Search

Purpose: This study aimed to evaluate the clinicopathological and prognostic significance of preoperative serum creatine kinase (CK) levels in colorectal cancer. Methods: This study analyzed 1169 patients with colorectal cancer at stages 0 (n = 35), I (n = 301), II (n = 456), III (n = 339), and IV (n = 38). The CK cut-off value was 52 U/L to predict recurrence based on receiver operative characteristics curve. Clinicopathological factors were compared between the low (< 52 U/L) and high CK groups (≥ 52 U/L). The multivariate analysis evaluated relapse-free survival (RFS) and overall survival (OS) following CK status. Results: The female sex, elderly age (≥ 75), deep tumor (pT4), and carcinoembryonic antigen (+) were independently associated with low CK status. The recurrent rate was significantly higher in the low CK group than in the high CK group (19.1% vs. 11.7%, p < 0.001). Elderly age, pT4, pN (+), preoperative carbohydrate antigen (CA) 19-9 (+), and low CK status were independent risk factors for RFS. Elderly age, pT4, pN (+), preoperative CA19-9 (+), and low CK status were independent risk factors for OS. Conclusion: Preoperative low CK status was associated with deep tumors and was a poor prognostic factor in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Aim: To clarify the usefulness of intraoperative lavage cytology in patients undergoing curative resection for pStage II‐III colorectal cancer in a prospective multicenter study. Methods: Patients preoperatively diagnosed with stage II‐III colorectal cancer between 2013 and 2017 from 20 hospitals were enrolled. Lavage cytology was performed twice during the surgery. The primary endpoint was the effect of lavage cytology on the 5‐year relapse‐free survival (RFS) in patients with pStage II‐III colorectal cancer. The secondary endpoint was the effect of lavage cytology on the 5‐year overall survival (OS) and peritoneal recurrence. Results: A total of 1378 patients were eligible for analysis. The number of patients with pStage II‐III colorectal cancer was 670 and 708, respectively. Fifty‐four patients (3.9%) had positive cytological results. In pStage II patients, the 5‐year RFS rates with positive and negative cytology were 61.1% and 81.6%, respectively (p = 0.023). The 5‐year OS rates were 67.1% and 91.7%, respectively (p = 0.0083). However, there was no difference in RFS or OS between pStage III patients with positive and negative cytology results. The peritoneal recurrence rates were 11.8% and 1.5% in pStage II patients with positive and negative cytology results, respectively (p = 0.032). These rates were 10.5% and 2.5% in patients with stage III disease, respectively (p = 0.022). Conclusion: Stage II colorectal cancer patients with negative cytology had better outcomes than those with positive cytology. Peritoneal lavage cytology is useful for predicting peritoneal recurrence after curative resection of stage II‐III colorectal cancer. [ABSTRACT FROM AUTHOR]

Background/Purpose: To investigate the safety of laparoscopic liver resections (LLRs) for high‐risk patients (HRs) with preoperative comorbidities affecting the heart, lungs, kidneys, glucose tolerance, and central nervous system. Methods: This retrospective study included 585 patients who had undergone total hepatectomies from 2006 to 2020. Among them, 239 patients underwent LLRs, and 349 underwent open liver resections (OLRs). The safety and validity of LLRs were analyzed by comparing outcomes and preoperative records between HRs and nonhigh‐risk patients (nHRs). HRs were defined as patients with any type of chronic heart disease rated New York Heart Association II or higher, chronic obstructive pulmonary disease rated stage III or higher, chronic kidney disease rated stage III or higher, insulin‐dependent diabetes mellitus, or cerebrovascular disease with neurological sequelae. Results: A total of 117 LLRs (49.0%) were performed in HRs, and there were more patients with ASA class III or higher than nHRs. Complications of Clavien‐Dindo classification grade 3b or higher were not observed in HRs and in only one nHR. Furthermore, no postoperative exacerbations of the five HRs factors were observed in either group. Conclusions: Rigorous assessment of surgical indications and perioperative management can promote safe LLRs, even in HRs with comorbidities. [ABSTRACT FROM AUTHOR]

Aim: To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods: This multi‐institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results: Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion: This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Hand-assisted laparoscopic surgery (HALS) is known as a useful option. However, the outcome and predictor of conversion to HALS in laparoscopic liver resection (LLR) are unclear. Methods: Data from consecutive patients who planned pure LLR between 2011 and 2020 were retrospectively reviewed. Univariate and multivariate analyses were performed and compared pure LLR, HALS, and converted open liver resection (OLR). Results: Among the 169 LLRs, conversion to HALS was performed in 19 (11.2%) and conversion to OLR in 16 (9.5%). The most frequent reasons for conversion to HALS were failure to progress (11 cases). Subsequently, bleeding (3 cases), severe adhesion (2 cases), and oncological factors (2 cases) were the reasons. In the multivariable analysis, the tumor located in segments 7 or 8 (p = 0.002) was evaluated as a predictor of conversion to HALS. Pure LLR and HALS were associated with less blood loss than conversion to OLR (p = 0.005 and p = 0.014, respectively). However, there was no significant difference in operation time, hospital stay, or severe complications. Conclusions: The predictor of conversion to HALS was a tumor located in segments 7 or 8. The outcome of conversion to HALS was not inferior to pure LLR in terms of bleeding, operation time, hospital stay, or severe complication. [ABSTRACT FROM AUTHOR]

Background and Aim: The rate of ulcerative colitis (UC)‐related colorectal cancer (colitis‐associated carcinoma) is increasing. Estrogen receptor (ER) beta expression has been studied separately in patients with sporadic colorectal cancer and those with colitis‐associated carcinoma. However, no study has compared the expression in both of these cancer types. The present study aimed to evaluate the relationship between colitis‐associated carcinoma and ERs and assess whether the expression of ER beta influences cell proliferation. Methods: This study included 45 surgically operated colitis‐associated carcinomas, 43 high‐grade dysplasias, 34 low‐grade dysplasias, 36 sporadic colorectal cancers, 44 high‐grade adenomas, and 34 low‐grade adenomas. ER beta expression was evaluated with immunohistochemistry. Results: Colitis‐associated carcinoma showed significantly lower ER beta immunoexpression than sporadic colorectal lesions and high‐ and low‐grade dysplasia. In seven colitis‐associated carcinoma harboring both intensity score 3 (strong immunoexpression) and score 1 (weak immunoexpression) areas, the correlation among ER beta intensity, Ki‐67, and p21 labeling index was assessed; an area with an ER beta intensity score of 3 showed a higher Ki‐67 labeling index than that with score 1. In four out of the seven lesions, p21 labeling index was higher in the area of ER beta score 1 than in that of ER beta score 3. Conclusions: The data suggest that ER beta expression is an accelerating factor in colorectal tumors. This association may be lower in colitis‐associated carcinoma than in sporadic colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: To compare the utility of preoperative immunonutritional parameter measures for predicting postoperative mortality following palliative surgery (PS) for malignant bowel obstruction (MBO) in patients with late-stage cancer. Methods: The subjects of this retrospective study were 83 late-stage cancer patients with MBO who underwent PS between January, 2005 and December, 2018, at a single institution in Japan. We compared the modified Glasgow prognostic score (mGPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for predicting postoperative mortality following PS in these patients. Results: The most prevalent cancer in the patients who underwent PS was colorectal cancer (54.2%), followed by gastric cancer (24.1%). Postoperative complications of Clavien–Dindo classification grade ≥ 2 developed in 32 (38.6%) patients and stoma-related complications developed in 26 (31.3%) patients. There were 15 (18.1%) patients with 60-day mortality, 22 (26.5%) with 90-day mortality, and 4 (4.8%) with 30-day mortality. Multivariable analysis identified only mGPS as being associated with 60-day mortality (odds ratio, 9.387; 95% confidence interval, 0.001–4.478; p = 0.049). The overall survival of patients with a mGPS score of 2 was significantly worse than that of those with a mGPS score of < 2 (p = 0.013). Conclusions: These results suggest that the mGPS is a good predictor not only of 60-day mortality, but also of the overall survival of patients with late-stage cancer and MBO. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the predictors of a difficult Pringle maneuver (PM) in laparoscopic liver resection (LLR) and to assess alternative procedures to PM. Methods: Data from patients undergoing LLR between 2013 and 2020 were reviewed retrospectively. Univariate and multivariate analyses were performed and the outcomes of patients who underwent PM or alternative procedures were compared. Results: Among 106 patients who underwent LLR, PM could not be performed in 18 (17.0%) because of abdominal adhesions in 14 (77.8%) and/or collateral flow around the hepatoduodenal ligament in 5 (27.8%). Multivariate analysis revealed that Child–Pugh classification B (p = 0.034) and previous liver resection (p < 0.001) were independently associated with difficulty in performing PM in LLR. We evaluated pre-coagulation of liver tissue using microwave tissue coagulators, saline irrigation monopolar, clamping of the hepatoduodenal ligament using an intestinal clip, and hand-assisted laparoscopic surgery as alternatives procedures to PM. There were no significant differences in blood loss (p = 0.391) or transfusion (p = 0.518) between the PM and alternative procedures. Conclusions: Child–Pugh classification B and previous liver resection were identified as predictors of a difficult PM in LLR. The alternative procedures were found to be effective. [ABSTRACT FROM AUTHOR]

