Colorectal cancer (CRC) is a heterogeneous disease caused by the accumulation of multistep genetic alterations under the influence of genomic instability. Different backgrounds of genomic instability, such as chromosomal instability, microsatellite instability, hypermutated-single nucleotide variants, and genome stable-induced transformation in the colonic epithelium, can result in adenomas, adenocarcinomas, and metastatic tumors. Characterization of molecular subtypes and establishment of treatment policies based on each subtype will lead to better treatment outcomes and an improved selection of molecularly targeted agents.
In Japan, cancer precision medicine has been introduced in the National Health Insurance program through the addition of the cancer genomic profiling (CGP) examination. It has also become possible to access a large amount of genomic information, including information on pathogenic somatic and germline variants, incomparable to conventional diagnostic tests. This information enables us to apply research data to clinical decision-making, benefiting patients and their healthy family members.
In this article, we discuss the important molecules and signaling pathways presumed to be the driver genes of CRC progression and the signal transduction system in which they are involved.
Molecular subtypes of CRC based on CGP examinations and gene expression profiles have been established in The Cancer Genome Atlas Network with the advent of next-generation sequencing technology. We will also discuss the recommended management of secondary/germline findings, pathogenic germline variants, and presumed germline pathogenic variants obtained from CGP examination and review the current challenges to better understand these data in a new era of cancer genomic medicine.
Objectives: To evaluate 20 Kampo medicines, which comprised 6 formulas, Otsujito, Junchoto, Tokakujokito, Bofutsushosan, Mashiningan, and Keishikashakuyakudaioto, from 7 brands, to create a ranking of Kampo medicines for appropriate selection of laxatives.
Methods: The amounts of sennosides A and B, the important components showing laxative effects contained in Kampo medicines, were analysed using High Performance Liquid Chromatography.
Results: We found that the amounts of sennosides A and B were different among brands, even when they had the same formula. Furthermore, the amounts of sennosides differed when the same amounts of rhubarb were used.
Conclusions: These results suggest that the differences in amounts of sennosides are caused by the quality of the rhubarb used. Kampo medicines containing laxatives other than rhubarb, including disodium sulphate and hemp seed, had synergistic laxative effects. Thus, in the future, it may be possible to adjust laxative potency of Kampo medicines through further clinical tests.
Objectives: Fusobacterium nucleatum, which is the predominant subgingival microbial species found in chronic periodontitis, has been recently proposed as a risk factor for both the initiation and progression of colorectal cancer. We evaluated whether the number of teeth, which represents oral health, is a marker for the prognosis of patients with colorectal cancer.
Methods: This retrospective single-center study recruited 179 patients who underwent primary colorectal cancer resection with curative intent between 2015 and 2017. The baseline characteristics and survival were analyzed according to the number of teeth observed in dental panoramic radiographs taken before surgical resection as a part of the perioperative surveillance for oral function and hygiene.
Results: The median number of teeth was 20 (interquartile range: 6-25), including 28 patients with no teeth. Patients with 20 or more teeth had better overall survival (p = 0.002) and colorectal cancer-specific survival (p = 0.032) than those with less than 20 teeth. Multivariate analyses confirmed that the number of teeth was a significant prognostic factor for overall survival (p = 0.045) but not for colorectal cancer-specific survival (p = 0.258). We also took a propensity score-weighting approach using inverse probability weighting, and the p-values of the number of teeth were 0.032 for overall survival and 0.180 for colorectal cancer-specific survival.
Conclusions: A low number of teeth, which can be easily and noninvasively assessed, has been a poor prognostic factor for overall survival in colorectal cancer patients who underwent surgery with curative intent.
Objectives: To evaluate future problems in colorectal cancer surgery for elderly patients.
Methods: We conducted a retrospective review of patients receiving colorectal cancer surgery in our hospital from January 2010 to December 2018. Patients were divided into the ≥ 85-year-old patient group and the younger patient group. We compared patient backgrounds, surgical outcomes (surgical procedure, reduction of lymph node dissection range, operative duration, and blood loss), postoperative short-term outcomes (mortality, morbidity, and postoperative length of stay) and prognosis.
