SOX17 enables immune evasion of early colorectal adenomas and cancers.

A hallmark of cancer is the avoidance of immune destruction. This process has been primarily investigated in locally advanced or metastatic cancer1-3; however, much less is known about how pre-malignant or early invasive tumours evade immune detection. Here, to understand this process in early colorectal cancers (CRCs), we investigated how naive colon cancer organoids that were engineered in vitro to harbour Apc-null, KrasG12D and Trp53-null (AKP) mutations adapted to the in vivo native colonic environment. Comprehensive transcriptomic and chromatin analyses revealed that the endoderm-specifying transcription factor SOX17 became strongly upregulated in vivo. Notably, whereas SOX17 loss did not affect AKP organoid propagation in vitro, its loss markedly reduced the ability of AKP tumours to persist in vivo. The small fraction of SOX17-null tumours that grew displayed notable interferon-γ (IFNγ)-producing effector-like CD8+ T cell infiltrates in contrast to the immune-suppressive microenvironment in wild-type counterparts. Mechanistically, in both endogenous Apc-null pre-malignant adenomas and transplanted organoid-derived AKP CRCs, SOX17 suppresses the ability of tumour cells to sense and respond to IFNγ, preventing anti-tumour T cell responses. Finally, SOX17 engages a fetal intestinal programme that drives differentiation away from LGR5+ tumour cells to produce immune-evasive LGR5- tumour cells with lower expression of major histocompatibility complex class I (MHC-I). We propose that SOX17 is a transcription factor that is engaged during the early steps of colon cancer to orchestrate an immune-evasive programme that permits CRC initiation and progression.

Long-term results of a phase 2 study of neoadjuvant chemotherapy with molecularly targeted agents for locally advanced rectal cancer.

BACKGROUND: We previously reported the feasibility and efficacy of neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer. Here, we report the results of a long-term follow-up study. METHODS: This was a multi-institutional, prospective phase 2 study of patients with locally advanced rectal cancer. Patients received neoadjuvant chemotherapy with molecularly targeted agents before undergoing total mesorectal excision. Six cycles of modified FOLFOX (mFOLFOX6) with bevacizumab were administered to KRAS-mutant patients, and mFOLFOX6 with cetuximab was administered to KRAS-wild-type patients. Here, we report the secondary end points of overall survival, relapse-free survival, and local recurrence rate. RESULTS: Sixty patients were enrolled in this study. R0 resection was achieved in 98.3% (59/60) patients, and pathological complete response was achieved in 16.7% (10/60) patients. After a median follow-up of 5.4 years, the 5 year overall survival was 81.6%, the 5 year relapse-free survival was 71.7%, and the 5 year local recurrence rate was 12.6%. None of the patients who achieved pathological complete response developed recurrence within 5 years. CONCLUSIONS: The use of molecularly targeted agents in the neoadjuvant setting for locally advanced rectal cancer has an acceptable prognosis.

Long-Term, Community-based Approach for Affected People Having Problems With Mental Health and Lifestyle Issues After the 2011 Fukushima Disaster: the Fukushima Health Management Survey.

A Mental Health and Lifestyle Survey (MHLS) has been conducted yearly as part of the Fukushima Health Management Survey since 2012, in order to monitor different health issues related to long-term evacuation of affected people after the 2011 Fukushima disaster. This survey is a mail-based one of nearly 210,000 affected people living in the evacuation zone at the time of the disaster. Another purpose of the MHLS is to provide efficient interventions by telephone based on the results of the survey. Significant findings contributing to understanding of non-radiological health effects caused by long-term evacuation were obtained from the MHLS, directly connecting to telephone-based interventions for over 3,000 respondents per year. In this article, the mental health outcomes of the MHLS, including depressive symptoms and posttraumatic responses, are reviewed, and the usefulness of telephone-based interventions is discussed. The evidence showed that, despite improvement of core mental health outcomes, the prevalence of respondents at high risk of some psychiatric problems remained high compared to that among the general population in Japan. In particular, several mental health consequences of respondents staying outside of Fukushima Prefecture were higher than those staying inside Fukushima. Along with further efforts to increase the response rate, we need to continue and modify the MHLS to meet the requirements of the affected people and communities.

