Randomized controlled trial comparing cosmetic results of midline incision versus off-midline incision for specimen extraction in laparoscopic colectomy.

PURPOSE: A notable advantage of laparoscopic colorectal surgery is that only a small incision at the extraction site is necessary, which is considered to be cosmetically beneficial. Meanwhile, the optimal extraction site for the resected specimen in laparoscopic colectomy is controversial in terms of cosmetic benefit. This randomized controlled trial compares midline and off-midline extraction sites in laparoscopic colectomy in patients with colon cancer, with consideration of cosmetic benefits as the primary endpoint. METHODS: Included were patients that underwent elective laparoscopic colectomy at WMUH between October 2014 and February 2017. Patients were randomly assigned to either midline incision group or off-midline incision group. Prospectively collected data included cosmetic results (patients and observer assessment scale) and complications including incidence of incisional hernia, SSI, and pain. This trial was registered with UMIN Clinical Trials (UMIN000028943). RESULTS: Finally, 98 patients with colorectal cancer were analyzed. No significant differences were found between the two groups in patient and observer assessment scales of cosmetic results (midline 8 ± 1.1 vs off-midline 11 ± 5.9 p = 0.16, midline 13.5 ± 6.6 vs off-midline 15 ± 11 p = 0.58, respectively) or in postoperative pain. However, incisional hernia occurred in four cases in the midline group (8%), which was significantly higher than that in the off-midline group (no cases, 0%). CONCLUSION: There was no significant difference in terms of cosmetic benefit, the primary endpoint, between the two groups. In this study, only the extraction site location was compared; future studies will examine differences depending on the incisional direction, including the incidence of incisional hernia.

New diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for patients with colorectal cancer.

BACKGROUND: Accurate tumor stage diagnosis during laparoscopic surgery remains difficult. We clarify the impact of new diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for colorectal cancer compared with other strategies. METHODS: We defined angiogenesis (Ag) and fibrosis (Fib) grades using NBI laparoscopy (lap-NBI), and assessed the clinicopathological features associated with these grades for 67 patients with colorectal cancer who underwent surgery. We assessed vessel density and gray scale with computer software. RESULTS: NBI-Ag-grade and NBI-Fib-grade of the serosal surface of cancer lesions and peritoneal nodules correlated with vessel density and gray scale of those assessed by Image J computer software. NBI-Fib-grades of liver nodules also correlated with gray scale. NBI-Ag- grade and Fib-grade of the serosal surface of cancer lesions correlated with pathological depth of invasion. These NBI grades of pathological metastatic peritoneal nodules were higher than those of pathologically benign peritoneal nodules. NBI- Fib grades of pathological metastatic liver nodules were higher than those of pathologically benign liver nodules. In multivariate analysis, lap-NBI was associated with different diagnosis for T3, T4 and non-T3, and non-T4. Moreover, lap-NBI was associated with different diagnosis for T4 and non-T4. Predictive value for T4 by lap-NBI showed high sensitivity (85%) specificity (87%), positive predictive value (74%), negative predictive value (93%), and overall accuracy (87%). Sensitivity and overall accuracy of lap-NBI was superior to that of other diagnostic modalities. CONCLUSION: We clarified the usefulness of the new diagnostic strategy using lap-NBI during laparoscopic surgery for colorectal cancer in comparison with other strategies.

High visceral to subcutaneous fat area ratio predicts early postoperative small bowel obstruction after surgery for colorectal cancer.

