Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn's disease.

T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4+ tissue-resident memory T cell (Trm) subset that is increased in Crohn's disease (CD) showing unique inflammatory properties. Functionally and transcriptionally distinct CD4+ Trm subsets are observed in the inflamed gut mucosa, among which a CD-specific CD4+ Trm subset, expressing CD161 and CCR5 along with CD103, displays previously unrecognized pleiotropic signatures of innate and effector activities. These inflammatory features are further enhanced by their spatial proximity to gut epithelial cells. Furthermore, the CD-specific CD4+ Trm subset is the most predominant producer of type 1 inflammatory cytokines upon various stimulations among all CD4+ T cells, suggesting that the accumulation of this T cell subset is a pathological hallmark of CD. Our results provide comprehensive insights into the pathogenesis of IBD, paving the way for decoding of the molecular mechanisms underlying this disease.

Association between the hypokalaemia index based on area over the serum potassium concentration curve and occurrence of acute kidney injury in patients administered liposomal amphotericin B.

BACKGROUND: Acute kidney injury (AKI) and hypokalaemia are common adverse events after treatment with liposomal amphotericin B (L-AMB). OBJECTIVES: Because excess potassium (K) leakage occurs during renal tubular injury caused by L-AMB, measuring the decrease in rate of serum K concentration might be more useful to assess the renal impact of L-AMB than hypokalaemia identified from a one-point measurement. The effects of a decrease in K concentration and duration of hypokalaemia on AKI were investigated. METHODS: A ≥ 10% decrease in K concentration from the reference concentration within a 7-day timeframe was evaluated. The hypokalaemia index, which combines the duration of K concentration lower than the reference and a marked low K concentration, was calculated from the area over the concentration curve. RESULTS: Eighty-six patients were included in the study. The incidences of AKI and decrease in K concentration were 36.0% and 63.9%, respectively. Of patients who developed both adverse events, a decrease in K concentration occurred first in 22 of 26 patients, followed by AKI 7 days later. Hypokalaemia did not increase AKI risk whereas a decrease in K concentration was an independent risk factor for AKI. The hypokalaemia index in patients with AKI was significantly higher than those without AKI (5.35 vs. 2.50 points, p = 0.002), and ≥3.45 points was a significant predictor for AKI. CONCLUSION: A ≥ 10% decrease in the K concentration was a significant factor for AKI in patients receiving L-AMB therapy. In such patients, dose reduction or alternative antifungals could be considered based on the hypokalaemia index.

Risk factors for the postoperative recurrence of ulcerative colitis-associated colorectal cancer.

PURPOSE: Although ulcerative colitis-associated colorectal cancer (UC-CRC) has been described, there are few reports regarding recurrent cases of UC-CRC. In this study, we investigated the risk factors for UC-CRC recurrence. METHODS: Recurrence-free survival (RFS) was determined for 144 stage I to III cancer patients among 210 UC-CRC patients from August 2002 to August 2019. The Kaplan‒Meier method was used to obtain the cumulative RFS rate, and the Cox proportional hazard model was used to extract recurrence risk factors. The interaction term between cancer stage and prognostic factors specific to UC-CRC was evaluated using the Cox model. The Kaplan‒Meier method was applied by cancer stage to the UC-CRC-specific prognostic factors for which interaction effects were indicated. RESULTS: There were 18 cases of recurrence involving patients with stage I to III cancer, and the recurrence rate was 12.5%. The cumulative 5-year RFS rate was 87.5%. Multivariable analysis showed that age at surgery (hazard ratio (HR): 0.95, 95% CI: 0.91-0.99, p = 0.02), undifferentiated carcinoma (HR: 4.42, 95% CI: 1.13-17.24, p = 0.03), lymph node metastasis (HR: 4.11, 95% CI: 1.08-15.69, p = 0.03), and vascular invasion (HR: 8.01, 95% CI: 1.54-41.65, p = 0.01) were significant risk factors for recurrence. Patients with stage III CRC in the young adult (age < 50 years) group had a significantly worse prognosis than those in the adult (age ≥ 50 years) group (p < 0.01). CONCLUSION: Age at surgery was identified as a risk factor for UC-CRC recurrence. Young adult patients with stage III cancer may have a poor prognosis.

