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Background Totally extraperitoneal (TEP) repair is a recommended procedure for inguinal hernia repair in European hernia guidelines. However, technical challenges have limited its uptake in Japan, where transabdominal preperitoneal (TAPP) repair is more common. We evaluated the association of preoperative subcutaneous fat area (preSFA) with surgical outcomes and identified factors associated with the difficulty of TEP repair.Methods Clinical data from 62 patients undergoing TEP repair were collected retrospectively. Using the median for the preoperative subcutaneous fat index (preSFI; 45.9 cm

Background: The short- and long-term results from several reports suggest that laparoscopic surgery (LAP) for elderly patients is expected to reduce the risk of complications due to its minimal invasiveness, However, little is known about the effect of LAP on long-term prognosis aside from cancer. Patients and Methods: Eighty-five cases over 80 years old with colorectal cancer whose primary lesions were resected consecutively were enrolled. Risk factors for complications were searched using categorized clinicopathological factors. The factors for death unrelated to cancer were analyzed in patients by excluding cancer-related death. Results: Incidence of all complications, those of Clavien–Dindo grade 2 or more, and surgical site infection were significantly lower in LAP-treated patients (p=0.0343, p=0.0015 and p=0.0015, respectively). By multivariate analysis, LAP (odds ratio=0.19, 95% confidence intervaI=0.05-0.75, p=0.0177) and no pulmonary dysfunction (odds ratio=0.24, 95% confidence intervaI=0.06-0.96, p=0.0441) were significantly associated with reduced risk of complications of Clavien–Dindo grade 2 or more. LAP, no pulmonary dysfunction and Eastern Cooperative Oncology Group performance status of 0 or 1 were also significantly associated with reduced risk for death from non cancer-related causes. Additionally, LAP was significantly associated with improved survival excluding cancer-related death in patients with pulmonary dysfunction (p=0.0020) or with poor performance status (p=0.0412). Conclusion: These results suggest that fewer complications and non cancer-related deaths were achieved in very elderly patients with colorectal cancer when treated by LAP.

This study aimed to clarify the effects of bridge to surgery(BTS)for malignant colorectal stenosis on the nutritional and immunological status.A total of 19 patients with colorectal cancer who underwent BTS were included. We examined the technical success of stenting, clinical improvement, treatment progress after BTS, and nutritional and immunological status changes before and after BTS.There were 19 technically successful cases and 18 clinically improved cases. One patient(Score 0)had an obstruction after BTS, which improved after stent repositioning. The CROSS Score before and after stenting improved in all patients. Scores 0 to 4 improved in 12 patients, Scores 0 to 3 in 5 patients, and Scores 3 to 4 in 2 patients. The median time to resume eating was 3 days, and the median surgery time was 25 days. The final diet before operation for colorectal consisted of a rokubugayu(rice gruel: polished rice content 12%)in 1 case, zengayu(rice gruel: polished rice content 20%)in 8 cases, soft diet in 5 cases, and regular diet in 5 cases. Before and after BTS, the nutritional and immunological status decreased significantly(p0.05)with albumin levels ranging from 3.9- 3.5 g/dL, BUN/Cr from 24.8-12.5, and neutrophil-to-lymphocyte ratio from 3.8-2.5; however, no significant fluctuations in the prognostic nutritional index were observed.BTS enabled the nutritional management using the intestinal tract and improved the patient's immune status.

The patient was a 72-year-old man with a chief complaint of abdominal pain. We performed laparoscopic left hemicolectomy of the colon after descending colon cancer ileus stenting, and postoperative pathology was pT4aN0M0, pStage Ⅱb. In 1.5 years postoperatively, 2 liver metastases and 1 lymph node metastasis were found, and each was resected. Chemotherapy was initiated for multiple lung metastases. Genetic testing was positive for BRAF V600E mutation, and the patient received 8 mFOLFOXIRI plus bevacizumab therapy courses. After 15 5-FU plus LV plus bevacizumab courses, the patient had a brain infarction and lung metastasis reincreased. Chemotherapy was changed to encorafenib plus binimetinib plus cetuximab. On day 2, visual impairment was observed, and serous retinal detachment CTCAE Grade 2 was diagnosed. On day 7, the symptoms improved and one-step dose reduction was resumed. On day 2 of re-treatment, serous retinal detachment recurred and treatment was discontinued. On day 4 of re-treatment, the symptoms improved, another dose reduction was performed, and treatment was resumed. Since subjective MEK inhibitor-induced ocular symptoms are often minor, conducting an interview and early ophthalmologic diagnosis is recommended.