Previous studies have reported low serum creatine kinase (s-CK) levels as a poor prognostic factor in various cancers. However, there have been no reports on its significance in hepatocellular carcinoma. The present study aimed to evaluate the association of the preoperative s-CK levels with clinicopathologic features and their prognostic impact on survival in patients with hepatocellular carcinoma. This retrospective study included 163 patients with hepatocellular carcinoma (127 male and 36 female patients; median age, 69 years) who underwent radical liver resection between January 2004 and December 2021. A cutoff preoperative s-CK level of 91 U/l determined by receiver operating characteristic curve analysis was used to evaluate the significance of s-CK in predicting overall and recurrence-free survival. In addition, the prognostic impact of s-CK was evaluated using univariate and multivariate analysis. s-CK level was not associated with clinicopathologic factors. Overall survival and recurrence-free survival of the low s-CK group were significantly worse compared with the high s-CK group (P=0.043 and P=0.029, respectively). By multivariate analysis, low s-CK was an independent risk factor for poor overall survival and recurrence-free survival (P=0.019 and P=0.014, respectively). This trend was the same for male patients, but no significant difference was observed for female patients. Low preoperative s-CK level might be a poor prognostic biomarker in patients with hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: In rectal cancer (RC) surgery, the complexity of total mesorectal excision (TME) in laparoscopic sphincter-preserving surgery (lap-SPS) for RC near the anus has been a critical issue. Recently, technical assistance via the anus for complete TME has been receiving attention. This study aimed at clarifying the transanal down-to-up dissection viability for achieving TME in lap-SPS for RC near the anus. Methods: We evaluated surgical and oncological outcomes of a total of 123 consecutive patients undergoing either a transanal rectal dissection (TARD) under direct vision mobilizing the most difficult portion of TME via the anus or the transanal TME by using an endoscopic system (TaTME) for achieving TME in lap-SPS for RC near the anus between January 2006 and February 2021. Results: A total of 123 consecutive patients (83 men) with a median age of 66 years (range 33–86 years) were included. TARD and TaTME were performed for 50 (40.7%) and for 73 (59.3%) patients, respectively. Preoperative treatment was performed for 40 (32.5%) patients, resulting in a complete pathological response in 5 (12.5%) patients. Intersphincteric resection was performed significantly more in the TARD group (p<0.001). Although the TaTME group needed a longer operative time at the transanal portion (p<0.001), the median blood loss was lower (p<0.001). Postoperative complications with the Clavien–Dindo classification grade ≧2 developed in 52 (42.3%) patients. Urinary dysfunction and stoma-related complications were found most frequently. More patients needing medication for urinary dysfunction were found in the TARD group, but a significant difference was not observed (10.0% vs. 6.8%, p=0.526). The quality of TME was good for almost all patients. Recurrence developed in 18 (14.6%) patients. The 5-year overall survival (OS) and relapse-free survival (RFS) rates in 123 patients were 95.8% and 88.8%, respectively. The 5-year OS and RFS between the two groups were comparable. Conclusions: Our data suggested that a transanal down-to-up dissection of the distal rectum might be a viable approach in lap-SPS for RC near the anus. Further studies are needed to examine the differences between TARD and TaTME. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the clinicopathological and prognostic significance of preoperative serum creatine kinase (CK) levels in gastric cancer. Patients and methods: The subjects of this retrospective study were 942 patients who underwent surgery without preoperative chemotherapy for gastric cancer (643 men and 299 women), excluding Stage IV gastric cancer, between January, 2001 and December, 2020. We set the cutoff values for CK according to gender, as 64 U/L for men and 57 U/L for women, and evaluated the clinicopathological, prognostic, and gender significance of low CK levels by multivariate analysis. Results: Tumor depth was significantly associated with low serum CK levels (p < 0.001). The low CK group showed significantly worse overall survival than the high CK group (p = 0.01). The prognostic impact of low CK levels was evident only in men (p = 0.009). In women, low CK levels were not an independent risk factor for poor prognosis (p = 0.33). These prognostic impacts of low CK levels on overall survival and recurrence-free survival were similar. Conclusion: Low preoperative CK levels in men with gastric cancer were predictive of poor survival. These prognostic impacts of low CK levels were not evident in women. [ABSTRACT FROM AUTHOR]

Midkine (MK) is a soluble cytokine, and its serum levels strongly correspond to protein expression levels in tumors. The present study aimed to clarify the clinicopathological and prognostic significance of serum MK (s-MK) in patients with hepatocellular carcinoma (HCC). Serum samples were obtained before surgery from 123 patients with HCC who had undergone surgery between January 2012 and December 2020. The receiver operating characteristic curve revealed that the best cut-off value for s-MK in differentiating HCC from healthy cases was 426 pg/ml. The clinicopathological variables and overall survival of patients were compared between the s-MK-positive group and s-MK-negative group. The sensitivity, specificity and accuracy of s-MK were 82.1, 97.4 and 88.0%, respectively. An s-MK-positive status was significantly associated with the number of tumors (≥2). The positivity rate of s-MK was significantly higher compared with that of α-fetoprotein and protein-induced by vitamin K absence-II. In total, only 28% of the patients were positive for s-MK. The s-MK-positive group showed significantly worse overall survival compared with the s-MK-negative group. Moreover, multivariate analysis revealed that an s-MK-positive status was independently associated with poor prognosis. s-MK was useful in detecting early HCC. The findings of this study indicated that the s-MK-positive status is associated with the number of tumors and can act as an independent prognostic risk factor. [ABSTRACT FROM AUTHOR]