Clinical features and surgical selection in colitis-associated colorectal cancer with ulcerative colitis.

PURPOSE: The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA. METHODS: Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively. RESULTS: The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2-590) in the cancer/dysplasia group and 48 (1-580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p < 0.01). The four nutrition factors of weight (55.2 (32.7-99.6) kg: 49.9 (20.3-85.2) kg), body mass index (21.0 (13.9-32.5) kg/m2: 18.3 (11.4-34.1)kg/m2), serum albumin level (4.3 (2.7-5.0)g/dl: 3.4 (1.4-5.2)g/dl) and prognostic nutrition index (49.2 (33.2-61.2): 40.9 (17.4-61.1)) were significantly higher in the cancer/dysplasia group (p < 0.01). The degree of obesity was also significantly higher in the cancer/dysplasia group (p < 0.01). CONCLUSION: UC patients with cancer/dysplasia were more likely than refractory patients to have mild inflammation; they also had a longer duration of UC disease and better nutritional status.

Effect of Changing Surgical Instruments Before Wound Closure to Prevent Wound Infection in Lower GI Surgery: A Randomized Controlled Trial.

BACKGROUND: Surgical site infection is a major surgical complication and has been studied extensively. However, the efficacy of changing surgical instruments before wound closure remains unclear. OBJECTIVE: The aim of this study was to investigate the efficacy of changing surgical instruments to prevent incisional surgical site infection during lower GI surgery. DESIGN: This was a randomized controlled trial. SETTINGS: This study was conducted at the Hyogo College of Medicine in Japan. PATIENTS: Patients undergoing elective lower GI surgery with open laparotomy were included. INTERVENTIONS: Patients were randomly assigned to 1 of 2 groups. In group A, the surgeon changed surgical instruments before wound closure, and in group B, the patients underwent conventional closure. MAIN OUTCOME MEASURES: The primary end point was the incidence of incisional surgical site infection. The secondary end point was the incidence of surgical site infection restricted to clean-contaminated surgery. RESULTS: A total of 453 patients were eligible for this trial. The incidence of incisional surgical site infection was not significantly different between group A (18/213; 8.5%) and group B (24/224; 10.7%; p = 0.78). In the clean-contaminated surgery group, the incidence of incisional surgical site infection was 13 (6.8%) of 191 in group A and 9 (4.7%) of 190 in group B (p = 0.51). LIMITATIONS: This was a single-center study. CONCLUSIONS: Changing surgical instruments did not decrease the rate of incisional surgical site infection in patients undergoing lower GI surgery in either all wound classes or clean-contaminated conditions. See Video Abstract at http://links.lww.com/DCR/B701. EFECTO DE REALIZAR CAMBIO DE LOS INSTRUMENTOS QUIRRGICOS ANTES DEL CIERRE DE LA INCISIN EN LA INFECCIN DE LA HERIDA DEL SITIO QUIRRGICO EN CIRUGA DEL TUBO DIGESTIVO BAJO ESTUDIO ALEATORIO CONTROLADO: ANTECEDENTES:La infección del sitio quirúrgico es una complicación importante y se ha estudiado ampliamente. Sin embargo, la eficacia de cambiar los instrumentos quirúrgicos antes del cierre de la herida sigue sin estar clara.OBJETIVO:El objetivo de este estudio es investigar la eficacia de cambiar el instrumental quirúrgico en la prevención de la infección del sitio quirúrgico en cirugía gastrointestinal inferior.DISEÑO:Estudio aleatorio controlado.AJUSTE:Este estudio se realizó en la Facultad de Medicina de Hyogo en Japón.PACIENTES:Se incluyeron pacientes sometidos a cirugía electiva de tubo digestivo bajo con laparotomía abierta.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente a uno de dos grupos. En el grupo A, el cirujano cambió el instrumental quirúrgico antes del cierre de la herida, y en el grupo B, los pacientes se sometieron a un cierre convencional.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la incidencia de infección del sitio quirúrgico de la incisión. El criterio de valoración secundario fue la incidencia de infección del sitio quirúrgico restringida a la cirugía limpia contaminada.RESULTADOS:Un total de 453 pacientes fueron elegibles para este ensayo. La incidencia de infección del sitio quirúrgico no fue significativamente diferente entre el grupo A (18/213; 8,5%) y el grupo B (24/224; 10,7%) (p = 0,78). En el grupo de cirugía limpia-contaminada, la incidencia de infección del sitio quirúrgico incisional fue 13/191 (6,8%) en el grupo A y 9/190 (4,7%) en el grupo B (p = 0,51).LIMITACIÓN:Estudio de un solo centro.CONCLUSIÓNES:El cambio de instrumentos quirúrgicos no disminuyó la tasa de infección del sitio quirúrgico en todas las clases de heridas o condiciones limpias-contaminadas. Consulte Video Resumen en http://links.lww.com/DCR/B701.