Subcuticular sutures for skin closure in non-obstetric surgery.

BACKGROUND: Following surgery, surgical wounds can be closed using a variety of devices including sutures (subcuticular or transdermal), staples and tissue adhesives. Subcuticular sutures are intradermal stitches (placed immediately below the epidermal layer). The increased availability of synthetic absorbable filaments (stitches which are absorbed by the body and do not have to be removed) has led to an increased use of subcuticular sutures. However, in non-obstetric surgery, there is still controversy about whether subcuticular sutures increase the incidence of wound complications. OBJECTIVES: To examine the efficacy and acceptability of subcuticular sutures for skin closure in non-obstetric surgery. SEARCH METHODS: In March 2019, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: All randomised controlled trials which compared subcuticular sutures with any other methods for skin closure in non-obstetric surgery were included in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials, extracted data and carried out risk of bias and GRADE assessment of the certainty of the evidence. MAIN RESULTS: We included 66 studies (7487 participants); 11 included trials had more than two arms. Most trials had poorly-reported methodology, meaning that it is unclear whether they were at high risk of bias. Most trials compared subcuticular sutures with transdermal sutures, skin staples or tissue adhesives. Most outcomes prespecified in the review protocol were reported. The certainty of evidence varied from high to very low in the comparisons of subcuticular sutures with transdermal sutures or staples and tissue adhesives; the certainty of the evidence for the comparison with surgical tapes and zippers was low to very low. Most evidence was downgraded for imprecision or risk of bias. Although the majority of studies enrolled people who underwent CDC class 1 (clean) surgeries, two-thirds of participants were enrolled in studies which included CDC class 2 to 4 surgeries, such as appendectomies and gastrointestinal surgeries. Most participants were adults in a hospital setting. Subcuticular sutures versus transdermal sutures There may be little difference in the incidence of SSI (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.80 to 1.52; 3107 participants; low-certainty evidence). It is uncertain whether subcuticular sutures reduce wound complications (RR 0.83; 95% CI 0.40 to 1.71; 1489 participants; very low-certainty evidence). Subcuticular sutures probably improve patient satisfaction (score from 1 to 10) (at 30 days; MD 1.60, 95% CI 1.32 to 1.88; 290 participants; moderate-certainty evidence). Wound closure time is probably longer when subcuticular sutures are used (MD 5.81 minutes; 95% CI 5.13 to 6.49 minutes; 585 participants; moderate-certainty evidence). Subcuticular sutures versus skin staples There is moderate-certainty evidence that, when compared with skin staples, subcuticular sutures probably have little effect on SSI (RR 0.81, 95% CI 0.64 to 1.01; 4163 participants); but probably decrease the incidence of wound complications (RR 0.79, 95% CI 0.64 to 0.98; 2973 participants). Subcuticular sutures are associated with slightly higher patient satisfaction (score from 1 to 5) (MD 0.20, 95% CI 0.10 to 0.30; 1232 participants; high-certainty evidence). Wound closure time may also be longer compared with staples (MD 0.30 to 5.50 minutes; 1384 participants; low-certainty evidence). Subcuticular sutures versus tissue adhesives, surgical tapes and zippers There is moderate-certainty evidence showing no clear difference in the incidence of SSI between participants treated with subcuticular sutures and those treated with tissue adhesives (RR 0.77, 95% CI 0.41 to 1.45; 869 participants). There is also no clear difference in the incidence of wound complications (RR 0.62, 95% CI 0.35 to 1.11; 1058 participants; low-certainty evidence). Subcuticular sutures may also achieve lower patient satisfaction ratings (score from 1 to 10) (MD -2.05, 95% CI -3.05 to -1.05; 131 participants) (low-certainty evidence). In terms of SSI incidence, the evidence is uncertain when subcuticular sutures are compared with surgical tapes (RR 1.31, 95% CI 0.40 to 4.27; 354 participants; very low-certainty evidence) or surgical zippers (RR 0.80, 95% CI 0.08 to 8.48; 424 participants; very low-certainty evidence). There may be little difference in the incidence of wound complications between participants treated with subcuticular sutures and those treated with surgical tapes (RR 0.90, 95% CI 0.61 to 1.34; 492 participants; low-certainty evidence). It is uncertain whether subcuticular sutures reduce the risk of wound complications compared with surgical zippers (RR 0.55, 95% CI 0.15 to 2.04; 424 participants; very low-certainty evidence). It is also uncertain whether it takes longer to close a wound with subcuticular sutures compared with tissue adhesives (MD -0.34 to 10.39 minutes; 895 participants), surgical tapes (MD 0.74 to 6.36 minutes; 169 participants) or zippers (MD 4.38 to 8.25 minutes; 424 participants) (very low-certainty evidence). No study reported results for patient satisfaction compared with surgical tapes or zippers. AUTHORS' CONCLUSIONS: There is no clear difference in the incidence of SSI for subcuticular sutures in comparison with any other skin closure methods. Subcuticular sutures probably reduce wound complications compared with staples, and probably improve patient satisfaction compared with transdermal sutures or staples. However, tissue adhesives may improve patient satisfaction compared with subcuticular sutures, and transdermal sutures and skin staples may be quicker to apply than subcuticular sutures. The quality of the evidence ranged from high to very low; evidence for almost all comparisons was subject to some limitations. There seems to be no need for additional new trials to explore the comparison with staples because there are high-quality studies with large sample sizes and some ongoing studies. However, there is a need for studies exploring the comparisons with transdermal sutures, tissue adhesives, tapes and zippers, with high-quality studies and large sample sizes, including long-term assessments.

