Nobuki Ichikawa

A novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice

BACKGROUND In inflammatory bowel disease (IBD), gut inflammation is associated with the activation of nuclear factor kappa B (NF-κB), a key pro-inflammatory transcription factor. AIM To investigate the therapeutic potential of a novel, specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), we examined its effect on IBD using murine experimental colitis models. METHODS The in vitro effect of DHMEQ was evaluated by inflammatory cytokine production and p65 immunostaining using HT-29 and RAW264.7 cells. The in vivo therapeutic effect of DHMEQ was studied in colitis induced by dextran sulphate sodium (DSS) and trinitrobenzenesulphonic acid (TNBS). In these, progression and severity of colitis was mainly assessed by the disease activity index (DAI), histopathology, cellular infiltration, and mRNA expression levels of pro-inflammatory cytokines in the colonic tissues. RESULTS In RAW264.7 cells, DHMEQ significantly inhibited tumour necrosis factor (TNF)-α and interleukin (IL)-6 production induced by LPS in a dose-dependent manner by blocking the nuclear translocation of NF-κB. In addition, DHMEQ inhibited IL-8 production induced by LPS in HT-29 cells. DHMEQ significantly ameliorated DSS colitis as assessed by DAI scores, colonic oedema, and histological scores. Immunohistochemistry revealed that DHMEQ inhibited colonic infiltration of nuclear p65(+) cells, CD4(+) lymphocytes, and F4/80(+) macrophages. mRNA expression levels of the pro-inflammatory cytokines, such as IL-1β, TNF-α, IL-6, IL-12p40, IL-17, and MCP-1 were also suppressed by DHMEQ administration. Furthermore, DHMEQ significantly ameliorated TNBS colitis as assessed by body-weight changes and histological scores. CONCLUSION DHMEQ ameliorated experimental colitis in mice. These results indicate that DHMEQ appears to be an attractive therapeutic agent for IBD.

Laparoscopic total gastrectomy for advanced gastric cancer in a patient with situs inversus totalis

Situs inversus totalis (SIT) is a rare congenital anomaly. Generally, laparoscopic surgery is difficult to perform in patients with SIT because of both the potential challenges associated with unexpected vascular anomalies and the lack of standardized strategy for handling such cases. This is the first report of laparoscopic total gastrectomy with lymph node dissection for advanced gastric cancer in a patient with SIT. A 79‐year‐old man with SIT was diagnosed with advanced gastric cancer. We performed laparoscopic total gastrectomy with modified D2 lymph node dissection (D2 without splenectomy) and esophagojejunal anastomosis using an overlap method involving retrocolic Roux‐en‐Y reconstruction. The total operating time was 232 min, and blood loss was 110 mL. There were no postoperative complications. In summary, laparoscopic total gastrectomy for gastric cancer can be performed safely, even in a patient with SIT.

Usefulness of PET/CT for early detection of internal malignancies in patients with Muir-Torre syndrome : report of two cases

BackgroundMuir–Torre syndrome (MTS) is a rare autosomal dominant genodermatosis caused by mutations in mismatch repair genes. It is characterized by the presence of at least one sebaceous skin tumor associated with internal malignancies. Whether positron emission tomography/computed tomography (PET/CT) is useful for the detection of malignancies in patients with MTS has not been determined. We herein report two cases in which PET/CT was useful for the diagnosis and follow-up of internal malignancies in patients with MTS.Case presentationIn case 1, a 57-year-old woman underwent excision of a sebaceous carcinoma on the left upper eyelid. She underwent follow-up PET/CT once yearly thereafter. Forty-two months after the eyelid surgery, PET/CT showed intense tracer uptake in the right lower abdomen. An ascending colon tumor was identified, and examination of a biopsy specimen showed adenocarcinoma. In case 2, a 77-year-old man presented for evaluation of three continuous papules with telangiectasia on his right cheek. Examination of a skin biopsy specimen of the cheek papule revealed a sebaceous carcinoma. He underwent PET/CT to detect other malignancies. PET/CT showed intense tracer uptake in the sigmoid colon. A sigmoid colon tumor was identified, and examination of a biopsy specimen showed adenocarcinoma. Both patients underwent resection of their tumors, and both were still free of recurrence of the sebaceous and colon carcinomas at the time of this writing.ConclusionPET/CT is a reliable imaging modality for the detection of internal malignancies and is useful for the diagnosis and follow-up of MTS.