PURPOSE: Risks for postoperative small bowel obstruction have been demonstrated in several reports, most of which indicated male sex was a risk factor, but with the reason remaining unknown. We tested the hypothesis that it could be because males have more visceral fat than females. This prospective observational study aims to examine risks of early postoperative small bowel obstruction (EPSBO) after colorectal cancer surgery and the association between visceral to subcutaneous fat area ratio (V/S ratio) and EPSBO. METHODS: Four hundred and seventy-four patients who underwent colectomy for colorectal cancer in our hospital were enrolled in this study. The influence of several factors including V/S ratio on the development of EPSBO was analyzed. RESULTS: Thirty-one of the 474 patients (6.5%) developed EPSBO. EPSBO occurred more frequently in males (p = 0.03) and cases who developed postoperative anastomotic leakage (p < 0.001) or wound infection (p = 0.02). Higher V/S ratio was strongly related to male sex (p < 0.001). Multivariate analysis revealed higher V/S ratio (OR 2.25; p = 0.049) and anastomotic leakage (OR 5.86; p < 0.001) were independent risk factors for EPSBO. CONCLUSION: Higher V/S ratio was significantly related to EPSBO, suggesting that one of the reasons EPSBO was more likely to occur in males because they have more visceral fat than females. Preoperative identification of this risk factor could help us watch out for this potential complication.

Defunctioning loop ileostomy for rectal anastomoses: predictors of stoma outlet obstruction.

PURPOSE: Creation of defunctioning loop ileostomy is a standard procedure in laparoscopic lower rectal surgery. Stoma-related obstruction sometimes occurs, but its cause has not been fully analyzed. This study aims to assess stoma obstructive complications and clarify the risk factors of stoma-related obstructions. METHODS: Two hundred and thirty consecutive patients who underwent laparoscopic rectal cancer surgery with defunctioning loop ileostomy between April 2007 and December 2017 were recruited, numbering 230. We statistically examined the frequency and risk factor of stoma outlet obstruction. RESULTS: Postoperative stoma-related complications developed in 41 patients (17.8%) overall, and there was no 30-day mortality. Stoma outlet obstructions occurred in 16 patients (7.0%) during postoperative course. Thick subcutaneous fat at the stoma-marking site (vertical distance ≥ 20 mm) and body mass index (≥ 22.2) were significantly associated with the risk of stoma outlet obstruction in univariate analysis. Thick subcutaneous fat was a significant predictive factor of stoma outlet obstruction according to multivariate analysis (odds ratio 3.80). CONCLUSIONS: This report investigates significant predictors of stoma outlet obstruction in laparoscopic rectal cancer surgery for the first time. In laparoscopic procedure, stoma outlet obstruction should be particularly considered in obese patients who have especially thick subcutaneous fat of the abdominal wall.

Possible Roles of New Mutations Shared by Asian and American Zika Viruses.

Originating in Africa, the Zika virus (ZIKV) has spread to Asia, Pacific Islands and now to the Americas and beyond. Since the first isolation in 1947, ZIKV strains have been sampled at various times in the last 69 years, but this history has not been reflected in studying the patterns of mutation accumulation in their genomes. Implementing the viral history, we show that the ZIKV ancestor appeared sometime in 1930-1945 and, at that point, its mutation rate was probably less than 0.2 × 10-3/nucleotide site/year and subsequently increased significantly in most of its descendants. Sustaining a high mutation rate of 4 × 10-3/site/year throughout its evolution, the Ancestral Asian strain, which was sampled from a mosquito in Malaysia, accumulated 13 mutations in the 3'-untranslated region of RNA stem-loops prior to 1963, seven of which generate more stable stem-loop structures and are likely to inhibit cellular antiviral activities, including immune and RNA interference (RNAi) pathways. The seven mutations have been maintained in all Asian and American strains and may be responsible for serious medical problems we are facing today and offer testable hypotheses to examine their roles in molecular interactions during brain development.

CEACAM1 is associated with recurrence after hepatectomy for colorectal liver metastasis.