A Multicenter Phase 2 Study on the Feasibility and Efficacy of Neoadjuvant Chemotherapy Without Radiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: This prospective multicenter phase 2 study aimed to evaluate the feasibility and efficacy of neoadjuvant chemotherapy (NAC) without radiotherapy for locally advanced rectal cancer (LARC). METHODS: Patients with LARC (cStage II and III) were included in the study. Those with cT4b tumor were excluded. Six cycles of modified FOLFOX6 (mFOLFOX6) plus either bevacizumab or cetuximab, depending on KRAS status, were administered before surgery. The primary end point of the study was the R0 resection rate. The secondary end points were adverse effect, rate of NAC completion, postoperative complications, and pathologic complete response (pCR) rate. RESULTS: The study enrolled 60 patients from eight institutions. For the study, mFOLFOX6 was administered with cetuximab to 40 patients who had wild-type KRAS and with bevacizumab to 20 patients who had KRAS mutations. The completion rate for NAC was 88.4%. Sphincter-preserving surgery was performed for 43 patients and abdominoperineal resection for 17 patients. The median operation time was 335 min, and the median blood loss was 40 g. The R0 resection rate was 98.3%, and the pCR rate was 16.7%. The overall postoperative complication rate (≥grade 2) was 21.7%. The complications included anastomotic leakage (11.6%), surgical-site infection (6.7%), and urinary dysfunction (3.3%). The patients with wild-type KRAS did not differ significantly from those with KRAS mutations in terms of response rate, postoperative complication rate, and pCR rate. CONCLUSION: The findings show that NAC is a feasible and promising treatment option for LARC (This study is registered with UMIN-CTR, UMIN000005654).

Multicenter analysis of transanal tube placement for prevention of anastomotic leak after low anterior resection.

