Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Recruitment of Peroxin 14 to lipid droplets affects lipid storage in Drosophila.

Both peroxisomes and lipid droplets regulate cellular lipid homeostasis. Direct inter-organellar contacts as well as novel roles for proteins associated with peroxisome or lipid droplets occur when cells are induced to liberate fatty acids from lipid droplets. We have shown a non-canonical role for a subset of peroxisome-assembly [Peroxin (Pex)] proteins in this process in Drosophila. Transmembrane proteins Pex3, Pex13 and Pex14 were observed to surround newly formed lipid droplets. Trafficking of Pex14 to lipid droplets was enhanced by loss of Pex19, which directs insertion of transmembrane proteins like Pex14 into the peroxisome bilayer membrane. Accumulation of Pex14 around lipid droplets did not induce changes to peroxisome size or number, and co-recruitment of the remaining Peroxins was not needed to assemble peroxisomes observed. Increasing the relative level of Pex14 surrounding lipid droplets affected the recruitment of Hsl lipase. Fat body-specific reduction of these lipid droplet-associated Peroxins caused a unique effect on larval fat body development and affected their survival on lipid-enriched or minimal diets. This revealed a heretofore unknown function for a subset of Pex proteins in regulating lipid storage. This article has an associated First Person interview with Kazuki Ueda, joint first author of the paper.

The usefulness of the endoscopic surgical skill qualification system in laparoscopic right hemicolectomy: a single-center, retrospective analysis with propensity score matching.

PURPOSE: Recently, a new certification system called the Endoscopic Surgical Skill Qualification System (ESSQS) has been launched in Japan to improve surgical safety. This study aimed to determine whether ESSQS-qualified surgeons affect the short- and long-term outcomes of laparoscopic right hemicolectomy. METHODS: A total of 187 colon cancer patients who underwent laparoscopic right hemicolectomy at Kindai University Hospital between January 2016 and December 2020 were enrolled. These patients were divided into two groups based on surgeries performed by ESSQS-qualified surgeons (QS group) and non-ESSQS-qualified surgeons (NQS group). The short- and long-term outcomes were compared between the two groups before and after propensity score matching (PSM). RESULTS: After PSM, 43 patients from each group were included in the matched cohort. In the short-term outcomes, the total operative time was significantly longer in the NQS group than in the QS group (229 vs. 174 min, p < 0.0001). However, there were no significant differences in the two groups regarding blood loss (0 vs. 0 ml, p = 0.7126), conversion (0.0% vs. 7.0%, p = 0.0779), Clavien-Dindo ≥ 2 complications (9.3% vs. 7.0%, p = 0.6933), mortality (2.3% vs. 0.0%, p = 0.3145), and postoperative hospital stay (9 vs. 9 days, p = 0.5357). In the long-term outcomes, there were no significant differences between the two groups in the 3-year overall survival (86.6% vs. 83.0%, p = 0.8361) and recurrence-free survival (61.7% vs. 72.0%, p = 0.3394). CONCLUSION: Laparoscopic right hemicolectomy performed by ESSQS-qualified surgeons contributed to shorter operative time. Under the supervision of ESSQS-qualified surgeons, almost equivalent safety and oncological outcomes are expected even in surgeries performed by non-ESSQS-qualified surgeons.

Lymphatic flow mapping during colon cancer surgery using indocyanine green fluorescence imaging.

With the development of surgical technology, indocyanine green (ICG) fluorescence navigation systems may be useful in various areas of colorectal surgery, including tumor location confirmation, bowel perfusion, ureter identification, and lymph node mapping. This review provides an overview of the current status of ICG-based navigation surgery in colorectal surgery, emphasizing its role in lymphatic flow mapping. This state-of-the-art approach will allow for appropriate oncological surgeries in the field of colorectal cancer and improve the patient's prognosis.

A Highly Conductive n-Type Coordination Complex with Thieno[3,2-b]thiophene Units: Facile Synthesis, Orientation, and Thermoelectric Properties.

