園田 洋史

BACKGROUND: Carcinoembryonic antigen (CEA) monitoring facilitates the detection of recurrence in patients with colorectal cancer (CRC) after resection. False-positive CEA has been reported in CRC patients with certain comorbidities or smokers. However, limited information is currently available on the frequency of and changes in falsely elevated CEA levels in patients without these conditions. MATERIALS AND METHODS: We retrospectively examined CRC patients who underwent surgical resection at our hospital between 2001 and 2017, had no recurrence for at least five years, and were free of known factors that may increase CEA. Postoperative CEA levels were retrieved until 2 years before the last contact. For comparison, we similarly selected patients who developed recurrence after resection of CRC during the same period, and CEA levels at initial presentation, at nadir, and at the time of recurrence were reviewed. The patterns of elevated CEA (>5 ng/ml) were classified as transient, repeated, or persistent based on longitudinal changes. The relationships between CEA and carbohydrate antigen 19-9, transaminases, creatinine, and C-reactive protein were examined. RESULTS: CEA elevation occurred in 90 (20%) out of 446 eligible patients without recurrence at least once during the mean postoperative period of 50.5 months, whereas CEA was >5 ng/ml in 117 (53%) of 221 patients when they developed recurrence. Twenty-seven patients without recurrence showed a transient elevation in CEA, 45 repeated elevations, and 18 a persistent elevation; the frequency of a high preoperative CEA level increased in this order. The majority (98%) of false elevations ranged between 5 and 15 ng/ml. CEA was not associated with other laboratory data. CONCLUSIONS: Unexplained CEA elevations were observed in 20% of recurrence-free CRC patients after surgery, and were classified into three patterns based on longitudinal changes. A more detailed understanding of patient-specific fluctuations in CEA will prevent unnecessary imaging studies and reduce medical costs.

Colonic metastasis from ovarian cancer is extremely rare, with only seven reported cases. A 77-year-old woman who had previously undergone surgery for ovarian cancer was admitted to a local hospital with anal bleeding. Histopathological analysis confirmed the presence of adenocarcinoma. Colonoscopy revealed a descending colon tumor. The patient was diagnosed with Union for International Cancer Control T3N0M0 descending colon cancer or colon metastasis of the ovarian cancer. Laparoscopic left colectomy was performed; intraoperative frozen section diagnosis confirmed metastasis from ovarian cancer, and the absence of invasion to the serosal surface suggested hematogenous metastasis. This is the first case of colonic metastasis from ovarian cancer that was diagnosed using an intraoperative frozen section and laparoscopically treated.

PURPOSE: We investigated the surgical outcomes of robotic low anterior resection (LAR) for lower rectal cancer after preoperative chemoradiotherapy (pCRT). METHODS: A total of 175 patients with lower rectal cancer who underwent LAR after pCRT between 2005 and 2020 were stratified into open (OS, n = 65), laparoscopic (LS, n = 64), and robotic surgery (RS, n = 46) groups. We compared the clinical, surgical, and pathological results among the three groups. RESULTS: The RS and LS groups had less blood loss than the OS group (p < 0.0001). The operating time in the RS group was longer than in the LS and OS groups (p < 0.0001). The RS group had a significantly longer mean distal margin than the LS and OS groups (25.4 mm vs. 20.7 mm and 20.3 mm, respectively; p = 0.026). There was no significant difference in the postoperative complication rate among the groups. The local recurrence rate in the RS group was comparable to those in the LS and OS groups. CONCLUSION: Robotic LAR after pCRT was performed safely for patients with advanced lower rectal cancer. It provided a longer distal margin and equivalent local control rates.

BACKGROUND: Anastomotic recurrence is thought to be caused by implantation of tumor cells to the anastomotic line; however, its risk factors and prognostic significance remain unclear. OBJECTIVE: This study aimed to clarify the risk factors for anastomotic recurrence in colorectal cancer and assess the prognosis in comparison to non-anastomotic local recurrence. DESIGN: A single-center retrospective observational study. SETTINGS: The medical records of the study participants were retrospectively collected from the Department of Surgical Oncology at the University of Tokyo Hospital database. PATIENTS: This study included 1584 patients with colorectal cancer who underwent surgical resection between January 2005 and December 2017. We focused on 15 patients who had anastomotic recurrence. MAIN OUTCOME MEASURES: The main outcome measures were the risk factors of anastomotic recurrence at the primary resection, and prognosis data in comparison to non-anastomotic local recurrence. RESULTS: There were 15 patients (0.95%) with anastomotic recurrence and 35 (2.21%) with non-anastomotic local recurrence. Univariate analysis revealed that lymph node metastasis and advanced T stage are the risk factors for anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that of those with non-anastomotic local recurrence who underwent resection. LIMITATIONS: The small number of patients with anastomotic recurrence is a major limitation of this study. Additionally, the retrospective study design may have increased the risk of selection bias. CONCLUSIONS: Lymph node metastasis and advanced T stage were associated with anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that with resected non-anastomotic local recurrence. Thus, surveillance should be carefully continued while considering the poor prognosis of patients with anastomotic recurrence. See Video Abstract at http://links.lww.com/DCR/C92 .