Palindromic rheumatism (PR) is an infrequent form of periodic arthritis. Based on the similarity of the pathogenesis of PR to autoinflammatory syndromes, we previously found that the dominant-active splice variant of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a CARD (ASC), which lacks exon 2 (Δexon2), is expressed in Japanese patients with PR.Elucidation of the mechanism of Δexon2 ASC production and the effect of IL-1β on splicing.The genomic DNA of Japanese patients with PR was sequenced. The effect of the observed single nucleotide polymorphisms (SNPs) on ASC splicing was determined via exon trapping using THP-1 cells stimulated with interleukin-1 beta (IL-1β) or ceramide. To investigate the genes that affect alternative splicing via IL-1β, we analyzed the transcriptome of IL-1β-treated THP-1 cells using RNA sequencing.We found the rs8056505 A-G SNP located in the 5'-untranslated region of the genomic ASC gene in patients and that Δexon2 expression was induced by this SNP, whereas it was suppressed by IL-1β or ceramide. We detected 131,426 transcripts and identified 52 differentially expressed genes (DEGs) consisting of 41 downregulated genes and 11 upregulated genes in IL-1β-stimulated THP-1 cells. The splicing-related gene MASCRNA was the most significantly induced gene by IL-1β.We propose a cyclic expression model in which ASC alternates between wild-type and Δexon2 expression regulated by the rs8056505 G allele and splicing factors induced by IL-1β. This cycle may be correlated with the formation of periodic PR pathologies.

In this study, we develop a system for efficiently measuring detailed information of trees in a forest environment using a small unmanned aerial vehicle (UAV) equipped with light detection and ranging (lidar). The main purpose of forest measurement is to predict the volume of wood for harvesting and delineating forest boundaries by tree location. Herein, we propose a method for extracting the position, number of trees, and vertical height of trees from a set of three-dimensional (3D) point clouds acquired by a UAV lidar system. The point cloud obtained from a UAV is dense in the tree’s crown, and the trunk 3D points are sparse because the crown of the tree obstructs the laser beam. Therefore, it is difficult to extract single-tree information from 3D point clouds because the characteristics of 3D point clouds differ significantly from those of conventional 3D point clouds using ground-based laser scanners. In this study, we segment the forest point cloud into three regions with different densities of point clouds, i.e., canopy, trunk, and ground, and process each region individually to extract the target information. By comparing a ground laser survey and the proposed method in an actual forest environment, it is discovered that the number of trees in an area measuring 100 m × 100 m is 94.6% of the total number of trees. The root mean square error of the tree position is 0.3 m, whereas that of the vertical height is 2.3 m, indicating that single-tree information can be measured with sufficient accuracy for forest management.

A 61-year-old woman underwent laparoscopy-assisted distal gastrectomy (LADG) with extragastric lymph node dissection (D2). Two months later, she was readmitted to hospital to be treated for chylous ascites. Oral intake was discontinued and total parenteral nutrition started, but increasing body weight and decreasing serum albumin concentration was not controllable. Percutaneous transabdominal thoracic duct embolization (PTTDE) was performed on the 8th day after the readmission. Five days after PTTDE, oral intake was resumed. Seventeen days after PTTDE, the patient was discharged without recurrence of ascites. She has remained asymptomatic. We describe here the first patient with chylous ascites two months after LADG with D2 dissection for early gastric cancer who was successfully treated by PTTDE.

Introduction Because splenic metastasis from colorectal cancer is usually a result of metastasis from widely disseminated disease, cases with resectable isolated splenic metastasis are uncommon. Case presentation We report here a case of synchronous isolated splenic metastasis from cecal cancer that was treated with sequential laparoscopic splenectomy after short-term observation following laparoscopic ileocecal resection. Both postoperative courses were uneventful, allowing the patient to be discharged early. Two years have passed, without recurrence, since the second operation. Conclusions There are very few case reports on synchronous isolated splenic metastasis from colorectal cancer. Sequential laparoscopic resection might contribute to obtaining an uneventful postoperative course, especially in elderly patients such as ours.

The patient was a 57-year-old man who visited the department of neurosurgery for headache and lightheadedness. He was admitted with a diagnosis of brain tumor based on imaging findings. Severe brain dysfunction and mild ataxia were observed, and craniotomy tumor resection was performed 5 days after admission. He was diagnosed with brain metastasis of colorectal cancer based on histopathological examination and endoscopic findings, and was therefore referred to our department. No extracranial metastases were observed, laparoscopic-assisted low anterior resection was performed 1 month after the craniotomy. The final diagnosis was rectal cancer(Ra), pT3N0M1a(BRA), Stage Ⅳa. Three months after the craniotomy, subsequent MRI examination revealed a new metastatic lesion inferior to the tumor excision cavity, and gamma knife radiosurgery was performed. However, because an increasing tendency was noted, craniotomy was performed again 7 months after the first craniotomy. Following operative treatment, follow up has been performed without adjuvant chemotherapy or prophylactic irradiation, the patient has survived without recurrence at 34 months postoperatively. Here, we report a valuable rare case of solitary brain metastasis of colorectal cancer in which prognosis could be expected by radical resections.