Background: Acute appendicitis (AA) in older patients can look different from AA in younger patients. Although it is crucial that primary care physicians can recognize AA in patients of any age, few Japanese studies have examined the characteristics of older AA patients. To address this, we evaluated the clinical characteristics of older Japanese patients with AA. Methods: We performed a post hoc analysis of the data from a previous Japanese single‐center study. We analyzed the clinical information of both younger (age: 16–64 years) and older patients (age: ≥65 years). Results: A cohort of 236 patients consisting of 219 (92.8%) younger patients and 17 (7.2%) older patients was evaluated. The median ages of the younger and older patients were 34 (interquartile range [IR], 24–45) and 78 years (IR, 74–81), respectively. The prevalence of complicated appendicitis (CA) (older: 41.2% vs. younger: 14.2%), comorbidities (70.6% vs. 13.2%), and thrombocytopenia (17.7% vs. 4.1%), along with serum C‐reactive protein (CRP) level (6.7 mg/dl vs. 1.0 mg/dl), was significantly higher in older patients. Significantly fewer older patients had epigastric pain (17.7% vs. 53.0%). Logistic regression evaluating the characteristics of older AA patients showed that CRP >5 mg/dl had a high odds ratio (OR) (5.01; 95% CI, 1.73–14.54), while epigastric pain had a low OR (0.24; 95% CI, 0.06–0.90). Conclusion: Our study reveals a higher prevalence of CA and comorbidities in older patients, and suggests that a lack of epigastric pain, thrombocytopenia, and higher serum CRP level are characteristics of older AA patients. [ABSTRACT FROM AUTHOR]

Background: The American Society of Surgery and American Society for Surgical Infections issued guidelines for surgical site infections (SSIs) in December 2016. These guidelines recommend a purse-string suture (PSS) for stoma closure as it facilitates granulation and enables open wound drainage. This study investigated the effect of using negative pressure wound therapy (NPWT) along with standard PSS and aimed to determine the optimal period of NPWT use.Methods: The patients were divided into three groups as follows: Group A, postoperative wound management alone with gauze exchange as the representative of conventional PSS; Group B, the performed management was similar to that of Group A plus NPWT for 1 week; and Group C, the performed management was similar to that of Group A plus NPWT for 2 weeks. Regarding objective measures, the wound reduction rate was the primary outcome, and the incidence of SSIs, length of hospital stay, and wound healing duration were the secondary outcomes.Results: In total, 30 patients (male: 18, female: 12) were enrolled. The average age was 63 (range: 43-84) years. The wound reduction rate was significantly higher in Group B than in Group A on postoperative days (PODs) 7 (66.1 vs. 48.4%, p = 0.049) and 10 (78.6 vs. 58.2%, p = 0.011), whereas no significant difference was observed on POD 14. Compared with Group A, Group C (POD 7: 65.9%, POD 10: 69.2%) showed an increase in the wound reduction rate on POD 7, although the difference was not significant (p = 0.075). SSIs were observed in Groups B (n = 2) and C (n = 2) (20%) but not in Group A (0%).Conclusions: The most effective duration of NPWT use for ileostomy closure with PSS in terms of the maximum wound reduction rate was from PODs 3 to 10. However, NPWT did not shorten the wound healing duration. NPWT may reduce the wound size but should be used with precautions for SSIs. The small sample size (30 cases), the use of only one type of NPWT system, and the fact that wound assessment was subjective and not blinded were the limitations of this study. Further studies are needed to confirm our findings.Trial Registration: UMIN Clinical Trials Registry; UMIN000032174 (10/04/2018). [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the clinical impact of the carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) values at the time of recurrence in gastric cancer patients. Methods: Among 790 patients with R0 resected gastric cancer without neoadjuvant therapy between 2004 and 2017, 89 recurrence cases were retrospectively evaluated. The clinical impact of CEA and CA19-9 values on recurrence sites and post-recurrent prognosis were evaluated using univariate and multivariate analyses. Results: The positive rates of CEA and CA19-9 at recurrence were significantly higher than the preoperative positive rates (CEA, 56% vs 24%; CA19-9, 37% vs 15%). Although CA19-9-positive patients at recurrence exhibited a poor survival, the difference was not significant. The positive rates of CEA at liver or lymph node recurrence were significantly higher than the preoperative positive rates. The positive rate of CA19-9 at peritoneal recurrence was significantly higher than the preoperative positive rate. CA19-9-positive patients at recurrence exhibited worse prognosis than CA19-9-negative patients, although the difference was not significant. At lymph node recurrence, CA19-9-positive patients exhibited a significantly worse survival than CA19-9-negative patients. Conclusion: In recurrent gastric cancer, the positive status of CA19-9 at recurrence might have a negative prognostic impact after recurrence; particularly, in patients with lymph node recurrence. [ABSTRACT FROM AUTHOR]

Background: A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test. Result: The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage. Conclusion: Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer often appears as postoperative metastasis or recurrence after radical surgery. Although we had previously reported that serum programmed cell death ligand 1 (PD-L1) level correlated with the prognosis of esophageal cancer, further novel biomarkers are required for more precise prediction of the prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with the cholesterol metabolism. But there was no report of relationship between serum PCSK9 antibody and cancer. Therefore, we investigated whether anti-PCSK9 antibodies could be a novel biomarker for solid cancer. Methods: Serum levels of anti-PCSK9 antibodies and antigens in patients with solid cancer were analyzed using amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The reactivity of serum antibodies against recombinant PCSK9 protein was investigated by Western blotting, and the expression of PCSK9 antigens in esophageal cancer tissues was examined by immunohistochemical staining. Results: AlphaLISA showed that serum anti-PCSK9 antibody (s-PCSK9-Ab) levels were significantly higher in patients with esophageal cancer, gastric cancer, colorectal cancer, lung cancer, and breast cancer than in healthy donors, and patients with esophageal cancer had the highest levels. The presence of serum antibody in patients was confirmed by Western blotting. There was no apparent correlation between s-PCSK9-Ab and PCSK9 antigen levels. Immunohistochemical staining demonstrated the expression of PCSK9 antigen in both the cytoplasm and nuclear compartments of esophageal squamous cell carcinoma tissue but not in normal tissue. Compared with patients with low s-PCSK9-Ab levels, those with high s-PCSK9-Ab levels had a favorable postoperative prognosis after radical surgery for esophageal cancer. In the multivariate analysis, tumor depth and s-PCSK9-Ab level were identified as independent prognostic factors. In the univariate analysis of clinicopathological features, high PCSK9 antibody levels were not associated with sex, age, location, tumor depth, lymph node status, squamous cell carcinoma antigen, or p53-Ab, whereas they correlated significantly with PD-L1 levels, which were associated with unfavorable prognosis. Correlation between s-PCSK9-Ab and PD-L1 levels was also confirmed in the logistic regression analysis; therefore, low s-PCSK9-Ab levels could discriminate another poor prognosis group other than high-PD-L1 group. Conclusions: Patients with solid cancer had higher s-PCSK9-Ab levels than healthy donors. High s-PCSK9-Ab levels indicated better prognosis for overall survival after surgery in patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). Methods: Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. Results: Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 μg/mL (range < 0.02–29.2 μg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 μg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer. Conclusions: The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates. [ABSTRACT FROM AUTHOR]