Odoribacter splanchnicus was recently reclassified from the genus Bacteroides. We present the first case of Odoribacter splanchnicus bacteremia following appendicitis. The species was identified using MALDI-TOF mass spectrometry and later confirmed with 16S rRNA sequencing. The patient was successfully managed with surgery and antibiotic administration for two weeks.

BACKGROUND/AIM: Even though epithelial-mesenchymal transition markers in primary tumors are identified as a helpful indicator of cancer metastasis and prognosis, their expression in lymph node metastases (LNMs) remains poorly described. We aimed to investigate the difference between snail family transcriptional repressor 1 (SNAI1) and E-cadherin expression in primary tumors and LNMs, and how it affects prognosis. PATIENTS AND METHODS: From 2010 to 2014, 127 patients who underwent radical surgery for stage III colonic adenocarcinoma without preoperative treatment were retrospectively reviewed for SNAI1 and E-cadherin expression in primary tumors and LNMs. RESULTS: High SNAI1 expression was found in 76% and 70% of primary tumors and LNMs, respectively, and low E-cadherin expression was found in 73% and 84%, respectively. High expression of SNAI1 in LNMs significantly correlated with poor overall and relapse-free survival rates. Even though the rate of liver metastasis at 5 years was similar for the groups with high and low SNAI1 expression in LNMs, the incidence in the group with low SNAI1 expression in the second year was higher than that in the first year (33% vs. 17%), whilst in the group with high SNAI1 expression, the incidence in the first year was higher than in the second year (71% vs. 29%). The rate of recurrence of lung metastasis was significantly lower when SNAI1 expression in LNMs was low (p=0.031). CONCLUSION: Low expression of SNAI1 in LNMs of colonic adenocarcinoma may indicate delayed recurrence in the liver and lung.

BACKGROUND/AIMS: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis and handsewn anastomosis for ulcerative colitis requires pulling down of the ileal pouch into the pelvis, which can be technically challenging. We examined risk factors for the pouch not reaching the anus. METHODS: Clinical records of 62 consecutive patients who were scheduled to undergo RPC with handsewn anastomosis at the University of Tokyo Hospital during 1989-2019 were reviewed. Risk factors for non-reaching were analyzed in patients in whom hand sewing was abandoned for stapled anastomosis because of nonreaching. Risk factors for non-reaching in laparoscopic RPC were separately analyzed. Anatomical indicators obtained from presurgical computed tomography (CT) were also evaluated. RESULTS: Thirty-seven of 62 cases underwent laparoscopic procedures. In 6 cases (9.7%), handsewn anastomosis was changed to stapled anastomosis because of non-reaching. Male sex and a laparoscopic approach were independent risk factors of non-reaching. Distance between the terminal of the superior mesenteric artery (SMA) ileal branch and the anus > 11 cm was a risk factor for non-reaching. CONCLUSIONS: Laparoscopic RPC with handsewn anastomosis may limit extension and induction of the ileal pouch into the anus. Preoperative CT measurement from the terminal SMA to the anus may be useful for predicting non-reaching.

BACKGROUND: The diagnosis of colitis-associated cancer or dysplasia is important in the treatment of ulcerative colitis. Immunohistochemistry of p53 along with hematoxylin and eosin (H&E) staining is conventionally used to accurately diagnose the pathological conditions. However, evaluation of p53 immunohistochemistry in all biopsied specimens is expensive and time-consuming for pathologists. In this study, we aimed to develop an artificial intelligence program using a deep learning algorithm to investigate and predict p53 immunohistochemical staining from H&E-stained slides. METHODS: We cropped 25 849 patches from whole-slide images of H&E-stained slides with the corresponding p53-stained slides. These slides were prepared from samples of 12 patients with colitis-associated neoplasia who underwent total colectomy. We annotated all glands in the whole-slide images of the H&E-stained slides and grouped them into 3 classes: p53 positive, p53 negative, and p53 null. We used 80% of the patches for training a convolutional neural network (CNN), 10% for validation, and 10% for final testing. RESULTS: The trained CNN glands were classified into 2 or 3 classes according to p53 positivity, with a mean average precision of 0.731 to 0.754. The accuracy, sensitivity (recall), specificity, positive predictive value (precision), and F-measure of the prediction of p53 immunohistochemical staining of the glands detected by the trained CNN were 0.86 to 0.91, 0.73 to 0.83, 0.91 to 0.92, 0.82 to 0.89, and 0.77 to 0.86, respectively. CONCLUSIONS: Our trained CNN can be used as a reasonable alternative to conventional p53 immunohistochemical staining in the pathological diagnosis of colitis-associated neoplasia, which is accurate, saves time, and is cost-effective.

