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Carbon ion beams have the unique property of higher linear energy transfer, which causes clustered damage of DNA, impacting the cell repair system. This sometimes triggers apoptosis and the release in the cytoplasm of damaged DNA, leading to type I interferon (IFN) secretion via the activation of the cyclic GMP–AMP synthase-stimulator of interferon genes pathway. Dendritic cells phagocytize dead cancer cells and damaged DNA derived from injured cancer cells, which together activate dendritic cells to present cancer-derived antigens to antigen-specific T cells in the lymph nodes. Thus, carbon ion radiation therapy (CIRT) activates anti-cancer immunity. However, cancer is protected by the tumor microenvironment (TME), which consists of pro-cancerous immune cells, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. The TME is too robust to be destroyed by the CIRT-mediated anti-cancer immunity. Various modalities targeting regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages have been developed. Preclinical studies have shown that CIRT-mediated anti-cancer immunity exerts its effects in the presence of these modalities. In this review article, we provide an overview of CIRT-mediated anti-cancer immunity, with a particular focus on recently identified means of targeting the TME.

Abstract Background Traditionally, the surgery for simultaneous double cancer of the stomach and colon required a large incision to the upper and lower region of the abdomen. In this case, an artificial blood vessel was located under the skin after revascularization. Considering ischemia due to graft compression by incision retractor during laparotomy, this was difficult to do. This is a report on laparoscopic surgery for simultaneous double cancer of the stomach and colon after revascularization. Case presentation A 69-year-old man had early gastric cancer and advanced sigmoid colon cancer. He had suffered from thromboangitis obliterans and has undergone revascularization many times due to poor blood flow in his lower limbs. He had had some artificial blood vessels inserted under the skin, confirmed by blood vessel construction image by preoperative computed tomography (CT). There was a bypass vessel from the left axillary artery to the left femoral artery under the skin of the left thoracoabdominal. In addition, there were two bypass vessels from the left external iliac artery to the right femoral artery under the skin of the lower abdomen. One of the two bypasses was occluded. In the blood flow to the intestinal tract, the inferior mesenteric artery was already occluded. Peripheral blood flow in the common iliac artery depended on blood flow from the artificial blood vessel, and blood flow from the internal iliac artery to the rectum was poor. Laparoscopic Hartmann’s operation was performed for Stage II B (UICC 8th Edition) sigmoid colon cancer. Because the blood flow in the intestinal tract on the anal side was poor, we thought that anastomosis was at a high risk for leakage. Laparoscopic total gastrectomy was also performed simultaneously for two Stage I (UICC 8th edition) gastric cancers in the cardia and body. The location of the port site and stoma was carefully determined preoperatively to prevent damage and infection to the artificial blood vessels. Minimal invasive surgery was performed using laparoscopic surgery. Conclusions Laparoscopic surgery with small incisions is useful for patients with double cancer who need an approach to the upper and lower abdomen. Furthermore, laparoscopic surgery has less interference on graft in patients with artificial blood vessels under the skin by intraperitoneal approach.

Abstract Background Nodular fasciitis (NF) is a type of rare and rapidly growing tumor that affects the muscular fascial layers. Due to its locally aggressive nature and rapid growth, NF can be mistaken as a malignant process on either clinical or histological grounds. Case presentation A 61-year-old man was affected by rectal cancer. We performed a robotic, high-anterior resection with lymph node dissection. According to the 8th edition of Union for International Cancer Control, the diagnosis was stage I pT2N0M0. During a routine follow-up 1.5 years after the robotic surgery, a computed tomography examination revealed a tumor in the upper right abdominal wall, at the site of the surgical port, that measured 45 mm. Magnetic resonance imaging indicated a hypo-intensive mass within the right straight muscle of the abdomen. Port site recurrence following the robotic surgery for rectal cancer was suspected, and an ultrasound-guided fine-needle aspiration was performed; it revealed a low-grade myofibroblastic tumor or benign neoplasm, but was inconclusive. We performed an excision of the lesion, and histopathology confirmed NF, seen as a solid, nodular, spindle-cell lesion. The patient was postoperatively followed for more than 1 year without any sign of recurrence of either cancer or NF. Conclusions NF is histologically benign, but local recurrence frequently occurs. We encountered a patient with NF at the port site after robotic surgery for rectal cancer.