BACKGROUND: Anastomotic leak (AL) is a serious complication of low anterior resection (LAR). This study aimed to evaluate the effect of transanal tube placement for prevention of AL. METHODS: This multicenter retrospective cohort study enrolled 328 consecutive patients who underwent LAR for rectal cancer at participating hospitals from 2009 to 2014. Multivariate logistic regression was used to adjust for confounding factors. RESULTS: A transanal tube was placed in 205 patients (TA group) and not placed in 123 patients (non-TA group). Symptomatic AL occurred in 36 cases (11%), with significantly higher incidence of symptomatic AL in the non-TA group than in the TA group (15% vs 8.3%, odds ratio [OR] 2.02, 95% confidence interval [CI] 1.01-4.06). After adjusting for confounding factors, multivariate analysis revealed that placement of a transanal tube could decrease the incidence of symptomatic AL (adjusted OR 0.37, 95%CI 0.15-0.91). There was no significant difference in postoperative morbidity, mortality, length of hospital stay, or local recurrence rate between the two groups. Local recurrence rate tended to be higher in patients with symptomatic AL (3/36) than in those without it (10/292). CONCLUSIONS: Transanal tube placement is effective for decreasing the incidence of symptomatic AL after LAR.

Differences in surgical site infection between laparoscopic colon and rectal surgeries: sub-analysis of a multicenter randomized controlled trial (Japan-Multinational Trial Organization PREV 07-01).

BACKGROUND: The incidence of surgical site infection (SSI) is reportedly lower in laparoscopic colorectal surgery than in open surgery, but data on the difference in SSI incidence between colon and rectal laparoscopic surgeries are limited. METHODS: The incidence and risk factors for SSI, and the effect of oral antibiotics in colon and rectal laparoscopic surgeries, were investigated as a sub-analysis of the JMTO-PREV-07-01 (a multicenter, randomized, controlled trial of oral/parenteral vs. parenteral antibiotic prophylaxis in elective laparoscopic colorectal surgery). RESULTS: A total of 582 elective laparoscopic colorectal resections, comprising 376 colon surgeries and 206 rectal surgeries, were registered. The incidence of SSI in rectal surgery was significantly higher than in colon surgery (14 vs. 8.2 %, P = 0.041). Although the incidence of incisional SSI was almost identical (7 %) between the surgeries, the incidence of organ/space SSI in rectal surgery was significantly higher than in colon surgery (6.3 vs. 1.1 %, P = 0.0006). The lack of oral antibiotics was significantly associated with the development of SSI in colon surgery. Male sex, stage IV cancer, and abdominoperineal resection were significantly associated with SSI in rectal surgery. The combination of oral and parenteral antibiotics significantly reduced the overall incidence of SSI in colon surgery (relative risk 0.41, 95 % confidence interval 0.19-0.86). CONCLUSION: The incidence of SSI in laparoscopic rectal surgery was higher than in colon surgery because of the higher incidence of organ/space SSI in rectal surgery. The risk factors for SSIs and the effect of oral antibiotics differed between these two procedures.

Antibiotics and antiseptics for pressure ulcers.

BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. A range of treatments with antimicrobial properties, including impregnated dressings, are widely used in the treatment of pressure ulcers. A clear and current overview is required to facilitate decision making regarding use of antiseptic or antibiotic therapies in the treatment of pressure ulcers. This review is one of a suite of Cochrane reviews investigating the use of antiseptics and antibiotics in different types of wounds. It also forms part of a suite of reviews investigating the use of different types of dressings and topical treatments in the treatment of pressure ulcers. OBJECTIVES: To assess the effects of systemic and topical antibiotics, and topical antiseptics on the healing of infected and uninfected pressure ulcers being treated in any clinical setting. SEARCH METHODS: In October 2015 we searched: the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid EMBASE, and EBSCO CINAHL Plus. We also searched three clinical trials registries and the references of included studies and relevant systematic reviews. There were no restrictions based on language or date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials which enrolled adults with pressure ulcers of stage II or above were included in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS: We included 12 trials (576 participants); 11 had two arms and one had three arms. All assessed topical agents, none looked at systemic antibiotics. The included trials assessed the following antimicrobial agents: povidone iodine, cadexomer iodine, gentian violet, lysozyme, silver dressings, honey, pine resin, polyhexanide, silver sulfadiazine, and nitrofurazone with ethoxy-diaminoacridine. Comparators included a range of other dressings and ointments without antimicrobial properties and alternative antimicrobials. Each comparison had only one trial, participant numbers were low and follow-up times short. The evidence varied from moderate to very low quality.Six trials reported the primary outcome of wound healing. All except one compared an antiseptic with a non-antimicrobial comparator. There was some moderate and low quality evidence that fewer ulcers may heal in the short term when treated with povidone iodine compared with non-antimicrobial alternatives (protease-modulating dressings (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.62 to 0.98) and hydrogel (RR 0.64, 95% CI 0.43 to 0.97)); and no clear difference between povidone iodine and a third non-antimicrobial treatment (hydrocolloid) (low quality evidence). Pine resin salve may heal more pressure ulcers than hydrocolloid (RR 2.83, 95% CI 1.14 to 7.05) (low quality evidence). There is no clear difference between cadexomer iodine and standard care, and between honey a combined antiseptic and antibiotic treatment (very low quality evidence).Six trials reported adverse events (primary safety outcome). Four reported no adverse events; there was very low quality evidence from one showing no clear evidence of a difference between cadexomer iodine and standard care; in one trial it was not clear whether data were appropriately reported.There was limited reporting of secondary outcomes. The five trials that reported change in wound size as a continuous outcome did not report any clear evidence favouring any particular antiseptic/anti-microbial treatments. For bacterial resistance, one trial found some evidence of more MRSA eradication in participants with ulcer treated with a polyhexanide dressing compared with a polyhexanide swab (RR 1.48, 95% CI 1.02 to 2.13); patients in the dressing group also reported less pain (MD -2.03, 95% CI -2.66 to -1.40). There was no clear evidence of a difference between interventions in infection resolution in three other comparisons. Evidence for secondary outcomes varied from moderate to very low quality; where no GRADE assessment was possible we identified substantial limitations which an assessment would have taken into account. AUTHORS' CONCLUSIONS: The relative effects of systemic and topical antimicrobial treatments on pressure ulcers are not clear. Where differences in wound healing were found, these sometimes favoured the comparator treatment without antimicrobial properties. The trials are small, clinically heterogenous, generally of short duration, and at high or unclear risk of bias. The quality of the evidence ranges from moderate to very low; evidence on all comparisons was subject to some limitations.

Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury.

Lgr5+ intestinal stem cells (ISCs) depend on niche factors for their proper function. However, the source of these ISC niche factors and how they support ISCs in vivo remain controversial. Here, we report that ISCs depend on lymphatic endothelial cells (LECs) and RSPO3+GREM1+ fibroblasts (RGFs). In the intestine and colon, LECs are surrounded by RGFs and are located near ISCs at the crypt base. Both LECs and RGFs provide the critical ISC niche factor RSPO3 to support ISCs, where RSPO3 loss in both cell types drastically compromises ISC numbers, villi length, and repair after injury. In response to injury, LEC and RGF numbers expand and produce greater amounts of RSPO3 and other growth/angiocrine factors to foster intestinal repair. We propose that LECs represent a novel niche component for ISCs, which together with RGFs serve as the major in vivo RSPO3 source for ISCs in homeostasis and injury-mediated regeneration.

Vulnerability of Evacuees Having No One to Consult after the Fukushima Nuclear Disaster: The Fukushima Health Management Survey.