Results: We performed colorectal cancer surgery on 1,240 patients during the study period. Of them, 109 (8.7%) were ≥ 85 years old, and 1,131 (91.2%) were < 85 years old. The American Society of Anesthesiologists physical status (ASA-PS) was significantly poorer in the elderly group than in the younger group and patients with a history of cardiac disease and anticoagulant use were significantly more in the elderly group. The rate of reduction of lymph node dissection range was significantly higher in the elderly group (16.8% vs. 3.8%, p < 0.05). Overall morbidity was significantly higher in the elderly group (42.2% vs. 21.9%, p < 0.05), as were the respective frequencies of pneumonia and thromboembolism (8.2% vs. 0.7%, p < 0.05 and 3.6% vs. 0.8%, p < 0.05, respectively). Postoperative hospital stay was significantly longer in the elderly group (17 vs. 12 days, p < 0.05). Overall survival was significantly lower in the elderly group (p < 0.05), but relapse-free survival and colorectal cancer-specific survival were not statistically different between the groups (p = 0.05 and p = 0.15, respectively).
Conclusions: Prevention of postoperative pneumonia and thromboembolism remains a problem. After proper assessment and careful management of peri-operative surgical risks, surgery can be indicated in elderly patients.
Objectives: Anastomotic leakage is one of the most severe complications of rectal cancer surgery. A diverting ileostomy was constructed for the purpose of reducing anastomotic failure risk. Outlet obstruction (OO) is one of the complications of diverting stoma that results in a lack of fecal discharge from the stoma. Detailed etiologies and preventive measures for outlet obstruction have not yet been identified.
Methods: We studied 125 patients who underwent rectal resection, anastomosis, and elective ileostomy. We evaluated the incidence of outlet obstruction and looked for any relationship between perioperative factors and outlet obstruction.
Results: Outlet obstruction was detected in 20 cases (16.0%). Outlet obstruction occurred 9 days after surgery in most cases. Inserting a decompressing tube improved obstructive symptoms in 4 days. Patients were divided into two cohorts according to the occurrence of outlet obstruction. Postoperative hospital stay was longer in the outlet obstruction group (19 vs. 15 days; p = 0.0003). A multivariate analysis identified that younger patients, a postoperative thicker rectus abdominis muscle at the stoma passage and high output syndrome were independent risk factors for outlet obstruction.
Conclusions: Younger patients, a postoperative thicker rectus abdominis muscle at stoma passage and high output syndrome were independent risk factors for outlet obstruction.
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.
Objectives: The present study aimed to explore whether symptoms of anal incontinence (AI) in patients who used electric bidet toilets to clean the anus may improve after discontinuing bidet use.
Methods: Fifty-three patients with AI who habitually used the bidets before or after defecation and were examined between June 2019 and September 2020 were included in this retrospective study. Questionnaires on Likert-scaled items that assessed bidet use were administered at baseline. The sum of all points was regarded as the "bidet use score". The patients were instructed to discontinue bidets until subsequent examination. Incontinence severity was documented using the fecal incontinence severity index (FISI) score.
Results: Follow-up data were available for 49 patients (92%). Of those, 43 had fecal incontinence and 6 had only mucus discharge at baseline. The median duration between the baseline and follow-up was 4 weeks. The median FISI score was significantly reduced at the follow-up [baseline vs. follow-up: 15 (range: 3-43) vs. 10 (range: 0-43); P < 0.0001]. The incidence of fecal incontinence was significantly lower at the follow-up than at the baseline (59% vs. 88%, P = 0.003). A higher maximum squeeze pressure and the absence of associated factors that may cause AI (such as rectoanal intussusception and/or rectocele, mucosal prolapse, and previous anorectal surgery) were significantly associated with a reduction of at least 50% in the FISI scores at follow-up; however, this was not observed for the bidet use score.
Conclusions: Our findings suggest that electric bidet use is a possible cause of AI.
Objectives: Surgery for colonic perforation has high morbidity and mortality rates. Predicting complications preoperatively would help improve short-term outcomes; however, no predictive risk stratification model exists to date. Therefore, the current study aimed to determine risk factors for complications after colonic perforation surgery and use machine learning to construct a predictive model.
Methods: This retrospective study included 51 patients who underwent emergency surgery for colorectal perforation. We investigated the connection between overall complications and several preoperative indicators, such as lactate and the Glasgow Prognostic Score. Moreover, we used the classification and regression tree (CART), a machine-learning method, to establish an optimal prediction model for complications.
Results: Overall complications occurred in 32 patients (62.7%). Multivariate logistic regression analysis identified high lactate levels [odds ratio (OR), 1.86; 95% confidence interval (CI), 1.07-3.22; p = 0.027] and hypoalbuminemia (OR, 2.56; 95% CI, 1.06-6.25; p = 0.036) as predictors of overall complications. According to the CART analysis, the albumin level was the most important parameter, followed by the lactate level. This prediction model had an area under the curve (AUC) of 0.830.