Purpose: The choice of surgical procedure for rectal prolapse (RP) is challenging because of the high recurrence and morbidity rates. We aimed to clarify whether laparoscopic suture rectopexy (lap-rectopexy) is suitable for Japanese patients with recurrent RP. Methods: We retrospectively evaluated 77 recurrent RP patients who had been treated on average 1.5 times between June 2008 and April 2016. Forty-one patients underwent lap-rectopexy and 36 underwent perineal procedures. We compared surgical outcomes and recurrence rate following surgery between the two groups. The multivariable logistic regression analysis was performed to determine risk factors of recurrent RP. Results: In patients' characteristics, significant differences were observed in the type of anesthesia (p < 0.01) and length of recurrent RP (p = 0.030). The mean operative time was significantly longer in the lap-rectopexy group (p < 0.001). Blood loss, length of hospitalization, and postoperative complications were similar. The recurrence rate was significantly lower in the lap-rectopexy group (17.1% vs. 38.9%, p = 0.032). Multivariate analysis showed that only the laparoscopic approach was significantly associated with a low recurrence following surgery (odds ratio 0.273, 95% CI − 2.568 to − 0.032). Conclusion: Lap-rectopexy is recommended for recurrent RP because its low recurrence rate and safety profile are similar to those of perineal procedures. [ABSTRACT FROM AUTHOR]

Aim: Neuroendocrine tumors (NETs) are one of the subtypes of neuroendocrine neoplasms and are defined as epithelial neoplasms with predominant neuroendocrine differentiation. The aim of this study was to clarify the clinicopathological characteristics of colorectal NETs through a nationwide retrospective study in Japan. Methods: This multicenter retrospective cohort study of NETs in Japan was conducted by the study group of the Japanese Society for Cancer of the Colon and Rectum. In this study, we aimed to clarify the characteristics of Japanese patients with colorectal NETs. This cohort study included patients with colorectal NETs who were treated from January 2011 to December 2015. Results: Most NETs developed in the lower rectum. Predictive factors of lymph node metastasis included size (>10 mm), depth of invasion (muscular propria or greater), NET grade (NET G2), depressed lesion of the tumor, and lymphovascular infiltration. In particular, depressed lesion of the tumor and lymphovascular infiltration were independent predictive factors of lymph node metastasis. The presence of an increased number of these predictive factors increased the lymph node metastasis rate. Conclusion: Surgical resection with lymph node dissection is considered in the colorectal NETs patients with predictive factors of lymph node metastasis, the number of which is correlated with incidence of lymph node metastasis. [ABSTRACT FROM AUTHOR]

We explored the effects of incisional negative pressure wound therapy in perineal wound infections after abdominoperineal resection. We retrospectively evaluated 146 patients who underwent abdominal perineal resection from December 2004 to December 2019 and compared conventional gauze dressing (controls) with incisional negative pressure wound therapy. We compared patients' characteristics, surgical factors, and perineal infection rates between groups, and patients' characteristics, surgical factors, and negative pressure therapy use between perineal infection vs non‐infection groups, as well as the risk factors for perineal infections. In the negative pressure therapy group, compared with controls, the number of men, smoking prevalence, blood transfusion, drainage via the perineal wound, and intraoperative blood loss were significantly lower (p < 0.05, p < 0.05, p < 0.05, p < 0.001, p < 0.01, respectively), and operation time was significantly longer (p < 0.05). Infections were significantly less common in the negative pressure group (p < 0.05). In the univariate analysis, the infection‐positive group had significantly higher laparoscopic surgery (p < 0.01) and negative pressure wound therapy‐free rates (p < 0.01), and significantly more intraoperative blood loss (p < 0.05). Multivariate analysis using these three factors and preoperative radiotherapy showed that incisional negative pressure wound therapy‐free status was a risk factor for infection. Incisional negative pressure wound therapy was beneficial in managing perineal wound infections after abdominoperineal resection. [ABSTRACT FROM AUTHOR]

Purpose: To establish the clinicopathological importance of serum p53 autoantibody (s-p53-Ab) titrations in patients with gastric cancer. Methods: Preoperative s-p53-Ab titers were analyzed in 448 gastric cancer patients between 2010 and 2017. Seropositive patients were divided into three groups based on their antibody titers: 1.31–10.0 U/mL (low group); 10.1–100 U/mL (medium group); and > 100 U/mL (high group). We evaluated the associations between the s-p53-Abs and clinicopathological factors, carcinoembryonic antigen (CEA) levels, and cancer antigen 19-9 (CA19-9) levels. Overall survival was analyzed by multivariate analyses. Results: A total of 72 patients (16%) were positive for s-p53-Abs. The rate of positivity for s-p53-Abs + CEA + CA19-9 was significantly higher than that for CEA + CA19-9, even in stage I gastric cancers. Gender, tumor depth, lymphatic node metastases, and distant metastases were all significantly associated with the presence of s-p53-Abs; however, overall survival was not associated with the antibodies. The patients in the high titer group (> 100 U/mL) had a relatively worse survival than those in the other groups. Conclusions: Based on our findings, s-p53-Abs improve the overall rate of positivity for detecting gastric cancer, but the prognostic value of a high s-p53-Ab titer for predicting overall survival is limited. [ABSTRACT FROM AUTHOR]

Purpose: Laser speckle flowgraphy (LSFG) is a noninvasive method for quantitative evaluation of blood flow using the mean blur rate (MBR) as the blood flow index. We investigated whether LSFG can intraoperatively detect the demarcation line after vessel dissection and reduce the incidence of anastomotic leakage (AL). Methods: This study included 36 patients who underwent left-sided colorectal surgery. First, we compared the demarcation line (determined by LSFG) with the transection line (TL) at which the marginal vessels were divided. We then measured the MBR on both sides of the TL to determine where the MBR changed significantly. We investigated the presence or absence of significant differences between the MBR on the proximal side and that on the distal side of the TL. Finally, we retrospectively compared the patient characteristics and AL rates in the LSFG group (n = 36) and control group (n = 87). Results: In total, 58.3% (21/36) of the demarcation lines determined by LSFG matched the TL. The median distance between the demarcation line determined by LSFG and the TL was 0.0 mm (0.0–12.1 mm). The MBR sharply decreased at the TL in 80.6% (29/36) of cases. The median MBR was significantly lower on the distal than proximal side. The AL rate was not significantly lower in the LSFG group than in the control group. Conclusion: LSFG accurately detected the demarcation line during surgery. However, LSFG did not reduce the incidence of AL. [ABSTRACT FROM AUTHOR]

Background: The clinical impact of monitoring serum p53 antibodies, carbohydrate antigen19-9, and carcinoembryonic antigen in patients with colorectal cancer has not been fully evaluated. Methods: A total of 420 surgically treated stage II/III colorectal cancer patients were retrospectively analyzed. Among them, 101 patients developed disease recurrence. The prognostic impact of preoperative and recurrence levels of serum p53 antibodies, carbohydrate antigen19-9, and carcinoembryonic antigen status was evaluated. Results: Although preoperative carcinoembryonic antigen- and carbohydrate antigen19-9-positive status was significantly associated with recurrence, preoperative serum p53 antibody levels were not. Among two marker combinations, carcinoembryonic antigen + serum p53 antibodies showed the highest positive rate at recurrence. Although carcinoembryonic antigen and carbohydrate antigen19-9 frequently converted from preoperative-negative status to positive status at recurrence, serum p53 antibodies converted to positive status in only one patient. Carcinoembryonic antigen- and carbohydrate antigen19-9-positive status were significant prognostic factors for overall survival after recurrence, but the presence of serum p53 antibodies at recurrence was not. Conclusions: Postoperative serum p53 antibody status should only be followed in patients with preoperative-positive status. Carcinoembryonic antigen and carbohydrate antigen19-9 should be followed even in preoperative-negative patients. Unlike carcinoembryonic antigen- and carbohydrate antigen19-9-positive status, serum p53 antibody-positive status as recurrence was not a poor prognostic indicator. [ABSTRACT FROM AUTHOR]