Association between preoperative biologic use and surgical morbidity in patients with Crohn's disease.

PURPOSE: We evaluated the influence of preoperative treatments with biologics on surgical morbidity in patients with Crohn's disease (CD). METHODS: We reviewed the surveillance data of patients with CD who underwent surgery between April 2018 and April 2021. The possible risk factors for morbidity were analyzed. RESULTS: A total of 305 surgically treated patients were included. Anti-TNF alpha agents and ustekinumab were used in 92 and 27 patients, respectively, within 12 weeks before surgery. There were no cases of mortality. In total, 70/305 (23.0%) patients developed a complication, and 42/305 (13.8%) patients developed a surgical site infection (SSI) (17 incisional SSIs and 35 organ/space SSIs). Current smoking status (OR 3.44), emergent/urgent surgery (OR 6.85), and abdominoperineal resection (APR) (OR 14.93) were identified as risk factors for total complications. Penetrating disease (OR 14.55) was identified as a risk factor for incisional SSIs. Current smoking status (OR 7.09), an American Society of Anesthesiologists (ASA) score greater than 3 (OR 5.85), a postoperative blood sugar level over 155 mg/dL (OR 4.37), and APR (OR 207.95) were identified as risk factors for organ/space SSIs. CONCLUSIONS: No correlation between preoperative treatment with biologics and surgical mortality or morbidity was found. However, we should perform further analyses on a larger number of patients because the analyses may be limited by selection bias for treatment and several confounding factors.

Being Elderly Is Associated with Infectious and Fatal Postoperative Complications in Ulcerative Colitis Patients.

INTRODUCTION: It is well known that the infectious complications and mortality rates are increased among elderly individuals with ulcerative colitis (UC) during medical treatment. However, there have been few reports on surgery in elderly individuals with UC, and some cohort studies have reported surgical complication and mortality rates similar to those in nonelderly individuals. METHODS: UC patients who underwent colectomy at the Hyogo College of Medicine between April 2012 and March 2020 were included in this study. The patients were classified as elderly (≥65) or nonelderly (<65). Characteristics and postoperative complications were analyzed and compared between the groups; possible risk factors for infectious and fatal complications were also analyzed. RESULTS: In all, 136/599 (22.7%) elderly patients were included. The incidence of infectious and fatal complications was 177/599 (29.5%) and 18/599 (3%), respectively. These complication rates were significantly higher in the elderly than the nonelderly group (p < 0.01). Age ≥65 years at surgery (OR = 2.92, 95% CI: 1.87-4.57, p < 0.01) was identified as an independent risk factor for infectious complications. Age ≥65 years at surgery (OR = 8.03, 95% CI: 2.16-29.83, p < 0.01), American Society of Anesthesiologists score ≥3 (OR = 6.00, 95% CI: 1.40-25.6 p = 0.02), and urgent/emergent surgery (OR = 16.24, 95% CI: 1.70-154.95, p = 0.02) were identified as independent risk factors for fatal complications. DISCUSSION/CONCLUSION: Age ≥65 years was identified as a risk factor for infectious and fatal complications. It is important to avoid urgent/emergent surgery in elderly patients with an ASA score >3 by emphasizing surgical and medical collaboration and optimizing the timing of surgery.

Rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features arising in a patient with ulcerative colitis: a case report.