Conclusions: Our results determined that both preoperative albumin and lactate levels were valuable predictors of postoperative complications among patients who underwent colonic perforation surgery. The CART analysis determined optimal cutoff levels with high AUC values to predict complications, making both indicators clinically easier to use for decision making.
Objectives: Systemic inflammatory response is strongly associated with poor oncological outcome in colorectal cancer (CRC). Perioperative inflammation caused by surgical stress can lead to the development of postoperative infectious complications (PIC) as well as cancer-related inflammation. We aimed to evaluate the prognostic potential of perioperative systemic inflammation by calculating the time-dependent cumulative C-reactive protein (CRP) levels during the perioperative period.
Methods: We analyzed clinicopathological data from 540 patients with CRC who underwent potentially curative surgery at our institution. The time-dependent aggregated CRP level was denoted "cumulative CRP," which represents the area under the line of time (days) and the CRP levels preoperatively and on postoperative days 1, 3, and 7.
Results: Cumulative CRP was significantly higher in patients with CRC undergoing open surgery than in patients undergoing laparoscopic surgery. In multivariate analysis, high cumulative CRP was an independent prognostic factor for disease-free survival (DFS) and overall survival (OS) in both the laparoscopic and open surgery groups. Patients with CRC and high cumulative CRP had significantly poorer DFS and OS than those with low cumulative CRP, including those patients without PIC.
Conclusions: Cumulative CRP is an independent predictive marker of OS and DFS in patients with CRC who undergo curative surgery.
Objectives: This retrospective, observational study aimed to evaluate the tolerance and efficacy of polyethylene glycol 4000 plus electrolytes (PEG 4000) in elderly patients with chronic constipation.
Methods: PEG 4000 powder was orally administered once daily at a dose of one or two 6.9 g sachets as the initial dose. The outcome measures were changes in the Cleveland Clinic Constipation Score (CCCS) and the Bristol Stool Form Scale (BSFS) value before and 2 weeks after drug administration.
Results: This study included 324 patients aged ≥65 years (mean age: 78.6 ± 7.6 years, range: 65-100 years) with chronic constipation. The total CCCS was noted to significantly improve from 11.5 ± 4.6 at baseline to 7.4 ± 5.2 after drug administration. All CCCS sub-scores also improved significantly. The average BSFS value at baseline (2.5 ± 1.6) significantly improved to 4.3 ± 1.1 after treatment. Side effects (16 events) were observed in 13 patients (4.0%), with the most common being diarrhea (6 patients, 1.9%). All events were mild in severity, with none of the symptoms being serious. The cumulative treatment continuation rate at 1 year was 83.1%.
Conclusions: PEG 4000 treatment was safe, effective, and well tolerated in elderly patients with chronic constipation. Thus, it appears to be a promising drug that can be continued for a long time.
Objectives: This study aims to clarify the bowel habit, change of bowel movement throughout the cycle of menstruation, and toilet use in Japanese medical personnel.
Methods: A questionnaire survey was completed by Japanese medical personnel after listening to lectures on bowel disorders. Constipation was defined according to Rome III criteria, whereas diarrhea was defined as Bristol stool form scale type 6 and 7.
Results: In total, 463 persons (mean age, 35.6 years, range 20-91, male/female/no answer: 132/324/7) have completed the questionnaire. Constipation was significantly more often observed in females (male/female: 3%/31%, p > 0.001, Chi-squared test), while diarrhea was noted to be less in females (male/female: 1%/7%). Constipation was observed in 20% of participants in their 20s, and the constipation rate was observed to gradually increase with age. It was observed in 45% of participants in their 70s or older. Bowel movement changed to constipation around menstruation in 18% of females and changed to diarrhea in 43% of females. Constipation often occurred before menstruation and diarrhea during menstruation. Only 2% of participants used a Japanese-style toilet, and 5% of participants claimed that they were unable to pass a stool on a Japanese-style toilet.
Conclusions: Constipation was significantly more frequent in females and increased with age among female Japanese medical personnel. Change of bowel movement occurred in 61% of females around menstruation. Five percent of participants were unable to pass stools on a Japanese-style toilet.
Objectives: Few studies have examined the correlations between the arteries and veins of the right colon. In this study, we aimed to use high-resolution CT scans to understand the vascular anatomy of Henle's gastrocolic trunk and review the terminology describing the arteries and veins of the right colon.
Methods: This retrospective study has examined patients who underwent laparoscopic colectomy for right colon cancer in a single institution in Japan. Scans from consecutive patients who underwent surgery between October 2017 and March 2020 (n = 165) were examined. Preoperative CT images were used to create multiplanar reformation images and volume rendering images.