After the accident at the Fukushima nuclear power plant in 2011, caused by the Great East Japan Earthquake, some evacuees had no one to consult despite many local care providers offering assistance. This study identified the characteristics of individuals who did not receive consultations and the relevant determinants, and proposed the available measures to address this issue. Altogether, 32,699 participants aged 16 years or older and residing in the disaster area at Fukushima were surveyed. Those with no one to consult showed a significantly higher prevalence of psychological distress (16.2%, p < 0.001) and drinking problems (21.5%, p < 0.001). Multivariate analysis revealed that these behaviors were associated with the middle age group (i.e., 40-64 years old) (odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.16-1.46), men (OR = 2.46; 95% CI, 2.27-2.66), bad financial circumstances (OR = 2.11; 95% CI, 1.96-2.27), and living alone (OR = 1.53; 95% CI, 1.39-1.68). This research verifies that people with such characteristics were more likely to be isolated and vulnerable to psychiatric problems, such as depression. We suggest that it is integral for local care providers to recognize those who have no one to consult and provide targeted support.

Associations of the COVID-19 pandemic with the economic status and mental health of people affected by the Fukushima disaster using the difference-in-differences method: The Fukushima Health Management Survey.

Although the coronavirus disease 2019 (COVID-19) pandemic and relevant preventive measures can affect the economic status and mental health of the public, their effect remains unraveled owing to a limited number of surveys conducted before and during the COVID-19 pandemic. We investigated the association of COVID-19 and relevant measures with multivariate outcomes among people affected by the Fukushima disaster in 2011 using the difference-in-differences (DID) method. We then analyzed the associations between sociodemographic factors and outcomes. We assessed psychological distress, problem drinking, insomnia state, unemployment, household economic decline, and interpersonal problems using three questionnaire surveys administered in 2018, 2019, and 2020. Participants were grouped according to three time periods by dates of voluntary stay-at-home requests (February 26) and the declaration of emergency (April 16) in Japan. The years 2020 and 2019 were regarded as the treatment group and control group, respectively, after confirming that no DIDs were found between 2018 and 2019. We performed regression analyses to identify the risk factors for outcomes. The DIDs were significant for household economic decline after the declaration of emergency, whereas problem drinking significantly improved. No significant DIDs were observed for other mental health outcomes including psychological distress and insomnia state. Absence of counselors was positively and significantly associated with all outcomes in 2020. Overall, people affected by the Fukushima disaster experienced more economic damage after the declaration of emergency during the COVID-19 pandemic but their mental health status did not reduce. Identifying people who have no counselors and providing them with support are emergent requirements to prevent a subsequent mental health decline.

Trajectories of peer relationship problems and emotional symptoms in children 5 years after a nuclear disaster: Fukushima Health Management Survey.

The Fukushima Daiichi Nuclear Power Station (NPS) accident, which occurred in March 2011, is having long-term effects on children. About 3 years after the accident, we identified three patterns of peer relationship problems and four patterns of emotional symptoms using group-based trajectory modeling. As a result, we reported that different factors might be related to very severe trajectories of peer relationship problems and emotional symptoms. In this study, we used five waves of data from fiscal year (FY) 2011 to FY2015 from the Mental Health and Lifestyle Survey, a detailed survey of the Fukushima Health Management Survey started in FY2011. We analyzed 7013 residents within the government-designated evacuation zone (aged 6-12 years old as of 11 March 2011) with responses to all items of psychological distress in at least one wave from FY2011 and FY2015. We planned this study to describe the trajectories of peer relationship problems and emotional symptoms in children and to examine potential risks and protective factors over the 5 years following the NPS accident. We identified four patterns of peer relationship problems and five patterns of emotional symptoms using latent class growth analysis. For peer relationship problems, male sex, experiencing the NPS explosion and lack of exercise habits were associated with the severe trajectory group. For emotional symptoms, experiencing the NPS explosion, experiencing the tsunami disaster and lack of exercise habits were associated with the severe trajectory group. Exercise habits are very important for the mental health of evacuees after a nuclear disaster.

Combined robotic and cystoscopic surgery for rectal cancer invading urinary bladder.

