Usefulness of the one-step technique in functional end-to-end anastomosis for colonic surgery: results of a prospective multicentre cohort study from the Japanese KYCC group.

BACKGROUND: Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown. METHODS: This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade 2 or higher were assessed. RESULTS: Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade 3, two patients; grade 2) while the TS group had one case (1.0%) of grade 2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66). CONCLUSIONS: The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate. TRIAL REGISTRATION NUMBER: UMIN000039902 (registration date 23 March 2020).

Evaluation of vascular anatomy for colon cancer located in the splenic flexure using the preoperative three-dimensional computed tomography angiography with colonography.

PURPOSE: The aim of this study is to reveal the vascular branching variation in SFC (splenic flexure cancer) patients using the preoperative three-dimensional computed tomography angiography with colonography (3D-CTAC). METHODS: We retrospectively analyzed patients with SFC who underwent preoperative 3D-CTAC between January 2014 and December 2019. RESULTS: Among 1256 colorectal cancer (CRC) patients, 96 (7.6%) manifested SFC. The arterial branching from the superior mesenteric artery (SMA) was classified into five patterns, as follows: (type 1A) the left branch of middle colic artery (LMCA) diverged from middle colic artery (MCA) (N = 47, 49.0%); (2A) the LMCA diverged from the MCA and the accessory middle colic artery (AMCA) (N = 26, 27.1%); (3A) the LMCA independently diverged from the SMA (N = 16, 16.7%); (4A) the LMCA independently diverged from the SMA and AMCA (N = 3, 3.1%); (5A) only the AMCA and the LMCA was absent (N = 4, 4.1%). Venous drainage was classified into four patterns, as follows: (type 1V) the SFV flows into the inferior mesenteric vein (IMV) then back to the splenic vein (N = 50, 52.1%); (2V) the SFV flows into the IMV then back to the superior mesenteric vein (SMV) (N = 19, 19.8%); (type 3V) the SFV independently flows into the splenic vein (N = 3, 3.1%); (type 4V) the SFV is absent (N = 24, 25.0%). CONCLUSION: 3D-CTAC could reveal accurate preoperative tumor localization and vascular branching. These classifications should be helpful in performing accurate complete mesocolic excision and central vessel ligation for SFC.

Robotic-assisted multivisceral resection for rectal cancer: short-term outcomes at a single center.

BACKGROUND: The safety and feasibility of robotic-assisted multivisceral resection for locally advanced rectal cancer remain unclear. The aim of this study was to assess the short-term outcomes of this procedure at our institution. METHODS: From December 2011 to December 2016, patients who underwent robotic-assisted multivisceral resection for rectal cancer were investigated. Patient demographics, treatment characteristics, perioperative outcomes, and pathological results were evaluated retrospectively. RESULTS: There were 31 patients; 17 men (54.8%) and 14 women (45.2%), with a median age of 65 years (range 40-82 years). Twenty-one patients (67.7%) had a cT4 tumor, 9 patients (29.0%) had a pT4b tumor, and all patients except one (96.8%) underwent complete resection of the primary tumor with negative resection margins. Eleven patients (35.5%) received neoadjuvant chemoradiation. The most commonly resected organ was the vaginal wall (n = 12, 38.7%), followed by the prostate (n = 10, 32.3%). Lateral lymph node dissection was performed in 20 patients (64.5%). The median operative time was 394 min (range 189-549 min), and the median blood loss was 41 mL (range 0-502 mL). None of the patients received intraoperative blood transfusions or required conversion to open. Overall, postoperative complications occurred in 11 patients (35.5%). The most frequent complication was urinary retention (n = 5, 16.1%), and none of the patients developed serious complications classified as Clavien-Dindo grades III-V. CONCLUSIONS: Robotic-assisted multivisceral resection for rectal cancer is safe and technically feasible.

Carbazole angular dioxygenation and mineralization by bacteria isolated from hydrocarbon-contaminated tropical African soil.

Four bacterial strains isolated from hydrocarbon-contaminated soils in Lagos, Nigeria, displayed extensive degradation abilities on carbazole, an N-heterocyclic aromatic hydrocarbon. Physicochemical analyses of the sampling sites (ACPP, MWO, NESU) indicate gross pollution of the soils with a high hydrocarbon content (157,067.9 mg/kg) and presence of heavy metals. Phylogenetic analysis of the four strains indicated that they were identified as Achromobacter sp. strain SL1, Pseudomonas sp. strain SL4, Microbacterium esteraromaticum strain SL6, and Stenotrophomonas maltophilia strain BA. The rates of degradation of carbazole by the four isolates during 30 days of incubation were 0.057, 0.062, 0.036, and 0.050 mg L(-1) h(-1) for strains SL1, SL4, SL6, and BA. Gas chromatographic (GC) analyses of residual carbazole after 30 days of incubation revealed that 81.3, 85, 64.4, and 76 % of 50 mg l(-1) carbazole were degraded by strains SL1, SL4, SL6, and BA, respectively. GC-mass spectrometry and high-performance liquid chromatographic analyses of the extracts from the growing and resting cells of strains SL1, SL4, and SL6 cultured on carbazole showed detection of anthranilic acid and catechol while these metabolites were not detected in strain BA under the same conditions. This study has established for the first time carbazole angular dioxygenation and mineralization by isolates from African environment.