Objective The purpose of this study was to determine the prognostic significance of preoperative neutrophil-lymphocyte ratio for disease-free survival and overall survival in patients with stage II colorectal cancer. Summary of Background Data Previous reports have indicated an association between neutrophil-lymphocyte ratio and poor prognosis and tumor progression in patients with colorectal cancer. However, the role of neutrophil-lymphocyte ratio as a prognostic marker specifically in patients with stage II colorectal cancer has not been well studied. Methods A total of 124 patients with colorectal cancer were included in this study. The disease-free survival and overall survival of patients were compared using preoperative neutrophil-lymphocyte ratio. Univariate and multivariate analyses using the Cox proportional-hazards model were performed to determine the prognostic significance of neutrophil-lymphocyte ratio. Results The overall survival and disease-free survival rates of patients with a neutrophil-lymphocyte ratio ≥ 4.0 were significantly lower than those of patients with a neutrophil-lymphocyte ratio < 4.0. Multivariate analysis showed that a neutrophil-lymphocyte ratio ≥ 4.0, performance status ≥ 1, and depth of tumor invasion (T4) were independent prognostic factors for disease-free survival, whereas age > 80 years, a neutrophil-lymphocyte ratio ≥ 4.0, and performance status ≥ 1 were independent prognostic factors for overall survival. Conclusion Neutrophil-lymphocyte ratio is an independent poor prognostic factor in patients with stage II colorectal cancer undergoing curative resection.

In recent times, the diagnosis and treatment of superficial laryngopharyngeal cancers has been receiving a lot of attention. Here, we present a case of superficial hypopharyngeal cancer and superficial esophageal cancer for which endoscopic laryngo-pharyngeal surgery (ELPS) and endoscopic submucosal dissection (ESD) were performed simultaneously. The patient was a 67-year-old male. During his follow-up for distal gastrectomy performed earlier for stomach cancer, an upper gastrointestinal endoscopy revealed three primary cancers: superficial hypopharyngeal cancer, superficial esophageal cancer, and esophagogastric junction cancer. Total resection of the remnant stomach was performed followed by hypopharyngeal ELPS combined with esophageal ESD. He developed aspiration pneumonia after the surgery; however, he recovered and was discharged on the 16th day. Thus, safe and effective endoscopic therapy can be performed even for double superficial cancers of the laryngopharynx and esophagus.

We report 4 cases of liver metastasis from renal cell carcinoma(RCC). Case 1: 72 years old, female. Pancreatic metastasis was resected 7 years after resection of left RCC, and hepatic posterior sectionectomy was performed for multiple liver metastases 2 years later. After that, multi-organ metastasis appeared and she died of the primary disease. Case 2: 72 years old, male. Liver metastasis and right RCC appeared 16 years after resection of left RCC, and hepatic posterior sectionectomy and partial resection of right kidney were performed. Nine months later, liver metastasis recurred and hepatic partial resection was performed. Case 3: 55 years old, male. After surgery for right RCC with tumor thrombus in the right atrium, multiple lung and liver metastases appeared, and hepatic central bisectionectomy was performed after chemotherapy. Case 4: 60 years old, male. Multiple pancreatic and lung metastases appeared 10 years after resection of left RCC, and most of them shrank or disappeared with chemotherapy. But increasing metastases appeared in the tail of pancreas and the right lobe of liver 16 months later, and hepatic subsegmentectomy and distal pancreatectomy were performed. Multidisciplinary treatment such as aggressive chemotherapy and excision is expected to improve the prognosis for liver metastasis from RCC.

We investigated the significance of transitions in the neutrophil-to-lymphocyte ratio(NLR)before and after TACE for HCC could be a predictor of prognosis. The subjects were 108 patients with the first TACE performed from January 2010 to December 2019. NLR was calculated before and 1 month after TACE, and the relationship with therapeutic effect and prognosis was examined. When the transition of NLR before and after TACE was classified into 3 groups with a cut-off value of 5.0, group A(less than 5.0 after TACE): 52 cases(48.1%), group B(5.0 or more after TACE): 33 cases(30.6%)and C group(5.0 or more before and after TACE): 23 cases(21.3%). Median survival time were 25.0 months in group A, 18.5 months in group B, and 12.7 months in group C(p=0.0005). In multivariate analysis, treatment effect, NLR transition, AFP value, and serum albumin level were prognostic factors for HCC after TACE. Changes in NLR before and after TACE may help predict more detailed prognosis.