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is re-expressed at the invasion front of colorectal cancer. CEACAM1 expression at metastatic sites remains to be investigated. The current study aims to clarify the association between CEACAM1 expression and recurrence after hepatectomy of colorectal liver metastasis and to address whether CEACAM1 induces tumor-initiating properties needed for growth at metastatic sites. METHODS: Immunohistochemical analyses for CEACAM1 were performed in 67 patients with liver metastasis of colorectal cancer who had undergone curative hepatectomy. The risk factors for postoperative recurrence were calculated based on a CEACAM1 cytoplasmic domain isoform at the primary tumor invasion front. To investigate the effects of CEACAM1 cytoplasmic isoforms on HT29 and HCT116 colorectal cancer cells, Western blotting for CD44 and CD133, flow cytometry for ALDH1 activity, and soft-agar colony formation assay were performed. RESULTS: CEACAM1 long (CEACAM1-L) and short (CEACAM1-S) cytoplasmic domain isoforms are strongly expressed on cancer cells in the liver metastases. Enhanced CEACAM1-S expression in the state of CEACAM1-L dominance at the primary tumor invasion front was an independent factor for colorectal cancer recurrence after curative hepatectomy. CEACAM1-4S-transfected HT29 and HCT116 cells had significantly higher CD44 expression and ALDH1 activity and increased the growth in anchorage-independent condition. CONCLUSIONS: High expression of CEACAM1-S at the primary lesion invasion front is associated with recurrence and prognosis of patients with colorectal liver metastasis after curative hepatectomy. The expression of CEACAM1-4S enhances the tumor-initiating property of colorectal cancer cells.

Perineural Invasion Is Associated with Poor Survival after Preoperative Chemoradiation Therapy for Advanced Lower Rectal Cancer.

BACKGROUND: Preoperative chemoradiation therapy (pCRT) is a standard procedure for patients with advanced lower rectal cancer. It has been reported that pCRT cannot prolong the survival of patients with advanced lower rectal cancer. The aim of this study is to address the controllable and uncontrollable pathological factors of pCRT in predicting local and distant recurrences. METHODS: One hundred two patients with stages 2 and 3 cancer were consecutively enrolled to the study. The first 51 patients (October 2008-August 2010) underwent curative resection without pCRT. The latter 51 patients (September 2010-May 2015) underwent curative resection after pCRT. Pathological factors of patients were evaluated to assess the association between local and distant recurrences. RESULTS: Multivariate analyses for local and distant recurrences of patients without pCRT revealed that the independent risk factors were tumor deposit and perineural invasion respectively. pCRT was able to diminish circumferential resection margin, tumor deposit, venous invasion, and lymphatic permeation but not neural invasion and lymph node involvement. Kaplan-Meier curve of local and distant recurrence-free survival of patients with pCRT illustrated that tumor deposit is controllable, whereas perineural invasion is uncontrollable by pCRT. CONCLUSION: pCRT-uncontrollable perineural invasion may be a factor for distant recurrence of advanced rectal cancer patients, leading to poor survival.

Epistatic adaptive evolution of human color vision.

Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation. This initial step may be untangled by analyzing appropriate ancestral molecules, but it is a daunting task to recapitulate the evolution of non-additive (epistatic) interactions of amino acids and function of a protein separately. To adapt to the ultraviolet (UV)-free retinal environment, the short wavelength-sensitive (SWS1) visual pigment in human (human S1) switched from detecting UV to absorbing blue light during the last 90 million years. Mutagenesis experiments of the UV-sensitive pigment in the Boreoeutherian ancestor show that the blue-sensitivity was achieved by seven mutations. The experimental and quantum chemical analyses show that 4,008 of all 5,040 possible evolutionary trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Phylogenetic analysis further suggests that human ancestors achieved the blue-sensitivity gradually and almost exclusively by epistasis. When the final stage of spectral tuning of human S1 was underway 45-30 million years ago, the middle and long wavelength-sensitive (MWS/LWS) pigments appeared and so-called trichromatic color vision was established by interprotein epistasis. The adaptive evolution of human S1 differs dramatically from orthologous pigments with a major mutational effect used in achieving blue-sensitivity in a fish and several mammalian species and in regaining UV vision in birds. These observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments.

A simple method for studying the molecular mechanisms of ultraviolet and violet reception in vertebrates.

