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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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: We aimed to identify risk factors for postoperative recurrence (PR) after Altemeier's and Delorme's procedures for full-thickness rectal prolapse (FTRP)., Methods: We enrolled 127 patients who underwent Altemeier's and Delorme's procedures for FTRP between April 2008 and September 2021. We divided the 127 patients into recurrence and non-recurrence groups and conducted univariate and multivariate analyses. We used six independent variables: age, body mass index (BMI), history of surgical repair for FTRP, coexistence of prolapse in other organs, poor fixation of the rectum on defecography before surgery, length of the prolapsed rectum, and type of surgical procedure (Altemeier's or Delorme's procedures)., Results: PR developed in 51 (40.1%) patients during a mean follow-up period of 453 (range, 9-3616) days. Comparing the recurrence group (n=51) with the non-recurrence group (n=76), significant difference was observed regarding the coexistence of prolapse in other organs (p=0.017) in the univariate analysis. In the multivariate analysis, significant differences were observed in BMI (OR 1.18, 95% CI 1.030-1.350, p=0.020), coexistence of prolapse in other organs (OR 3.38, 95% CI 1.200-9.500, p=0.021), length of the prolapsed rectum (OR 1.030, 95% CI 1.010-1.060, p=0.015), poor fixity of the rectum on defecography (OR 0.332, 95% CI 0.129-0.852, p=0.022), and surgical procedures (OR 0.192, 95% CI 0.064-0.573, p=0.003)., Conclusions: The study suggested that increasing BMI, coexistence of prolapse in other organs, length of the prolapsed rectum, poor fixation of the rectum on defecography before surgery, and types of surgical procedure might be risk factors of PR after perineal surgery for FTRP., Competing Interests: Conflicts of Interest K. Funahashi received a research grant from Taiho pharmaceutical Co., Ltd. The other authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 The Japan Society of Coloproctology.)

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., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

BACKGROUND Although recurrence after surgery for esophagogastric junction (EGJ) adenocarcinoma frequently develops in the mediastinal and para-aortic lymph nodes (LN), distant LN recurrence in the mesocolon is rare. We report a rare case of ileocecal LN metastasis in the ascending mesocolon after radical surgery for an EGJ adenocarcinoma. CASE REPORT We performed subtotal esophagectomy with mediastinal and para-gastric LN dissection in a patient with an advanced EGJ adenocarcinoma. Clinicopathologically, the patient was diagnosed with type I EGJ adenocarcinoma based on Siewert's classification (pathological T3N1M0). One year after surgery, computed tomography showed enlarged lymph nodes around the ileocolic artery, and further examination was performed. Although positron emission tomography-computed tomography showed that the lesion had moderate uptake of fluorodeoxyglucose, we did not find the reason for the enlarged lymph nodes. Finally, laparoscopic ileocecal resection was performed for diagnostic and therapeutic purposes. Clinicopathological tests revealed that the specimen was a moderately differentiated adenocarcinoma, which was strongly suspected to be a metastasis of the EGJ adenocarcinoma. CONCLUSIONS We encountered a rare case of EGJ adenocarcinoma that spread to the ileocecal LN in the ascending mesocolon. To the best of our knowledge, this is the first such report in the literature to date. Laparoscopic ileocecal resection for metastasis to the ascending mesocolon seems reasonable as a local control.