Abstract Background Postoperative pancreatic fistula (POPF) is one of the most serious complications after pancreaticoduodenectomy (PD). Various factors have been reported as POPF risks, but the most serious of these is soft pancreas. To reduce POPF occurrences, many changes to the PD process have been proposed. This study evaluates short-term results of anastomosis technique for PD. Methods In total, 123 patients with soft pancreases who had undergone PD at Yamanashi University between January 2012 and August 2020 were retrospectively analyzed. We divided these patients into two groups depending on the time PD was performed: a conventional group (n = 67) and a modified group (n = 56). Results The rate of clinically relevant POPF was significantly lower in the modified group than that in the conventional group (5.4% vs 22.4%, p value

Behçet’s disease (BD) is a multisystem inflammatory disease of unknown origin. Rarely, BD occurs together with myelodysplastic syndrome (MDS). Interestingly, it is speculated that these are not simple coexistence but that the etiology of intestinal BD is at least partly derived from MDS itself. Furthermore, there is a relationship between MDS in patients with intestinal BD and trisomy 8. Immunosuppressive agents alone are insufficient to control MDS-associated BD, and many of these patients die of infection or hemorrhage. Surgery is considered for intestinal BD patients who are unresponsive to medical treatment or those with bowel complications such as perforation or persistent bleeding. We report a case of intestinal BD associated with MDS and trisomy 8. The patient was unresponsive to oral steroids and immunosuppressive treatment; the patient improved by surgical repair of a bowel perforation. Five years after the surgery, the patient is free of recurrence and not on medication. Our experience suggests that surgery may provide an effective therapeutic option for the treatment of MDS-related BD.

Objectives: Rectal stump washout has been widely performed to prevent the implantation of exfoliated cancer cells (ECCs) in patients with rectal cancer. However, it remains unclear whether intraluminal washout before transection is required in patients with sigmoid colon cancer. Therefore, this pilot study was conducted to elucidate the necessity of intraluminal washout for sigmoid colon cancer patients in comparison with rectal cancer patients by cytological assessments. Methods: A total of 16 patients with sigmoid colon cancer and 24 patients with rectal cancer who underwent sigmoidectomy or anterior resection with anastomosis using double-stapling technique were enrolled. A transanal washout sample was collected before washout and after irrigation with 500 and 1,000 mL of saline. Cytological assessments were conducted according to the Papanicolaou classification, and class IV and V cells were defined as malignant. Results: Before washout, exfoliated cancer cells were found in 15 of 24 (62.5%) patients with rectal cancer and in 1 of 16 (6.2%) patients with sigmoid colon cancer (p < 0.001). Distal-free margin from the tumor was significantly shorter in patients with cancer cells (p = 0.002), and the length of the distal-free margin was significantly associated with the tumor location. After irrigation with 500 and 1,000 mL of saline, no cancer cell was found in all patients with sigmoid colon cancer, whereas ECCs were still found in five patients with rectal cancer (20.8%). Conclusions: Intraluminal washout with 1,000 mL may be sufficient for sigmoid colon cancer patients with longer distal-free margin. A large-scale, randomized controlled study is necessary to confirm these results.

Abstract Background The indications for extrahepatic bile duct (EHBD) resection remain a major controversy in the surgical management of patients with gallbladder cancer. On the other hand, perineural invasion (PNI) was reported as an important factor in patients with gallbladder cancer because gallbladder cancer cells frequently spread to the tissues surrounding the EHBD via perineural routes. We assessed the correlation of PNI with clinicopathological factors in patients with gallbladder cancer to elucidate EHBD resection indications specifically in patients with PNI. Methods This retrospective study assessed the PNI status of 50 patients with gallbladder cancer who underwent curative resection and examined the correlation between the presence of PNI and clinicopathological factors. Results Thirteen patients (26%) were PNI positive. PNI was significantly correlated with male sex, proximal-type tumor, lymphatic and vascular invasion, and advanced T stage. Multivariate analysis found that PNI positivity (p < 0.001), lymphatic invasion (p = 0.007), and nodal stage (p < 0.001) were independent prognostic factors. PNI was never observed in patients with stage T1 cancer. Conversely, PNI was detected rarely in distal-type tumors, all of whom developed various types of recurrences. Conclusions These results clearly demonstrated the prognostic impact of PNI in patients with gallbladder cancer. We suggest that EHBD resection in combination with cholecystectomy may not be useful for distal-type tumors from a perspective of PNI.