BACKGROUND: Colorectal carcinoma with enteroblastic differentiation is a rare subtype of colorectal carcinomas expressing at least one characteristic immunohistochemical marker among α-fetoprotein, glypican-3, and spalt-like transcription factor 4. On the other hand, colorectal carcinoma with neuroendocrine differentiation is also a unique subtype of colorectal carcinomas showing expression of at least one distinctive marker among chromogranin A, synaptophysin, and CD56. CASE PRESENTATION: We experienced an extremely rare case of rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features in a 53-year-old male patient with long-standing ulcerative colitis (UC). Most of the tumor cells were positive for enteroblastic differentiation markers and approximately a half of them for neuroendocrine differentiation markers. Some tumor cells showed only enteroblastic differentiation, and some did only neuroendocrine feature, but some showed both enteroblastic and neuroendocrine differentiation. CONCLUSION: Colorectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features has not been reported yet. Neoplastic transformation from pluripotent stem cells in dysplastic epithelium of long-standing UC patients may be associated with such dual differentiation features.

Clinical results following colonic resection for ulcerative colitis in elderly individuals (elderly-onset vs. nonelderly onset).

BACKGROUND: The incidence of ulcerative colitis (UC) is increasing, but there are few reports comparing elderly UC patients undergoing colectomy for elderly-onset UC (EO) and nonelderly-onset UC (NEO). The aim of this study was to analyze the differences between EO and NEO patients who underwent UC-related surgery. METHODS: We identified 1973 patients with UC who underwent colectomy at Hyogo College of Medicine between January 1, 1984, and December 31, 2018. Only patients aged 65 years old and older who underwent colectomy were enrolled in this study (n = 221, 11.2%), and their clinical records were retrospectively reviewed. Patients were divided into two groups according to their age at disease onset: those with onset at younger than 60 years old (NEO) and at 60 years old or older (EO). RESULTS: In the 221 UC patients who underwent colectomy at 65 years old or older, there were 155 cases of EO and 66 cases of NEO. The main surgical indication in NEO patients was colitis-associated cancer/dysplasia (32/66, 47%). In contrast, refractory to medical treatment was the leading cause of surgery in EO patients (80/155, 52%). The distributions of surgical indications were different between the two groups (p < 0.01). The preoperative daily dose of steroids was significantly higher in the EO group than in the NEOgroup (0 mg vs. 10 mg, p < 0.01). The rates of immunosuppressant, infliximab (IFX) and adalimumab use did not differ significantly between the groups. Significantly more patients underwent emergency surgery in the EO group than in the NEO group (14% vs. 35%, p < 0.01). The proportions of patients with postoperative morbidity (Clavien-Dindo grade III or higher) were 17.4% (27/155) in the EO group and 13.6% (9/66) in the NEO group. There was no significant difference between the two groups (p = 0.48). The prognosis of the EO patients who underwent UC-related emergency surgery was worse than that of the NEO patients (p < 0.01). In the EO group, 8 (14.8%) of 54 patients died within 30 postoperative days, while there were no deaths in the NEO group. CONCLUSION: Among elderly UC patients undergoing UC-related surgery, EO patients undergoing emergency surgery had very poor outcomes, and the mortality rate was 14.8%. In such cases, it is important for physicians and surgeons to begin communication at an early stage so that the optimal surgical timeframe is not missed.

Intestinal cancer in patients with Crohn's disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Although surveillance colonoscopy is recommended by several guidelines for Crohn's disease (CD), the evidence is insufficient to support the validity of this recommendation. Moreover, the efficacy of surveillance colonoscopy for anorectal cancer remains unclear. Therefore, we performed a systematic review of cancer in patients with CD before considering the proper surveillance methods. METHODS: We conducted a systematic review and meta-analysis examining the incidence of intestinal cancer and a literature review to clarify the characteristic features of cancer in CD. We performed the systematic literature review of studies published up to May 2019. RESULTS: Overall, 7344 patients were included in eight studies. The standardized incidence ratios (95% confidence intervals) of colorectal cancer (CRC) and small bowel cancer (SBC) were 2.08 (1.43-3.02) and 22.01 (9.10-53.25), respectively. The prevalence of CRC and SBC was 57/7344 (0.77%) and 17/7344 (0.23%), respectively, during a median follow-up of 12.55 years. Additionally, 54 studies reporting 208 anorectal cancer cases were identified. In patients with anorectal cancer, the prognosis for survival was 2.1 ± 2.3 years, and advanced cancer greater than stage T3 occurred in 46/74 patients (62.1%). Many more reports of anorectal cancer were published in Asia than in Western countries. CONCLUSION: Although we were unable to state a recommendation for surveillance for SBC, we should perform cancer surveillance for CRC in patients with CD. However, the characteristics of cancer may differ according to geography or race. We must establish proper and effective surveillance methods that are independently suitable to detect these differences.