BACKGROUND: Persistent descending mesocolon (PDM) is a fetal abnormality in which the left-sided colon is not fused to the retroperitoneum, and it is often accompanied by the adhesion between the mesocolon and small bowel mesentery. Due to its rarity, whether PDM exhibits anatomical characteristics of the inferior mesenteric artery (IMA) and left colic artery (LCA), and how the anomaly affects laparoscopic surgery are largely unknown. We investigated the branches of these arteries and outcomes of patients who underwent laparoscopic surgery. METHODS: Based on computed tomography (CT) and three-dimensional CT angiography, branching patterns of the IMA, LCA and branches originating from the LCA were analysed in 954 patients with left-sided colon or rectal cancer. PDM was diagnosed by preoperative CT colonography, and confirmed at time of surgery. The anatomical features of the vessels and short-term outcomes of laparoscopic surgery were compared between patient groups stratified by PDM. RESULTS: Twelve patients (1.3%) were diagnosed with PDM. No branching pattern of the IMA specific to PDM was noted. On the other hand, patients with PDM had fewer branches (mean: 1.0) from the LCA than those without PDM (mean: 1.8, p = 0.009). In patients undergoing laparoscopic surgery, outcomes such as operative time, intraoperative blood loss, and number of harvested nodes were comparable between the two patient groups. CONCLUSION: Few branches of the LCA characterize PDM. PDM does not complicate laparoscopic surgery of the left-sided colon and rectum. However, the above anatomical feature increases the risk of poor colonic perfusion when dividing the LCA.

BACKGROUND: Several studies have demonstrated that right-sided tumors have poorer prognosis than left-sided tumors in patients with unresectable colorectal cancer (CRC). The predictive ability of the tumor sidedness in CRC treated with chemotherapy in each sex is unclear. METHODS: Subjects were 964 unresectable recurrent patients treated with chemotherapy with stage II-III CRC after curative resection between 2004 and 2012. Post-recurrence cancer-specific survival (CSS) for each sex was examined. RESULTS: Patients were 603 males (222 right-side tumors (cecum to transverse colon) and 381 left-sided tumors (descending colon to rectum)), and 361 females (167 right-side tumors and 194 left-sided tumors). Right-sided tumors developed peritoneal recurrences in males and females. Left-sided tumors were associated with locoregional recurrences in males and with lung recurrences in females. Right-sided tumors were associated with shorter post-recurrence CSS in both sexes. In males, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.53, P < 0.0001) together with the presence of regional lymph node metastasis histopathological type of other than differentiated adenocarcinoma, the recurrence of liver only, the recurrence of peritoneal dissemination only, and relapse-free interval less than one-year. In females, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.50, P = 0.0019) together with advanced depth of invasion, the presence of regional lymph node metastasis, and recurrence of liver only. CONCLUSIONS: Primary tumor sidedness in both sexes in unresectable recurrent CRC patients treated with chemotherapy may have prognostic implications for post-recurrence CSS.

Surgical treatment of the transverse colon is difficult because of the many variations of blood vessels. We reviewed the patterns of vascular anatomy and the definition of the vessels around the splenic flexure. We searched the PubMed database for studies on the vascular anatomy of the splenic flexure that were published from January 1990 to October 2020. After screening of full texts, 33 studies were selected. The middle colic arteries were reported to arise independently without forming a common trunk in 8.9-33.3% of cases. The left colic artery was absent in 0-7.5% of cases. The accessory middle colic artery was present in 6.7-48.9% of cases and was present in > 80% of cases without a left colic artery. The reported frequency of Riolan's arch was 7.5-27.8%. The frequency was found to vary widely across studies, partially due to the ambiguous definition of Riolan's arch. A comprehensive preoperative knowledge of the branching patterns of the middle colic artery and left colic artery and the presence of collateral arteries would be helpful in surgery for colon cancer in the splenic flexure.

PURPOSE: We investigated whether or not computed tomographic colonography (CTC) is a viable alternative to double-contrast barium enema (BE) for a preoperative rectal cancer evaluation. METHODS: The size and distance from the anal canal to the lower or upper tumor borders were laterally measured in 147 patients who underwent CTC and BE. Measurements were grouped into early cancer, advanced, and after chemoradiation therapy (CRT). RESULTS: In the early and advanced cancer groups, all lesions were visualized by BE. In contrast, 3 (7.8%) early and 8 (7.3%) advanced cases, located at the anterior wall near the anal canal, were not visualized by CTC because of liquid level formation. In the CRT group, 16 (23.5%) and 4 (5.8%) cases were not visualized by CTC and BE, respectively. The BE and CTC size measurements were similar among cohorts. However, the distance from the anal canal's superior margin tended to be longer with BE, especially in early cancer. The differences in distance from the anal canal were significantly larger in the early cancer group than in the other two groups (p = 0.0024). CONCLUSION: CTC may be a viable alternative imaging modality in some cases. However, BE should be employed in anterior wall cases near the anal canal and CRT cases.