Abstract Background The low accuracy of preoperative diagnosis of lymph node metastasis in gastric cancer (GC) complicates decisions on patient indication for neoadjuvant chemotherapy. Methods We investigated the use of preoperative clinical diagnosis of lymph node involvement (cN) in GC patients compared with postoperative pathological diagnosis. Results In a series of 265 patients enrolled at the University of Yamanashi Hospital, the overall sensitivity was 44.4% and specificity was 93.4% of CT for detecting lymph node metastasis. The positive and negative predictive values were 80.0% and 73.8%, respectively. The negative predictive value was lower for undifferentiated adenocarcinoma than that for differentiated adenocarcinoma (64.9% vs. 78.7%, p = 0.034). In cT2 ≤ and cN2 ≤ GC, overdiagnosis of lymph node metastasis was significantly more frequent in patients with differentiated (50.0%) than in undifferentiated (13.3%) adenocarcinoma (p = 0.046). Conclusions Diagnostic accuracy of lymph node involvement depended on histological type and cT-stage. Thus, considering preoperative histological type in GC, it may be useful to decide treatment plan.

Abstract Background and purpose Approximately 20% of all patients with colorectal cancer (CRC) are diagnosed at more advanced stages with synchronous distant metastasis, and the prognosis in these patients is usually poor. The aim of this study was to determine the factors that can identify subgroup(s) of patients with stage IV CRC who could benefit from curative (R0) resection of both primary and metastatic lesions. Patients and methods A total of 126 patients with stage IV CRC who underwent surgical resection of primary tumor were retrospectively analyzed. Among these patients, 26 cases of R0 resection were further examined subsequently. Information on various clinicopathological factors of the patients were obtained from hospital records. Overall survival was estimated using the Kaplan-Meier method, and log-rank tests were used to compare survival distribution. All the factors with P

B acute lymphoblastic leukemia (B-ALL) cells are distinctively vulnerable to endoplasmic reticulum (ER) stress. Recently, inhibition of p97 was shown to induce ER stress and subsequently cell death in solid tumors and in multiple myeloma. We investigated the role of a novel, orally available, p97 inhibitor (CB-5083; Cleave Biosciences) in B-ALL. CB-5083 induced a significant reduction in viability in 10 human B-ALL cell lines, harboring the most common fusion-genes involved in pediatric and adult B-ALL, with IC50s ranging from 0.34 to 0.76 μM. Moreover, CB-5083 significantly reduced the colony formation of OP1 and NALM6 cells. Early and strong induction of apoptosis was demonstrated in BALL1 and OP1 cells, together with a robust cleavage of PARP. CB-5083 induced ER stress, as documented through: 1) prominent expression of chaperones (GRP78, GRP94, PDI, DNAJC3, and DNAJB9); 2) increased activation of IRE1-alpha, as demonstrated by the splicing of XBP1; and 3) activation of PERK, which resulted in a significant overexpression of CHOP, and its downstream genes. CB-5083 reduced the viability also in GRP78−/−, GRP94−/−, and XBP1−/− cells, suggesting that none of these proteins alone was strictly required for CB-5083 activity. Moreover, we showed that the absence of XBP1 (XBP1−/−) increased the sensitivity to CB-5083, leading to the hypothesis that XBP1 splicing counteracts the activity of CB-5083, probably mitigating ER stress. Finally, vincristine was synergistic with CB-5083 in both BALL1 and OP1 cells. In summary, the targeting of p97 with CB-5083 is a novel promising therapeutic approach that should be further evaluated in B-ALL.