Objectives The current carbohydrate antigen 125 (CA125) cutoff value demonstrated high specificity but low sensitivity. Therefore, we used new cutoff values to evaluate the clinical impact of perioperative CA125 in gastric cancer. Methods This study retrospectively analyzed 525 patients with gastric cancer (349 males and 176 females), of whom 445 patients underwent R0 resection and 80 patients underwent R1/R2 resection between 2011 and 2020. The receiver operating characteristic curve indicated preoperative and postoperative cutoff CA125 values of 15.7 IU/mL and 17.3 IU/mL, respectively, to predict overall survival. Furthermore, we analyzed changes in postoperative CA125 levels and evaluated their prognostic impact using multivariate analysis. Results The preoperative CA125-positive rate was 25%. Males, advanced TNM factors, and noncurative resection cases demonstrated significantly higher positive rates than the other group. The preoperative CA125-positive group exhibited a significantly higher noncurative resection rate than the preoperative CA125-negative group (32% versus 10%, P < 0.01). Preoperatively, CA125-positive status was an independent poor prognostic factor (P < 0.01), and at three months postoperatively, it tended to be a poor prognostic factor. Conclusions High preoperative CA125 (>15.7 IU/mL) was a significant predictor for noncurative resection and poor overall prognosis in gastric cancer. Furthermore, postoperative CA125-positive status three months postoperatively was also a potential predictor of recurrence and poor prognosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Toho University Omori Medical Center (Tokyo, Japan) issued approval M20196 19056 18002. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Moriyama et al.)

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., Competing Interests: Hideki Ueno, Ichiro Takemasa, and Yusuke Kinugasa are editorial board members of the Annals of Gastroenterological Surgery., (© 2024 The Author(s). Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Purpose: To investigate the accuracy of laser speckle flowgraphy (LSFG), a noninvasive method for the quantitative evaluation of blood flow using mean blur rate (MBR) as a blood flow parameter in the assessment of bowel blood perfusion compared to indocyanine green fluorescence angiography (ICG-FA)., Methods: We enrolled 46 patients who underwent left-sided colorectal surgery. LSFG and ICG-FA were applied to assess blood bowel perfusion, with MBR and luminance as parameters, respectively. In both measurement methods, the position where the parameter suddenly decreased was defined as the blood flow boundary line. Subsequently, the blood flow boundaries created after processing the blood vessels flowing into the intestinal tract were determined using LSFG and ICG-FA, and concordance between the two was examined. Blood flow boundaries were visually identified using color tone changes on a color map created based on MBR in LSFG and using differences in luminance in ICG-FA. The distances between the transection line and blood flow boundaries determined using each method were compared., Results: The location of blood flow boundaries matched in 65% (30/46) of cases. Although locations differed in the remaining 35% (16/46), all were located on the anal side near the transection line, and the difference was not clinically significant. The average distances between the transection line and blood flow boundary were 2.76 (SD = 3.25) and 3.71 (SD = 4.26) mm, respectively. There was no statistically significant difference between the two groups (p = 0.38)., Conclusion: LSFG was shown to have comparable accuracy to ICG-FA, and may be useful for evaluating bowel perfusion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

A 27-year-old man was referred to our hospital for a detailed examination of abdominal distention, bloody stool, anorectal pain, and weight loss. A colonoscopy revealed a circumferential type 2 tumor at 9 cm from the anal verge which was diagnosed as an adenocarcinoma based on biopsy. Contrast-enhanced CT of the abdomen showed an elevated perineal lipid concentration in the rectum(Ra)which was suspicious for clinical T4a stage, and simultaneous S7/8 liver metastasis. We strongly suspected familial adenomatous polyposis(FAP)because his mother had a past history of total proctocolectomy for FAP. We decided to first create a loop stoma at the transverse colon for the obstructive rectal cancer, and then administer neoadjuvant chemotherapy(mFOLFOX6 plus panitumumab). We performed total proctocolectomy with permanent stoma and S8 ventral resection for the liver metastasis after 5 courses of mFOLFOX6 plus panitumumab. As for clinicopathological findings, round 50 polyps were identified in the colon and rectum, and rectal cancer invaded into the muscularis propria. Finally, the patient was diagnosed as a clinically attenuated FAP with ypT2 rectal cancer.

