Truncated GPNMB, a microglial transmembrane protein, serves as a scavenger receptor for oligomeric ß-amyloid peptide1-42 in primary type 1 microglia.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is up-regulated in one subtype of microglia (MG) surrounding senile plaque depositions of amyloid-beta (Aß) peptides. However, whether the microglial GPNMB can recognize the fibrous Aß peptides as ligands remains unknown. In this study, we report that the truncated form of GPNMB, the antigen for 9F5, serves as a scavenger receptor for oligomeric Aß1-42 (o-Aß1-42) in rat primary type 1 MG. 125I-labeled o-Aß1-42 exhibited specific and saturable endosomal/lysosomal degradation in primary-cultured type 1 MG from GPNMB-expressing wild-type mice, whereas the degradation activity was markedly reduced in cells from Gpnmb-knockout mice. The Gpnmb-siRNA significantly inhibits the degradation of 125I-o-Aß1-42 by murine microglial MG5 cells. Therefore, GPNMB contributes to mouse MG's o-Aß1-42 clearance. In rat primary type 1 MG, the cell surface expression of truncated GPNMB was confirmed by a flow cytometric analysis using a previously established 9F5 antibody. 125I-labeled o-Aß1-42 underwent endosomal/lysosomal degradation by rat primary type 1 MG in a dose-dependent fashion, while the 9F5 antibody inhibited the degradation. The binding of 125I-o-Aß1-42 to the rat primary type 1 MG was inhibited by 42% by excess unlabeled o-Aß1-42, and by 52% by the 9F5 antibody. Interestingly, the 125I-o-Aß1-42 degradations by MG-like cells from human-induced pluripotent stem cells was inhibited by the 9F5 antibody, suggesting that truncated GPNMB also serve as a scavenger receptor for o-Aß1-42 in human MG. Our study demonstrates that the truncated GPNMB (the antigen for 9F5) binds to oligomeric form of Aß1-42 and functions as a scavenger receptor on MG, and 9F5 antibody can act as a blocking antibody for the truncated GPNMB.

Feasibility and safety of robotic surgery for low rectal cancer combined with transanal total mesorectal excision.

PURPOSE: Laparoscopic surgery for low rectal cancer is often challenging. Transanal total mesorectal excision (TaTME) and robotic surgery have been introduced to overcome the technical difficulties in laparoscopic surgery and achieve more favorable outcomes. Hybrid robotic surgery, which combines TaTME with the abdominal robotic approach, incorporates the advantages of each of these surgical techniques and might achieve less invasive and safer surgery. This study evaluated the safety and feasibility of hybrid robotic surgery with TaTME (hybrid TaTME). METHODS: We retrospectively reviewed 162 TaTME cases performed at our department from September 2016 to May 2022. Among them, 92 cases of conventional TaTME and 30 of hybrid TaTME were eligible. We used propensity score matching analysis (PSM) to adjust for patients' characteristics and compared the short-term outcomes of the two treatment groups. RESULTS: Twenty-seven cases in each group were extracted using PSM. The operation time in hybrid TaTME was comparable to that in conventional TaTME. There was no significant difference in the postoperative hospital stay between the two groups. Other intra- and post-operative outcomes were also comparable between the two groups. Furthermore, no significant differences were observed between the two groups in the curative resection and recurrence rates. CONCLUSION: Hybrid TaTME for low rectal cancer was as favorable as conventional TaTME in producing satisfactory short-term outcomes. However, furthermore, larger-scale studies conducted over longer study periods are needed to evaluate the validity of the findings.

[A Case of HER2 Positive Unresectable Gastric Cancer Leading to Conversion Therapy with Chemotherapy].

A 72‒year‒old man visited our hospital with a chief complaint of epigastralgia. Upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer at the body of the stomach. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2‒positive gastric cancer with invasion to the pancreas as well as the paraaortic lymph node, and multiple liver metastases were also observed. The cancer was judged to be cT4a, N2M1(H1 LYM: No. 16), cStage Ⅳ and thus was considered suitable for chemotherapy. We performed capecitabine plus cisplatin plus trastuzumab therapy. After 3 courses, the primary lesion and swollen lymph nodes decreased in size. After 20 chemotherapy courses, the primary lesion relapsed, so conversion surgery was performed. The patient underwent total gastrectomy, distal pancreatectomy, and partial resection of the liver. We planned to perform adjuvant chemotherapy, but the patient declined it because of anorexia. At 18 months after the operation, recurrence of the tumor was detected at the celiac artery. Chemotherapy was performed as follows: capecitabine plus trastuzumab 10 courses, ramucirumab plus paclitaxel, irinotecan, and nivolumab. However, the patient eventually died 71 months after the first visit.