Results: Among the 139 patients with Henle's gastrocolic trunk (GCT) present, arteries accompanying the accessory right colic vein (ARCV) were most common on the right branch of the middle colic artery (MCA) (71.2%), followed by the right colic artery (RCA) (19.4%); meanwhile, 9.4% of the patients had no accompanying arteries. Of patients with no accompanying arteries to the ARCV, RCA was present in 15.4%. Among the 26 patients with no GCT, the right colic vein (RCV) existed in 15 patients, with the artery accompanying the RCV most commonly being the right branch of the MCA (66.6%), followed by the RCA (33.3%).
Conclusions: Irrespective of the presence of GCT, approximately 70% of the arteries accompanying the drainage vein from the right colon were the right branch of the MCA. We suggest that vascular branch formation be considered preoperatively in surgical management for right colon cancer.
Objectives: The colonoscopic identification of stigmata of recent hemorrhage (SRH) in patients with colonic diverticular bleeding (CDB) is difficult. Factors that influence the identification of SRH in the diagnosis of CDB were investigated.
Methods: This was a retrospective study of 487 early colonoscopy patients with acute lower gastrointestinal bleeding who were diagnosed with CDB. Comorbidities, medications, bowel preparation, use of a transparent cap, use of a water-jet scope, colonoscopy by an expert colonoscopist, and use of a nontraumatic (NT) tube were assessed. A multivariate analysis was used to estimate the odds ratio and 95% confidence interval.
Results: Of the 487 colonoscopy patients diagnosed with CDB, 191 (39%) were definitively identified with SRH. The use of a transparent cap, a water-jet scope, an expert colonoscopist, and an NT tube were independent predictive factors for SRH on univariate analysis. A multivariable logistic regression model showed that colonoscopy by an expert colonoscopist and the use of an NT tube were predictive factors for SRH.
Conclusions: Intradiverticular water injection with an NT tube by an expert colonoscopist is useful in identifying CDB, and may help achieve effective endoscopic hemostasis.
Objectives: Recent findings suggest that the combination of mechanical bowel preparation (MBP) and preoperative oral antibiotics (OA) decreases the risk of surgical site infection (SSI) in colorectal surgery; however, this remains controversial. The present study examined the efficacy of OA plus MBP in laparoscopic colorectal cancer (CRC) surgery using propensity score matching (PSM).
Methods: A total of 1080 patients with CRC underwent MBP followed by laparoscopic surgery between 2007 and 2019. OA was administered to all patients with CRC who underwent colectomy from 2018. PSM was performed to compare the effects of OA plus MBP (OA) versus MBP only (non-OA) on the rate of superficial SSI.
Results: Overall, 128 patients received OA. Significant differences were observed in age, the American Society of Anesthesiologists performance status (ASA-PS), liver disease, and preoperative serum albumin (Alb) between the OA and non-OA groups. The enrolled patients were matched using PSM into two groups based on the following factors: sex, age, body mass index, ASA-PS, diabetes mellitus, liver disease, Alb, and tumor location, which resulted in the disappearance of significant differences. A univariate analysis showed that blood loss of 100 g or more, non-OA, and preoperative chemotherapy or radiation correlated with SSI (p = 0.021, 0.010, 0.038). A multivariate analysis of these three variables identified blood loss of 100 g or more and non-OA as independent risk factors for SSI (hazard ratio (HR): 3.238, p = 0.031; HR: 2.547, p = 0.033).
Conclusions: The present study revealed that OA plus MBP markedly reduced SSI rate. OA with MBP needs to be adopted in laparoscopic CRC surgery.
Pelvic tumor resection with sacrectomy for locally recurrent rectal cancer is a challenging operation with a high complication rate and poor prognosis. We report a case of pelvic tumor resection with sacrectomy by transperineal endoscopy following laparoscopic dissection for locally recurrent rectal cancer. A 70-year-old man underwent laparoscopic abdominoperineal resection for rectal cancer and was diagnosed with local pelvic recurrence on follow-up computed tomography (CT) three years postoperatively. As the recurrence was in contact with the front of the sacrum, we concluded that distal sacrectomy was necessary to ensure a surgical margin. We safely performed combined laparoscopic and transperineal endoscopic pelvic tumor resection with sacrectomy by exposing the surface of the sacrum from both abdominal and transperineal approach. The operative time was 200 minutes, with minimal blood loss. There was no tumor exposure on the surgically dissected surface, and the patient was discharged without complications 14 days postoperatively. Transperineal endoscopy may be useful for pelvic tumor resection with sacrectomy for locally recurrent rectal cancer.