An organometallic nickel complex containing thieno[3,2-b]thiophene units was designed and synthesized. Composite films of the resulting nickel complex and polyvinylidene difluoride, which can be fabricated via a simple solution process under atmospheric conditions, exhibit remarkably high n-type conductivity (>200 S cm-1). Moreover, the thermoelectric power factor of the n-type composite film was proven to be air stable. A grazing-incidence wide-angle X-ray diffraction analysis indicated a significant impact of introducing the thieno[3,2-b]thiophene core into the backbone of the nickel complex on the orientation within the composite films.

Laparoscopic complete mesocolic excision with central vascular ligation for splenic flexure colon cancer: short- and long-term outcomes.

BACKGROUND: Complete mesocolic excision (CME) with central vascular ligation (CVL) for colon cancer is an essential procedure for improved oncologic outcomes after surgery. Laparoscopic surgery for splenic flexure colon cancer was recently adopted due to a greater understanding of surgical anatomy and improvements in surgical techniques and innovative surgical devices. METHODS: We retrospectively analyzed the data of patients with splenic flexure colon cancer who underwent laparoscopic CME with CVL at our institution between January 2005 and December 2017. RESULTS: Forty-five patients (4.8%) were enrolled in this study. Laparoscopic CME with CVL was successfully performed in all patients. The median operative time was 178 min, and the median estimated blood loss was 20 g. Perioperative complications developed in 6 patients (13.3%). The median postoperative hospital stay was 9 days. According to the pathological report, the median number of harvested lymph nodes was 15, and lymph node metastasis developed in 14 patients (31.1%). No metastasis was observed at the root of the middle colic artery or the inferior mesenteric artery. The median follow-up period was 49 months. The cumulative 5-year overall survival and disease-free survival rates were 85.9% and 84.7%, respectively. The cancer-specific survival rate in stage I-III patients was 92.7%. Recurrence was observed in 5 patients (11.1%), including three patients with peritoneal dissemination and two patients with distant metastasis. CONCLUSIONS: Laparoscopic CME with CVL for splenic flexure colon cancer appears to be oncologically safe and feasible based on the short- and long-term outcomes in our study. However, it is careful to introduce this procedure to necessitate the anatomical understandings and surgeon's skill. The appropriate indications must be established with more case registries because our experience is limited.

The technique for less infectious and earlier healing of stoma closure wound: negative pressure wound therapy with instillation and dwelling followed by primary closure.

BACKGROUND: Temporary stomas have been widely used to avoid the risk of complications such as anastomotic leakage after colorectal resection. Stoma closure is relatively easy; however, postoperative surgical site infection (SSI) may be a problem. Various methods have been used to reduce the incidence of SSI. We aimed to evaluate a new technique for stoma wound closure. METHODS: We enrolled patients who underwent stoma closure at our hospital between September 2019 and May 2020. We selected patients who lived far from our hospital and had difficulty visiting the hospital regularly and who agreed to undergo this surgical technique. We used negative pressure wound therapy with instillation and dwelling (NPWTi-d) and delayed primary closure for these patients. RESULTS: Four patients underwent NPWTi-d and delayed primary closure without the occurrence of SSI. The median postoperative hospital stay was 9 days (range: 7-14 days), and the median number of days to confirmation of epithelialization was 11.5 days (range: 10-16 days). CONCLUSION: The combined use of NPWTi-d and delayed primary closure for the stoma wound was very effective. This method may be a valuable new technique for wound management after stoma closure.

MYB transcription factor gene involved in sex determination in Asparagus officinalis.

Dioecy is a plant mating system in which individuals of a species are either male or female. Although many flowering plants evolved independently from hermaphroditism to dioecy, the molecular mechanism underlying this transition remains largely unknown. Sex determination in the dioecious plant Asparagus officinalis is controlled by X and Y chromosomes; the male and female karyotypes are XY and XX, respectively. Transcriptome analysis of A. officinalis buds showed that a MYB-like gene, Male Specific Expression 1 (MSE1), is specifically expressed in males. MSE1 exhibits tight linkage with the Y chromosome, specific expression in early anther development and loss of function on the X chromosome. Knockout of the MSE1 orthologue in Arabidopsis induces male sterility. Thus, MSE1 acts in sex determination in A. officinalis.

Novel autophagy modulators: Design and synthesis of (+)-epogymnolactam analogues and structure-activity relationship.