Carcinoma in the residual rectum of a long‑standing Crohn's disease patient following subtotal colectomy: A case report

The development of colorectal cancer in long-standing Crohns disease (CD) patients has become a major complication. Therapeutic guidelines for CD-associated cancer (CDAC) have already been established in Western countries; however, specific guidelines are not currently available in Japan. Surveillance of the residual intestine for cancer screening is important for long-standing CD patients. The present case report describes the occurrence of rectal carcinoma in a patient with a 25-year history of CD. A 37-year-old male with a 17-year history of CD underwent semi-emergent subtotal colectomy and ileostomy for bowel obstruction secondary to the transverse colon stenosis, and multiple severe stenosis and inflammation. Postoperatively, the patient resumed pharmacological treatment and underwent follow-up colonoscopies at ~1-2-year intervals. Despite continued pharmacological treatment, inflammation continued in the residual rectum. A total of 8 years following the primary operation, colonoscopy revealed inflammatory polyposis at the remnant rectum, which was diagnosed as adenocarcinoma. The interval between the last colonoscopy was 16 months. The patient then underwent laparoscopic abdominoperineal resection, and remained without recurrence for 12 months following resection. Thus, in long-standing CD patients, annual colonoscopy of the residual intestine may be considered for cancer screening, and specific surveillance guidelines for CDAC should be established.

Mentor Tutoring: An Efficient Method for Teaching Laparoscopic Colorectal Surgical Skills in a General Hospital

Objective: We retrospectively assessed the efficacy of our mentor tutoring system for teaching laparoscopic colorectal surgical skills in a general hospital. Materials and Methods: A series of 55 laparoscopic colectomies performed by 1 trainee were evaluated. Next, the learning curves for high anterior resection performed by the trainee (n=20) were compared with those of a self-trained surgeon (n=19). Results: Cumulative sum analysis and multivariate regression analyses showed that 38 completed cases were needed to reduce the operative time. In high anterior resection, the mean operative times were significantly shorter after the seventh average for the tutored surgeon compared with that for the self-trained surgeon. In cumulative sum charting, the curve reached a plateau by the seventh case for the tutored surgeon, but continued to increase for the self-trained surgeon. Conclusions: Mentor tutoring effectively teaches laparoscopic colorectal surgical skills in a general hospital setting.

The Balance Between Surgical Resident Education and Patient Safety in Laparoscopic Colorectal Surgery: Surgical Resident’s Performance has No Negative Impact

Objective: This study aimed to evaluate the feasibility and effectiveness of a comprehensive theoretical and hands-on training program in performing laparoscopic colonic resections under supervision of an expert surgeon. Materials and Methods: Laparoscopic right colectomy was performed in 78 patients (10 with benign disease, 68 with carcinoma). Demographic, intraoperative, pathologic examination, and short-term outcome data were retrospectively compared between 25 patients operated by surgical residents (R group) and 53 patients operated by senior surgeons (S group). The residents who performed surgeries in the R group had between 1 and 6 years after graduation; no experience with open or laparoscopic colorectal surgery was necessary. The residents completed a training program under supervision of a single expert laparoscopic colorectal surgeon, which included 6 steps, from basic skills to certification. Results: There were no differences in patient age, sex, and body mass index between the R and S groups. Significantly more patients in the R group had early cancer and benign lesions (P<0.05). Thirteen of the 16 residents (81.2 %) had not had prior experience with colonic resection. The time of suturing and knot tying in the dry box did not differ between residents and senior surgeons (68 and 69 s, respectively). All the residents performed laparoscopic right colectomy without intraoperative complications. There were no significant differences in operating time (R group: 173±34 min, S group: 172±52 min), mean estimated blood loss (50±111 vs. 49±100 mL), number of lymph nodes dissected (20.8±12.8 vs. 17.1±9.0), and mean postoperative hospital stay (9.1±3.3 vs. 10.7±4.1 d). On the basis of the year of their residency period, all 3 residents at 6 years after graduation had far greater experience than the other residents and therefore performed the surgery with minor verbal support from the expert. However, residents with 1 or 2 years after graduation had to receive guidance provision by the expert during surgery. Conclusions: When supervised and led by an expert laparoscopic surgeon, surgical residents are capable of performing laparoscopic surgery without negative effects on outcomes.