According to the Japanese Colorectal ESD/EMR guidelines, radical surgery should be recommended for additional treatment of T1 colorectal cancer(CRC)if pathological findings of the lesion after endoscopic resection show unfavorable factors to be evaluated as curative resection, considering the probability of lymph node metastasis and general condition of patients. We report a case of a 74-year-old man with T1b rectosigmoid(RS)cancer, whose pulmonary metastasis(PM) was curatively resected during the postoperative period of ESD for primary lesions. The patient underwent ESD in November 2018 for Type 0-Isp CRC in the RS junction, revealed using colonoscopy, which was performed for the examination of blood stool in September 2018. The patient had suffered from pulmonary tuberculosis in his thirties and regularly visited our hospital for COPD. He was under close observation after ESD because the depth of the lesion, which was pathologically diagnosed as T1b, was the only factor evaluated as non-curative. In April 2020, chest CT and FDG-PET/CT findings revealed the occurrence of PM. Subsequently, video-assisted wedge resection of the lung was performed for the treatment of PM, which was pathologically confirmed with a size of 10 mm. The patient has survived relapse-free to date, for 30 months after the resection of the primary lesion.

Summary Pathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We, instead, studied the integrity of host's immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host's steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing the guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8+Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and disease were healed by anti-DOCK8 antibody in the mice including SLE-model (NZBxNZW) F1 mice. Thus, DOCK8+Tfh cells generated after repeated TCR stimulation by immunogenic form of pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system's self-organized criticality, cause SLE., Graphical abstract, Highlights • Autoimmunity seldom takes place under integrated steady-state immune response • Repeated invasion by pathogen, such as measles virus, is not exceptional but routine in life • DOCK8+Tfh is generated upon TCR overstimulation by pathogen beyond self-organized criticality • Newly generated DOCK8+Tfh induces autoantibodies and SLE, i.e., autoimmunity, Immunology; Immune response; Cell biology

Background/Aim: We investigated the clinical efficacy of inflammation-based indexes in predicting unfavourable relapse-free survival (RFS) in patients with stage II/III colorectal cancer (CRC) receiving oxaliplatin-based adjuvant chemotherapy. Patients and Methods: A retrospective analysis was performed on 45 patients who underwent curative resection for stage II/III CRC followed by oxaliplatin-based adjuvant chemotherapy after 8 weeks. Upon adjuvant chemotherapy initiation, all patients were evaluated for lymphocyte count (LC), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS) and prognostic nutritional index (PNI), after which their correlation with relapse was analysed. Results: Univariate analysis identified LC 209 and mGPS 2 as significant independent risk factors for unfavourable RFS. Conclusion: Measurement of LMR, PLR, and mGPS upon adjuvant therapy initiation can be a useful tool for predicting recurrence after curative surgery for stage II/III CRC.

This study examined the impact of the degree of occlusion in colorectal cancer during the perioperative period. The subjects included 207 patients who underwent elective colorectal cancer resection. The degree of obstruction at the first medical examination was evaluated using the ColoRectal Obstruction Scoring System(CROSS). We classified the subjects into two groups(CROSS score 0-2, CROSS score 3-4)and assessed their associations with clinicopathological factors, nutritional immune status, and postoperative course. Compared to the CROSS score 3-4 group, the CROSS score 0-2 group(42 subjects [20.3%])had a higher proportion of subjects with ≥2 lesions, T4, Stage classification Ⅳ, CEA5.0 ng/mL, prognostic nutritional index( PNI)≤40, controlling nutritional status( CONUT) score ≥2, modified Glasgow prognostic score (mGPS)2, weight loss rate2.3, mini nutritional assessment-short form(MNA®-SF)score12, neutrophil lymphocyte ratio(NLR) ≥4.0, postoperative complications, and postoperative hospital stay16 days( p0.05). Our findings suggest that the degree of occlusion in colorectal cancer is associated with clinicopathological and nutritional/immune factors and is reflected by the postoperative course.

The patient was a 65-year-old man for whom a right hemicolectomy was performed for transverse colon cancer and multiple lymph node metastases. Peritoneal dissemination was observed throughout the abdominal cavity, and curative resection was not possible. Postoperative diagnosis: pT4bN2M1c(P3), Stage Ⅳc, and mutant RAS status. Therapy consisting of mFOLFOX6 plus bevacizumab was started 1 month after surgery, and up to 25 courses were completed. FOLFIRI plus bevacizumab therapy was performed up to 13 courses as the second-line therapy. Regorafenib 80 mg/day was started as the third-line therapy and the dose was gradually increased. It was performed up to 14 courses for about 13 months, without major adverse events, to keep the disease stable or slow its progression. Although up to 5 courses of FTD/TPI plus bevacizumab therapy were delivered as the fourth-line therapy, he died of disease progression. Regorafenib, which has been approved as a salvage line for metastatic colorectal cancer, features many adverse events, and there are few cases in which the approved dose can be administered. In our case, starting at a low dose resulted in fewer adverse events, adequate disease control, and long-term administration.