Background: Programmed death ligand 1 (PD‐L1) inhibitor has been approved as one of the standard therapies for various cancers. Some reports have shown that serum PD‐L1 level is associated with advanced tumor stages and poor prognosis; however, corresponding pathological information in esophageal cancer patients is lacking. Therefore, we evaluated the clinicopathological and prognostic impact of serum PD‐L1 levels in surgically treated esophageal cancer. Methods: A total of 150 patients who underwent radical resection for esophageal cancer were included in the study. Preoperative serum PD‐L1 levels were analyzed using the enzyme‐linked immunosorbent assay kit. A cutoff level of 65.6 pg/mL was used to divide the patients into two groups, and univariate and multivariate analyses were conducted to compare the clinicopathological characteristics and prognoses between these two groups. Results: Although significant associations between serum PD‐L1 levels and clinicopathological variables were observed, serum PD‐L1 level was significantly associated with high neutrophil counts, high CRP levels, low albumin levels, and high squamous cell carcinoma antigen levels. Furthermore, serum PD‐L1 level was associated with poor overall survival independent to TNM factors. Conclusions: High preoperative level of serum PD‐L1 is a prognostic factor for poor overall survival in patients with surgically treated esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Rectal amputation (RA) remains an important surgical procedure for salvage despite advances in sphincter-preserving resection, including intersphincteric resection. The aim of this study was to compare short- and long-term outcomes of RA with an initial perineal approach to those of RA with an initial abdominal approach (conventional abdominoperineal resection (APR)) for primary anorectal cancer.Methods: We retrospectively analyzed the short- and long-term outcomes of 48 patients who underwent RA with an initial perineal approach (perineal group) and 21 patients who underwent RA with an initial abdominal approach (conventional group).Results: For the perineal group, the operation time was shorter than that for the conventional group (313 vs. 388 min, p = 0.027). The postoperative complication rate was similar between the two groups (43.8 vs. 47.6%, p = 0.766). Perineal wound complications (PWCs) were significantly fewer in the perineal group than in the conventional group (22.9 vs. 57.1%, p = 0.006). All 69 patients underwent complete TME, but positive CRM was significantly higher in the conventional group than in the perineal group (0 vs. 19.0%, p = 0.011). There were no significant differences in the recurrence (43.8 vs. 47.6%, p = 0.689), 5-year disease-free survival (63.7% vs. 56.7%, p = 0.665) and 5-year overall survival rates (82.5% vs. 66.2%, p = 0.323) between the two groups.Conclusion: These data suggest that RA with an initial perineal approach for selective primary anorectal carcinoma is advantageous in minimizing PWCs and positive CRMs. Further investigations on the advantages of this approach are necessary. [ABSTRACT FROM AUTHOR]

Background: In Japan, R0 resection has been recommended for colorectal cancer patients with peritoneal metastases confined to the adjacent peritoneum and those with a few metastases to the distant peritoneum. R0 resection for M1c disease has drawn attention in Western countries and is currently considered an acceptable therapeutic option in the US National Comprehensive Cancer Network guidelines. However, clinical factors that affect the choice of R0 resection are unknown. Methods: This multicenter, prospective, observational study was conducted by the Japanese Society for Cancer of the Colon and Rectum. Colorectal cancer patients with synchronous peritoneal metastases were enrolled at 28 institutions in Japan from October 2012 to December 2016. To determine factors affecting R0 resection and R1 resection with intended R0 resection, stepwise logistic regression analyses were performed on clinical factors including age, sex, performance status (PS), body mass index, peritoneal cancer index (PCI) score, presence of ascites, presence of distant metastases, and primary tumor site. Results: R0/R1 resection was performed in 36 (31/5; 25%) of 146 patients. No distant metastases [odds ratio (OR) 52.9; 95% confidence interval (CI) 13.3–210.1; p < 0.0001], low PCI score (1–6) (OR 20.0; 95% CI 4.8–83.4; p < 0.0001), and high PS (0) (OR 2.40; 95% CI 0.66–8.68; p = 0.18) were independent factors affecting R0/R1 resection. PCI score and PS were also independent factors affecting R0/R1 resection in M1c patients without non-peritoneal distant metastases (n = 59). Conclusion: Distant metastases, PCI score, and PS are three factors which affect R0 resection for M1c disease. [ABSTRACT FROM AUTHOR]

Background: Studies investigating serum midkine (s-MK) concentrations have employed a polyclonal antibody enzyme-linked immunosorbent assay system (ELISA), because the targeted polyclonal antibody has low specificity. We used a newly developed monoclonal antibody ELISA to investigate the prognostic and diagnostic capabilities of s-MK in patients with esophageal squamous cell carcinoma. Methods: Serum samples from 102 patients with esophageal squamous cell carcinoma were analyzed using a newly developed monoclonal antibody ELISA specifically developed to detect s-MK. s-MK cutoff value was set at 421 pg/mL (mean + 2 SD) based on data from healthy controls. Clinicopathological characteristics, including tumor stage and positivity rates for two conventional tumor markers, serum p53 (s-p53-Abs) antibodies and SCC-antigen, were evaluated to assess a possible correlation with s-MK. The prognostic capability of a high s-MK level was evaluated using univariate and multivariate methods. Results: Overall positive rate for s-MK concentrations: 21%. Large tumors (> 50 mm) showed significantly higher concentrations than smaller specimens, but other clinicopathological factors were not associated with s-MK. A combination assay using SCC-antigen together with s-p53-Abs and s-MK clearly increased our capability to detect esophageal squamous cell carcinoma. Although the difference was not statistically significant (P = 0.310), the high s-MK group experienced worse overall survival than our low s-MK group. Conclusions: s-MK and conventional tumor marker combination increased our capability to detect esophageal squamous cell carcinoma. Although s-MK might be associated with esophageal squamous cell carcinoma progression, it was not an independent risk factor reducing patient survival. This study was registered as UMIN000014530. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the diagnostic impact of serum midkine (s‐MK) levels in patients with gastric cancer using a monoclonal antibody enzyme‐linked immunosorbent assay system (ELISA) to detect s‐MK levels. Methods: Serum samples were obtained from 131 patients with gastric cancer including stage I (n = 71), stage II (n = 28), stage III (n = 16), and stage IV (n = 16) before surgery. Serum samples were analyzed using ELISA to detect soluble midkine. A cut‐off value was fixed at 421 pg/mL, and the sample divided into two groups: a high s‐MK group and a low s‐MK group. Clinicopathological factors and prognosis were compared between these two groups using univariate and multivariate analyses. Comparison of two groups was analyzed by Fisher's exact probability test. Statistical significance was considered at P < 0.05. Results: High s‐MK was significantly associated with high carcinoembryonic antigen (CEA) (P < 0.01). Positive rate of s‐MK was higher than the positive rates of CEA in patients with stage I/II gastric cancer. Combination with CEA + CA19‐9 + s‐MK increased the positive rates of patients with stage I/II gastric cancer. No other clinicopathological factors were associated with s‐MK. Although the high s‐MK group showed worse overall survival than the low s‐MK group, the difference was not statistically significant. Conclusion: s‐MK level is increased even during early‐stage gastric cancer. Combined with s‐MK, the positive rate of CEA + CA19‐9 was increased in patients with stage I/II gastric cancer. s‐MK level is increased even during early‐stage gastric cancer. Combined with s‐MK, the positive rate of CEA + CA19‐9 was increased in patients with stage I/II gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The p53 protein overexpression that usually results from genetic alterations reportedly induces serum antibodies against p53. However, little information is available about the prognostic significance of perioperative serum p53 antibody (s-p53-Abs) titers in patients with esophageal squamous cell carcinoma.Methods: In this study, we retrospectively evaluated the clinical significance of perioperative s-p53-Abs in 135 patients with esophageal squamous cell carcinoma. Of these, 58 patients received neoadjuvant chemotherapy comprising 5-FU and CDDP. While the cutoff level at 1.3 U/ml indicated seropositive patients, level of 13.4 U/ml was used to identify high-titer patients. We monitored serum titers seropositive patients after surgery and evaluated the prognostic significance by the univariate and multivariate analyses.Results: In this study, 29 patients (21.5%) were positive for s-p53-Abs before treatment. The frequency of both seropositive patients and high-titer patients (> 13.4 U/ml) was not significantly associated with tumor progression. While seropositive patients did not demonstrate significant poor overall survival, high-titer patients demonstrated significant poor overall survival based on the multivariate analysis (P < 0.001). Moreover, the s-p53-Abs titer did not correlate with the response to neoadjuvant chemotherapy. Among seropositive patients, the negative conversion of s-p53-Abs more likely led to be long-term survival.Conclusions: This study determined that the high-titer of s-p53-Abs was an independent risk factor to reduce the overall survival of patients with esophageal cancer patients. The negative conversion of s-p53-Abs could be a good indicator of favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: Although serum p53 autoantibodies (s-p53-Abs) are induced even in the early stages of colorectal cancer, their positive rate is only approximately 20%. Therefore, we assessed the possibility of using other serum autoantibodies to increase the positive rates for detecting colorectal cancer.Methods: Autoantibodies against 17 tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, NY-ESO-1, p90, Sui1, HSP40, CyclinB1, HCC-22-5, c-myc, PrxVI, VEGF, HCA25a, p62, and Annexin II) were evaluated in 279 patients with colorectal cancer and 74 healthy controls. Cutoff values were fixed at mean + 3 standard deviations of serum titers in healthy controls.Results: Autoantibodies with the highest positive rates were p53 (20%), RalA (14%), HSP70 (12%), and Galectin1 (11%). Combination assays using multiple autoantibodies increased the positive rates based on the number of autoantibodies used. Positive rates of 56, 62, 66, 71, and 73% were obtained with 6, 9, 11, 14, and 17 antibodies, respectively, for the overall disease. Moreover, these autoantibodies showed relatively high positive rates even during stage 0/I disease (55 and 70% with 6 and 17 antibodies, respectively).Conclusion: The measurement of set of 17 autoantibodies allowed autoantibody profiling in patients with colorectal cancer. The combination assay of six tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, and NY-ESO-1) achieved a positive rate of 56%. Such high positive rates will be helpful for detecting colorectal cancer regardless of tumor stages. [ABSTRACT FROM AUTHOR]