(+)-Epogymnolactam (1) was discovered as a novel autophagy inducer from a culture of Gymnopus sp. in our laboratory. To determine structure-activity relationships among (+)-epogymnolactam analogues comparing with cerulenin (2), we synthesized 5 analogues including (-)-epogymnolactam (3) having each different functional group, and 3 analogues with different side-chain lengths. Five analogues, 3, 4, 5, 6, and 7 did not significantly increase the ratio of LC3-II to LC3-I as an autophagy marker in NIH3T3 cells. These results suggest that presence and stereochemistry of (2R,3S)-epoxy group and cyclic syn-form (1b) of 1 are important for the activity as autophagy inducer. Hexyl analogue (8) as well as 1 having butyl side-chain dose-dependently increased the ratio of LC3-II to LC3-I, whereas octyl analogue (9) and 2 rather decreased the ratio. Decyl analogue (10) did not give a change in the ratio. Although 8 seemed to be an excellent autophagy inducer, it dose-dependently increased SQSTM1 (p62) as in the case of 2, whereas 1 showed a slight dose-dependent decrease of p62 as an index of autophagic protein degradation. These observations suggest that 8 is an autophagy modulator with different molecular target from 1 or 2.

Eyelid reanimation using crossface nerve graft: Relationship between surgical outcome and preoperative paralysis duration.

BACKGROUND: To reanimate the mimetic muscles, crossface nerve graft (CFNG) is an effective surgical option. However, muscle atrophy after facial paralysis may influence the surgical result. We analyzed the relationship between surgical result and preoperative paralysis duration. METHODS: We performed CFNG on 15 patients. The sural nerve was transferred between the affected and nonaffected sides of the zygomatic branch. Eyelid function and eyelid lid were evaluated using the modified House-Brackmann scale. The effects of age, sex, cause of facial paralysis, graft nerve length, and preoperative paralysis duration were evaluated. RESULTS: The mean follow up period was 9.3 ± 3.3 (range 4-14) years. Eyelid closure was excellent in four patients, good in six, fair in one, and poor in four. Statistically, no significant difference was observed between those patients with excellent or good outcomes and fair or poor outcomes regarding age (40.9 ± 11.0 years vs. 22.6 ± 20.8; P = .067), sex (male/female = 2/8 vs. 3/2; P = .250), cause (tumor/trauma = 10/0 vs. 3/2; P = .095), and length of nerve graft (14.4 ± 0.8 cm vs. 13.8 ± 1.6 cm; P = .375). The average preoperative paralysis duration in the excellent/good patients was significantly shorter than that in the fair/poor patients (P = .005). All eight cases with preoperative paralysis of less than 6 months showed a marked excellent/good result. Two of the seven patients with preoperative paralysis was 6 months or longer marked fair/poor result. (P = .007). CONCLUSIONS: To achieve successful results with CFNG, surgery should be performed within 6 months of the onset of paralysis.

[A Case of Cecal Cancer Associated with Dermatomyositis].

We report a relatively rare case of cecal cancer with dermatomyositis. An 81-year-old man was diagnosed with dermatomyositis associated with the symptoms of eruption, limb muscle weakness, and difficulty swallowing. Colonoscopy revealed a type 2 tumor in the cecum. The patient underwent laparoscopic ileocecal resection. Although it was impossible for the patient to stand before the surgery, he could stand 10 days after the surgery and walk without assistance 14 days after the surgery. In addition, the eruption disappeared, and the preoperatively high creatine kinase(CK)value normalized. Dermatomyositis with malignant tumor has been reported to be associated with poor prognosis. Symptoms related to dermatomyositis may be improved by the resection of the associated tumor. Therefore, it is important to treat the malignant tumor when the patient's condition permits.

Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism.

BACKGROUND: We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed. CASE PRESENTATION: A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 × 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection. CONCLUSION: A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

The great importance of normalization of LC-MS data for highly-accurate non-targeted metabolomics.

