Increased Risk for CRC in Diabetic Patients with the Nonrisk Allele of SNPs at 8q24

Background

Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated.

Methods

A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures.

Results

Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06?C1.27, P?=?0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM.

Conclusions

We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.     

Use of computed tomography colonography to detect a synchronous early colorectal cancer in a patient with obstructive colorectal tumour

In patients with obstructive colorectal cancer, it is difficult to evaluate the oral site of the large bowel by colonoscopy. Instead of colonoscopy, previous studies have shown that computed tomography (CT) colonography is effective for detection of neoplastic lesions in the large bowel. In the present case, we carried out CT colonography and found superficial early cancer at the oral side of the obstructive cancer, and carried out surgical resection for both lesions. A 60‐year‐old man was admitted with complaints of abdominal pain and distension. Total colonoscopy could not be carried out because of the stricture of the lesion. To evaluate the proximal site of the large bowel, we carried out CT colonography, which showed a superficial lesion in the transverse colon suggestive of early cancer. He underwent surgery and an intraoperative colonoscopy of the transverse colon, which confirmed the findings of the CT colonography. The patient underwent R0 resection for both an advanced lesion and a superficial lesion. Pathological examination of the superficial lesion showed adenocarcinoma‐invading submucosa. The postoperative course was uneventful and the patient was discharged a week after the operation. The present case suggests the importance of CT colonography for patients with obstructive colorectal cancers to detect synchronous neoplastic lesions, including superficial early cancers.     

Role of uremic toxins and oxidative stress in the development of chronic kidney disease-mineral and bone disorder

The kidney plays an important role in the regulation of mineral metabolism. As kidney function declines, there is a progressive deterioration in mineral homeostasis, along with various abnormalities, including bone disease and vascular calcification, which has recently been named as "Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)." Although the precise mechanisms of this systemic disorder remain to be elucidated, accumulating evidence suggest that uremic toxins contribute substantially to the development of CKD-MBD, partly through evoking oxidative stress in the bone and cardiovascular systems. This brief review summarizes recent work on the role of uremic toxins and oxidative stress in the development of CKD-MBD.     

Single-incision multiport laparoendoscopic surgery using a newly developed short-type flexible endoscope: a combined procedure of flexible endoscopic and laparoscopic surgery

Background and objective

We hypothesized that using a flexible endoscope as a working scope in laparoscopic surgery through a single incision might provide many benefits. To this end, a short-type flexible endoscope with a working length of 600?mm was newly developed. In this animal experimental study, we aimed to evaluate the technical feasibility of our new approach, single-incision multiport laparoendoscopic (SIMPLE) cholecystectomy, using this endoscope.

Methods

Eight pigs were subjected to SIMPLE cholecystectomy using the short-type flexible endoscope. The endoscope was inserted through a 12-mm trocar in an SILS? Port followed by the insertion of two additional 5-mm trocars in the SILS? Port. Encirculation and ligation of the pedicle of the cystic artery and duct were carried out using laparoscopic instruments through the 5-mm trocars, while the dissection of the gallbladder from the intrahepatic fossa was predominantly performed using a cutting device through the endoscope.

Results

A complete gallbladder excision, with complete encirculation and ligation of the pedicle, was completed in all cases. The mean operating time was 58?min (range 34–78?min). The endoscope provided a good view of the operating field, and it allowed some degree of freedom to the working laparoscopic instruments without compromising the field of view. Dissection of the gallbladder using the cutting device through the endoscope was much easier than that using the laparoscopic device, because the articulating instruments together with the endoscope enabled operation with triangulation. Furthermore, the water-jet and suctioning functions and the self-cleaning lens capability of the endoscope served the surgery well.

Conclusions

SIMPLE cholecystectomy using the newly developed short-type flexible endoscope is a technically feasible procedure. Using this flexible endoscope for various tasks, such as resection, suctioning, and smoke evacuation, can make the surgical procedures easier.     

Clinical features of uveitis in elderly patients in central Tokyo (2013–2018)

International Ophthalmology - To clarify the clinical features of uveitis in elderly patients in central Tokyo. We retrospectively identified 1424 patients with uveitis who visited the Uveitis...     

Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes

Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets. Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored. Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs). Hepatic LN DCs preferentially produced CXCL10 to attract 5'-bromo-2'-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-gamma-producing CD4+ T cells by day 7 after antigen challenge. Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells. BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody. This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-gamma leading to exacerbation of liver injury. Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses.     

Systemic administration of liposome-encapsulated OK-432 prolongs the survival of rats with hepatocellular carcinoma through the induction of IFN-gamma-producing hepatic lymphocytes

BACKGROUND: OK-432 is known to increase the host antitumor response. We previously reported that systemic administration of OK-432 (OK-Lipo) specifically induced hepatic lymphocytes in mice. Here we aimed to investigate the antitumor effect of OK-Lipo on hepatocellular carcinomas (HCC) in experimental rats. METHODS: Diethylnitrosamine was administered for 12 weeks to all rats (n = 36). Rats were divided into three groups of 12 rats each. One group was injected with OK-Lipo from week 5 (OK-5w group) and another from week 9 (OK-9w group). A control group was injected with saline from week 5 (Non-OK group). At week 13, five rats from each group were used for histological analysis and immunofluorescence assays (surface phenotypic and intracellular cytokine analysis of the mononuclear cells in the liver, spleen and peripheral blood). The remaining rats were observed for the remainder of their survival period. RESULTS: The mean survival times of Non-OK, OK-5w, and OK-9w groups differed significantly (98.0 +/- 5.3 days, 116.0 +/- 5.8 days, and 106.0 +/- 5.4 days, respectively, P < 0.01). Histological examination revealed many apoptotic tumor cells, infiltration of lymphocytes and macrophages in the OK-5w group. The two-color immunofluorescence assay showed that the proportion of natural killer (NK) cells and IFN-gamma-producing cells in the liver were significantly higher in the OK-5w group. CONCLUSIONS: These findings showed that systemic administration of OK-Lipo contributed to prolonging the survival of rats with HCC. OK-Lipo induced NK cells and IFN-gamma-producing cells specifically in the liver and these cells seemed to reduce hepatocarcinogenesis and tumor growth.     

Conditional recurrence analysis of intrahepatic cholangiocarcinoma: Changes in recurrence rate and survival after recurrence resection by disease-free interval

Aim

The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC.

Methods

This study included patients who underwent hepatectomy for ICC during 1995–2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed.

Results

A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2 years after initial resection and 2.6% in patients free from recurrence at 4 years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11–0.40, p < 0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05–5.40, p = 0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95–1.00, p = 0.067) were significantly associated with longer OS after recurrence.

Conclusions

Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.