BACKGROUND: Many vertebrate species use ultraviolet (UV) reception for such basic behaviors as foraging and mating, but many others switched to violet reception and improved their visual resolution. The respective phenotypes are regulated by the short wavelength-sensitive (SWS1) pigments that absorb light maximally (λmax) at ~360 and 395-440 nm. Because of strong epistatic interactions, the biological significance of the extensive mutagenesis results on the molecular basis of spectral tuning in SWS1 pigments and the mechanisms of their phenotypic adaptations remains uncertain. RESULTS: The magnitudes of the λmax-shifts caused by mutations in a present-day SWS1 pigment and by the corresponding forward mutations in its ancestral pigment are often dramatically different. To resolve these mutagenesis results, the A/B ratio, in which A and B are the areas formed by amino acids at sites 90, 113 and 118 and by those at sites 86, 90 and 118 and 295, respectively, becomes indispensable. Then, all critical mutations that generated the λmax of a SWS1 pigment can be identified by establishing that 1) the difference between the λmax of the ancestral pigment with these mutations and that of the present-day pigment is small (3 ~ 5 nm, depending on the entire λmax-shift) and 2) the difference between the corresponding A/B ratios is < 0.002. CONCLUSION: Molecular adaptation has been studied mostly by using comparative sequence analyses. These statistical results provide biological hypotheses and need to be tested using experimental means. This is an opportune time to explore the currently available and new genetic systems and test these statistical hypotheses. Evaluating the λmaxs and A/B ratios of mutagenized present-day and their ancestral pigments, we now have a method to identify all critical mutations that are responsible for phenotypic adaptation of SWS1 pigments. The result also explains spectral tuning of the same pigments, a central unanswered question in phototransduction.

P4H9-detected molecule expression on spindle-shaped fibroblasts indicates malignant phenotype of colorectal cancer.

BACKGROUND: Our previous study using a mammary fat pad mouse model showed that P4H9, produced by the ß2 integrin epitope, detected a molecule on fibroblasts in response to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-expressing cancer cells. P4H9-detected molecule (PDM) expression appeared to be associated with myofibroblast differentiation. In this study, we investigated whether PDM is expressed on fibroblasts and cancer cells in clinical tissue samples, and whether the presence of PDM-expressing colorectal cancer cells is correlated with clinicopathological features of patients. METHODS: Immunohistochemistry was conducted to detect P4H9 on clinical tissue samples from 156 patients with colorectal cancer. Risk factors for metastases and survival were calculated for clinical implication of PDM-expressing spindle-shaped fibroblasts. RESULTS: Multivariate analysis showed that PDM-expressing spindle-shaped fibroblasts were an independent risk factor for lymph node metastasis, hematogenous metastasis, and poor survival. A Kaplan-Meier survival curve indicated that PDM-expressing spindle-shaped fibroblasts were associated with shorter survival time (P<0.0001). Immunofluorescence showed PDM expression on CCD-18Co fibroblasts and two colorectal cancer cell lines (HCT116 and HCT-15). CONCLUSIONS: PDM-expressing spindle-shaped fibroblasts are associated with metastasis and shorter survival in colorectal cancer patients. PDM-expressing spindle-shaped fibroblasts may have a role in eliciting the malignant phenotype of colorectal cancer.

Clinical characteristics of anastomotic leakage after an anterior resection for rectal cancer by assessing of the international classification on anastomotic leakage.

PURPOSE: The International Study Group of Rectal Cancer (ISREC) has proposed a new definition of anastomotic leakage (AL) which was simply classified into three grades; however, these criteria have not been assessed well. The aims of this study are to assess the new definition and to show the clinical features of AL after an anterior resection for rectal cancer. METHODS: Fifty consecutive patients developed AL after an anterior resection for rectal cancer was retrospectively assessed. AL was defined by the ISREC criteria. RESULTS: Twenty-seven (54 %) patients with AL were diagnosed by drain contents. The postoperative day of diagnosis for AL was later in grade A versus grades B and C (p = 0.038 vs p = 0.006, respectively). Permanent stoma (PS) was significantly more frequent in patients with grade C but not grade B compared to the patients with no AL (p < 0.001 and p = 0.171, respectively). In patients without diverting stoma, there was more serious grade of AL (p < 0.001). CONCLUSIONS: Differences were observed in the postoperative day of diagnosis, the creation rate of PS, and impact on diverting stoma after AL between each grade of leakage. The new classification was easy and reasonable to evaluate AL. As a result, it should be widely used in future studies.