Biosimilar(BS)drugs have recently been introduced owing to concerns with healthcare economics. In this report, we present a case in which a patient discontinued bevacizumab treatment following an allergic reaction to a BS formulation of bevacizumab but was able to safely continue treatment by switching to an original bevacizumab formulation in the late-line setting. The patient was a 66-year-old man diagnosed with unresectable colorectal cancer with synchronous multiple liver metastases. After primary tumor resection, chemotherapy including the original bevacizumab formulation was initiated. Allergic reactions to the BS formulation of bevacizumab occurred during the second-line treatment; however, in the late-line setting, switching back to the original bevacizumab formulation enabled the safe continuation of therapy. Overall, our case study suggests that switching of biologic agents may contribute to the ongoing management of chemotherapy.

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., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Purpose: The lactate dehydrogenase-to-albumin ratio (LAR) has been reported as a potential prognostic biomarker in various cancers; however, only a few pieces of information have been reported on esophageal cancer. Therefore, this study aimed to evaluate the prognostic significance of preoperative LAR in patients with esophageal cancer., Methods: This study included 236 patients (193 men and 43 women; mean age of 66 years [range, 41-83 years]) with esophageal cancer who underwent curative surgery between September 2008 and March 2020. A total of 107 patients underwent upfront surgery, and 129 patients received neoadjuvant treatment. Patients were assigned into two groups, high and low LAR, based on preoperative LAR using a cutoff value of 6.2. The clinicopathological and prognostic significance of preoperative LAR was evaluated in univariate and multivariate analyses., Results: Patients with deep tumors and neoadjuvant treatment were significantly associated with high LAR (p <0.05). The high LAR group showed a significantly poorer prognosis than the low LAR group (p <0.01). The multivariate analysis for the overall survival showed that deep tumors, lymph node metastasis, and high LAR were independent poor prognostic factors (p <0.05)., Conclusion: High LAR was a useful poor prognostic biomarker in patients with esophageal cancer.

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.

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., Competing Interests: Hideki Ueno, Hideo Baba, Jun Watanabe, and Kenichi Hakamada are editorial board members of Annals of Gastroenterological Surgery., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background: Preoperative chemoradiotherapy (CRT) for patients with rectal cancer is not yet established in Japan. We aimed to evaluate the efficacy and safety of preoperative CRT with S-1, a fixed-dose combination of tegafur, gimeracil, and oteracil potassium., Materials and Methods: We conducted a prospective, interventional, non-randomized single-center study. Radiotherapy was administered at a total dose of 45 Gy (1.8 Gy in 25 fractions) for five weeks. S-1 was administered orally for nine weeks (five weeks during and four weeks after radiotherapy) at a dose of 80 mg/m 2 /day. The endpoint was the pathological complete response (pCR) rate., Results: Twenty-eight patients were finally enrolled. The following patient characteristics were recorded: clinical Stage (II: n = 12, III: n = 16), median age (66 years, range 40-77 years), male/female ratio (20/8), and lesion site (Ra-Rb:3/Rb:23/Rb-P:2). Preoperative treatment was completed in 27 patients (96%). Treatment abandonment occurred because of diarrhea. Grade 3 or higher adverse events were observed in one (4%) patient with two events. No serious adverse events occurred in the ≥ 70 years group. The response rate was 68% in all patients and 68% among elderly patients. Radical resection was achieved in all patients, including 19 (68%) who underwent sphincter-preserving surgery. The pCR rate was 11% (three patients). The five-year disease-free survival rate was 68%, and the overall survival rate was 82%. Local recurrence occurred in only one patient five years after surgery., Conclusion: Preoperative CRT with S-1 alone may be a safe and acceptable regimen from the perspective of adverse events and oncological outcomes., Trial Registration: UMIN Clinical Trial Registry: UMIN000013598. Registered 1 April 2014, https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recpt-no=R000015887., Competing Interests: Conflict of interests K.F. received research grants from Taiho Pharmaceutical Co., Ltd., Tokyo, Japan; Yakult Honcha Co., Ltd., Tokyo, Japan; Eisai Co., Ltd., Tokyo, Japan; and Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. The other authors have no conflicts of interest associated with the present study., (© 2023 Greater Poland Cancer Centre.)