The non-targeted metabolomics analysis of biological samples is very important to understand biological functions and diseases. LC combined with electrospray ionization-based MS has been a powerful tool and widely used for metabolomic analyses. However, the ionization efficiency of electrospray ionization fluctuates for various unexpected reasons such as matrix effects and intraday variations of the instrument performances. To remove these fluctuations, normalization methods have been developed. Such techniques include increasing the sensitivity, separating co-eluting components and normalizing the ionization efficiencies. Normalization techniques allow simultaneously correcting of the ionization efficiencies of the detected metabolite peaks and achieving quantitative non-targeted metabolomics. In this review paper, we focused on these normalization methods for non-targeted metabolomics by LC-MS.

[A Case of Local Resection for Rectal GIST Following Neoadjuvant Imatinib Mesylate Treatment].

A 67-year-old woman presented with bloody stools and constipation. A rectal digital examination revealed a smooth and elastic hard tumor in the posterior wall of the rectum. We diagnosed the tumor as rectal GIST measuring 5 cm in diameter. Because the patient desired anal preservation, neoadjuvant imatinib mesylate(IM)(400mg/day)treatment was administered. Although the diameter of the tumor reduced to 2 cm in the third week of administration, the patient experienced erythema-type drug eruption(Grade 3). We discontinued the IM treatment and initiated steroid therapy. After the eruption had disappeared, IM treatment was resumed, initially with half doses. Local transanal resection was performed 36days after the neoadjuvant IM treatment. Currently, the indication and the administration period of IM for preoperative treatment is not clear. It may be necessary to accumulate cases to evaluate neoadjuvant IM therapy.

Accumulation of cells expressing macrophage colony-stimulating factor receptor gene in the ovary of a pregnant viviparous fish, Neoditrema ransonnetii (Perciformes, Embiotocidae).

Macrophage colony-stimulating factor receptor (M-CSFR), a member of the group of type III protein tyrosine kinase receptors, is expressed primarily by monocyte/macrophage lineage cells. In order to describe the distribution of macrophages at the maternal-fetal interface in Neoditrema ransonnetii, a viviparous fish species, M-CSFR cDNA was sequenced. Two sequences were obtained: NrM-CSFR1 (4381 bp, encoding 980 amino acids), and NrM-CSFR2 (3573 bp, encoding 1016 amino acids). Both the genes were expressed in the ovary of pregnant females. In situ hybridization revealed that a number of cells that were positive for NrM-CSFR1 and/or NrM-CSFR2 populated the ovigerous lamellae of the ovary during pregnancy. Following parturition, M-CSFR-positive cells disappeared from the subepithelial region of ovigerous lamellae, and were localized in perivascular tissues. These results suggest the role of M-CSFR-positive cells, which appear to be macrophages, in N. ransonnetii during pregnancy.

Facial reanimation using hypoglossal-facial neurorrhaphy with end-to-side coaptation between the jump interpositional nerve graft and hypoglossal nerve: Outcome and duration of preoperative paralysis.

BACKGROUND: In this report, we described the use of hypoglossal-facial neurorrhaphy with end-to-side coaptation between the jump interpositional nerve graft and the hypoglossal nerve for facial reanimation and analyzed the relationship between the outcome of surgery and duration of preoperative paralysis. METHODS: We performed hypoglossal-facial neurorrhaphy with the jump interpositional nerve graft on nine men and 10 women with unilateral complete facial paralysis. The patients, with a mean age of 39.7 ± 18.1 years (range, 8-65 years) at the time of surgery, experienced preoperative paralysis ranging from 1 to 150 months (mean, 16.9 ± 34.9 months). The movement of the corners of the mouth was evaluated 12 months after surgery using a unique method based on the House-Brackmann grading scale. RESULTS: The mean follow-up was 5.6 ± 1.6 years (range, 3-9 years). The movement of the corners of mouth was classified as excellent in two cases, good in seven cases, fair in two cases, and poor in eight cases. Nine of the 11 cases with preoperative paralysis of 6 months or less had excellent or good results, whereas none of the eight cases with preoperative paralysis of 7 months or longer yielded excellent or good results, showing a significant difference (P = 0.01). CONCLUSIONS: To achieve successful reanimation of the corners of the mouth, hypoglossal-facial neurorrhaphy with end-to-side coaptation between the jump interpositional nerve graft and the hypoglossal nerve should be performed within 6 months after the onset of facial nerve paralysis. © 2015 Wiley Periodicals, Inc. Microsurgery 36:460-466, 2016.