PURPOSE Augmented rectangle technique (ART) anastomosis is a totally intracorporeal anastomosis of laparoscopic distal gastrectomy (LDG), Billroth I (B1) reconstruction for gastric cancer, which secures a wide anastomotic stoma. Since the conventional extracorporeal hemi-double stapling technique (HD) may have a narrow anastomotic stoma, our aim of this study was to evaluate the feasibility and usefulness of ART anastomosis by comparing the surgical outcomes with HD anastomosis. METHODS Clinical data of 89 patients undergoing LDG with B1 reconstruction were retrospectively collected. Patients were divided into ART group (n = 40) and HD group (n = 49). Surgical outcomes including short-term outcomes, postoperative endoscopic findings, and nutritional factors 1 year after surgery were compared between the groups. RESULTS Baseline characteristics were similar between the groups. In terms of short-term outcomes, blood loss was less (11.5 mL vs 40 mL, P = 0.011) and postoperative hospital stay was shorter (10 days vs 12 days, P = 0.022) in the ART group. In terms of endoscopic findings, residual food was less (P = 0.032) in the ART group. In terms of nutritional factors, percent decrease of visceral fat area (- 27.6% vs - 40.5%, P = 0.049) and subcutaneous fat area (- 25.7% vs - 39.3%, P = 0.050) 1 year after surgery attenuated in the ART group. CONCLUSIONS ART anastomosis is superior in perioperative course such as postoperative hospital stay. Moreover, a better nutritional recovery is expected by securing a wide anastomotic stoma leading to a favorable food passage.

We hereby report a case of advanced and recurrent colon cancer with long-term survival after 7 repeated surgical resections. A 73-year-old woman initially underwent right hemicolectomy and partial hepatectomy for an ascending colon cancer with synchronous liver metastasis. Pathological diagnosis of the tumors were moderately differentiated adenocarcinoma and metastasis to the liver compatibly. Final clinical stage was diagnosed as fT3N2M1(H1), fStage Ⅳ. But she was interrupted oxaliplatin-based adjuvant chemotherapy after 6 courses of CAPOX because of adverse drug reaction. One year after first operation, partial resection of right lung was performed for lung metastasis. Two years after first operation, 2nd resection of liver was performed for 2 liver metastatic lesions. Three years after first operation, 3rd partial liver resection, 2nd and 3rd partial lung resections were performed for metachronous metastases during 1 year. After 3 years recurrence free period, she complained of an induration of right neck and diagnosed as neck and supra clavicular lymph nodes metastases. Lymph nodes resection was performed. After the last operation, she has no sign of cancer recurrence for 1 year and 7 months, eventually she has been alive for 7 years and 7 months after the initial operation.

Pathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We studied, instead of pathogen, the integrity of host’s immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host’s steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8+Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and lupus lesions were healed by anti-DOCK8 antibody in the mice including (NZBxNZW)F1 and not raised in DOCK8-/- mice. Thus, DOCK8+Tfh cells, generated after repeated TCR stimulation by pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system’s self-organized criticality, cause SLE.

Background During totally extraperitoneal (TEP) repair, peritoneal injury (PI) may result in technical difficulty due to the imparied working space inside the preperitoneal space. We aimed to clarify the factors causing PIs by focusing on the size of the hernia and to provide the prevention and recovery method for PI.Methods A total of 71 inguinal hernia with unilateral TEP repairs were classified by the size of hernia; Small group (Results Operative time (PP=0.015) were higher in the Large group. PI cases in the Large group showed a higher PI rate in Phase 3 (P=0.036) and PI mostly occurred by a sharp dissection of the medial side of hernia sac with using an ultrasonically activated device. In terms of recovery methods, pre-tied suture loop ligation and endoscopic suturing tended to be faster than doing nothing and conversion to TAPP but showed no significance (P=0.059).Conclusions Hernia size and a sharp dissection during the medial side of the hernia sac may be important factors causing PIs. A careful dissection combined with an appropriate blunt dissection is required for the prevention of PI because of the strong adhesion at the medial side and thin peritoneum in most cases of large hernia sacs. In cases of PI, extension of operative time could be prevented by ligation or suturing of the peritoneal defect.