We experienced a case of resection of a metastatic umbilical tumor(Sister Mary Joseph's nodule: SMJN)derived from a pancreatic tail carcinoma. The patient was a 70-year-old woman. She visited her previous doctor with a chief complaint of lower abdominal pain and came to our hospital due to suspicion of pancreatic tail cancer. She was found to have metastases to multiple organs which was unresectable by surgery. After chemotherapy up to the second-line of treatment, she was diagnosed to have progressive disease. The decision was made to provide the best supportive care for the patient. Thereafter, the patient developed SMJN. She had hemorrhage from the tumor accompanied by body movement, and her activity of daily living became impaired. She had difficulty controlling the bleeding despite repeated hemostatic treatment at the outpatient clinic and at her home. However, she required frequent blood transfusions for her severe anemia. Therefore, we performed a resection of the SMJN to control bleeding and to relieve her symptoms. She had a good postoperative course and was discharged on the fifth postoperative day. Due to deterioration of her general condition, she expired on the 59th day after surgery. However, the patient was able to live at home without bleeding or pain by the umbilical tumor. The local resection was considered to be useful as a palliative surgical treatment for SMJN.

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., Competing Interests: Professor Hideaki Shimada received research grants from the Medical & Biological Laboratories Co., Ltd. (Nagoya, Japan). All other authors have no competing interests., (Copyright © 2023, Spandidos Publications.)

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., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

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., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objectives: We evaluated the prognostic impact of a novel C-reactive protein (CRP) cut-off value (0.6 mg/dl) and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) in stage II/III colorectal cancer., Methods: Four hundred ninety-eight patients with stage II (n = 275) or stage III (n = 223) colorectal cancer, surgically treated between January 2010 and December 2016, were analyzed. The optimal CRP cut-off value was fixed at 0.6 mg/dl to predict recurrence based on the receiver operating characteristic curve. Prognostic factors, including CRP/CEA/CA19-9 status, for relapse-free survival (RFS) were evaluated by multivariate analysis., Results: Recurrent rates were 15% and 32% in stages II and III, respectively. In stage II, CRP, CEA, and CA19-9 were not significant prognostic factors for RFS. In stage III, the RFS of the low CRP group was significantly better than that of the high CRP group ( p = 0.002). In stage III, the RFS of CRP(-)/CEA(-) or CRP(-)/CA19-9(-) was significantly better than the other group, as opposed to the RFS of the CEA(-)/CA19-9(-) group that was not. The CRP(-)/CEA(-)/CA19-9(-) group recurrence rate in stage III was significantly better than the CRP(+)/CEA(-)/CA19-9(-) group (20% vs. 50%, p = 0.006). Multivariate analysis revealed that CRP(-)/CEA(-)/CA19-9(-) ( p = 0.04) and non-T4 ( p < 0.001) were good independent prognostic factors in stage III. The CRP(-)/CEA(-)/CA19-9(-)/non-T4 group recurrence rate in stage III was 11% (8 out of 73)., Conclusions: In stage III, the CRP(-)/CEA(-)/CA19-9(-)/non-T4 group is favorable risk for recurrence., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2022 The Japan Society of Coloproctology.)

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above-mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors., Methods: A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53., Results: CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer., Conclusion: CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.

Purpose: Hypercalcemia has been reported as a poor prognostic factor in malignant tumors. However, no report has shown the clinical impact of serum calcium levels on patients with esophageal cancer. We evaluated the prognostic impact of preoperative serum calcium levels on patients with esophageal cancer., Methods: We evaluated 240 patients (197 men, 43 women; mean age, 66 years; age range, 34-85 years) with esophageal cancer who underwent radical surgery between September 2008 and December 2017. After assigning the patients to two groups (high calcium group, 8.8 mg/dL or more and low calcium group, 8.7 mg/dL or less), we compared the groups' overall survival and the clinicopathological features. The clinicopathological and prognostic significance of preoperative serum calcium levels were evaluated in a univariate and multivariate analysis., Results: The patients with deep tumors showed low serum calcium levels significantly more frequently (P <0.05). The low calcium group showed a significantly worse prognosis than the high calcium group (P <0.05). However, low serum calcium level was not an independent poor prognostic factor., Conclusions: Preoperative low serum calcium levels were associated with advanced tumors. Low serum calcium might be associated with esophageal cancer progression.