Synthetic biology of phenotypic adaptation in vertebrates: the next frontier.

For over the last 2 decades, positively selected amino acid sites have been inferred almost exclusively by showing that the number of nonsynonymous substitutions per nonsynonymous site (dn) is greater than that of synonymous substitutions per synonymous site (ds). However, virtually none of these statistical results have been experimentally tested and remain as hypotheses. To perform such experimental tests, we must connect genotype and phenotype and relate the phenotypic changes to the environmental and behavioral changes of the organism. The genotype-phenotype relationship can be established only by synthesizing and manipulating "proper" ancestral phenotypes, whereas the actual functions of adaptive mutations can be learned by studying their chemical roles in phenotypic changes.

CEACAM1 long cytoplasmic domain isoform is associated with invasion and recurrence of hepatocellular carcinoma.

BACKGROUND: The two isoforms of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), 1 with a long cytoplasmic domain (CEACAM1-L) and 1 with a short (CEACAM1-S), are involved in different signaling pathways. ß2-spectrin (ß2SP) is an adaptor protein that plays critical roles in the proper control of Smad access to activate receptors involved in regulation of TGF-ß signaling. In this study, we examined the association between CEACAM1 isoform balance and hepatocellular carcinoma (HCC) malignant potential and investigated the possibility of a molecular interaction between CEACAM1 and ß2SP. METHODS: Immunohistochemical analysis was carried out with CEACAM1-L or CEACAM1-S antibodies on 154 HCC tissues to correlate with the factors of malignancy. Invasion assay was performed for the effect of CEACAM1 expression on HCC cell lines. Moreover, immunohistochemical analysis and immunoprecipitation analysis were performed to investigate the association between CEACAM1 isoform balance and ß2SP. RESULTS: In immunohistochemical analysis, CEACAM1-L expression dominance was a risk factor for HCC recurrence (p = 0.04) and was significantly associated with a shorter survival compared with CEACAM1-S expression dominance. Invasion assay indicated that CEACAM1-4L-transfected HLF and PLC/PRF/5 cells showed significantly increased invasion (p < 0.0001) and CEACAM1-4S-transfected HLF cells showed significantly decreased invasion. Immunohistochemical analysis of ß2SP suggested that the HCCs with CEACAM1-L-dominant expression were more strongly stained with ß2SP than the HCCs with CEACAM1-S-dominant expression (p = 0.013), and coprecipitation assays indicated that CEACAM1-L could bind to ß2SP. CONCLUSIONS: CEACAM1-L may enhance the HCC invasiveness through an interaction with ß2SP and subsequent effects on TGF-ß signaling.

Survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved.

PURPOSE: The effectiveness of lateral lymph node dissection for extending the survival of patients with advanced lower rectal cancer remains unclear. The purpose of this study was to clarify the survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved. METHODS: We reviewed 131 consecutive patients with advanced lower rectal cancer, who had undergone curative resection with total mesorectal excision plus extended lateral lymph node dissection at Wakayama Medical University Hospital. Twenty-six (19.1 %) of these patients had lateral lymph involvement. We performed univariate and multivariate analyses for the 3-year disease-free and overall survival of these patients. RESULTS: Multivariate analysis revealed that the number (>1) and the region (common iliac artery region or external iliac artery region) of lateral lymph node metastasis are independent predictive factors for recurrence and survival. The Kaplan-Meier analysis demonstrated that patients with one lymph node metastasis in the internal iliac artery or obturator region had better survival. CONCLUSIONS: Lateral lymph node dissection resulted in survival benefit for patients with single lateral lymph node involvement in the internal iliac artery region or the obturator region.

Impact of the post/preoperative serum CEA ratio on the survival of patients with rectal cancer.