A wavelength-division multiplexing/time-division multiplexing (WDM/TDM) network exploiting the broad wavelength range of T-band (1000–1260 nm) is proposed. The network is based on different wavebands of downlink and uplink channels, with each transmitter consisting of a wavelength tunable laser utilized for more than one user through wavelength tuning. The downlink section of the network also introduces interconnecting optical lines and semiconductor optical amplifiers (SOAs), pairing up each of the downlink wavebands to provide structural redundancy by allowing transmitters to be shared between the paired wavebands through TDM. Quantum dot (QD)-based wavelength tunable lasers and SOAs were fabricated for a preliminary demonstration experiment. Error-free transmission with less than 1 dB of power penalty was obtained for a wavelength range of 24.2 nm (5.6 THz). The QD-SOAs exhibited a decent rise and fall time, as well as extinction ratios throughout the wavelength range, which enable it to be used as path switches.

Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain-Barré syndrome and multifocal motor neuropathy, which are caused by anti-ganglioside antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain-Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoantibody binding to ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.

Introduction Sigmoid conduit is one of the methods for achieving urinary diversion, but it is performed less frequently than ileal conduit and ureterostomy. Herein, we report a case in which a sigmoid colon conduit was performed after nephrostomy and transverse colostomy. Case presentation A 70‐year‐old man was referred to our hospital because of a bladder tumor. Computed tomography and transurethral biopsy revealed advanced bladder cancer with ureteral and rectal invasion. Despite drug therapy, the tumor progressed. Thus, nephrostomy and transverse colostomy were performed for urinary and fecal diversion, respectively. Subsequently, chemotherapy was administered for 8 months. As nephrostomy‐related complications occurred frequently during chemotherapy, a sigmoid colon conduit was performed instead of nephrostomy for urinary diversion to improve the patient's quality of life. Conclusion In patients with advanced bladder cancer requiring a double stoma of the urinary and fecal tracts, sigmoid colon conduit may be selected as a urinary diversion method.

Abstracts Background The number of elderly patients with gastric cancer has been increasing. Most elderly patients have associated reduced physiologic functions that can sometimes become an obstacle to safe surgical treatment. The National Clinical Database Risk Calculator, which based on a large Japanese surgical database, provides predicted mortality and morbidity in each case as the surgical-related risks. The purpose of this study was to investigate the clinical significance of the risk for operative mortality (NRC-mortality), as calculated by the National Clinical Database Risk Calculator, during long-term follow-up after gastrectomy for elderly patients with gastric cancer. Methods We enrolled 73 patients aged ≥ 80 years and underwent gastrectomy at our institution. Their surgical risk was evaluated based on the NRC-mortality. Several clinicopathologic factors, including NRC-mortality, were selected and analyzed as the possible prognostic factors for elderly patients who have undergone gastrectomy for gastric cancer. Statistical analysis was performed using the log-rank test and Cox proportional hazard model. Results NRC-mortality ranged from 0.5 to 10.6%, and the median value was 1.7%. Dividing the patients according to mortality, the overall survival was significantly worse in the high mortality group (≥ 1.7%, n = 38) than in the low mortality group (< 1.7%, n = 35), whereas disease-specific survival was not different between the two groups. In the Cox proportional hazard model, multivariate analysis revealed NRC-mortality, performance status, and surgical procedure as the independent prognostic factors for overall survival. For disease-specific survival, the independent prognostic factors were performance status and pathological stage but not NRC-mortality. Conclusion The NRC-mortality might be clinically useful for predicting both surgical mortality and overall survival after gastrectomy in elderly patients with gastric cancer.

Abstracts Background Treatment guidelines for early gastric cancer (EGC) recommend additional gastrectomy for lesions which do not achieve curative resection after ESD, due to the potential risk of lymph node metastasis (LNM). However, many cases are found to have no LNMs, and additional gastrectomy itself can be a considerable risk especially in elderly patients. Methods We retrospectively stratified the risk of LNM according to the total number of four LNM risk factors (RFs) that resulted in non-curative resection for ESD in 861 EGC patients who underwent gastrectomy. Next, we compared this stratification risk to the surgical risk based on the National Clinical Database (NCD) risk calculator in 58 patients who underwent additional gastrectomy. Results As the total number of LNM RFs increased, the frequency of LNM also increased significantly (0/1RF 0.76%, 2RFs 15.08%, 3RFs 33.87%, 4RFs 50.00%; p