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., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ito et al.)

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)., (© 2021. The Author(s).)

Case: An 83-year-old female. At 82 years of age, the patient sought evaluation with a complaint of rectal bleeding. A 35-mm rectal gastrointestinal stromal tumor(GIST)was treated by laparoscopic ultra-low rectal resection and transanal anastomosis following trans-anal rectal dissection by perineal manipulation. Approximately 1 year later, a 20-mm metastatic lymph node within the right lateral lymph node group at the pelvic cavity was detected. The patient was diagnosed with a recurrence of rectal GIST. The patient had no symptoms and did not wish to undergo surgery. After 7 weeks of treatment with an imatinib dose reduction(200 mg), the dosage was increased and the patient was admitted to the hospital with edema of the face and lower limbs, and pleural and pericardial effusions(grade 2). After discharge from the hospital, the medication was terminated early at the patient's request. One year later, the lymph nodes had decreased in size to 7.5 mm, indicating a partial response. The treatment-free period continued, and after 5 years at 89 years of age the lymph nodes had not enlarged, thus the patient was thought to be clinically cured. We report a rare case of long-term tumor suppression using short-term low-dose imatinib therapy.

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., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

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., (© 2021. Springer Nature Singapore Pte Ltd.)

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 18 F-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., (© 2021. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ito, Hiwasa, Oshima, Yajima, Suzuki, Nanami, Sumazaki, Shiratori, Funahashi, Li, Iwadate, Yamagata, Jambaljav, Takemoto, Yokote, Takizawa and Shimada.)

Purpose: To compare efficacy and safety of dual docetaxel/nedaplatin treatment versus docetaxel alone as second-line chemotherapy for advanced esophageal cancer., Methods: In all, 36 patients with metastatic and/or recurrent esophagus squamous cell carcinoma resistant to first-line chemotherapy (fluorouracil/cisplatin) were recruited from 2011 to 2018 and randomized into two groups. Treatment response and survival were compared between the docetaxel/nedaplatin (60/80 mg/m 2 /day) group and docetaxel (70 mg/m 2 /day) group. Treatment was repeated every 3 weeks until tumor progression. Patients were followed up until March 2019 or death., Results: The frequency of Grade 3 or higher adverse events in the docetaxel/nedaplatin group (58.8%) was higher compared with the docetaxel group (26.3%) (P = 0.090). We found a treatment response rate of 52.9% and 36.8% and a median survival of 8.9 and 7.0 months in the docetaxel/nedaplatin-treated and docetaxel-treated group, respectively (P = 0.544)., Conclusion: No significant survival advantage was found for docetaxel/nedaplatin-treated patients, although there was an increased frequency of high-grade adverse events compared to docetaxel-treated patients. Because of the limited cohort size, a Phase III study based on our findings is not warranted to assess the clinical impact of docetaxel/nedaplatin treatment. This trial is registered with the University Hospital Medical Information Network (UMIN 000005877).