Does anti-tumor necrosis factor alpha prevent the recurrence of Crohn's disease? Systematic review and meta-analysis.

BACKGROUND AND AIM: Anti-tumor necrosis factor (TNF) α agents are now well known to function as effective treatments for Crohn's disease (CD). Several meta-analyses have revealed the efficacy of anti-TNF therapy for preventing recurrence after surgery; however, the efficacies reported in some prospective studies differed according to the outcomes. Moreover, adverse events (AEs) were not well evaluated. We conducted this systematic review and meta-analysis to evaluate both the efficacy of anti-TNF therapy after stratification by the outcome of interest and the AEs. METHODS: We performed a systematic literature review of studies investigating anti-TNF therapy, CD, and postoperative recurrence. Meta-analyses were performed for endoscopic and clinical recurrence and AEs. RESULTS: A total of 570 participants, including 254 patients in the intervention group and 316 patients in the control group, in eight studies, were analyzed for recurrence. Based on the results of the meta-analysis, the efficacies of anti-TNF therapy at preventing endoscopic and clinical recurrence were as follows: relative risk (RR) 0.34, 95% confidence interval (CI) 0.22-0.53 and RR 0.60, 95% CI 0.36-1.02, respectively. The RR of AEs with anti-TNF therapy was 1.75 (95% CI 0.81-3.79). CONCLUSIONS: Anti-TNF therapy after surgery for CD displays efficacy at preventing endoscopic recurrence for 1-2 years, without increasing the incidence of AEs. However, clinical recurrence was not significantly reduced. The efficacy of postoperative anti-TNF therapy may differ in terms of the outcomes, which include long-term prevention, the avoidance of further surgery, and cost-effectiveness.

Localization of recurrent lesions following ileocolic resection for Crohn's disease.

BACKGROUND: Crohn's disease (CD) recurrence can occur not only at the site of anastomosis but also elsewhere in the bowel following an ileocolic resection (ICR) procedure. The aims of the present study were to assess long-term outcomes of a primary ICR procedure for CD in consecutive patients and examine the location of the reoperation causative lesion. METHODS: We examined cases of surgery with ICR initially performed at our institution. Those with simultaneous multiple bowel resection or bowel resection with strictureplasty were excluded. RESULTS: A total of 169 patients who underwent ICR due to CD were enrolled. The median follow-up period was 12.6 years (range 4-27 years). A reoperation was needed in 45 (26.6%), of whom 14 had lesions causative of the reoperation at other than the anastomotic site. The most common causative lesion location was in the colon rather than the oral side of the small intestine. Furthermore, we investigated the relationship between presence of residual lesions following the initial surgery and lesions causative of reoperation. In the group without residual disease (n = 31), 29.0% (n = 9) had non-anastomotic lesions involved in indications for reoperation, while that was 35.7% (n = 5) in the group with residual disease (n = 14). CONCLUSIONS: Anastomotic site lesion is not the only causative factor for reoperation following ICR. Regular examinations and applicable treatment with awareness that the cause of reoperation is not limited to the site of anastomosis are important in these cases.

Functional Outcomes and Quality of Life in Elderly Patients after Restorative Proctocolectomy for Ulcerative Colitis.