Background Benefit of chemotherapy for patients with metastatic colorectal cancer is well known, however, that for those patients with poor performance status is little known. Patients and methods We retrospectively evaluated efficacy of chemotherapy with capecitabine and bevacizumab for patients with poor PS (PS 3). Results Seven patients were included and the median age of the patients was 82 years (range, 65-91 years). The response was not ascertained; nonetheless, the disease control rate was 83.3%. The median PFS and OS were 10.0 and 25.8 months, respectively. Hand foot syndrome (HFS) was the most common toxicity observed (three patients; 42.9%). Grade 3 toxicities were found in one patient with proteinuria and one with hypertension. Conclusion This limited study indicated that chemotherapy using capecitabine and bevacizumab for patients with poor PS may provide favorable OFS and OS. Needless to say, we should be careful not to impose extra burden to patients with poor PS.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease of unknown cause. We show here that a novel T follicular helper cell type expressing the guanine nucleotide exchange factor DOCK8 on the cell surface causes SLE. These cells, which we have designated autoantibody-inducing CD4 T (aiCD4 T) cells, are generated after resuscitation from anergy following strong TCR stimulation by antigen. When mice normally not prone to autoimmune disease were repeatedly immunized with an antigen such as OVA, they generated DOCK8+ CD4 T cells. These DOCK8+ CD4 T cells, in vivo and also upon transfer to naïve mice, induced a variety of autoantibodies and lesions characteristic of SLE. TCR repertoire analyses showed that a substantial number of novel TCR repertoires were generated in the DOCK8+ CD4 T cells, which induced novel autoantibodies upon transfer to naïve mice. DOCK8+ CD4 T cells are localized in splenic red pulp, the space immunoreactive against a variety of antigens, and specifically increased in the peripheral blood of SLE patients in association with disease activity. Anti-DOCK8 antibody treatment ameliorated the lesions induced by DOCK8+ CD4 T cells and in lupus model (NZB x W) F1 mice. Thus, when CD4 T cells are overstimulated by an external disturbance, i.e., repeatedly stimulated with antigen, to levels that surpass the system’s self-organized criticality, these cells express DOCK8 on the cell surface and acquire autoreactivity via TCR re-revision at the periphery. These DOCK8+ CD4 T cells subsequently induce a variety of autoantibodies and SLE.

Incidence of infusion related reaction (IR) is more common with cetuximab (Cmab) than with panitumumab (Pmab). Although little is known about rechallenge IR with monoclonal antibodies, we experienced a successful rechallenge to Cmab after IR to Pmab. A 67-year-old female patient was scheduled for chemotherapy with mFOLFOX6 plus Pmab against unresectable advanced rectal cancer in the hope of tumor shrinkage. On the first administration of Pmab, she complained of dyspnea with shortness of breath and wheezing, even after premedication with steroids and antihistamines. Her reaction was judged as Grade 2 IR to Pmab. For the next course, we tried Cmab. No IRs were observed. Since then, she has undergone seven further courses of treatment, followed by surgical resection. The patient benefited from administration of Cmab after experiencing IR to Pmab, suggesting this treatment to be an option for patients of this type who experience IR to Pmab.

Aim To investigate the clinical significance of ATP-binding cassette transporter 11 (ABCC11) protein expression in colon cancer. Materials and methods One hundred thirty nine patients with colon cancer resection between 2009 and 2011 were enrolled. The relationship with immunohistochemical ABCC11 staining and clinicopathological factors was retrospectively analyzed. Results Median age was 70 years including 67 males and 72 females. The patients with Stage 0, 1, 2, 3a and 4 were 4, 20, 43, 35, 7 and 30, respectively. The patients with curability (Cur) A, B and C were 109, 11 and 19, respectively. Positive expression of ABCC11 was observed in 31 patients (22.3%). There were no significant differences regarding age, gender, location, serum tumor markers, T category, lymphatic invasion and stage in relation to ABCC11 protein expression. Cases with node metastasis and venous invasion as well as unresectable cases were significantly more often found negative for ABCC11 protein (p=0.0246, 0.0285 and 0.0422, respectively). Concerning the 3 year disease free survival (DFS) and the 5 year overall survival (OS) in Stage 2/3 and in Stage 3 with adjuvant chemotherapy, no significant differences were found. However, OS in ABCC11 negative cases was 81.1%, which was significantly lower compared to positive cases, where OS was 96.2%. Conclusion There was significant correlation with ABCC11 expression and lymph node metastasis, venous invasion and curability. The prognosis in ABCC11 negative cases was poor because of increased cases without curative resection.

A 74-year-old man underwent a medical examination for anemia and had a positive fecal occult blood test. Ascending colon cancer was detected by colonoscopy. Since it was unresectable, a bypass operation was performed to prevent digestive symptoms prior to chemotherapy. The bypass was performed by cutting the ileum and attaching the oral side to the transverse colon with side to side anastomosis. The other end of the terminal ileum was anastomosed to the transverse colon on the oral side of the prior anastomosis, making a pretzel shaped bypass. There were no postoperative complications and the patient was treated with chemotherapy from postoperative day 23.