Serum p53 antibody (s-p53-Ab) titers were postoperatively monitored for over 5 years in a 67-year-old man with locally advanced esophageal squamous cell carcinoma. The tumor stage was classified as clinical stage II (cT3N0M0). Serum SCC antigen (s-SCC-Ag; 6.2 ng/mL) and s-p53-Ab (3.83 U/mL) were noted to be positive before surgery. Radical esophagectomy with three-field lymph node dissection was performed without neoadjuvant therapy. Pathological findings of the surgically resected specimens revealed a stage II tumor (pT3N0M0). Postoperatively, the patients did not receive any adjuvant therapy. Although the s-SCC-Ag was found to be negative at 2 months postoperatively, s-SCC-Ag was found to be six times positive despite no signs of recurrence. The s-p53-Ab titers constantly decreased to less than the cutoff value at 6 months postoperatively and continuously decreased over 5 years postoperatively. Finally, s-p53-Ab titers became less than the detection limit value at 60 months postoperatively. No recurrence was observed throughout the postoperative course. This case report is the first to describe the five-year monitoring of postoperative changes in s-p53-Ab titers in a patient with locally advanced esophageal squamous cell carcinoma without recurrence. s-p53-Ab titers seemed to be more useful than s-SCC-Ag for disease monitoring in this case. [ABSTRACT FROM AUTHOR]

Aim: Previous studies have shown sex and age differences in anal sphincter function, but few morphological studies have focused on the quality and quantity of the nerves that control the sphincter muscles. The present study aimed to determine whether there are morphological and quantitative sex and age differences in the nerves in the conjoined longitudinal muscle. Methods: This was a single‐center, retrospective study using surgical specimens from 44 patients who underwent abdominoperineal resection between 2003 and 2012. Hematoxylin–eosin‐ and S‐100‐stained peripheral nerves (nerve fibers and ganglion cells) in the conjoined longitudinal muscle beneath the dentate line were observed microscopically. A qualitative examination assessed the degeneration score, which was based on the presence or absence of karyopyknosis, vacuolar degeneration, acidophilic degeneration of the cytoplasm, denucleation and adventitial neuronal changes. For quantitative examinations, each neuronal and muscular area was traced to calculate the neuronal area ratio in S‐100‐immunostained photomicrographs at the observation site. Results: Women had a significantly lower quantity of nerves than men. Older individuals (aged ≥80 years) had a significantly lower quantity of nerves than younger individuals. Furthermore, older individuals tended to show greater morphological changes that appeared to be a result of degeneration. Conclusions: The present findings suggest that anal hypofunction in women and older individuals might result from differences in the quantity and quality of the neurons controlling the anal sphincter muscle. Geriatr Gerontol Int 2018; 18: 495–500. [ABSTRACT FROM AUTHOR]

Purpose: A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6). Methods: Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m + leucovorin at 200 mg/m + fluorouracil as a 400 mg/m bolus followed by infusion of 2400 mg/m over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician. Results: mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3-4 were neutropenia ( n = 5), leukopenia ( n = 1), thrombocytopenia ( n = 1), febrile neutropenia ( n = 1), nausea ( n = 1), vomiting ( n = 1), and peripheral neuropathy ( n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable. Conclusions: The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]

Jumonji domain-containing 6 (JMJD6) protein has been reported to be upregulated in different cancer cells; however, to the best of our knowledge, no report has analyzed serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with cancer. Therefore, the present study evaluated the clinical significance of s-JMJD6-Abs in patients with colorectal cancer. Preoperative serum samples were analyzed from 167 patients with colorectal cancer who underwent radical surgery between April 2007 and May 2012. The pathological stages were as follows Stage I (n=47), stage II (n=56), stage III (n=49) and stage IV (n=15). In addition, 96 healthy participants were analyzed as controls. s-JMJD6-Abs were analyzed by amplified luminescent proximity homology assay-linked immunosorbent assay. The cutoff value of s-JMJD6-Abs for detecting colorectal cancer was calculated to be 5,720 using the receiver operating characteristic curve. The positive rate of s-JMJD6-Abs was 37% in patients with colorectal cancer (61 of 167), independent of carcinoembryonic antigen or carbohydrate antigen 19-9 and p53-Abs. Clinicopathological factors and prognosis were compared between the s-JMJD6-Abs-positive group and the s-JMJD6-Abs-negative group. The s-JMJD6-Ab-positive status was significantly associated with older age (P=0.03), but was not associated with other clinicopathological variables. Regarding recurrence-free survival, the s-JMJD6-positive status was a significant poor prognostic factor in both univariate (P=0.02) and multivariate (P<0.01) analyses. Similarly, regarding overall survival, the s-JMJD6-Abs-positive status was a significant poor prognostic factor in both univariate (P=0.03) and multivariate (P=0.01) analyses. In conclusion, preoperative s-JMJD6-Abs was positive in 37% of patients with colorectal cancer and may be considered an independent poor prognostic biomarker. [ABSTRACT FROM AUTHOR]

