Super Carbonate Apatite-miR-497a-5p Complex Is a Promising Therapeutic Option against Inflammatory Bowel Disease.

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. It is reported that TGF-ß/Smad signal pathway is inactivated in patients with Crohn's disease by overexpression of Smad 7. With expectation of multiple molecular targeting by microRNAs (miRNAs), we currently attempted to identify certain miRNAs that activate TGF-ß/Smad signal pathway and aimed to prove in vivo therapeutic efficacy in mouse model. Through Smad binding element (SBE) reporter assays, we focused on miR-497a-5p. This miRNA is common between mouse and human species and enhanced the activity of TGF-ß/Smad signal pathway, decreased Smad 7 and/or increased phosphorylated Smad 3 expression in non-tumor cell line HEK293, colorectal cancer cell line HCT116 and mouse macrophage J774a.1 cells. MiR-497a-5p also suppressed the production of inflammatory cytokines TNF-α, IL-12p40, a subunit of IL-23, and IL-6 when J774a.1 cells were stimulated by lipopolysaccharides (LPS). In a long-term therapeutic model for mouse dextran sodium sulfate (DSS)-induced colitis, systemic delivery of miR-497a-5p load on super carbonate apatite (sCA) nanoparticle as a vehicle restored epithelial structure of the colonic mucosa and suppressed bowel inflammation compared with negative control miRNA treatment. Our data suggest that sCA-miR-497a-5p may potentially have a therapeutic ability against IBD although further investigation is essential.

Analgesic efficacy of modified thoracoabdominal nerves block through the perichondrial approach in laparoscopic cholecystectomy: A retrospective study with propensity analysis.

Modified thoracoabdominal nerves block through the perichondral approach (M-TAPA) was recently reported to provide broad analgesia with only a single injection of local anesthetics (LA) on each side. However, the effectiveness of M-TAPA in laparoscopic cholecystectomy (LC) is not often reported. We retrospectively evaluated the analgesic efficacy of M-TAPA in patients who underwent LC and compared it with conventional LA infiltration (LAI) by calculating the propensity score. The primary outcome was the frequency of analgesic use after surgery. Although there was no difference in the frequency of analgesic use within 48 hours (P = .063), there was significantly less analgesic use 24-48 hours after surgery in the TAPA group (P = .02). Intraoperative remifentanil administration also significantly decreased in the TAPA group (P < .001). We found that pre-incisional M-TAPA may have an advantage over LAI with respect to analgesia on postoperative day 1.

[A Resected Case of Mesenteric Nodal Metastases from Small Cell Lung Carcinoma].

A 65-year-old woman with small cell lung carcinoma(T2N2M0, Stage ⅢA)underwent chemoradiation therapy. During the follow-up study after the partial response of chemoradiation therapy, the serum level of ProGRP was elevated. X-ray computed tomography(CT)showed a 8 cm long mesenteric mass adjacent to ileocecal vessels, which indicated high level of standardized uptake value(SUV)max(12.6)by fluorodeoxyglucose-positron emission tomography/computed tomography( FDG-PET/CT). No gastrointestinal malignancy was observed. Mesenteric nodal metastasis from lung carcinoma was primarily diagnosed, however, possible malignant lymphoma was differentiated. Surgical resection was planned as a diagnostic treatment, thus laparoscopic ileocecal resection was performed. The resected specimen presented a fused mass of several lymph nodes. Histopathology found consistent with mesenteric nodal metastases from small cell lung carcinoma. After surgery, adjuvant chemotherapy was administered. Spontaneous metastasis in the mesenteric lymph node from lung cancer is extremely rare. A case report and a review of the literature is presented.

The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis.

The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis. RNA sequencing analysis revealed that miR-29a and miR-29b could inhibit the interferon-associated inflammatory cascade. Subcutaneous injection of sCA-miR-29b also potently inhibited inflammation, and it efficiently targeted CD11c+ dendritic cells (DCs) among various types of immune cells in the inflamed mucosa. RT-PCR analysis indicated that the miR-29 RNAs in CD11c+ DCs suppressed the production of interleukin-6 (IL-6), transforming growth factor ß (TGF-ß), and IL-23 subunits in DSS-treated mice. This may inhibit Th17 differentiation and subsequent activation, which is critical in IBD pathogenesis. In vivo experiments using a non-natural artificial microRNA sequence revealed that targeting of DCs in the inflamed colon is an exceptional feature of sCA. This study suggests that sCA-miR-29s may open a new avenue in nucleic acid-based medicine for IBD treatment.