BACKGROUND: In recent years, it has become clear that, in addition to normal cytokines, phospholipid mediators play an important role in the development, growth, infiltration, and metastasis of cancer and in the cancer microenvironment. A phospholipid analysis method using tandem mass spectrometry (LC-MS/MS) with high detection sensitivity has enabled quantification of phospholipids, even when using a very small sample. To date, we had applied this MS technology to colorectal cancer tissue. Therefore, in this study, this mass spectrometry technique was applied to ulcerative colitis (UC) and UC-related colorectal cancer, and an analysis was conducted with the aim of clarifying which lysophospholipids specifically change in each type of tissue. MATERIALS AND METHODS: UC-associated colorectal cancer tissue and UC mucosa were collected from surgical specimens of colitic cancer (n=3). Cancerous and non-cancerous tissues were collected from surgical specimens from patients with sporadic colorectal cancer (n=11). After extraction from these tissues, the amounts of lysophospholipids were quantified by LC-MS/MS. In addition, lysophosphatidylserine (LPS) and lysophosphatidylinositol (LPI) were quantified for each molecular species of fatty acids. RESULTS: Compared to normal mucosa, LPI was increased 3.8-fold (p<0.001) and LPS 3.5-fold (p<0.001) in UC-related colorectal cancer. Molecular species of LPI which were increased in UC-related colorectal cancer were 18:0 (p=0.001), 16:0 (p=0.03) and 20:4 (p=0.004), and of LPS were 18:0 (p<0.001) and 22:6 (p=0.014). CONCLUSION: Lysophospholipids increased in colorectal cancer and in UC-associated colorectal cancer. In particular, LPI may have contributed significantly to colitis-associated carcinogenesis.

BACKGROUND/AIM: CD133 and hypoxia-inducible factor 1α (HIF-1α) have been reported to be affected by chemoradiotherapy (CRT), but the combinatorial assessment of these markers for prognosis after CRT has not been fully investigated. Therefore, we aimed to predict recurrence and prognosis in patients with rectal cancer by assessing changes in the expression of both CD133 and HIF-1α after CRT. MATERIALS AND METHODS: CD133 and HIF-1α expression was evaluated by immunohistochemistry in surgical specimens from 243 patients with advanced low rectal cancer who received CRT followed by curative resection. RESULTS: The positivity rate of CD133 expression showed increase with increased HIF-1α expression. The combination of these two markers showed that the CD133(+)HIF-1α(-) group exhibited a markedly shorter relapse-free survival (p=0.007), higher liver recurrence (p=0.004), and higher local recurrence (p=0.006). CONCLUSION: CD133(+)HIF-1α(-) expression after CRT is a promising marker to predict recurrence in rectal cancer.

PURPOSE: Obstructive colitis (OC) is a risk factor of anastomotic leakage in colorectal cancer resection. We aimed to clarify the relationship between the severity of OC and clinicopathological findings and to detect predictive factors of OC. METHODS: We retrospectively reviewed 43 cases of colectomy after self-expandable metallic stent placement for left-sided colorectal cancer. Preoperative diagnosis of OC was made by multiple modalities (initial computed tomography (CT), presurgical CT, and colonoscopy). We classified OC macroscopically in resected specimens into five groups (Grade 0: none, 1: mild [mild edema], 2: moderate [severe edema, redness, erosion], 3: severe [ulceration, bleeding], 4: very severe [necrosis, perforation]), and investigated the relationship between the preoperative assessment, surgical findings and the severity of OC. RESULTS: OC of Grade 2 or more (53.5%) was significantly correlated with severe edema in initial CT. There was no significant correlation between OC and anastomosis rate. The creation of covering stoma was significantly higher in the Grade 2 or more OC group. No leakage was observed in either group. CONCLUSIONS: Initial CT may be most useful for prediction of OC. It is important to make a preoperative diagnosis of OC by combining multiple modalities, which enables to determine the appropriate location for resection, anastomosis, and construction of a covering stoma.

BACKGROUND: Para-aortic lymph node (PALN) metastasis is an ominous manifestation indicating a poor prognosis in colorectal cancer (CRC) patients; however, some treatments prolong survival. In this study, we investigated predictors of prolonged survival in CRC patients after PALN metastasis. METHODS: We examined 141 patients with CRC that metastasized to the PALNs from CRC with or without extra-PALN metastasis. Among clinicopathological parameters, factors associated with survival after PALN metastasis were identified by multivariate analyses using Cox's proportional hazard models. RESULTS: The mean hemoglobin and albumin values at diagnosis were 12.3 g/dL and 3.7 g/dL, respectively. Rectal cancer was predominant (n = 81). Mutated RAS was detected in 43%. One hundred and four patients had differentiated adenocarcinoma. Patients underwent PALN dissection (n = 11), radiotherapy (n = 6), and systemic therapy (n = 120). Biologics were administered to 95 patients. The median survival time was 29.1 months. On multivariate analysis, independent factors associated with reduced survival after PALN metastasis were low albumin (hazard ratio [HR] 2.33 per -1 g/dL), mutated RAS (HR 2.55), other than differentiated adenocarcinoma (HR 2.75), rectal cancer (HR 3.38 against right-sided colon, and 3.48 against left-sided colon), the presence of extra-PALN metastasis (HR 6.56), and no use of biologics (HR 3.04). CONCLUSIONS: This study revealed that hypoalbuminemia as well as RAS mutation, undifferentiated histology, rectal cancer, other site metastasis, and no use of biologics contribute to poor prognosis in CRC patients with PALN metastasis. Nutritional management may be important for improving survival of these patients.