Influence of experimental oesophageal acidification on masseter muscle activity, cervicofacial behaviour and autonomic nervous activity in wakefulness.

Recent studies have been revealing the relationship between the stomatognathic system and the gastrointestinal tract. However, the effect of oesophageal acid stimulation on masticatory muscle activity during wakefulness has not been fully elucidated. To examine whether intra-oesophageal acidification induces masticatory muscle activity, a randomised trial was conducted investigating the effect of oesophageal acid infusion on masseter muscle activity, autonomic nervous system (ANS) activity and subjective symptoms. Polygraphic monitoring consisting of electromyography of the masseter muscle, electrocardiography and audio-video recording was performed in 15 healthy adult men, using three different 30-min interventions: (i) no infusion, (ii) intra-oesophageal saline infusion and (iii) intra-oesophageal infusion of acidic solution (0·1 N HCl; pH 1·2). This study was registered with the UMIN Clinical Trials Registry, UMIN000005350. Oesophageal acid stimulation significantly increased masseter muscle activity during wakefulness, especially when no behaviour was performed in the oro-facial region. Chest discomfort, including heartburn, also increased significantly after oesophageal acid stimulation; however, no significant correlation was observed between increased subjective symptoms and masseter muscle activity. Oesophageal acid infusion also altered ANS activity; a significant correlation was observed between masticatory muscle changes and parasympathetic nervous system activity. These findings suggest that oesophageal-derived ANS modulation induces masseter muscle activity, irrespective of the presence or absence of subjective gastrointestinal symptoms.

Global histone modification of H3K27 correlates with the outcomes in patients with metachronous liver metastasis of colorectal cancer.

BACKGROUND: We evaluated the methylation patterns of histone H3 lysine 27 (H3K27), H3 lysine 36 (H3K36) and the expression of H3K27 methylase EZH2 in patients with colorectal carcinomas with metachronous liver metastasis to search for biomarkers identifying these patients. METHODS: Double 2-mm core tissue microarrays were made from 54 paraffin-embedded samples of primary colorectal adenocarcinomas and corresponding liver metastases and examined using an immunohistochemical analysis of dimethylation and trimethylation in H3K27, H3K36 and EZH2. Positive tumor cell staining for each histone modification (H-score) was used to classify patients into low- and high-staining groups, which were then examined to identify any correlations between the clinicopathological parameters and the clinical outcomes. RESULTS: The H-scores of H3K27me2 were lower in the liver metastases than in the corresponding primary tumors, while the H-scores of H3K36me2 were higher in the liver metastases than in the corresponding primary tumors (P < 0.001). H3K27me2 in the primary tumors correlated with tumor size (P = 0.016), H3K36me2 in the primary tumors correlated with histological type (P = 0.038), and H3K36me3 in the primary tumors correlated with lymph node metastasis (P = 0.017). In addition, lower levels of H3K27me2 in the primary tumors correlated with poorer survival rates (P = 0.039). The multivariate survival analysis showed that the H3K27me2 status is an independent prognostic factor for colorectal cancer patients (P = 0.047). CONCLUSIONS: Our findings suggest that the methylation level of H3K27me2 detected with immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.

Does the trace element composition of brown trout Salmo trutta eggs remain unchanged in spawning redds?

The temporal stability of trace element concentrations in fertilized, artificially incubated anadromous brown trout Salmo trutta eggs and newly hatched fry was investigated. The anadromous status of the parental fish was confirmed using strontium isotopic analysis of otoliths. Whilst manganese concentrations in eggs varied over time, concentrations of aluminium, potassium, magnesium, strontium, barium and calcium were all unchanged 1 week and 6 weeks post-fertilization as well as in recently hatched larvae. The results clearly suggest that the distinctive trace element signature present in the eggs and newly hatched larvae of anadromous S. trutta (typically characterized by high strontium, low barium) is stable over time. Therefore analysis of the trace element composition of eggs is concluded to be a cost-effective and reliable method for determining the spatial and temporal extent of upstream spawning migration by anadromous salmonids. The temporal variability of at least one element in this study suggests the stability of untested multi-element signatures cannot automatically be assumed.