Signal intensity of small hepatocellular carcinoma on apparent diffusion coefficient mapping and outcome after radiofrequency ablation.

AIM: It has been reported that the apparent diffusion coefficient (ADC) value of hepatocellular carcinomas (HCC) on diffusion-weighted magnetic resonance imaging (MRI) is associated with their histological grade. The present study aimed to evaluate whether the signal intensity of small hypervascular HCC on the ADC map is related to the treatment outcome of radiofrequency ablation (RFA). METHODS: Between February 2008 and August 2012, 136 consecutive patients with initial small hypervascular HCC (≤3 tumors and ≤3 cm in diameter) were examined by diffusion-weighted MRI before RFA. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense and non-hypointense. Critical recurrence was defined as more than three intrahepatic recurrences, recurrence with vascular invasion, seeding, dissemination and/or extrahepatic metastasis. RESULTS: The median follow up was 619 days. The cumulative 2-year recurrence rates of the hypointense and non-hypointense on the ADC map groups were 79% and 50% (P < 0.001), respectively, with cumulative 2-year local recurrence rates of 18% and 7% (P = 0.014) and cumulative 2-year critical recurrence rates of 38% and 13% (P = 0.005), respectively. The cumulative 3-year survival rates were 60% and 82% (P = 0.007), respectively. On multivariate analysis, hypointensity on the ADC map was the strongest independent factor related to recurrence and survival after RFA. CONCLUSION: The signal intensity of HCC on the ADC map was strongly associated with outcome after RFA. These results suggest that treatment strategy should be determined carefully even for small HCC when they appear hypointense on the ADC map.

Hemi-Bernard method: straightforward reconstruction of lower lip after malignant tumor resection.

The Bernard method is a straightforward method for reconstructing lower lip defects after tumor resection. However, this method is difficult to apply when the defect is located on the unilateral side of the lower lip. This report describes the reconstruction of unilateral lower lip defects using a modified Bernard method, which is referred to as the hemi-Bernard method. Three patients (2 male and 1 female; mean defect, 55%) underwent reconstruction using the hemi-Bernard method after lower lip malignant tumor resection. No infection or flap necrosis occurred, and none of the 3 patients had difficulty with oral ingestion. Movement of the orbicularis oris muscle was retained in all patients. The hemi-Bernard method is straightforward and has several advantages, including extension of lower lip length. This method could be useful for reconstructing full-thickness defects located on the unilateral side of the lower lip.

How Can Paresthesia After Zygomaticomaxillary Complex Fracture Be Determined After Long-Term Follow-Up? A New and Quantitative Evaluation Method Using Current Perception Threshold Testing.

PURPOSE: The aims of the present study were to analyze the effectiveness of current perception threshold (CPT) testing to determine patients' minor paresthesia of the infraorbital region after open reduction and internal fixation (ORIF) for unilateral zygomaticomaxillary bone fracture (UZF) and to clarify which nerve fiber was related to the paresthesia. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients who had undergone ORIF after UZF. We also performed neurosensory testing for healthy volunteers who served as the control group. The predictor variables were the period of measurement of Semmes-Weinstein monofilament (S-W) testing and CPT testing (preoperatively and 1 and 5 years postoperatively), measurement side, and disease status (UZF or control). The outcome variables were paresthesia status of the infraorbital nerve region and the results of S-W and CPT testing in both UZF and control groups. The differences in the S-W and CPT values between the affected and unaffected sides in the UZF group and between the UZF and control groups were analyzed by t test (P < .05 was considered significant). RESULTS: The present study included 10 patients (6 males and 4 females), with an average age of 25.0 ± 12.7 years, and 21 controls (10 males and 11 females), with an average age of 24.3 ± 1.7 years. In the control group, the CPT and S-W test results did not show any significant differences between the left and right sides. All 10 patients had paresthesia at 1 and 5 years postoperatively. At 5 years postoperatively, the S-W values in all patients showed normalization. From the results of CPT testing, only the A-ß fiber function showed significant improvement at 5 years postoperatively. CONCLUSION: The CPT test was an effective sensory test for determining minor paresthesia that could not be detected using S-W testing. Paresthesia of the infraorbital nerve region was caused by the damaged A-δ and C fibers.