BACKGROUND/AIM: This study aimed to determine the effectiveness of surgical site infection (SSI) prevention approaches in rectal cancer surgery. PATIENTS AND METHODS: A total of 1,408 patients who underwent elective rectal cancer surgery between 1995 and 2017 were reviewed. Patients were divided into three groups: control group (group A, n=245), SSI prevention intervention group (group B, n=516), and laparoscopic or robotic surgery group (group C, n=647). The groups were compared in terms of SSI and anastomotic leakage (AL) incidences, and risk factors for SSI were investigated. RESULTS: The overall SSI and AL rates were 19.4% and 3.6%, respectively. These rates were significantly lower in Group C (9.3%, 1.7%), compared to Groups A (40.0%, 6.1%) and B (22.5%, 3.5%). Abdominoperineal resection, open surgery, operation time, intraoperative bleeding, lack of absorbable sutures, lack of mechanical bowel preparation, and lack of oral antibiotics were independently associated with SSI. CONCLUSION: SSI reduction after rectal cancer surgery was achieved through various intervention strategies.

BACKGROUND: Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients. METHODS: Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed. RESULTS: The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer. CONCLUSION: Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard therapy for locally advanced rectal cancer (LARC). However, the changes that the patient's physical status during CRT, such as host systemic inflammatory response, nutritional status, and muscle depletion, are still unclear. We evaluated the clinical significance of malnutrition and sarcopenia for patients with LARC undergoing CRT. PATIENTS AND METHODS: Patients with LARC treated with CRT following radical surgery at our institution between 2006 and 2016 (N = 225) were retrospectively analyzed. A new prognostic score (PNSI) was devised based on the prognostic nutritional index (PNI) and the psoas muscle mass index (PMI): patients with malnutrition/sarcopenia were scored 2; patients with one and neither abnormality were scored 1 and 0, respectively. RESULTS: Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and platelet/lymphocyte ratio increased, whereas PNI and PMI decreased after CRT. There were 130, 73, and 22 patients in the PNSI 0, 1, and 2 groups, respectively. Patients with higher PNSI had higher residual tumor size (p = 0.003), yT stage (p = 0.007), ypStage (p < 0.001), post-CRT platelet/lymphocyte ratio (p = 0.027), and post-CRT C-reactive protein/albumin ratio (p < 0.001). Post-CRT PNSI was associated with overall survival and was an independent poor prognosis factor (PNSI 1 to 0, hazard ratio 2.40, p = 0.034, PNSI 2 to 0, hazard ratio 2.66, p = 0.043) together with mesenteric lymph node metastasis, lateral lymph node metastasis, and histology. CONCLUSION: A combined score of post-CRT malnutrition/sarcopenia is promising for predicting overall survival in LARC.

BACKGROUND: This study aimed to investigate the effect of sarcopenia on the prognosis of advanced lower rectal cancer patients receiving neoadjuvant chemoradiotherapy (CRT). Sarcopenia has been recognized as an adverse factor for surgical outcomes in several malignancies. However, the impact of preoperative sarcopenia on rectal cancer patients receiving CRT is still unknown. METHODS: This retrospective study included cT3-T4 anyN M0 lower rectal cancer patients who underwent CRT followed by R0 resection at our institution between October 2003 and December 2016. CRT consisted of 5-fluorouracil-based oral chemotherapy and long course radiation (50.4 Gy/28 fr). The psoas muscle area at the third lumbar vertebra level was evaluated by computed tomography before and after CRT, and was adjusted by the square of the height to obtain the psoas muscle mass index (PMI). Sarcopenia was defined as the sex-specific lowest quartile of the PMI. We assessed the association between pre- and post-CRT sarcopenia and postoperative prognosis. RESULTS: Among 234 patients, 55 and 179 patients were categorized as sarcopenia and non-sarcopenia patients, respectively. Although post-CRT sarcopenia correlated with residual tumor size, it had no association with other pathological features. The median follow-up period was 72.9 months, and the 5-year DFS and OS were 67.0% and 85.8%, respectively. Multivariate analysis showed that post-CRT sarcopenia was independently associated with poor DFS (HR: 1.76; P = 0.036), OS (HR: 2.01; P = 0.049), and recurrence in the liver (HR: 3.01; P = 0.025). CONCLUSIONS: Sarcopenia is a poor prognostic indicator in lower advanced rectal cancer patients treated with CRT.