Correction to: Surgery Today https://doi.org/10.1007/s00595-022-02538-z In the original publication affiliations were published incorrectly. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

The overexpression of mutant p53 stimulates serum p53 antibody production in patients with colorectal carcinoma even in superficial tumors. Although the short-term perioperative monitoring of serum p53 antibody titers is reported to be useful in predicting tumor recurrence and patient survival in colorectal carcinoma, the clinical utility of the long-term monitoring of serum p53 antibody titers in patients with colorectal cancer remains unknown. Here, we report the 3-year monitoring of serum p53 antibody titers in a 60-year-old man with rectal cancer, clinical stage IV (T2N2M1b, lung and liver metastases), who was treated with chemotherapy and surgery. Screening tests for CEA (29.4 ng/ml), CA19-9 (41.1 U/ml), and serum p53 antibody (2170 U/ml) were positive before treatment. After chemotherapy with mFOLFOX6 + bevacizumab (B-mab), CEA and CA19-9 decreased to the normal range. However, serum p53 antibody titer remained positive (283 U/ml). After low anterior resection, the serum p53 antibody titer still remained positive (63.4 U/ml). Serum p53 antibody titer significantly changed and was associated with treatment response and tumor recurrence. In the last 6 months of the patient's life, serum p53 antibody titer gradually decreased, which possibly reflects the modification of the patient's immune response to p53 antigens. [ABSTRACT FROM AUTHOR]

Purpose: Although the definitive risk factors for parastomal hernia development remain unclear, potential contributing factors have been reported from Western countries. The aim of this study was to identify the risk factors for parastomal hernia in Japanese patients with permanent colostomies. Methods: All patients who received abdominoperineal resection or total pelvic exenteration at our institution between December 2004 and December 2011 were reviewed. Patient-related, operation-related and postoperative variables were evaluated, in both univariate and multivariate analyses, to identify the risk factors for parastomal hernia formation. Results: Of the 80 patients who underwent colostomy, 22 (27.5 %) developed a parastomal hernia during a median follow-up period of 953 days (range 15-2792 days). Hernia development was significantly associated with increasing patient age and body mass index, a laparoscopic surgical approach and the transperitoneal route of colostomy formation. In the multivariate analysis, the body mass index ( p = 0.022), the laparoscopic approach ( p = 0.043) and transperitoneal stoma creation ( p = 0.021) retained statistical significance. Conclusions: Our findings in Japanese ostomates match those from Western countries: a higher body mass index, the use of a laparoscopic approach and a transperitoneal colostomy are significant independent risk factors for parastomal hernia formation. The precise role of the stoma creation route remains unclear. [ABSTRACT FROM AUTHOR]

Background: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis. Methods: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum. Results: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases ( p < 0.0001) were associated with R0 resection. Conclusions: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential. [ABSTRACT FROM AUTHOR]

The Wilms tumor 1 gene, WT1, is overexpressed in various types of cancer, including gastric cancer. The product of WT1 is highly immunogenic and is a promising target molecule for cancer immunotherapy. The current study aimed to examine the production of WT1-specific IgG and IgM autoantibodies to identify biomarkers of diagnostic value in patients with gastric cancer. IgG antibodies that bind to WT1-derived peptides were obtained, the serum levels of which correlate with those of IgG antibodies against the WT1 protein in patients with intestinal malignancies. The serum levels of IgG and IgM antibodies against the WT1-271 peptide (271-288 amino acids) were examined in 39 healthy individuals and 97 patients with gastric cancer. The positivity cutoff value was determined according to the receiver operating characteristic curve. The association between WT1-271 IgM and the clinicopathological factors and prognosis of patients was additionally analyzed. The results revealed that serum WT1-271 IgM antibody levels in patients with gastric cancer were significantly higher than those in healthy individuals. The sensitivity and specificity of this antibody for gastric cancer were 67.0 and 71.8%, respectively; this sensitivity was improved when compared with conventional tumor markers (P<0.001). There was no statistical difference in WT1-271 IgG antibody levels between patients with gastric cancer and healthy individuals. Serum WT1-271 IgM antibody levels were not significantly associated with clinicopathological factors but were associated with unfavorable prognosis. Serum WT1-271 IgM antibody levels could serve as a diagnostic biomarker in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Metastasis to the abdominal wall including port sites after laparoscopic surgery for colorectal cancer is rare. Resection of metastatic lesions may lead to greater survival benefit if the abdominal wall metastasis is the only manifestation of recurrent disease. A 57-year-old man, who underwent laparoscopic surgery for advanced mucinous adenocarcinoma of the cecum 6 years prior, developed a nodule in the surgical wound at the lower right abdomen. Although tumor markers were within normal limits, the metastasis to the abdominal wall and abdominal cavity from the previous cecal cancer was suspected. An abdominal computed tomography scan did not provide detective evidence of metastasis. 18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) was therefore performed, which demonstrated increased 18F-fluorodeoxyglucose uptake (maximum standardized uptake value: 3.1) in the small abdominal wall nodule alone. Histopathological examination of the resected nodule confirmed the diagnosis of metastatic mucinous adenocarcinoma. Prognosis of intestinal mucinous adenocarcinoma is reported to be poorer than that of non-mucinous adenocarcinoma. In conclusion, this case suggests an important role of 18F-FDG PET/CT in early diagnosis and decision-making regarding therapy for recurrent disease in cases where a firm diagnosis of recurrent colorectal cancer is difficult to make. [ABSTRACT FROM AUTHOR]

Purpose: Fecal incontinence is a frequently observed symptom after lower rectal surgery with sphincter manipulation. The aim of this study was to evaluate a proposed modification to the fecal incontinence quality of life (FIQL) scale for the assessment of the quality of life among patients with very low rectal cancer who have undergone intersphincteric resection. Methods: A single 14-item composite scale was prepared that was derived from items in the “Lifestyle” and “Coping” subscales of the original FIQL. The scale was tested with a convenience sample of 152 postoperative patients. In addition to classic psychometric evaluation, newer statistical techniques, such as a multiple correspondence analysis and partial credit model, were performed to evaluate the item response patterns. Results: The proposed scale exhibited an item-rest correlation of 0.66–0.84 and a Cronbach’s alpha of 0.96, and was correlated with concurrently measured Social Functioning subscale of the Medical Outcomes Study Short Form 36 (−0.70), physical role limitation (−0.61), and Wexner continence grading scale (−0.61). Multiple correspondence analysis supported a uni-dimensional construct, and the partial credit model showed a varying yet overlapping range of item response thresholds across items. Several items, such as “Locating bathroom whenever going out”, reflected more a serious condition than items such as “Avoiding eating-out.” Weighted item scores based on estimated thresholds provided results comparable with those based on non-weighted scores. Conclusions: The proposed modification to the FIQL scale exhibited high internal consistency and satisfactory concurrent and convergence validity. The modified scale is practical to administer and is sensitive to a range of functional problems associated with fecal incontinence among patients who have undergone intersphincteric resection. [ABSTRACT FROM AUTHOR]