The cellular level of histone H3 lysine 4 dimethylation correlates with response to adjuvant gemcitabine in Japanese pancreatic cancer patients treated with surgery.

BACKGROUND: To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. METHODS: Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. RESULTS: High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type (p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion (p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine (p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival (p = 0.007). CONCLUSION: H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.

[Experience of chest wall reconstruction with newly developed material].

After the chest wall resection, its reconstruction is often needed. A 45-year-old male lung adenocarcinoma patient with chest wall invasion underwent upper lobectomy of the right lung with partial resection of 4-6th ribs. The size of the removed chest wall was 11 x 6.5 cm. We reconstructed the chest wall with Bard Composix E/X Mesh. This prosthesis is consisted of a polypropylene mesh and an expanded polytetrafluoroethylene sheet This material is seems to be useful in the reconstruction of chest wall in both preventing pulmonary adhesion and enabling good wound healing.

Effects of early intervention with inhaled sodium cromoglycate in childhood asthma.

International and Japanese guidelines classify childhood asthma as mild, moderate, or severe, and recommend treatment with "as needed" bronchodilators, inhaled sodium cromoglycate, and inhaled corticosteroids, respectively. Alternatively, some investigators proposed inhaled corticosteroids as first-line therapy to prevent airway inflammatory obstruction. This article describes a clinical study assessing the effect of early intervention with inhaled sodium cromoglycate in childhood asthma. This was a retrospective study of 189 asthmatic children treated with inhaled sodium cromoglycate for five years and whose age of onset of asthma was six year of age or younger. An end-of-study questionnaire completed the examination. Children administered oral or inhaled corticosteroids simultaneously with sodium cromoglycate, were excluded. Asthma scores as defined by the Japanese Pediatric Allergic Committee, were reduced continuously during the five years after the start of sodium cromoglycate treatment. The frequency of emergency department visits and hospitalizations also decreased. Significant between-period intervention differences showed improvement of clinical outcomes for children with severe asthma during the five years of sodium cromoglycate inhalation. The early intervention regime of starting sodium cromoglycate inhalation within two years of the onset of asthma shows a large improvement in the long-term prognosis of childhood asthma, especially for children with severe asthma. It is possible that starting inhaled sodium cromoglycate earlier than the present recommendation of corticosteroids could further improve clinical outcomes, but a prospective study should be performed to verify our results.

Possible pathologic involvement of receptor for advanced glycation end products (RAGE) for development of encapsulating peritoneal sclerosis in Japanese CAPD patients.

Encapsulating peritoneal sclerosis (EPS) is a serious complication of PD. The cause(s) of EPS are unknown but may include peritonitis and long duration of PD treatment. However, EPS may also develop in some patients without a history of peritonitis or with rather short duration of PD therapy. It has been suggested that an increasing peritoneal solute transport rate (PSTR) as a function of time on PD treatment is a risk factor for EPS development after transfer to hemodialysis, and that high PSTR is associated with an increased peritoneal microvessels surface area. Other putative mechanisms might include advanced glycated end products (AGE) and their receptors, RAGE. The purpose of this study was to investigate genetic variations in PD patients developing EPS in comparison to PD patients without EPS. SNPs in genes related to angiogenesis as well as RAGE were analyzed. Twenty patients (M/F: 12/8, mean age at start of PD 42.2 years, mean duration of PD 8.4 years) who were diagnosed as EPS during the period 1982 - 2002 at Jikei University Hospital and a matched control group (n = 20) of nonEPS PD patients were studied. The following 5 SNPs were analyzed: VEGF 936 C/T, ecNOS -786 T/C, 298 Glu/Asp, and RAGE -374 T/A, and -429 T/C. The SNPs were analyzed by the pyrosequencing method. The C allele (T/C and C/C) in the RAGE -429T/C genotype was not found in any of the EPS patients (EPS, T/T: 20/20 (100%), nonEPS, T/T: 15/20 (75%), T/C: 4/20 (20%), C/C: 1/2 0(5%), nonC allele vs C allele, p = 0.013), although every allele was found in other SNPs. We conclude that these preliminary data show that whereas genotypes directly related to angiogenesis did not differ between EPS and nonEPS patients, it is noteworthy that no patients in the EPS group had a C allele in the RAGE -429T/C genotype. This might indicate a possible genetic contribution to the development of EPS that is related to RAGE.

Bone growth oscillation: longitudinal metabolic process of bone growth in congenital adrenal hyperplasia and nonendocrine short stature.