According to the Japanese Gastric Cancer Treatment Guideline(GL), radical surgery is recommended as an additional treatment for early gastric cancer(EGC)patients with endoscopic submucosal dissection(ESD)evaluated as non-curative for fear of lymph node metastasis(LNM). However, the reported probability of LNM was approximately 10%. Therefore, the recommendation might be aggressive for elderly patients or those in poor physical conditions. Under this context, surveillance post non-curative ESD has emerged as an acceptable option. We reported a case of an elderly patient who survived EGC for over 54 months as relapse-free with ESD resection evaluated as non-curative. An 84-year-old woman underwent ESD in July 2014 for EGC, which was deemed as non-curative with negative surgical margins. The patient had pre-existing severe bronchial asthma. Given the age and the comorbidities, the patient preferred close surveillance to radical surgery. After 54 months of surveillance, no recurrence of the initial EGC was found. However, during the annual check-ups, 2 metachronous cancers were found in July 2016 and June 2018 respectively. Both metachronous cancers were curatively resected with ESD.

The efficacy of laparoscopic surgery for elderly patients aged over 80 years who have colorectal cancer was investigated concerning complications. Sixty-five patients over 80 years old who underwent colorectal cancer resection until January 2018 were enrolled. Factors that led to complication were analyzed retrospectively. Thirty-three men and 32 women were included, with a median age of 83 years. Forty-eight cases were located at the colon; and 17, at the rectum. The median operating time was 164 minutes, including 39 cases treated with the laparoscopic approach. Postoperative complications were observed in 28 cases(43.1%), of which 15(23.1%)had a Clavien-Dindo(CD)classification of Grade BⅡ. These cases had significantly prolonged postoperative hospital stay. Complications included 10 cases of incisional surgical site infection(SSI), 9 cases of ileus, 6 cases of melena, 2 cases of urinary infection, 2 cases of urinary disorder, and 1 case of postoperative death. Open surgery was the only significant factor associated with the incidence of CD classification of BⅡ(p=0.0330). Among the complications, the incisional SSI was reduced by laparoscopic surgery(p=0.0050). The number of laparoscopic surgeries reduced the incidence of CD classification BⅡ of complications in elderly patients aged over 80 years who had with colorectal cancer resection. The use of incisional SSI also decreased with the use of laparoscopic surgery. Laparoscopic surgery for colorectal cancer in elderly patients may lead to reduced complication rates.

Malignant colorectal obstruction results in a worse quality of life and makes it difficult for patients to continue chemotherapy. In this paper, we present a case of rectal obstruction caused by gastric cancer dissemination for which rectal stent insertions were performed twice. The patient was a 72-year-old woman. She underwent gastrectomy for Stage Ⅳ gastric cancer (ypT3, N1, M1, P0, H0, CY+). Twenty-eight months after gastrectomy, she experienced rectal obstruction due to peritoneal dissemination. A rectal stent was placed at the stenosis site. She was administered chemotherapy after stenting. Seven months later, she developed rectal obstruction due to tumor in-growth. Rectal stenting was performed again. Subsequently, the patient had no abdominal symptoms until she died, 2 months after the second stenting.

Superficial thoracic esophageal cancer with a solitary metastasis to a lymph node outside the usual target area of lymphadenectomy is extremely rare. We report a case of superficial esophageal cancer with a solitary, giant metastasis to the right upper deep cervical lymph node that was treated with surgery. A 57-year-old man presented to our institution with a chief complaint of a mass in the right neck. Fine needle cytology showed squamous cell carcinoma. No lesion was found in the pharyngolaryngeal area or the lungs. Upper gastrointestinal endoscopy revealed superficial squamous cell carcinoma of the thoracic esophagus. Detailed examinations showed no other lymph node enlargement or metastasis to distant organs. The patient was diagnosed with esophageal cancer with a solitary lymph node metastasis (N4; No.102upR). Subtotal esophagectomy and 3-field lymphadenectomy were performed. The patient received adjuvant chemotherapy. At 3 years postsurgery, no recurrence has been found. We think this case is extremely rare.