PURPOSE: This study demonstrated the usefulness of the post/preoperative serum carcinoembryonic antigen (CEA) ratio as a predictor of survival after surgery for stage III rectal cancer patients. METHODS: One hundred and four patients with stage III rectal cancer who underwent surgery between 1991 and 2000 were enrolled. The ratio of the postoperative serum CEA value divided by the preoperative serum CEA value was defined as post/preoperative serum CEA ratio, and the patients were separated into two groups: post/preoperative serum CEA ratio ≤ 1 (n = 86) and >1 (n = 18). RESULTS: The multivariate analyses demonstrated that the intraoperative blood loss, lack of a sphincter-saving procedure and a post/preoperative serum CEA ratio >1 were independent factors predicting a poor prognosis for the overall and disease-free survival. The overall and disease-free survival rates among patients with a high preoperative serum CEA level (>5 ng/ml) or patients with a high postoperative serum CEA (>5 ng/ml) were longer in patients with a post/preoperative serum CEA ratio ≤ 1, in comparison to those with a post/preoperative serum CEA ratio >1. Liver metastasis was observed more frequently in patients with a post/preoperative serum CEA ratio >1. CONCLUSIONS: The post/preoperative serum CEA ratio may be a predictor of the prognosis after surgery for stage III rectal cancer patients.

Cancer histology in metastatic lymph node predicts prognosis in patients with node-positive stage IV colorectal cancer.

Background: Appropriate prognostic indicators are required for patients with stage IV colorectal cancer (CRC). Lymph node metastasis mainly involves four histological types of CRC. Some metastatic lymph nodes (mLNs) showing cribriform carcinoma are associated with distant metastasis in patients with node-positive CRC and are correlated with recurrence and survival in stage III disease. However, the significance of mLN histology in the prognosis of patients with node-positive stage IV disease remains unclear. Methods: We enrolled 449 consecutive patients with CRC who underwent primary tumor resection with lymph node dissection between January 2011 and November 2018. This study included 88 patients with node-positive stage IV CRC and synchronous or metachronous distant metastases. We retrospectively investigated the association between cancer histology in the mLNs based on our classification and cancer-specific survival (CSS) in patients with node-positive stage IV CRC. Results: Kaplan-Meier analysis showed that CSS was better in patients with CRC and all the mLNs showing tubular-type carcinoma. In contrast, patients with at least some mLNs showing poorly differentiated-type carcinoma had poor prognosis. Multivariate analysis showed that "all mLNs showing tubular-type carcinoma" was an independent good prognostic factor for CSS in patients with node-positive stage IV CRC. In addition, "at least some mLNs showing poorly differentiated-type carcinoma" was an independent poor prognostic factor for CSS in patients with node-positive stage IV disease. Conclusions: The histological type of the mLN may indicate a better or poor prognosis for patients with stage IV CRC.

Predicting lymph node metastasis in early colorectal cancer using the CITED1 expression.

BACKGROUND: The identification of molecular markers that are useful for predicting lymph node metastasis is urgently needed to determine treatment strategies for T1 colorectal cancer (CRC). We previously showed that 10 candidate genes are correlated with de-differentiation at the invasion front of CRC using a gene expression analysis. These 10 genes are potential markers that may predict lymph node metastasis by CRC. MATERIALS AND METHODS: Samples were obtained from 161 patients with CRC. Quantitative real-time reverse transcription-polymerase chain reaction assays were performed using 66 T3 samples in order to extract genes correlated with lymph node metastasis. Immunohistochemical studies of the extracted genes were performed on 66 T3 and 95 T1 samples. A univariate analysis followed by a multivariate logistic regression model was used to examine independent risk factors for lymph node metastasis. RESULTS: The CITED1 messenger RNA expression was found to be an independent risk factor for lymph node metastasis in T3 CRC patients (P = 0.040). A high CITED1 protein expression, as detected with immunohistochemistry, was also an independent risk factor in T3 CRC patients (P = 0.035). In T1 colorectal cancer patients, a high CITED1 protein expression was found to be an independent risk factor for lymph node metastasis (P = 0.010). The positive predictive and negative predictive values in the T1 colorectal cancer patients were 27.5% and 95.5%, respectively. CONCLUSIONS: The CITED1 expression is correlated with lymph node metastasis in patients with CRC. In T1 colorectal cancer patients, CITED1 has the potential ability to predict the presence of lymph node metastasis.