Objectives: There was an urgent need to create a simple, reliable hemorrhoidectomy procedure for high-risk cases in our university hospital. We performed linear pinched hemorrhoidectomy (LPH) and evaluated its effectiveness compared to conventional hemorrhoidectomy (CH)., Methods: We included 215 Goligher grade 3 and 4 hemorrhoid cases in this study. Of these cases, 167 were in the CH group, and 48 patients were in the LPH group. We retrospectively compared the lengths of hospital stay, operative times, blood loss, and complications., Results: The age tended to be higher in the LPH group (mean: CH 60 years, LPH 68 years). In the univariate analysis, LPH had more resections, shorter operative times, and less blood loss. LPH had shorter operative times in the multivariate analysis, less blood loss, and more anticoagulant use. There were no significant differences between the two groups in terms of complications. Five and two patients in the CH and LPH groups, respectively, had postoperative hemorrhage requiring hemostasis. Only the CH group had three and four cases of anal stenosis and wound edema, respectively., Conclusions: We studied simplified hemorrhoidectomy using an ultrasonic scalpel and cylindrical proctoscope in a university hospital. We found that it a useful procedure with few complications and was easy for residents to learn. We believe that advances in surgical devices will make it possible to perform safer and simpler hemorrhoidectomy in the future., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2021 by The Japan Society of Coloproctology.)

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.

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., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article., (© 2021 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Background: Laparoscopic liver resection (LLR) has been spread as minimally invasive surgery for liver disease. Advances in surgical technique and devices enabled us to perform various procedures of LLR. Indocyanine green (ICG) fluorescence imaging has been suggested as useful tool to identify liver tumors, anatomical territory of liver parenchyma, and cholangiography in open liver surgery. Due to recent development, this technology can be applied in LLR. we describe safe and effective using of the ICG fluorescence imaging during LLR., Methods: From September 2013 to August 2019, 34 patients were performed LLR using a total of 46 procedures by ICG fluorescence imaging system for purposes including identification of anatomic domain of the liver in 12 LLRs, detection of liver tumors in 30 nodules, or intraoperative cholangiography in 4 LLRs., Results: During the detection of liver tumors, 25 nodules in 30 malignant to benign tumors were positively detected (83.3%). Although there has been no publication regarding information on ICG fluorescence imaging of low grade malignant or benign tumors, we found positive emission in focal nodular hyperplasia, an angiomyolipoma, and an intraductal papillary neoplasm of the bile duct. The identification of anatomic domain in the liver was successful in all 12 LLRs with negative and positive staining techniques. In the intraoperative cholangiography, all 4 tests were successfully performed. One of 4 patients were found to have biliary leakage which was repaired intraoperatively., Conclusions: The ICG fluorescence imaging could be useful in safe and precise performance of LLR.

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.

The case is a 59‒year‒old woman. A detailed examination of fecal occult blood revealed a diagnosis of cStage Ⅳ sigmoid colon cancer cT3N1M1b(liver H2, hilar liver and celiac artery lymph nodes). After excision of the primary lesion, decided to give chemotherapy. The gene test was RAS gene mutation negative and EGFR positive, and mFOLFOX6 plus panitumumab (pani)was started as the first‒line treatment. Imaging tests at the end of 13 courses showed that the maximum diameter of liver metastases was reduced from 54 mm to 16 mm, and CEA was normalized from 93.9 ng/mL. However, metastasis was found in the hilar lymph nodes, it was judged that hepatectomy is not indicated, radiofrequency ablation therapy was performed. But FOLFIRI plus pani was restarted because metastatic liver tumor relapsed on CT 5 months later. After 6 courses, she felt tired, so I consulted her and changed to TAS‒102 plus bevacizumab. Sudden headache and vomiting appear during 3 courses, head CT revealed subarachnoid hemorrhage. No brain metastases or organic lesions such as cerebral aneurysms and stenotic lesions, the relationship with bevacizumab was strongly suspected.

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., (© 2020 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

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., (Copyright: © Ushigome et al.)

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., Competing Interests: Funding: The present study was supported in part by the Japanese Society for Cancer of the Colon and Rectum. Conflict of Interest: None declared., (© 2020 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

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.

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., (Copyright © 2020, Spandidos Publications.)

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.

