph nodes and liver metastasis. Magnetic Resonance Imaging (MRI) revealed a solitary lesion on liver (S2). We performed a laparoscopic ileocolic resection and liver partial resection. Tumor pathology showed that these tumors were moderate-differentiated adenocarcinoma (pT3N2bM1 Stage IVA). Genetic examination revealed MSI-high, KRAS wild type, and BRAF wild type. After surgery, two liver metastases were found in S4 and S7 as new lesion in EOB-MRI. We started chemotherapy with the FOLFOFIRI plus bevacizumab regimen, but two liver metastases were enlarged after six cycles of chemotherapy. As a second-line treatment, nivolumab and ipilimumab combination therapy was started. After three cycles of these therapy, both of these tumors shrinkage were observed. We performed laparoscopic liver resection. In specimens, there were no malignant cells. Pathological study revealed that in the initial surgery specimen, PD-L1 protein was detected in both primary and metastatic lesions, and HLA-DR, CK5/6 in liver. No recurrence was observed at 6 months after the surgery. In conclusion, we reported the case of anticancer drug-resistant MSI-high colon cancer liver metastasis was resected after treatment with immune-checkpoint inhibitors and a pathological complete response was found.

Electrochemical synthesis of the protected cyclic (1,3;1,6)-ß-glucan dodecasaccharide.

Automated electrochemical assembly is an electrochemical method to synthesise middle-sized molecules, including linear oligosaccharides, and some linear oligosaccharides can be electrochemically converted into the corresponding cyclic oligosaccharides effectively. In this study, the target cyclic oligosaccharide is a protected cyclic (1,3;1,6)-ß-glucan dodecasaccharide, which consists of two types of glucose trisaccharides with ß-(1,3)- and ß-(1,6)-glycosidic linkages. The formation of the protected cyclic dodecasaccharide was confirmed by the electrochemical one-pot dimerisation-cyclisation of the semi-circular hexasaccharide. The yield of the protected cyclic dodecasaccharide was improved by using a stepwise synthesis via the linear dodecasaccharide.

Pathologic complete response after laparoscopic surgery following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high descending colon cancer: a case report and literature review.

BACKGROUND: Preoperative treatment is performed for locally advanced colon cancer with extensive tumor proximity or suspected invasion of skeletal muscles, major organs, and blood vessels. Oxaliplatin-based regimens are often used in preoperative chemotherapy. However, microsatellite instability (MSI)-high colorectal cancer is often resistant to cytotoxic anticancer agents. Herein, we describe a case of treatment of anticancer drug-resistant MSI-high locally advanced colon cancer and review cases of complete response to immune checkpoint inhibitor therapy for colorectal cancer. CASE PRESENTATION: A 57-year-old woman was referred to our hospital with a large tumor in the descending colon and extensive thoracic and abdominal wall involvement, including the ribs and diaphragm. No distant metastasis was observed. The tumor had perforated the abdominal wall and formed an abscess. Upon visiting our hospital, emergency surgery was performed. An abdominal wall incision was made to drain the abscess and laparoscopic colostomy was performed. Histopathological examination of biopsy specimens revealed an adenocarcinoma with positive immunohistochemical expressions of both CDX2 and CK20. The patient was diagnosed with a descending colon cancer. Genetic examination found MSI-high, Kras mutation (F12G), and wild-type BRAF. After the inflammation improved, chemotherapy with the FOLFIRI regimen was initiated, but the tumor grew rapidly. As a second-line treatment, nivolumab and ipilimumab combination therapy was initiated. After four cycles of these therapies, the patient was administered nivolumab alone for five cycles. Tumor shrinkage was observed and radical surgery was performed. The patient underwent laparoscopic descending colon and partial thoracic and abdominal wall resection. The abdominal wall muscle was dissected from the abdominal cavity, and subcutaneous tissues, diaphragm, ribs were dissected from the body surface. Pathological examination revealed mucus components, fibrous tissues, and no malignant cells, indicating a complete pathological response (pCR). The patient had a good postoperative course and returned to work after being discharged. No recurrence was observed six months postoperatively. CONCLUSIONS: Herein, we report a case of anticancer drug-resistant MSI-high colon cancer that was resected after treatment with immune checkpoint inhibitors, and a pCR was achieved. This new treatment strategy can be used for the treatment of cases that are not responsive to conventional therapies.

Effect of the vertical position of the canine on the frictional/orthodontic force ratio of Ni-Ti archwires during the levelling phase of orthodontic treatment.

This study investigated the effect of the vertical position of the canine on changes in the frictional/orthodontic (F/O) force ratio of nickel-titanium (Ni-Ti) archwires during the initial levelling phase of orthodontic treatment. Frictional and orthodontic forces were measured by using low-friction brackets and Ni-Ti archwires with three different cross-sectional sizes and force types. To simulate canine malocclusion (first premolar extraction case), the upper right canine was displaced gingivally by 1 to 3 mm and the inter-bracket distance between the upper right lateral incisor and second premolar was set at 15 mm or 20 mm. A three-point bending test was performed to measure the orthodontic force of each Ni-Ti archwire. Frictional forces were measured with a universal testing machine and dental arch models by pulling parallel to the end of the archwire at a crosshead speed of 0.5 mm/min. F/O force ratio was calculated and analysed statistically. At a displacement of 3 mm, few archwires had F/O force ratios of less than 1.0, at which orthodontic force overcame frictional force, thus ensuring extrusion of the canine. For effective tooth movement, orthodontists should use Ni-Ti archwires with an F/O force ratio of less than 1.0.

Cone-beam computed tomographic evaluation of changes in maxillary alveolar bone after orthodontic treatment.

This study examined the relationship of vertical and horizontal changes in the alveolar bone crest with upper incisor movement after orthodontic treatment. Tooth movement was measured on lateral cephalograms. Vertical and horizontal changes in the median alveolar crest and distance from the cementoenamel junction and anterior nasal spine to the alveolar crest were measured with cone-beam computed tomography. The incisal edge moved distally, and the cervical point intruded significantly and moved distally. The median alveolar crest decreased by 3.80 ± 2.05 mm. The distance from the labial cementoenamel increased significantly, by 0.35 ± 0.38 mm. The vertical distance from the anterior nasal spine decreased significantly, and the alveolar crest moved distally. Vertical tooth movement was positively associated with change in the distance from the labial cementoenamel junction and inversely associated with vertical change in the distance from the anterior nasal spine on the labial and palatal sides. Lingual tooth movement was positively and negatively correlated with horizontal changes in the labial and palatal alveolar crest and vertical change in the palatal alveolar crest. The lingual movement of incisors was related to labial bone resorption. Greater lingual and extrusive movement of incisors led to a greater decrease in the alveolar bone crest.