Intraabdominal actinomycosis resulting in a difficult to diagnose intraperitoneal mass: A case report.

INTRODUCTION: Actinomycosis is a chronic suppurative granulomatous disease caused by Actinomyces israelii. Preoperative confirmed diagnosis is very difficult, so most cases are diagnosed preoperatively as malignant tumors. We report a case of intraabdominal actinomycosis which was difficult to diagnose preoperatively. PRESENTATION OF THE CASE: A woman, 60 years old, experienced discomfort in her lower right abdomen. She complained of nausea and anorexia and visited our hospital. Laboratory blood tests, abdominal CT, and abdominal MRI led to a diagnosis of a uterine sarcoma or primary intestinal mass, and she underwent surgery. Her histopathological diagnosis was intraabdominal actinomycosis. DISCUSSION: Actinomycosis is a chronic purulent granulomatous inflammation caused by Actinomyces israelii. No clinical symptoms or laboratory findings are characteristic of abdominal actinomycosis, so this disorder is very difficult to diagnose preoperatively. Therefore, many cases are diagnosed as malignant tumors and undergo surgery. After surgery, long-term antibiotic treatment (penicillin) is usually administered. CONCLUSIONS: We reported a case of intraabdominal actinomycosis that resulted in a difficult to diagnose intraperitoneal mass. When a large intraperitoneal mass is found, actinomycosis needs to be included as one of differential diagnoses.

[A Case of Complete Response to Lower Rectal Cancer after Preoperative Chemotherapy with CapeOX Therapy].

A 70 -year-old male patient was referred to our hospital with the chief complaint of hemafecia. Colonoscopy was performed and revealed bulky rectal cancer at 10 cm from the anal verge. After 4 courses of capecitabine plus oxaliplatin(Ca peOX)therapy as preoperative chemotherapy, colonoscopy and computed tomography(CT)revealed significant reduction of the tumor. We performed laparoscopic lower anterior resection and ileostomy. Histopathological examination revealed no residual tumor cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 1 year postoperatively.

CUBIC pathology: three-dimensional imaging for pathological diagnosis.

The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this conventional method has some limitations in x-y axes due to its relatively narrow range of observation area and in z-axis due to its two-dimensionality. In this study, we applied a CUBIC pipeline, which is the most powerful tissue-clearing and three-dimensional (3D)-imaging technique, to clinical pathology. CUBIC was applicable to 3D imaging of both normal and abnormal patient-derived, human lung and lymph node tissues. Notably, the combination of deparaffinization and CUBIC enabled 3D imaging of specimens derived from paraffin-embedded tissue blocks, allowing quantitative evaluation of nuclear and structural atypia of an archival malignant lymphoma tissue. Furthermore, to examine whether CUBIC can be applied to practical use in pathological diagnosis, we performed a histopathological screening of a lymph node metastasis based on CUBIC, which successfully improved the sensitivity in detecting minor metastatic carcinoma nodules in lymph nodes. Collectively, our results indicate that CUBIC significantly contributes to retrospective and prospective clinicopathological diagnosis, which might lead to the establishment of a novel field of medical science based on 3D histopathology.

Single-incision laparoscopically assisted appendectomy performed by residents is safe and feasible: A single institution, retrospective case series.

INTRODUCTION: To confirm the safety and feasibility of single-incision laparoscopically assisted appendectomy (SILA) performed by resident doctors. MATERIALS AND METHODS: We retrospectively analyzed 86 consecutive patients who underwent SILA between August 2010 and August 2016 at Kinki Central Hospital. During this period, 9 residents and 6 board-certified attending surgeons performed SILA. Data on the patients' characteristics and perioperative complications were collected from their medical records. RESULTS: Resident doctors operated on 55% (47/86) of patients undergoing SILA. There were no significant differences between the groups with regard to patient characteristics. Mean operative time in the resident and staff surgeon groups was 74 min and 71 min, respectively (p = 0.5). Median blood loss in both the resident and staff surgeon groups was 0 mL (p = 0.3). The rate of conversion to a different operative procedure was 4% (2/47) in the resident group and 3% (1/39) in the staff surgeon group (p = 1). All three above-mentioned procedures, two (4%, 2/47) in the resident group and one (3%, 1/39) in the staff surgeon group, were converted to multi-port laparoscopic appendectomy. The mean postoperative hospital stay was 5 days for both the resident and staff surgeon groups (p = 0.7). Perioperative complications developed in 9% (4/47) of the patients in the resident group and 21% (8/39) of the patients in the staff surgeon group (p = 0.1). CONCLUSIONS: SILA performed by residents under the guidance of a staff surgeon is safe and feasible.