[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab].

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.

[A Case Report of Sigmoid Colon Cancer with Para-Aortic Lymph Node Metastases and Multiple Liver Metastases Resected after FOLFOX Therapy].

The patient, a male in his 70s, visited our hospital with a chief complaint of general fatigue and weight loss. Upon a detailed examination, he was diagnosed with sigmoid colon cancer, para-aortic lymph node metastases, and multiple liver metastases, for which he was hospitalized due to a poor performance status(PS). FOLFOX therapy was administered as the symptoms caused by the primary lesion were not recognized and his general condition was considered to be poor and thus he was deemed to be inoperable. After completing 2 courses of the chemotherapy, although his PS improved, laparoscopic sigmoidectomy was carried out with colonic stent placement due to the occurrence of an intestinal obstruction as a result of an enlargement of the primary lesion. Following surgery, 2 courses of FOLFOX therapy and 4 courses of FOLFOX plus bevacizumab therapy were administered and he is alive at 5 months after the operation without progression.

[Case of Peritoneal Dissemination from Gastrointestinal Stromal Tumor of Jejunum Treated with Repeated Non-Curative Surgery].

A 71-year-old male presented with abdominal distension and fever to our hospital. Abdominal CT revealed a huge tumor in abdomen, and non-curative surgery was performed. Peritoneal dissemination was widespread and the tumor invaded the bladder and sigmoid-colon mesenterium. Two months after the initial surgery, CT showed liver metastasis, and oral administration of imatinib mesylate was started. The peritoneal dissemination and liver metastasis showed a decrease, and this was well controlled for 45 months without severe side effects. Abdominal CT revealed peritoneal dissemination in the ileocecum after 43 months since the administration of imatinib. Therefore, sunitinib treatment was initiated. After 3 months of sunitinib administration, the tumor perforated. Emergency operation was performed to resect the ileocecum, and sunitinib was continued for 1 year. In GIST with liver metastasis and peritoneal dissemination, repeated surgical resection combined with chemotherapy is important to improve the patient's survival.

[A Super-Elderly Patient with Recurrent Colon Cancer with Metastasis Effectively Treated with Capecitabine plus Bevacizumab Chemotherapy-A Case Report].

The safety and feasibility of chemotherapy for elderly patients is unclear. We report a super-elderly patient with liver metastases from colorectal cancer successfully treated with capecitabine plus bevacizumab chemotherapy. An 87-year-old woman underwent a colectomy for transverse colon. At 4 months postoperatively, she underwent hepatectomy for liver metastases. At 9 months after the first surgery, a new liver metastases(S4)was found. At this time, she rejected another hepatectomy. Therefore, we selected capecitabine plus bevacizumab chemotherapy, considering her age. After 18 courses of administration, the liver metastasis did not progress, and no new metastatic lesions were found on CT examination. Although as adverse events Grade 2 hand-foot syndrome developed, no other adverse event occurred. The patient's PS score was maintained at 0. We suggest capecitabine plus bevacizumab chemotherapy is an effective regimen for super-elderly patients with colorectal cancer.

[A Study of Therapy for Locally Advanced Breast Cancer with Metastasis].

We reviewed 21 patients with locally advanced breast cancer with distant metastasis.The median age was 61 years.The median time to presentation at hospital was 13 months, and the median neoplasm diameter on the first visit was 10 cm.The main histological type was scirrhous carcinoma.Sixteen cases tested positive for hormone receptor(76%), 4 tested positive for HER2(19%), and 3 were triple negative(14%).Four patients underwent surgery.The techniques performed included mastectomy and axillary lymph node dissection.Three patients experienced local recurrence.The first-line treatment was surgery for 1 patient, chemotherapy for 12 patients, hormonal therapy for 7 patients, and trastuzumab for the HER2 positive patients.The median follow-up period was 49 months.The patients for where an operation was performed were 49 months and the operation not- enforcement patients were 54 months.If treatment is possible for patients with locally advanced breast cancer with distant metastasis, multidisciplinary treatment according to individual patient characteristics is recommended. In the case of surgical treatment, careful consideration must also be given to these characteristics.

[Resection of Paraaortic Lymph Node Recurrence Wherein Complete Response to Bevacizumab Was Observed after Surgery for Sigmoid Colon Cancer].