Clinical outcome of up-front surgery in patients with asymptomatic, incurable synchronous peritoneal carcinomatosis.

PURPOSES: The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC. METHODS: Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively. RESULTS: A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p < 0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001). CONCLUSION: Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.

Genomic organization, evolution, and expression of photoprotein and opsin genes in Mnemiopsis leidyi: a new view of ctenophore photocytes.

BACKGROUND: Calcium-activated photoproteins are luciferase variants found in photocyte cells of bioluminescent jellyfish (Phylum Cnidaria) and comb jellies (Phylum Ctenophora). The complete genomic sequence from the ctenophore Mnemiopsis leidyi, a representative of the earliest branch of animals that emit light, provided an opportunity to examine the genome of an organism that uses this class of luciferase for bioluminescence and to look for genes involved in light reception. To determine when photoprotein genes first arose, we examined the genomic sequence from other early-branching taxa. We combined our genomic survey with gene trees, developmental expression patterns, and functional protein assays of photoproteins and opsins to provide a comprehensive view of light production and light reception in Mnemiopsis. RESULTS: The Mnemiopsis genome has 10 full-length photoprotein genes situated within two genomic clusters with high sequence conservation that are maintained due to strong purifying selection and concerted evolution. Photoprotein-like genes were also identified in the genomes of the non-luminescent sponge Amphimedon queenslandica and the non-luminescent cnidarian Nematostella vectensis, and phylogenomic analysis demonstrated that photoprotein genes arose at the base of all animals. Photoprotein gene expression in Mnemiopsis embryos begins during gastrulation in migrating precursors to photocytes and persists throughout development in the canals where photocytes reside. We identified three putative opsin genes in the Mnemiopsis genome and show that they do not group with well-known bilaterian opsin subfamilies. Interestingly, photoprotein transcripts are co-expressed with two of the putative opsins in developing photocytes. Opsin expression is also seen in the apical sensory organ. We present evidence that one opsin functions as a photopigment in vitro, absorbing light at wavelengths that overlap with peak photoprotein light emission, raising the hypothesis that light production and light reception may be functionally connected in ctenophore photocytes. We also present genomic evidence of a complete ciliary phototransduction cascade in Mnemiopsis. CONCLUSIONS: This study elucidates the genomic organization, evolutionary history, and developmental expression of photoprotein and opsin genes in the ctenophore Mnemiopsis leidyi, introduces a novel dual role for ctenophore photocytes in both bioluminescence and phototransduction, and raises the possibility that light production and light reception are linked in this early-branching non-bilaterian animal.

Elective colorectal cancer surgery in nonagenarians and postoperative outcomes.

OBJECTIVES: The population of very elderly patients is increasing, and nonagenarians have significantly higher mortality rates and poorer rates of survival than younger patients. Meanwhile, recent studies have shown colorectal cancer surgery in nonagenarian patients to be feasible regarding postoperative outcomes. This retrospective study aims to evaluate the postoperative outcomes of nonagenarians in the latest clinical settings. METHODS: Consecutive nonagenarian patients who underwent elective colorectal cancer surgery between 2018 and 2020 retrospectively enrolled (Trial registration number: UMIN000046296 on December 7th, 2021). Clinicopathological data and short-term postoperative outcomes were collected for statistical analysis. RESULTS: This study included 81 nonagenarian patients (31 males, 50 females). Postoperative complications occurred in 21 patients (25.9%), and 3 patients died within 90 days (3.7%). Multivariate analysis revealed prognostic nutritional index was a significant predictor of postoperative complications (OR 2.99, 95% CI 0.78-9.10, P = 0.048), and performance status ≥ 3 could be an independent risk factor of 90-day mortality (HR 32.30, 95% CI 3.20-326.10, P = 0.032). CONCLUSIONS: Short-term outcomes after surgical treatment for nonagenarian patients with colorectal cancer were acceptable. Low prognostic nutritional index was closely related to postoperative complications and poor performance status could also lead to 90-day mortality. In aging populations, risk stratification to prevent poorer postoperative outcomes in nonagenarian patients is needed.