INTRODUCTION: Preoperative chemoradiotherapy (CRT) is the standard therapy for downstaging in locally advanced lower rectal cancer. However, it remains unclear whether rectal cancers downstaged by preoperative therapy show similar prognoses to those of the same stage without preoperative therapy. We previously demonstrated that preoperative CRT did not affect prognosis of rectal cancer with pathological T1N0 (pT1N0) stage in a single institute. Here, using a larger dataset, we compared prognoses of (y)pT1 rectal cancer stratified by the use of preoperative therapy and analyzed prognostic factors. METHODS: Cases of pT1N0 rectal cancer, registered between 2004 and 2016, were extracted from the Surveillance, Epidemiology, and End Results database. Patients were categorized as the "ypT1 group" if they had undergone preoperative therapy before surgery or as the "pT1 group" if they had undergone surgery alone. Overall survival (OS) and cancer-specific survival (CSS) between these groups of patients were compared. Factors associated with CSS and OS were identified by univariate and multivariate analyses. RESULTS: Among 3,757 eligible patients, ypT1 and pT1 groups comprised 720 and 3,037 patients, respectively. While ypT1 patients showed poorer CSS than ypT1 patients, there was no significant difference in OS. Preoperative therapy was not an independent prognostic factor for CSS or OS. Multivariate analysis identified age and histological type as significant factors associated with CSS. Sex, age, race, and number of lymph nodes dissected were identified as significant factors associated with OS. CONCLUSIONS: Prognosis among patients with (y)p T1N0 rectal cancer was similar irrespective of whether they underwent preoperative therapy, which is consistent with our previous observations.

AIM: Oxaliplatin-based adjuvant chemotherapy was demonstrated to be beneficial for stage III or high-risk stage II colorectal cancer (CRC). Moreover, a recent international collaborative trial suggested 3-months CAPOX as an alternative regimen for low-risk stage III colorectal cancer (CRC) patients. Thus, it is important to clarify the frequency and predictive markers of dose-limiting toxicities (DLTs) developed within the short-course CAPOX cycles. METHODS: We investigated CRC patients who underwent radical surgery and adjuvant CAPOX therapy at our hospital between December 2010 and February 2021. Patients who received initially reduced doses of CAPOX and those who had early recurrence were excluded. We reviewed the age, sex, comorbidities, physical, laboratory and oncological data and other perioperative factors. The associations between these variables and early DLTs within four cycles of CAPOX were examined by multivariate analyses using logistic regression models. RESULTS: Among 168 patients (96 men, mean age: 58.3 years), 120 (71%) developed early DLTs. Patients with early DLTs were predominantly women and sarcopenic and habitual alcohol consumers. On multivariate analyses, only the female sex was an independent predictive factor for early DLTs (odds ratio: 2.61, P = .027). CONCLUSION: Women were prone to early DLTs during adjuvant CAPOX in the current study. Doctors should be aware of the sex difference in the incidence of early DLTs, adjust the CAPOX dosage and provide supportive care for female CRC patients.

The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor in patients with colorectal carcinoma. However, there is no English literature on neuroendocrine tumor (NET) with EX. We report a patient with rectal NET with extracapsular metastasis of a regional lymph node that was considered to be EX. A 51-year-old Japanese woman with diabetes was referred to our hospital for further examination of a submucosal tumor in the lower rectum. She was diagnosed as having rectal NET by immunohistochemical analysis of a biopsy, and underwent laparoscopic low anterior resection with lymph node dissection and covering ileostomy. Pathological findings of the resected specimen showed that the primary tumor was NET-G1 without any lymphatic or venous invasion. A single metastatic deposit was found near the capsule of a NET-negative regional lymph node. She has been free from recurrence for nine months without adjuvant treatments. Extracapsular metastasis of NET on a dissected lymph node in our case was considered to correspond to EX as defined for colorectal carcinoma. This rare case suggests that NET can disseminate to form EX in a similar manner to colorectal carcinoma.

BACKGROUND/AIM: The inferior mesenteric arteries (IMA) are occluded in some colorectal cancer patients. This study evaluated the impact of IMA occlusion on the calibre of collateral arteries. PATIENTS AND METHODS: As an IMA obstruction model, 20 patients who underwent abdominal aortic aneurysm surgery, with ligated, excluded, or embolised IMA, were enrolled. Changes in the calibre of the left colic arteries (LCAs) and marginal arteries after surgeries were evaluated. RESULTS: The cross-sectional area of the LCA significantly increased after surgery (4.34 mm2 vs. 6.34 mm2, p=0.0009) and that of the marginal artery did not change significantly (2.69 mm2 vs. 3.01 mm2, p=0.33). CONCLUSION: The calibre of the LCA increased after IMA occlusion. The descending branch of the LCA should be confirmed preoperatively to preserve blood flow during a low tie procedure.

BACKGROUND: Enoxaparin, a low molecular weight heparin, has been used to prevent thrombotic events during major surgery without increasing the rate of hemorrhage. On the other hand, it was reported to cause liver injury, but the details of liver injury induced by prophylactic enoxaparin after abdominal surgery remain unclear. AIMS: This study aimed to clarify the relationship between prophylactic enoxaparin and liver injury after colorectal surgery, and characterize the injury profile. METHODS: We retrospectively reviewed 732 Japanese patients who underwent elective resection of the colorectum, and compared their clinicopathological background, details of surgery, postoperative complications, including liver injury, and the type of liver injury according to prophylactic use of enoxaparin. Univariate and multivariate analyses were performed to identify risk factors for liver injury during the postoperative period. RESULTS: The rate of liver injury was 8.9% for patients treated by prophylactic enoxaparin and 1.4% for those who did not receive enoxaparin after colorectal surgery (p < 0.0001). The median onset of liver injury among patients receiving enoxaparin was seven days, and the majority demonstrated the hepatocellular pattern. Enoxaparin was one of the independent risk factors for postoperative liver injury by multivariate analysis (odds ratio: 7.63, p < 0.0001). CONCLUSIONS: Prophylactic use of enoxaparin markedly increased the rate of postoperative liver injury in patients who underwent colorectal surgery. Our study confirmed that close monitoring of liver function parameters is essential for patients receiving enoxaparin during the postoperative period.