BACKGROUND/AIM: Ileal pouch anal anastomosis (IPAA) has become the surgical procedure of choice for patients with ulcerative colitis (UC). However, to date few studies have examined functional outcomes or quality of life (QOL) in elderly patients after pouch construction. METHODS: In December 2017, we sent questionnaires to 224 patients aged 65 years and older at the time who underwent an IPAA at our hospital between June 1987 and May 2015 regarding issues related to QOL and functional outcomes. Responders aged 65-69 years old were defined as the elderly group (EG), while those 70 years old and over comprised the super-EG (SEG). RESULTS: The response rate was 60.7% (136/224); 70 patients were classified as EG, and 66 were classified as SEG. The SEG were older at the time of the IPAA and during the follow-up period (p < 0.01). The stool frequency per day was 8 times in both groups (p = 0.21). There was no significant difference between the EG and SEG with regard to daytime (53 vs. 56%, p = 0.73) or nighttime (65.7 vs. 53%, p = 0.16) soiling. There was also no difference in the exacerbation of daytime or nighttime soiling compared to the first year after the operation (daytime 5.7 vs. 12.1%, p = 0.23; nighttime 7.1 vs. 9.1%, p = 0.76). QOL was evaluated using the modified fecal incontinence QOL (mFIQL) scale, with no significant difference between the EG and SEG (27 vs. 31 points). Since both groups had mFIQL scores <50, QOL was considered to be maintained. CONCLUSION: In our analysis of elderly patients in the long-term period following surgery for UC, some noted fecal soiling, though QOL was largely maintained, and there were no serious effects on daily life.

Associations between multiple immunosuppressive treatments before surgery and surgical morbidity in patients with ulcerative colitis during the era of biologics.

PURPOSE: It is unclear whether immunomodulators or biologics, with the exception of corticosteroids, can be risk factors for postoperative infectious complications of ulcerative colitis (UC). Moreover, many immunosuppressive therapies including some biologics are used mainly to treat UC, and many patients are on multi-agent immunosuppressive therapy at the time of surgery. Therefore, we evaluated the influence of pre-operative multiple immunosuppressive agents on the occurrence of surgical site infection (SSI) in UC during the era of biologics. METHODS: We reviewed surveillance data from 301 patients who underwent surgery between January 2015 and April 2018. The incidences of SSI and possible risk factors among patients receiving different immunosuppressive therapies were compared and analyzed. RESULTS: The incidence of incisional SSI was 6.6%, and that of organ/space SSI was 7.0%. Doses of corticosteroids were significantly decreased because of the recent shift toward the use of biologics. The types and numbers of immunosuppressive agents did not significantly correlate with each incidence. Age ≥ 65 years (odds ratio (OR) 3.0), total prednisolone dose ≥ 9000 mg (OR 2.7), and perioperative blood transfusion (OR 3.6) were shown to be independent risk factors for incisional SSI, whereas duration of surgery ≥ 252 min (OR 3.8), urgent/emergent surgery (OR 2.9), and perioperative blood transfusion (OR 2.6) were identified as independent risk factors for organ/space SSI. CONCLUSIONS: Although no correlation between pre-operative immunosuppressive therapies, except for corticosteroids, was found, selection bias may have occurred due to treatment before surgery. However, biologics, calcineurin inhibitors, and thiopurines did not affect surgical morbidity in UC.

[A Case of Sigmoid Colon Cancer with Distant Metastasis Successfully Treated with First-Line Cetuximab Monotherapy].

The patient was a 59-year-old woman with progressive sigmoid colon cancer with multiple metastasis(T3N2M1b[P2, H3, PUL2]Stage IV ). As the RAS gene in the patient was wild-type, we administered cetuximab monotherapy every week. One month after chemotherapy initiation, the tumor marker levels declined and the tumor size reduced. Patient's general condition was improved and mFOLFOX6 therapy was then continued in addition to cetuximab. As a side effect, acne-like rash is only grade 1 to 2, and there are no other serious side effects. Cetuximab monotherapy may contribute to the treatment of poor PS patients.

[Adjuvant Chemotherapy for Hemophilia B - A Case Report].

A 80s-year-old man with hemophilia B underwent operation for rectal cancer.Metastasis of the lymph nodes was revealed, so he was treated with adjuvant chemotherapy involving capecitabine and oxaliplatin(CapeOX).For safety, we measured tissue factor IX before every course of chemotherapy, and he completed 8 courses safely.