We report a case of resection of a paraaortic lymph node recurrence, wherein complete response to bevacizumab was observed. Our patient was a 50-year-old woman who had a paraaortic lymph node recurrence during adjuvant chemotherapy with FOLFOX 6 months after surgery for sigmoid colon cancer. She was treated with chemotherapy consisting of FOLFOX plus bevacizumab/FOLFIRI plus bevacizumab, which suppressed progression of the periaortic lymph node recurrence. She underwent surgery for the paraaortic lymph node recurrence, and the pathologic result was complete response. We report that bevacizumab was effective for her paraaortic lymph node recurrence.

Sigmoid volvulus is associated with a decrease in enteric plexuses and ganglion cells: a case-control study.

PURPOSE: Although sigmoid volvulus (SV) causes acute obstruction, its pathogenesis and mechanism of torsion are unknown, and few reports have described its pathological findings. Here, we evaluated the clinicopathological characteristics of volvulus and factors contributing to volvulus of the sigmoid colon. METHODS: We compared 14 patients with SV (10 men and 4 women; median age, 78.5 years) with 14 age- and sex-matched control patients for differences in clinical characteristics, focusing on dysmotility (enteric visceral myopathy, neuropathy, and mesenchymopathy). RESULTS: Of the 14 SV patients, 7 had recurrent volvulus, 11 had an associated condition, and 5 required emergency surgery. Atrophy and fibrosis of the inner muscle were more prevalent in the SV than control patients (p = 0.041). Median extent (per centimeter of muscularis propria) of the myenteric plexus (12.5 versus 17.5, p < 0.001) and submucous plexus (15.0 versus 25.5, p < 0.001) was lower in the SV patients, as were the median numbers of myenteric (9.7 versus 30.4, p < 0.001) and submucous ganglion cells (10.0 versus 23.2, p < 0.001). Inflammatory neuropathy was more prevalent in the SV than control patients (p = 0.046); whereas, the prevalence of mesenchymopathy did not differ (p = 0.481). CONCLUSIONS: A decrease in the extent of enteric plexus and ganglion cells precedes the clinical manifestation of SV. Although further elucidation is needed, this decrease may play an important role in the diagnosis of SV and in identifying the mechanism leading to torsion in SV.

[A case of multiple liver metastases from colon cancer treated with complete resection via two-stage hepatectomy after regeneration of the liver].

A 55-year-old woman underwent low anterior resection for sigmoid colon cancer with multiple bilobar metastases. She then received 23 courses of Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX) plus bevacizumab and 13 courses of Leucovorin, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab as down staging chemotherapy. A two-stage hepatectomy was planned to avoid the risk of hepatic failure due to radial resection of bilobar metastases. Therefore, a right lobectomy was performed, and curative resection was achieved 54 days after the first hepatectomy. Two-stage hepatectomy as well as a combination of induction chemotherapy and portal vein embolization may have contributed to the improved prognosis of the initially unresectable multiple bilobar liver metastases.

[Efficiency of pre-operative chemoradiotherapy in treating a case of advanced rectal cancer].

There is insufficient evidence for the pre-operative use of chemoradiotherapy (CRT) in treatment of advanced rectal cancers, and its efficiency and safety are unclear. However, it has recently been suggested that a new class of carcinostatic agents are more effective during preoperative CRT. Under the National Comprehensive Cancer Network (NCCN) guidelines, 5-FU and capecitabine have been recommended as the standard drugs for use during combination chemoradiotherapy. The Japanese Society for Cancer of Colon and Rectum (JSCCR) guidelines for 2014 also recommend the use of both drugs during preoperative CRT. We report a case of rectal cancer, which was successfully treated with radical resection and neoadjuvant chemoradiotherapy.

[A case of liver metastasis from sigmoid colon cancer treated effectively by second-line chemotherapy].