Although the application of laparoscopic rectal surgery has been widely accepted by accumulated evidence, it remains technically difficult in some cases of obesity, narrow male pelvis, bulky tumors, or involvement of adjacent organs. After robotic rectal surgery has been covered by the health insurance system in Japan since April 2018, we have employed robotic rectal surgery for an increasing number of cases by taking advantages of its 3D vision and wrist function. When a colorectal cancer involves the urinary bladder, the surgical treatment of choice is an anterior resection with en bloc (partial or total) bladder resection, depending on the site and extent of bladder involvement. In the attached video, robotic surgery was conducted with the aid of intraoperative cystoscopy, which resulted in curative resection with negative margin. Given that the robotic system provides excellent stability and dexterity for bladder reconstruction, the robotic approach can be technically suitable for locally advanced T4 colorectal cancer with urinary involvement.

Killian-Jamieson diverticulum safely resected using a manual intraoperative neural monitoring system: a case report.

BACKGROUND: Killian-Jamieson diverticulum is a rare pharyngoesophageal diverticulum. The risk of intraoperative injury of the recurrent laryngeal nerve (RLN) is high during surgical resection of Killian-Jamieson diverticulum because the RLN usually runs next to the base of the diverticulum. We present a case of Killian-Jamieson diverticulum that was safely resected with effective use of an intraoperative nerve monitoring (IONM) system with a handheld stimulating probe to prevent RLN injury. CASE PRESENTATION: A 69-year-old man complaining of dysphagia was diagnosed with Killian-Jamieson diverticulum and underwent open transcervical diverticulectomy. Because the anterior aspect of the diverticulum was expected to be close to the RLN, the accurate location of the RLN was checked during dissection by intermittent stimulation using a handheld probe of the IONM system to avoid mechanical and thermal injury. The diverticulum was transected longitudinally using a linear stapler, and the staple line was buried using absorbable sutures from the distal end. During its closure, RLN was identified very close to the diverticulum stump by IONM, and the upper side of the stump was left unburied to avoid RLN injury. The postoperative course was uneventful and the patient was discharged on postoperative day 7. Postoperative evaluation showed no vocal cord paralysis. CONCLUSION: IONM may be beneficial during open surgery for Killian-Jamieson diverticulum, which usually protrudes just lateral to the RLN.

Laparoscopic rectal tumor surgery after administration of a new sclerosing therapy (aluminum potassium sulfate and tannic acid injection) for internal hemorrhoids: A report of three cases.

Aluminum potassium sulfate and tannic acid (ALTA) injection is a new sclerosing therapy for internal hemorrhoids that has been gaining widespread use. However, there have been few reports about rectal cancer after ALTA injection. We performed laparoscopic surgery for three patients who had underwent ALTA therapy 6 months or 1 year earlier: (i) a 51-year-old man with neuroendocrine tumor; (ii) a 44-year-old woman with rectal cancer; and (iii) 77-year-old man with rectal cancer. All three patients had sclerosis of the resected rectal wall stump, making transection of the rectum difficult. Histological examination of the specimens also showed an inflammatory reaction and/or fibrosis of the resection stump. Although laparoscopic low anterior resection was planned for all three patients, we had to construct a diverting stoma for two patients and could not perform sphincter-preserving surgery for the other. We must be well prepared for laparoscopic rectal surgeries after ALTA therapy, and these cases suggest sigmoidoscopy before ALTA therapy should be recommended.

Simultaneous robotic surgery with low anterior resection and prostatectomy/hysterectomy.

Cooperation with multiple departments is essential for the treatment of patients with rectal cancer and other pelvic cancers. In our department, we experienced two cases of rectal cancer that underwent robotic low anterior resection (LAR) and simultaneous resection of other pelvic organs (case 1 with prostatectomy and case 2 with hysterectomy) using the da Vinci Xi system. Here, we show the precise procedures of these two robotic surgeries. Under general anesthesia and lithotomy position, five da Vinci ports were symmetrically placed along the umbilical horizontal line with a 7 cm interval, and a 5 mm AirSeal Access Port was added in the right or left upper quadrant. Patients were placed with 22-degree Trendelenburg and 8-degree tilt to the right. The operators used the center port on the umbilicus as a camera port and chose the docking arms with either two-left-one-right or one-left-two-right setting depending on their preference. This port setting was quite useful for the operators from multiple departments to change the docking arms, even if their preference may be different. Moreover, assistants could use the remaining two ports to provide a well-expanded and safer surgical field. "With a familiar view" and "with a wide view" are our two concepts to safely perform extended pelvic surgeries. We have employed this symmetrical horizontal port site position as a general setting for usual rectal surgeries.