Complete Nucleotide Sequence of pKOI-34, an IncL/M Plasmid Carrying blaIMP-34 in Klebsiella oxytoca Isolated in Japan.

We determined the complete nucleotide sequence of a self-transmissible IncL/M plasmid, pKOI-34, from a Klebsiella oxytoca isolate. pKOI-34 possessed the core structure of an IncL/M plasmid found in Erwinia amylovora, pEL60, with two mobile elements inserted, a transposon carrying the arsenic resistance operon and a Tn21-like core module (tnp and mer modules) piggybacking blaIMP-34 as a class 1 integron, In808, where blaIMP-34 confers a resistance to carbapenems in K. oxytoca and Klebsiella pneumoniae.

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience].

BACKGROUND: Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan. METHODS: We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer.Between December 2014 and March 2016, 11 patients received nab-paclitaxel plus GEM as follows: nab-paclitaxel(125mg/m2 of body-surface area)followed by GEM(1,000mg/m2)on days 1, 8, and 15 every 4 weeks.The treatment was continued until disease progression, unacceptable adverse events, discontinuation as decided by the investigators, or patient refusal. RESULTS: The mean age was 65.6 years(range, 48-75 years), and 8 out of 11 patients were men.Ten patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0.Ten patients had metastatic disease.Only 4 patients had no prior therapy.The mean duration of treatment was 10.2 weeks(range, 2-41 weeks).The relative dose intensities of nab-paclitaxel and GEM were 90.6%(66.7-100%)and 87.5%(62.9-100%), respectively.The major Grade 3 or 4 hematological toxicities were leucopenia(54.5%), neutropenia(36.4%), anemia (27.3%), and thrombocytopenia(18.2%).The major grade 2 or 3 non-hematological toxicities were fatigue(45.6%), skin rash(27.3%), peripheral sensory neuropathy(9.1%), anorexia(9.1%), and stomatitis(9.1%).There were no treatmentrelated deaths.Interstitial lung disease was not observed.The 6 month progression-free and overall survival rate were 25.7% and 66.7%, respectively. The disease control rate was 90.9%(complete response, n=0; partial response, n=1; stable disease, n=9; progressive disease, n=1). CONCLUSIONS: Nab-paclitaxel plus GEM is well tolerated and associated with efficacy and improved survival outcomes.Nab -paclitaxel plus GEM can be the standard treatment for patients with metastatic pancreatic adenocarcinoma.

[A Case of Malignant Anorectal Melanoma with Laparoscopic Abdominoperineal Resection].

A 69-year-old man with anemia underwent colonoscopy. Colonoscopy showed a black tumor, 2 cm from the anal verge. The biopsy specimen revealed malignant melanoma, which was preoperatively diagnosed as T1(SM), N0, M0, Stage I . We performed laparoscopic abdominoperineal resection. The tissue type and diagnosis were malignant melanoma, pT1b(10 mm), pN0, pM0, ly0, v0, pDM0, pPM0, pRM0, pStage I b, according to the Colon Cancer Handling Terms, 8th edition). The patient did not receive adjuvant chemotherapy. However, he survived postoperatively for 9 months, with no sign of recurrence.

[Multiple Metachronal Liver Metastases from a Rectal Neuroendocrine Tumor Controlled by Repeated Transcatheter Arterial Chemoembolization].

A 60-year-old woman was diagnosed with a rectal neuroendocrine tumor(NET)with SM invasion.We performed laparoscopic low anterior resection with D3 lymph node dissection.Pathological findings were rectal NET, G1, pSM(9,000 mm), ly0, v0, pN0, PM0, DM0, pR0, pStage I .Four years and 6 months later, contrast enhanced abdominal computed tomography (CECT)and contrast enhanced magnetic resonance imaging revealed multiple liver metastases.The tumors were unresectable because they were bilobar; therefore, we performed transcatheter arterial chemoembolizaion(TACE).One month later, CECT showed the lesions had shrunk.The metastases were well controlled via repeated TACE.For unresectable liver metastases from rectal NET, TACE can be an effective treatment.