A case of successful chemotherapy for a metachronous liver metastasis following resection for sigmoid colon cancer is presented. A 51-year-old man underwent sigmoidectomy, ileocecal resection, and descending colon colostomy for sigmoid colon cancer with ileum invasion. Six courses of FOLFOX4 were performed as adjuvant chemotherapy. One year after sigmoidectomy, a liver metastasis was detected on computed tomography (CT) examination. Chemotherapy with FOLFOX+bevacizumab was restarted. Three courses were administered, but hepatic dysfunction occurred after the second and third courses, and FOLFOX was discontinued. Subsequent chemotherapy was reinitiated with FOLFIRI+bevacizumab. After 9 courses, the carcinoembryonic antigen level was normalized and appeared to be decreased by imaging studies. Upon the patient's request, only oral S-1 was administered. After 2 courses, CT revealed that the diameter of the tumor had increased by 2 cm. Therefore, right lobectomy of the liver, colostomy closure, and anastomosis were performed. During these procedures, a nodule was found in the omentum and was removed. Rapid intra-operative diagnosis revealed peritoneal dissemination. The pathological diagnosis was liver metastasis of sigmoid colon cancer, with necrosis and fibrosis seen in approximately one-half of specimens. The surgical margins were negative. Neither metastatic cancer nor dissemination were found in the resected greater omentum.

[A case of rectal cancer with multiple liver metastases successfully treated by repeated hepatectomy].

A 61-year-old man was diagnosed with rectal cancer with multiple liver metastases in December 2009, and low anterior resection of the rectum was performed. Postoperative adjuvant chemotherapy with 6 courses of oxaliplatin, Leucovorin, and 5-FU (FOLFOX4) and bevacizumab was initiated, followed by 5 courses of fluorouracil, Leucovorin, and irinotecan (FOLFIRI) and bevacizumab. Right posterior segment (S6, S7) hepatectomy with enucleation of S2, S3 and S5 was performed, and chemotherapy with FOLFOX4 (11 courses) was administered. New metastases in the S5 segment were observed in August 2011 and right hepatic lobectomy was performed. The patient then underwent 8 courses of adjuvant chemotherapy with FOLFOX4. However, left hepatic lobe lateral segment and caudate lobe metastases then appeared. Subsequent repeated chemotherapy with FOLFIRI plus cetuximab (3 courses) and irinotecan plus cetuximab was interrupted in August 2013 owing to adverse events resulting in rapid growth of hepatic metastases. The patient underwent hepatic left lateral segmentectomy and left caudate lobectomy. The postoperative course was uneventful and the patient has currently survived 4 years and 7 months after the initial surgery.

[Self-expanding antireflux stents for malignant esophageal stenosis - a report of three cases].

Use of a standard open stent or self-expanding metal stent for patients with malignant dysphagia is associated with a risk of gastroesophageal reflux especially when placed across the esophagogastric junction. We report 3 cases of malignant esophageal stenosis treated with a long cover-type Niti-STM stent with an antireflux mechanism. Case 1: A 87-year-old man presented with dysphagia due to esophageal cancer at the middle thoracic esophagus. Two months after surgery using a standard open stent, the dysphagia relapsed because of tissue overgrowth. Case 2: A 73-year-old woman presented with lung cancer and severe dysphagia due to enlarged mediastinal lymph nodes. Case 3: A 66-year-old man presented with dysphagia due to esophageal cancer at the lower thoracic esophagus. All 3 patients received an antireflux stent across the esophagogastric junction. In cases 1 and 2, dysphagia was relieved immediately without complications. In case 3, the patient experienced severe reflux and chest pain associated with stent placement and could not ingest any solid food. We conclude that the antireflux stent may be useful for palliation in patients with severe malignant esophageal obstruction; however, patients should be informed about the risk of failure to prevent reflux.

[A case of Stage IV gastric cancer was successfully treated with multi combination chemotherapy with S-1].

Stage IV gastric cancer has poor prognosis, and median survival time (MST) is reported to range from 6 to 13 months. We report a case of long-term survival in a Stage IV gastric cancer patient who was successfully treated with multi combination chemotherapy with S-1. A 73-year-old woman presenting with gastric cancer with pyloric stenosis and peritoneal dissemination at the sigmoid colon underwent distal gastrectomy with D2 lymphadenectomy and sigmoidectomy. She received adjuvant chemotherapy with S-1 and CDDP after surgery. During the twelfth administration of S-1 and CDDP, she developed an anaphylactic reaction against CDDP; therefore, only S-1 was administered for the next 6 courses. Thirty one months postgastrectomy, a left ovarian metastasis (about 4 cm) was detected by computed tomography. Two courses of S-1 and CPT-11 were administered; however, the ovarian metastasis grew to twice its initial size. She underwent hysterectomy and bilateral ovariectomy. The pathological diagnosis was metastatic tumors in the uterus and ovary(Krukenberg tumor). After the second surgery, S-1 and docetaxel therapy was initiated. A metastasis (S2, 5mm diameter) appeared in the right lung around 65 months after the gastrectomy. The patient received a total of 28 courses, up until 69 months post-gastrectomy. At present, she hopes to finish the chemotherapy and is consulting a palliative care facility. At 80 months post-gastrectomy, she has no symptoms because the lung metastasis exhibits slow growth (15 mm diameter), and is maintaining her quality of life (QOL).