[Eight Cases of Esophagus and Tracheobronchial Stenting for Advanced Esophageal Cancer].

Malignant stricture and fistula of the esophagus and tracheobronchus adversely affect the quality of life(QOL)in patients with advanced esophageal cancer. Stenting is one ofthe therapies available for these patients. We investigated the outcomes ofesophagus and tracheobronchial stenting in our institution. Eight patients with advanced esophageal cancer underwent double stenting from 2010 to 2016. Among them, 4 patients underwent double stenting as planned. One patient underwent an emergency tracheal stenting because ofstenosis ofthe trachea caused by esophageal stenting. Three patients underwent tracheobronchial stenting later on because ofan increase in the tumor size after esophageal stenting. Dysphagia score was improved in 5(67.5%)out ofthe 8 patients. Respiratory symptoms were improved in all patients, and 4 patients(50.0%) were discharged. The median survival time after esophageal stenting was 70.5 days. Esophagus and tracheobronchial stenting for advanced esophageal cancer was useful for the improvement of the QOL.

A resected case of medullary carcinoma of the ascending colon followed by infarction of the greater omentum mimicking anastomotic leakage.

INTRODUCTION: Medullary carcinoma is a rare type of colorectal adenocarcinoma, and omental infarction is a rare cause of acute abdomen. PRESENTATION OF CASE: A 72-year-old woman underwent single-incision laparoscopic right hemicolectomy for ascending colon cancer. Pathological examination showed a medullary carcinoma (MC) of T4aN0M0 Stage IIB. Her postoperative course was uneventful, and she was discharged on postoperative day (POD) 6. From POD 7, she suffered from fever, and she returned to the hospital on POD 9. Plain computed tomography showed free air beside the anastomotic site around the elevated density of fat tissue and gallbladder wall thickening with a gallstone. Suspecting anastomotic leakage with acute cholecystitis, probe laparotomy was performed. Intraoperative observation confirmed omental infarction with acute cholecystitis, and no leakage was found at the anastomotic site. Therefore, the necrotic part of the greater omentum was resected, and cholecystectomy was performed. She has remained well, with no evidence of recurrent cancer during the 12 months of follow-up without chemotherapy after the surgery for MC of the ascending colon. DISCUSSION: MC should be distinguished from other more aggressive, non-glandular tumors of the colon because MC appears to have a better survival outcome than undifferentiated colon adenocarcinoma. Omental infarction should be considered in the differential diagnosis of acute abdomen after surgery. CONCLUSION: A rare case of medullary carcinoma of the ascending colon followed by infarction of the greater omentum mimicking anastomotic leakage is presented.

[A Case of Recurrent Gastric Cancer with Recurrent Celiac Lymph Node Metastasis Successfully Treated with Chemoradiotherapy and CPT-11 plus CDDP Therapy].

Chemotherapy is performed for the recurrence of gastric cancer in many cases. We report a case of recurrent lymph node metastasis successfully treated with chemoradiotherapy and chemotherapy. A man in his 60s underwent total gastrectomy and D2 dissection in 2009. The pathological diagnosis was poorly differentiated adenocarcinoma, T4a, int, INF b, ly2, v2, LN#2: 2/3, #3: 1/4, #7, 8, and 9: 3/4, stage III B. Although we administered S-1/UFT as postoperative adjuvant chemotherapy, a strong rash appeared and the patient ceased chemotherapy. Eight months later, the rash had disappeared. We started chemotherapy with paclitaxel(PAC). CT performed 1 year postoperatively showed celiac lymph node(#9)metastasis. Chemoradiotherapy( RT+PAC)and additional CPT-11(98mg)and CDDP(49mg)treatment were administered. The lymph node (#9)was cicatrized after 8 cycles. Forty-two months after the end of treatment, the patient has had no recurrence. It is thought that chemoradiotherapy is an effective cure for local recurrence of gastric cancer.