To clarify the longitudinal metabolic process of bone growth in children, we observed the relationship between the level of serum osteocalcin (OC), a marker of bone metabolism, and growth velocity in 10 prepubertal patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and 9 prepubertal patients with nonendocrine short stature (NESS), but no major hormonal abnormalities influencing bone metabolism. Observations were made every 6 months over a 7-year period. In patients with CAH who exhibited a wide variation in growth velocity during the course of the investigation, the levels of OC fluctuated over a wide range, suggesting metabolically variable bone growth. In contrast, in patients with NESS who exhibited a relatively stable growth velocity, the OC level remained within a narrow range, suggesting metabolically stable bone growth. The meaning of such divergent metabolic processes of bone growth observed in CAH and NESS and its relationship to actual bone structure or bone intensity should be further investigated.

Sodium sulfite and N-acetylcysteine: new additives to dialysate for inhibiting formation of glucose degradation products and advanced glycation end-products.

The present study evaluated the inhibiting effect of various chemicals on the advanced glycation end-product (AGEs) cross-linking caused in protein by glucose degradation products (GDPs). We evaluated a few dozen organic and inorganic chemicals--in addition to previously reported AGE inhibitors, such as thiazolium derivatives and aminoguanidine--for their inhibiting effect. Collagen IV (from human placenta) or human serum albumin (HSA) was incubated with an AGE accelerator and one of the selected chemicals in phosphate buffer solution at 37 degrees C for as long as 14 days. Fluorescence intensity (440 nm) was determined after a given incubation time. Among 36 chemicals tested, 8 new chemicals and 5 previously known AGE inhibitors significantly suppressed the increase in fluorescence intensity seen after incubation of HSA with methylglyoxal. We believe that 6 chemicals may effectively quench GDPs and inhibit AGE cross-link formation, in a manner different from that of aminoguanidine and thiazolium.

Systemic effects of transdermal testosterone for the treatment of microphallus in children.

OBJECTIVES: To elucidate the metabolic effects of topical testosterone for the treatment of microphallus in children. METHODS: We administered 5% testosterone ointment to 50 prepubertal boys for the treatment of microphallus, allowing us to observe its metabolic effect on plasma concentrations of testosterone as a marker of transdermally absorbed testosterone, insulin-like growth factor (IGF)-I as a marker of growth hormone secretion status, and osteocalcin as a marker of bone metabolic turnover. RESULTS: Transdermal application of testosterone for 30 days at a dose that affects penile growth increased mean (+/-SD) plasma testosterone concentrations from 7.5+/-5.1 to 31.0+/-8.2 ng/dL (pre- vs. post-treatment, respectively; P<0.01). This was associated with a slight but statistically significant elevation of IGF-I concentrations (117.2+/-76.9 vs. 154.4+/-81.5 ng/mL; P<0.05). No significant change in osteocalcin levels was found. CONCLUSIONS: When using testosterone ointment as a treatment for microphallus, it should be borne in mind that this application has systemic effects.

Preliminary report: effect of adrenal androgen and estrogen on bone maturation and bone mineral density.

To clarify the independent physiological roles of adrenal androgen and estrogen on bone growth, we compared the lumbar spine bone mineral density (BMD) in prepubertal girls with virilizing congenital adrenal hyperplasia (CAH) (n = 17) and girls with central precocious puberty (CPP) (n = 18). When BMD was analyzed according to chronologic age, no significant differences were found between CPP and CAH patients. However, when adjusted to bone age, BMD was statistically higher in CAH than in CPP subjects. This finding suggests that adrenal androgen, as well as estrogen, plays an important role in increasing BMD. Adrenal androgen may act on bone not only as androgen, but as estrogen after having been metabolized into an aromatized bone-active compound in peripheral tissues, such as bone and fat. Therefore, adrenal androgen may have a more important role in increasing BMD than previously realized.

Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network.

The luminal pH of organelles along the secretory and endocytic pathways of mammalian cells is acidic and tightly regulated, with the [H+] varying up to 100-fold between compartments. Steady-state organellar pH is thought to reflect a balance between the rates of H+ pumping by the vacuolar-type H+-ATPase and H+ efflux through ill-defined pathways. Here, we describe the cloning of a novel gene (NHE7) in humans that is homologous to Na+/H+ exchangers, is ubiquitously expressed, and localizes predominantly to the trans-Golgi network. Significantly, NHE7 mediates the influx of Na+ or K+ in exchange for H+. The activity of NHE7 was also found to be relatively insensitive to inhibition by amiloride but could be antagonized by the analogue benzamil and the unrelated compound quinine. Thus, NHE7 displays unique functional and pharmacological properties and may play an important role in maintaining cation homeostasis of this important organelle.