[Preoperative chemotherapy for advanced gastric cancer].

In the present study, we evaluated the outcome of preoperative treatment with S-1 and CDDP for the treatment of advanced gastric cancer. Fifty-five cases of advanced gastric cancer received pre-operative treatment with S-1 and CDDP. The tumor control rate( PR and CR according to RECIST criteria) was 55%. The clinical response and histological response to the treatment and curative resection were closely related to favorable postoperative survival. We noted that patients who demonstrated CR or PR received S-1 as postoperative treatment, whereas those with SD or PD were more likely to receive paclitaxel as postoperative treatment. Preoperative treatment with S-1 and CDDP was not only an effective initial treatment, but also demonstrated favorable results in a S-1 in vivo sensitivity test.

[Insertion of percutaneous transhepatic biliary endoprosthesis for unresectable lower cholangiocellular carcinoma following cholangitis due to endoscopic biliary plastic stent obstruction].

The patient was an 87-year-old woman who was diagnosed with atrial fibrillation, which was treated with an anticoagulant, and with chronic kidney disease. The patient was diagnosed as having liver dysfunction and lower cholangiocellular carcinoma (cStage I) on ultrasonography and magnetic resonance cholangiopancreatography. Since it was impossible to perform curative resection owing to the patient's decreased cardiac and renal function, we performed palliative endoscopic retrograde biliary drainage (ERBD) with a plastic stent (PS), and the patient was discharged 11 days later. However, the patient was readmitted because of fever (>38.0°C) and vomiting 124 days after ERBD. We assumed that the patient had developed cholangitis due to PS obstruction. Moreover, her blood culture was positive for Klebsiella pneumoniae. We were unable to replace the PS as the tumor had increased in size and hemorrhage from the papilla of Vater continued after the stent had been removed. The signs of inflammation improved after treatment of sepsis with antibiotics and immunoglobulins, and we performed percutaneous transhepatic cholangio drainage( PTCD) and eventually inserted a percutaneous transhepatic biliary endoprosthesis (PTBE) with an expandable metallic stent (EMS). The patient died 2 months later; no stent occlusion was observed. Our experience suggests that endoscopic biliary stents should be selected bearing in mind the patency of the stent and the prognosis.

[A case of successful radical resection of rectal cancer with neo-adjuvant chemoradiotherapy].

In cases of advanced rectal cancer, preoperative chemoradiotherapy( CRT) serves to improve the local control rate, survival rate, radical resection rate, and/or probability of sphincter muscle preservation. According to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer, preoperative CRT is the standard treatment for rectal cancer in Europe and the United States. However, there is insufficient evidence in support of its efficacy and safety in Japan, and therefore, CRT needs to be evaluated in properly designed clinical trials. Recently, several studies have reported on the efficacy of preoperative CRT in Japan. Herein, we report a case of rectal cancer in which radical resection was successfully performed with neo-adjuvant CRT.

[Long-term survival of a case with advanced sigmoid colon cancer and Virchow's lymph node metastasis].

A 63-year-old man presented with a tumor in his left supraclavicular fossa. Aspiration biopsy of the tumor revealed metastasis of an adenocarcinoma. Further examination indicated the presence of advanced sigmoid colon cancer with metastases to Virchow's lymph nodes and the para-aortic lymph nodes. Sigmoidectomy with D3 lymph node dissection was performed. Histological examination revealed moderately and well differentiated adenocarcinomas( double cancers) that had invaded the subserosa as well as metastases of the para-aortic lymph nodes. Twelve days after the operation, systemic chemotherapy with FOLFOX4 (8 courses), followed by FOLFIRI (8 courses) was administered. Six months later, CT examination determined that the metastases of Virchow's lymph nodes and the para-aortic lymph nodes had completely disappeared. Capecitabine was administered for approximately 1 year, and complete response was achieved. However, a pancreatic tumor measuring 2×3 cm was detected 44 months after the operation. Distal pancreatectomy was performed and pathological examination that included immunohistochemical staining (CK7 and CK20) of the tumor indicated the primary pancreatic cancer. The patient was treated with chemoradiotherapy after the operation and survived for 5 years and 9 months after the initial operation.