[A Case of Small Intestinal Cancer Repeating an Ileus Symptom Complicated with Refractory Arrhythmia].

A 56-year-old man had been treated for hypertrophic cardiomyopathy since childhood. He had been treated for refractory ventricular tachycardia (VT) with interventricular septum cauterization, catheter ablation, and implantation of a defibrillator. He had been treated at home for several years. The ileus that developed in July 2014 was relieved by conservative medical treatment once, but it recurred after oral intake of food a short time later. The obstruction was due to a small intestine cancer that was diagnosed by enteroscopy. After considering the risks of surgery due to the cardiac problem and the quality of life due to ileus caused by the mass, we resected it. This surgery was not a radical resection because of peritoneal dissemination. He started oral food intake postoperatively, and returned to home care. Three months after surgery, oral chemotherapy was administered after considering his stable cardiac function in addition to his coherent mental status. An adverse event of severe watery diarrhea developed, and VT caused by dehydration occurred. After the chemotherapy was discontinued, he recovered in intensive care. He returned to home care at his prior status for 9 months postoperatively.

[A Case of Carcinosarcoma of the Esophagus Treated with Chemoradiotherapy].

Carcinosarcoma of the esophagus is a rare malignant neoplasm. We report a case of an 87-year-old man treated with chemoradiotherapy. The main presenting complaint was hiccups. Histological analysis of a biopsy from the tumor demonstrated a carcinosarcoma. The clinical diagnosis was T2N0M0, cStageⅡ. In consideration of his advanced age, a past history of cerebral infarction, high blood pressure, aortic valve sclerosis, and chronic renal failure (Cr 1.5-1.8 mg/dL), chemoradiotherapy consisting of TS-1 40 mg/day with radiotherapy of 66 Gy was administered to the patient. The carcinosarcoma decreased in size on endoscopic examination in response to the chemoradiotherapy. Surgery with extended lymphadenectomy for esophageal carcinosarcoma is the standard treatment, but chemotherapy may be a good choice for local control for patients who cannot undergo surgical resection.

[A case of resection of pancreatic head lymph node metastasis of rectal carcinoid].

An 80-year-old woman was treated with low anterior resection and D3 lymph node dissection for rectal carcinoid in August 2007. Pathological diagnosis was a tumor 23 × 22 mm in size with muscularis propria invasion, ly1, v0, n1 (No. 251[1/12]). Partial hepatectomy was performed for liver metastasis in March 2010 and September 2011. In June 2013, an isolated tumor of 17 mm in diameter was detected between the inferior vena cava and the stomach using abdominal ultrasonography. The tumor was diagnosed as pancreatic head lymph node metastasis using abdominal enhanced computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), and positron emission tomography (PET); fluorodeoxyglucose (FDG) uptake was noted at the site of the tumor, but not at other parts of the body. Curative resection was the chosen treatment option. Open surgery was performed in September 2013, and a tumor 30 mm in diameter located at the ventral side of the inferior vena cava, lateral side of the portal vein, and cranial side of duodenum was resected. No surrounding tissue infiltration was found. Pathological analysis of the resected specimen indicated lymph node metastasis of the rectal carcinoid. The patient has been disease free for 9 months after surgery.

[A case of gastric cancer with multiple liver metastases that was successfully treated by chemotherapy].

A man in his 60s received SP (S-1+CDDP) therapy for gastric cancer with multiple liver metastases. After completion of 3 courses, liver metastases had reduced significantly, and the paraaortic lymph nodes, which had swelled previously, had reduced in size. Furthermore, the serum carcinoembryonic antigen (CEA) level had also improved to the standard value from 814.3 ng/mL. The patient was able to discontinue the opioid he had needed for pain control. The chemotherapy was continued for 18 courses, with the dose reduced at the time of the adverse events along the way. By completion of the 18 courses, we recognized regrowth of the primary lesion and a rise in the serum CEA over the standard value. There was no sign of the regrowth of liver metastases and distant lymph nodes according to examinations for enhanced computed tomography (CT) and ¹8F-fluorodeoxyglucose positron-emission tomography (FDG-PET) CT.The patient received distal gastrectomy. The CEA level decreased in standard value or less after surgery and we believed the cancer was limited to the primary stomach lesion.