Solid cancers have a poor prognosis, and their morbidity and mortality after surgery is high. Even after radical surgery for esophageal cancer, there have been cases of early postoperative death. The present study therefore aimed to explore new tumor markers that can predict the early postoperative prognosis. To identify antibody markers, serological antigens were identified using recombinant cDNA expression cloning (SEREX). The results identified striatin 4 (STRN4) as the antigen recognized by serum IgG antibodies in patients with esophageal cancer. After performing an amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), it was revealed that when compared with healthy donors, serum anti-STRN4 antibody (STRN4-Ab) levels were significantly higher not only in patients with esophageal cancer but also to lesser extent, in those with gastric cancer, colorectal cancer, lung cancer and breast cancer. Compared with STRN4-Ab-negative patients with esophageal cancer, STRN4-Ab-positive patients had a poorer postoperative prognosis at early stages, suggesting that STRN4-Abs may be useful for predicting poor early-stage prognoses of patients with esophageal cancer. The positive diagnosis rates of esophageal cancer using the STRN4-Ab marker and conventional markers, including squamous cell carcinoma antigen and p53 antibody alone, were 26.4, 35.2 and 19.1% respectively; a result that increased up to 59.1% by combining all three markers. Serum STRN4-Ab may serve as a novel marker of esophageal cancer. [ABSTRACT FROM AUTHOR]

RalA protein, a member of the Ras superfamily of small GTPases, is a tumor antigen that induces serum RalA antibodies (s-RalA-Abs). The present study explored the clinicopathological and prognostic significance of s-RalA-Abs in patients with colorectal cancer. Serum samples were obtained from 314 patients with colorectal cancer at stage 0/I (n=71), stage II (n=86), stage III (n=78), stage IV (n=64) and recurrence (n=15). Samples were analyzed for the presence of s-RalA-Abs using ELISA. The cutoff optical density value was fixed at 0.324 (mean of heathy controls + 3 standard deviations). The overall positive rate for serum anti-RalA antibodies was 14%. The presence of s-RalA-Abs was not significantly associated with clinicopathological characteristic factors. Additionally, the s-RalA-Abs(+) group demonstrated significantly poor relapse-free survival rates. The s-RalA-Abs (+)/carcinoembryonic antigen (CEA)(+) group exhibited the worst prognosis and s-RalA-Abs(+)/CEA(+) was an independent risk factor for poor relapse-free survival. Although the positive rate was not high, s-RalA-Abs may be a useful predictor of poor relapse-free survival in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Ras-like GTPases, RalA and RalB, are members of the Ras superfamily of small GTPases. RalA expression has been shown to be associated with aggressive clinicopathological characteristics and progression in cancer. RalA protein has been shown to be involved in immune reactions in some patients with cancer; however, the clinicopathological significance of serum RalA antibody in patients with gastric cancer has not been investigated. Serum samples of 291 patients with gastric cancer and 73 healthy controls were analyzed for serum RalA antibody using enzyme-linked immunosorbent assay. A cut-off optical density value was fixed at 0.255 (mean of control + 2 standard deviations). The clinicopathological and prognostic significance of s-RalA-Abs was evaluated. The positivity rate for serum RalA antibody (s-RalA-Abs) was 15%. The presence of serum RalA antibody was higher in younger patients compared with elderly patients, however this tendency was not statistically significant. s-RalA-Abs was not associated with tumor stage. Since s-RalA-Abs was independent of CEA (carcinoembryonic antigen) and carbohydrate antigen 19-9 (CA19-9), the combination of s-RalA-Abs with CEA and CA19-9 significantly increased the detection rate of gastric cancer at each tumor stage. Patients who were tested positive for s-RalA-Abs showed poor long-term survival; however, this association was not statistically significant by multivariate analysis. In conclusion, s-RalA-Abs may be a candidate serum marker for gastric cancer, when used in combination with CEA and/or CA19-9. Additionally, the presence of s-RalA-Abs, in combination with CEA and/or CA19-9, was associated with poor survival in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Surgical management of malignant bowel obstruction carries with high morbidity and mortality. Placement of a trans-anal decompression tube (TDT) has traditionally been used for malignant bowel obstruction as a bridge to surgery. Recently, colonic metallic stent (CMS) as a bridge to surgery for malignant bowel obstruction, particularly left-sided malignant large bowel obstruction (LMLBO) caused by colorectal cancer, has been reported to be both a safe and feasible option. The aim of this retrospective study is to evaluate the clinical effects of CMS for LMLBO as a bridge to surgery compared to TDT. Methods: Between January 2000 and December 2015, we retrospectively evaluated outcomes of 59 patients with LMLBO. We compared the outcomes of 26 patients with CMS for LMLBO between 2013 and 2015 (CMS group) with those of 33 patients managed with TDT between 2003 and 2011 (TDT group) by the historical study. LMLBO was defined as a large bowel obstruction due to a colorectal cancer that was diagnosed by computed tomography and required emergent decompression. Results: All patients in the CMS group were successfully decompressed (p = 0.03) and could initiate oral intake after the procedure (p < 0.01). Outcomes in the CMS group were superior to the TDT group in the following areas: duration of tube placement (p < 0.01), surgical approach (p < 0.01), operation time (p < 0.01), number of resected lymph nodes (p < 0.001), and rate of curative resection (p < 0.01). However, no significant differences were found in the overall postoperative complication rate (p = 0.151), surgical site infection rate (p = 0.685), hospital length of stay (p = 0.502), and the need for permanent ostomy (p = 0.745). The 3-year overall survival rate of patients in the CMS and TDT groups was 73.0% and 80.9%, respectively, and this was not significant (p = 0.423). Conclusions: Treatment with CMS for patients with LMLBO as a bridge to surgery is safe and demonstrated higher rates of resumption of solid food intake and temporary discharge prior to elective surgery compared to TDT. Oncological outcomes during mid-term were equivalent. [ABSTRACT FROM AUTHOR]

Background Serum antibodies are induced even ata the eraly phase of carcinogenesis. Serum p53 antibodies (s-p53-Abs) have been developed and approved as routine blood test for monitoring esophageal squamous cell carcinoma (SCC). Recently, we have developed new ELISA systems to detect serum anti-IgG auto-antibodies against tumor antigens in patients with esophageal (SCC). In this paper, we focused on serum auto-antibodies against p53, NY-ESO-1, Galectin-1 and RalA. Methods Serum samples of patients with esophageal SCC were obtained before surgery. Serum anti-IgG antibodies against several tumor antigens were analyzed by newly developed ELISA systems. Target tumor antigens were p53, NY-ESO-1, Galectin-1 and RalA. Cut-off values were fixed using mean + 3SD of values of a total of 74 healthy controls. Changing pattern of serum p53 antibodies titers was also assessed during postoperative follow-up. Results Positive rates of serum antibodies were 18% for p53, 31% for NY-ESO-1, 10% for Galectin-1 and 9% for RalA. Positive rates of these antibodies in healthy controls were 0%. Combination assay improved positive rates without increased false positive rates as follows; p53 + NY-ESO-1 = 40%, p53 + NY-ESO-1 + Galectin-1 = 47%, p53 + NY-ESO-1 + Galectin-1 + RalA = 51%. Although some patients with extremely-high antibody titer for p53 persistently positive even after curative surgery, changing patterns of serum titers seemed to be associated with clinical outcome. Conclusion Although antibody titer of s-p53-Abs seemed to be associated with tumor burden, the titer gradually decresed at the last several months of the terminal stage. Such independent changing pattern of serum autoantibodies may have adding information to conventinal serum markers. We have developed new ELISA system to detect serum autoantibodies for patients with esophageal SCC. Although the positive rates of single serum auto-antibody were still relatively low, combination assay with plural auto-antibodies may be useful. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Purpose: A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6).Methods: Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m2 + leucovorin at 200 mg/m2 + fluorouracil as a 400 mg/m2 bolus followed by infusion of 2400 mg/m2 over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician.Results: mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3-4 were neutropenia (n = 5), leukopenia (n = 1), thrombocytopenia (n = 1), febrile neutropenia (n = 1), nausea (n = 1), vomiting (n = 1), and peripheral neuropathy (n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable.Conclusions: The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]