PURPOSE: The descending branch of the left colic artery (dLCA) is under-recognized and has not been clearly defined. The dLCA is often confused with the sigmoid artery (SA) originating from the left colic artery (LCA). We clarified the anatomical characteristics of the dLCA and searched for surrogate measures to identify it. METHODS: Arterial phase, venous phase, and three-dimensional images of abdominal arteries were created in 411 patients using contrast-enhanced computed tomography (CT). We analyzed the branching patterns of the inferior mesenteric artery (IMA) based on CT. The dLCA was defined as the artery originating from the LCA that flows into the marginal artery along the descending colon. We tested three candidate diagnostic measures for the dLCA using positional relationships and the segment length of vessels. RESULTS: Arteries from the LCA were present in 360 patients, among which 459 dLCAs and 165 SAs were identified in 333 and 146, respectively. By the first measure of identifying the artery with its root lateral to the inferior mesenteric vein (IMV) as the dLCA, the sensitivity, specificity, and accuracy rate were 94%, 87%, and 92%, respectively. The second measure of identifying the artery with its root higher than the root of the IMA as the dLCA and the third of identifying the artery with its root located > 27.6 mm from the root of LCA as the dLCA yielded lower accuracy rates (69% and 89%, respectively). CONCLUSION: Our study demonstrated that dLCAs are prevalent (93%) and may be easily found lateral to the IMV in clinical practice.

BACKGROUND: Applications of three-dimensional (3-D) printed solid organ models for navigation and simulation were previously reported for abdominal surgeries, and their usefulness was shown by subjective evaluation. However, thus far, no study has examined the effect of intraoperative movements for tissue handling. Novel, deformable 3-D printed models of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) were created to optimize laparoscopic right hemicolectomy. The aim of this study was to establish a method using these individualized models for use in surgical practice. METHODS: Deformable 3-D models for laparoscopic right hemicolectomy were created using a 3-D printing flexible filamentous material (thermoplastic polyurethane). Five patients with transverse colon cancer who underwent laparoscopic right hemicolectomy with D3 lymphadenectomy between April 2017 and September 2019 were enrolled in this study. Then, the created patient-specific models were compared with the previously recorded intraoperative video views. RESULTS: Transverse colon mobilization changed the spatial arrangement of the branches of the SMA and SMV. The 3-D models reproduced the intraoperative view, although approaches to the dominant vessels to complete D3 lymphadenectomy may vary. CONCLUSIONS: Deformable 3-D models of the SMA and SMV with added branches may aid in optimizing laparoscopic right hemicolectomy operations.

PURPOSE: This study aimed to elucidate the benefits and limitations of preoperative chemoradiotherapy (CRT) in rectal cancer treatment, specifically in T4b rectal cancer. METHODS: This retrospective cohort study reviewed 1014 consecutive patients with clinical T3/4a/T4b adenocarcinomas of the lower rectum, who underwent total mesorectal excision at the Department of Surgical Oncology of the University of Tokyo Hospital and 22 referral institutions affiliated with the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. Patients were divided into two cohorts: cohort 1 comprised 298 consecutive patients who underwent CRT followed by radical surgery and cohort 2 comprised 716 consecutive patients who underwent curative surgery without preoperative therapy. We assessed the prognostic differences between the two cohorts, focusing particularly on T stages. RESULTS: In T3/4a patients, cohort 1 showed a significantly lower local recurrence rate than cohort 2 (4.8% vs. 9.4%, p=0.024), but not in T4b patients (23.5% vs. 16.0%, p=0.383). In contrast, no significant differences in survival were observed between T3/4a and T4b patients. T4b classification was found to be an independent predictive factor of local recurrence in cohort 1, but not in cohort 2. CONCLUSION: In T4b rectal cancer, preoperative CRT demonstrated a limited benefit for local control and survival. In cases of suspected T4b rectal tumors, additional therapies such as induction chemotherapy to conventional CRT may contribute to better outcomes.