Objective We evaluated the preoperative patient status including nutrition, immunity, and inflammation as a predictive factor of remote infection (RI) in colorectal cancer surgery. Subjects and methods A total of 351 patients who underwent colorectal cancer resection were retrospectively analyzed. Factors correlated with RI incidence were identified by logistic analysis and stepwise selection. Results RI occurred in 27 patients, with an incidence of 7.7%. In univariate logistic analysis, a significantly high incidence of RI was associated with excessive blood loss (>423 mL), long duration of surgery (>279 minutes), ileus, pulmonary dysfunction, performance status (PS) ≥1, American Society of Anesthesiologists (ASA) classification>2, prognostic nutritional index (PNI) ≤40, and controlling nutritional status (CONUT) ≥2, modified Glasgow Prognostic Score (mGPS) (Score 2).In multivariate analysis, pulmonary dysfunction (odds ratio=2.83; 95% CI: 1.14-6.97; p=0.02) and PNI≤40 (odds ratio=3.87; 95% CI: 1.45-10.31; p=0.006) were independent risk factors of RI incidence. Conclusion RI is caused by poor nutrition, immune system dysfunction and pulmonary dysfunction.

Incisional surgical site infection (SSI) is a leading complication of stoma reversal procedures. This retrospective study was conducted to assess the incidence of incisional SSI and other wound complications when wound closure was achieved by subcuticular suturing and closed suction drainage following stoma reversal. We analyzed data from a total of 49 patients, all of whom had undergone insertion of a 10 Fr closed suction drainage tube in the fascia, following irrigation with approximately 300 mL of physiological saline. We then performed subcuticular suturing with 4-0 monofilament absorbable sutures. The median age of our patient population (34 men and 15 women) was 68 (range, 35-84) years. Six patients had an end stoma and 43 had a loop stoma. The wound category was 'contaminated' in 18 patients, while an incisional SSI was observed in one patient (2.0%). No wound disruptions, seromas, or drain infections were evident. Our data are reliable, but our study is limited in terms of general applicability; however, the low SSI rate indicates that the procedure is acceptable. Further research into this procedure will require a randomized trial design.

Rheumatoid arthritis (RA) is a chronic polyarthritis of unknown etiology. To unravel the molecular mechanisms in RA, we performed targeted DNA sequencing analysis of patients with RA. This analysis identified a variant of the death receptor 3 (DR3) gene, a member of the family of apoptosis-inducing Fas genes, which contains four single-nucleotide polymorphisms (SNPs) and a 14-nucleotide deletion within exon 5 and intron 5. We found that the deletion causes the binding of splicing regulatory proteins to DR3 pre-mRNA intron 5, resulting in a portion of intron 5 becoming part of the coding sequence, thereby generating a premature stop codon. We also found that this truncated DR3 protein product lacks the death domain and forms a heterotrimer complex with wildtype DR3 that dominant-negatively inhibits ligand-induced apoptosis in lymphocytes. Myelocytes from transgenic mice expressing the human DR3 variant produced soluble truncated DR3, forming a complex with TNF-like ligand 1A (TL1A), which inhibited apoptosis induction. In summary, our results reveal that a DR3 splice variant that interferes with ligand-induced T cell responses and apoptosis may contribute to RA pathogenesis.

BACKGROUND/AIM Pancreaticoduodenectomy (PD) treatment outcomes in elderly patients have been reported to be acceptable, but the eligibility criteria are not clear. To elucidate the importance of PD in octogenarians in particular, we set five eligibility criteria for elderly patients based on preoperative cardiac and pulmonary function, nutritional status, daily activity status, and psychological independence status for the first time and evaluated prospectively whether the validity of patient selection was adaptable. PATIENTS AND METHODS The study population consisted of 222 patients with pancreaticobiliary cancer aged over 70 years. The patients were divided into two groups: 192 patients as septuagenarians and 30 as octogenarians. Postoperative morbidity and long-term outcome were compared between the two groups, and prognostic factors relating to survival time were identified. RESULTS Octogenarians had a significantly higher frequency of two or more comorbidities (p

Postoperative chylothorax after surgery for esophageal cancer is a rare but serious complication. Treatment initially consists of conservative therapy and, if it fails to provide improvement, it is important to perform surgical treatment without delay. We report on a recent case of intractable chylothorax. This report describes a 72-year-old man with Stage III esophageal squamous cell carcinoma. Subtotal esophagectomy, through a right thoracoabdominal approach with two-field lymphadenectomy, and cervical esophagogastric anastomosis via the retrosternal route, were performed. On the 12th postoperative day, a diagnosis of chylothorax was made. Conservative treatment was initiated, but it proved to be ineffective. Therefore, ligation of the thoracic duct via a thoracotomy was performed, but this was not effective, either. Lymphangiography undertaken to identify the site of the leak in the thoracic duct enabled a diagnosis of an extremely rare double thoracic duct and identification of the site of the leak in the thoracic duct, thereby allowing curative direct ligation of the site. This case underscores the remarkable usefulness of lymphangiography in dealing with intractable postoperative chylothorax.