Two cases of melanomas paradoxically metastasizing to the intestinal tract during nivolumab therapy

We report two cases of melanomas in patients who developed intestinal metastasis despite other metastatic sites responding to nivolumab and despite the patients having favorable findings such as vitiligo and normal lactate dehydrogenase. The first case is an 85‐year‐old man who had been administrated nivolumab for lung/cutaneous metastases. After 22 courses of nivolumab therapy, fever and anorexia had appeared and his bodyweight had decreased. An intussusception on the ileocecal valve was revealed by computed tomography, and emergency surgery revealed metastatic lesions on the colon. The second case is an 87‐year‐old woman treated with nivolumab for lymph node metastases. After 10 courses, laboratory tests had revealed anemia and positive fecal occult blood. Her bodyweight had decreased. Capsule endoscopy showed scattered tumors and clots, indicating metastases of melanoma. The frequency of symptomatic intestinal metastasis of melanoma is very low. Further, intestinal metastasis of melanoma is difficult to detect through routine examinations. Our cases suggest that fecal occult blood test and decreased bodyweight are indications of intestinal metastases.

Safety of Laparoscopic Colorectal Resection in Patients With Severe Comorbidities

We aimed to assess the safety of laparoscopic colorectal resection in patients with severe comorbidities. High operative risk was defined as an American Society of Anesthesiologists (ASA) class 3 score. Outcomes in 34 patients with an ASA score of 3 undergoing laparoscopic surgery (LAP3) were compared with 172 laparoscopic surgery patients with an ASA score ⩽2 (LAP2) and 32 laparotomy patients with an ASA score of 3 (OP3). The postoperative complication rate in LAP3 was similar to that seen in LAP2 and significantly lower than that seen in OP3 (LAP2, 4.0%; LAP3, 5.9%; OP3, 31.2%). The incidence of postoperative hemorrhage, infection, ileus, and anastomotic leakage was similar between LAP3 and LAP2 and between LAP3 and OP3. However, the systemic complication rate in LAP3 was similar to that seen in LAP2 and significantly lower than that seen in OP3. Laparoscopic colorectal resection can be performed safely in patients with severe comorbidities.

Advanced technique of reduced-port laparoscopic total gastrectomy for gastric cancer

We started reduced-port laparoscopic gastrectomy (RPG) through an umbilical multichannel port and an additional port [dual-port laparoscopic gastrectomy (DP-LG)] for gastric cancer in December 2009, and accumulated experience of 100 cases. In the DP-LG group, 79 patients underwent DP-laparoscopic distal gastrectomy and 21 underwent DP-laparoscopic total gastrectomy (DP-LTG). In this report, we explained our methods and devices of DP-LTG, which is the most difficult procedure in the field of PRGs. Patients were placed in Fowler’s position with legs abducted. A SILS™ port (Covidien Japan Inc, Tokyo, Japan) was inserted into an umbilical incision, while another 5-mm port was inserted in the right flank region. A 5-mm flexible scope was inserted through the 5-mm trocar at the extreme caudal position of the SILS™ port. The surgeon used two trocars in the SILS™ port to manipulate the greater curvature side of the stomach, or one trocar in the SILS™ port and another in the right flank port to manipulate the other side. The surgeon stood between the patient’s legs in the former situation and on the right side of the patient in the latter. The assistant used the remaining trocar to provide support.

A Novel Anti-Inflammatory Agent, 3-[(Dodecylthiocarbonyl)-Methyl]-Glutarimide, Ameliorates Murine Models of Inflammatory Bowel Disease

Objective and design To examine the effect of 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G), a novel anti-inflammatory agent that inhibits lipopolysaccharide (LPS) activation of RAW264.7 macrophages, on murine models of colitis and RAW264.7 cells.