Background: Although several reports have shown that diabetes is a poor prognostic factor for esophageal cancer, no reports assessed prognostic impact of hemoglobin A1c (HbA1c) in the patients with esophageal cancer. Therefore, we evaluated the prognostic significance of HbA1c in patients with esophageal cancer., Methods: A total of 137 patients with esophageal carcinoma surgically treated at our institute between 2009 and 2017 were enrolled in this retrospective study. We divided these patients into quarters according to pretreatment levels of HbA1c. We used 5.5% as a cutoff for classifying patients into low (Q1; n = 30) and high (Q2, Q3, Q4; n = 107) HbA1c groups. Univariate and multivariate analyses were then used to evaluate the clinicopathological and prognostic significance of pretreatment level of HbA1c., Results: There was no significant relationship between HbA1c level and clinicopathological factors. The low HbA1c group had a significantly worse survival rate as compared to that of the high HbA1c group (overall survival p = 0.04, relapse-free survival p = 0.02). However, the difference was not confirmed in the multivariate analysis., Conclusion: Although low level of pretreatment HbA1c might be associated with poor prognosis for patients with esophageal cancer, low HbA1c was not an independent risk factor.

Background: Since high-quality evidence on conservative treatment of acute appendicitis using antibiotics has increased, differentiation of patients with complicated appendicitis (CA) from those with simple appendicitis (SA) has become increasingly important. Previous studies have revealed that male gender, advanced age, comorbid conditions, prehospital delay, fever, and anorexia are risk factors of perforated appendicitis. Elevated serum C-reactive protein (CRP) level and hyponatremia have also been reported as predictive biomarkers of CA. However, confounding between various factors is problematic because most previous studies were limited to univariate analysis., Aim: To evaluate non-laboratory and laboratory predictive factors of CA using logistic regression analyses., Methods: We performed an exploratory, single-center, retrospective case-control study that evaluated 198 patients (83.9%) with SA and 38 patients (16.1%) with CA. Diagnoses were confirmed by computed tomography images for all cases. We compared age, sex, onset-to-visit interval, epigastric/periumbilical pain, right lower quadrant pain, nausea/vomiting, diarrhea, anorexia, medical history (of previous non-surgically treated appendicitis, diabetes, hypertension, dyslipidemia, liver cirrhosis, hemodialysis, chronic lung diseases, malignant tumors, immunosuppressant use, and antiplatelet use), vital signs, physical findings, and laboratory data to select the explanatory variates for logistic regression. Based on the univariate comparisons, we performed logistic regression for clinical differentiation between CA and SA using only non-laboratory factors and also including both non-laboratory and laboratory factors., Results: The 236 eligible patients consisted of 198 patients (83.9%) with SA and 38 patients (16.1%) with CA. The median ages were 34 years old [interquartile ranges (IR), 24-45 years] in the SA group and 49 years old (IR, 35-63 years) in the CA group ( P < 0.001). The median onset-to-visit interval was 1 d (IR, 0-1) and 1 d (IR, 1-2) in the SA and CA groups, respectively ( P < 0.001). Heart rate, body temperature, and serum CRP level in the CA group were significantly higher than in the SA group; glomerular filtration rate and serum sodium were significantly lower in the CA group. Anorexia was significantly more prevalent in the CA group. The regression model including age, onset-to-visit interval, anorexia, tachycardia, and fever as non-laboratory predictive factors of CA (Model 1) showed that age ≥ 65 years old, longer onset-to-visit interval, and anorexia had significantly high odds ratios. The logistic regression for prediction of CA including age, onset-to-visit interval, anorexia, serum CRP level, hyponatremia (serum sodium < 135 mEq/L), and glomerular filtration rate < 60 mL/min/1.73 m 2 (Model 2) showed that only elevated CRP levels had significantly high odds ratios. Under the curve values of receiver operating characteristics curves of each regression model were 0.74 for Model 1 and 0.87 for Model 2., Conclusion: Our logistic regression analysis on differentiating factors of CA from SA showed that high CRP level was a strong dose-dependent predictor of CA., Competing Interests: Conflict-of-interest statement: None., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

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.