PURPOSE: D3 dissection is the standard treatment modality for locally advanced low rectal cancer in Japan. The benefit of lateral pelvic lymph node (LPLN) dissection (LPLND) and lymph nodes along the root of inferior mesenteric artery (253 LN) dissection (253 LND) for low rectal cancer has often been studied separately, and few studies have investigated their benefit in the same cohort. This study aimed to clarify the therapeutic significance of dissection of the LPLN in comparison to that of dissection of the 253 LN for low rectal cancer. METHODS: We retrospectively evaluated 3508 patients with treatment-naïve stage I-III low rectal cancer who underwent mesorectal excision between 1997 and 2012. They were identified from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database. The rates of metastasis, survival, and therapeutic value index (5-year overall survival (OS) rate multiplied by metastatic rate for lymph node metastasis) were compared between LPLN and 253 LN. RESULTS: The rates of LPLN metastasis and 253 LN metastasis were 17.9% and 1.5%, respectively. The 5-year OS was significantly different between patients with and without LPLN metastasis (55.0% vs 85.5%, P < 0.0001) and between patients with and without 253 LN metastasis (36.2% vs 83.3%, P < 0.0001). The therapeutic value indexes of LPLN and 253 LN were 9.85 and 0.54, respectively. CONCLUSIONS: LPLND may have more therapeutic value than 253 LND for patients with treatment-naïve low rectal cancer, although both the patients with LPLN metastasis and those with 253 LN metastasis remained to have poor prognosis.

BACKGROUND: Evaluating anorectal function using real-time tissue elastography (RTE) has not been reported. A previous study reported that in the internal anal sphincter (IAS) of surgical specimens of patients with rectal cancer who underwent abdominoperineal resection, there was an increased fibrosis trend in those who underwent pre-operative chemoradiotherapy (CRT) compared with non-CRT. We speculated that CRT might have induced sclerosis of the IAS because of fibrosis. Therefore, we aimed to establish a method of quantitating the degree of IAS hardness using RTE on endoanal ultrasonography. METHODS: RTE was performed with freehand manual compression under a defined pressure at the middle anal canal. Using the most compressive point in the strain graph, we traced the region of interest in the IAS. The strain histogram showed a frequency distribution of colours according to the degree of strain (numeric scan ranging from 0 to 255; smaller number indicated harder tissue). We defined the mean of the strain histogram as 'elasticity'. Ten patients with locally advanced rectal cancer who underwent pre-operative CRT were prospectively enrolled. We statistically evaluated the correlation between IAS elasticity and maximum resting pressure (MRP) values both at pre- and post-CRT. MRP was examined concurrently with the examination of IAS elasticity. RESULTS: Representativity of elasticity measurements was demonstrated. It revealed a trend: IAS elasticity had a moderate inverse correlation with MRP (r = 0.41, P = 0.07), regardless of whether measurements were made before or after CRT. CONCLUSION: We established a completely novel method for the assessment of elasticity of the IAS, using RTE on endoanal ultrasonography.

Preoperative chemoradiotherapy (CRT) for rectal cancer contributes to tumor down-staging and decreases locoregional recurrence. However, each patient shows a significantly different response to CRT. Therefore, the identification of predictive factors to CRT response would be beneficial to avoid unnecessary treatment. Cancer immunity in patients has been suggested to play an important role in the eradication of the tumor by CRT. In the present study, the utility of CD8+ and forkhead box P3 (FoxP3)+ tumor-infiltrating lymphocytes (TILs) and the expression of a novel immuno-regulatory factor, lactadherin (MFG-E8), in predicting CRT effectiveness in patients with rectal cancer was examined. A total of 61 patients with rectal cancer, who underwent curative resection following CRT were included in the study. The numbers of CD8+ and FoxP3+ TILs in a biopsy taken before CRT and MFG-E8 expression level in the specimens obtained at the time of the surgery after CRT were examined using immunohistochemical staining, and their association with clinicopathological characteristics, including patient survival, was determined. The tumors with more CD8+ TILs in the biopsy samples before CRT showed a significantly more favorable CRT response. The patients with tumors and a higher number of CD8+ TILs before CRT also exhibited significantly longer disease-free and overall survival times. Higher MFG-E8 expression level in post-CRT specimens was significantly associated with favorable CRT response; however, no significant association was found with any other clinicopathological characteristics, including survival time. The number of CD8+ TILs before CRT was a valuable predictor for CRT response and was associated with favorable prognosis in patients with lower rectal cancer and who were treated with CRT. High MFG-E8 expression level after CRT was also associated with a favorable CRT response.

BACKGROUND/AIM: Lysophosphatidylinositol (LPI) is a subspecies of the lysophospholipid mediators produced when phospholipase hydrolyzes membrane phosphatidylinositol. Previously, we used mass spectrometry-based lipidomics to demonstrate that LPI is selectively elevated in colorectal cancer (CRC) tissues. Here, we hypothesized that the expression levels of the LPI biosynthetic enzyme and LPI receptor - DDHD domain containing 1 (DDHD1) and G protein-coupled receptor 55 (GPR55), respectively - may be correlated with malignant potential, and we evaluated their roles in the context of CRC. MATERIALS AND METHODS: Colorectal specimens from 92 CRC patients underwent DDHD1 and GPR55 immunolabeling. Correlation between protein expression levels and clinicopathological variables was examined. RESULTS: Depth of tumor invasion was positively correlated with DDHD1 expression. Regardless of the degree of invasion depth, GPR55 was highly expressed in CRC tissues. Neither DDHD1 nor GPR55 expression levels were associated with disease-free survival. CONCLUSION: DDHD1 expression is associated with depth of tumor invasion in CRC tissues and may be involved in tumor progression.