N-terminal region of alpha-synuclein is essential for the fatty acid-induced oligomerization of the molecules.

Exposure of alpha-synuclein (alphaS), a major component of Lewy bodies in Parkinson's disease, to polyunsaturated fatty acids (PUFAs) triggers the formation of soluble alphaS oligomers. Here, we demonstrate that PUFA binds recombinant alphaS protein through its N-terminal region (residues 2-60). In HEK293 cells, alphaS mutants lacking the N-terminal region failed to form oligomers in the presence of PUFA. The PUFA-induced alphaS oligomerization was accelerated by C-terminal truncation or Ser129 phosphorylation of alphaS; however, this effect was abolished by deletion of the N-terminus. The results indicate that the N-terminus of alphaS is essential for the PUFA-induced alphaS oligomerization.

The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease.

Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the pathogenesis of the disease remains undetermined, phosphorylation of alpha-synuclein and its oligomer formation seem to play a key role. However, the protein kinase(s) involved in the phosphorylation in the pathogenesis of sPD has not been identified. Here, we found that G-protein-coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with alpha-synuclein in the pathological structures of the brains of sPD patients. In cotransfected cells, GRK5 phosphorylated Ser-129 of alpha-synuclein at the plasma membrane and induced translocation of phosphorylated alpha-synuclein to the perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of alpha-synuclein. Genetic association study revealed haplotypic association of the GRK5 gene with susceptibility to sPD. The haplotype contained two functional single-nucleotide polymorphisms, m22.1 and m24, in introns of the GRK5 gene, which bound to YY1 (Yin Yang-1) and CREB-1 (cAMP response element-binding protein 1), respectively, and increased transcriptional activity of the reporter gene. The results suggest that phosphorylation of alpha-synuclein by GRK5 plays a crucial role in the pathogenesis of sPD.

Multicenter analysis of impact of anastomotic leakage on long-term oncologic outcomes after curative resection of colon cancer.

BACKGROUND: In rectal cancer, anastomotic leakage was reported to have a negative impact on both short- and long-term outcomes. However, there is limited data on the impact of anastomotic leakage on oncologic outcomes in patients with colon cancer. We aimed to evaluate the impact of anastomotic leakage on disease recurrence and long-term survival after curative resection of colon cancer. METHODS: This multicenter, retrospective cohort study of 4,919 consecutive patients utilized data from the Japanese Society for Cancer of the Colon and Rectum. Multivariable Cox regression analysis was used to adjust for confounding. RESULTS: The incidence of anastomotic leakage was 2.5% and 30-day mortality was 0.21%. The 5-year overall survival rate was 80.8% in the anastomotic leakage group, compared with 90.3% in the no leak group (P = .001). In the multivariable analysis, anastomotic leakage was significantly associated with reduced overall survival rate (hazard ratio = 1.84; 95% confidence interval, 1.06-2.96). Overall disease recurrence rate was 14.1%: 21.2% in the anastomotic leakage group and 13.9% in the no leak group. There was a significant association between anastomotic leakage and local recurrence (hazard ratio = 4.63; 95% confidence interval, 1.60-10.6). In contrast, anastomotic leakage was not significantly associated with total distant recurrence. However, anastomotic leakage did show a tendency toward increasing peritoneal recurrence, although it did not reach statistical significance (hazard ratio = 2.59; 95% confidence interval, 0.79-6.29). CONCLUSION: In our study population, anastomotic leakage was associated with reduced overall survival and with increased rate of local recurrence after curative resection for colon cancer.