Publications by authors named "Manabu Kaneko"

94 Publications

Prognostic Impact and Clinicopathological Features of Multiple Colorectal Cancers and Extracolorectal Malignancies: A Nationwide Retrospective Study.

Digestion 2021 Jul 14:1-10. Epub 2021 Jul 14.

Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan.

Introduction: Multiple primary malignancies (MPMs) are likely to develop in patients with colorectal cancer (CRC); however, their prognoses are unclear. This study aims to investigate the prognostic impacts and clinicopathological features of multiple CRCs and extracolorectal malignancies (EMs) with CRC.

Methods: We retrospectively evaluated a total of 22,628 patients with stage I-III CRC who underwent curative resection at 24 referral institutes in Japan between January 2004 and December 2012. MPMs were classified as synchronous CRCs (SCRCs), metachronous CRCs, synchronous EMs (SEMs), and metachronous EMs.

Results: The presence of SCRCs (odds ratio 1.54, p < 0.001) was independently associated with SEMs in the multivariate analyses. SEMs were the strongest poor prognostic factor for OS (hazard ratio [HR] 2.21, p < 0.001) and RFS (HR 1.69, p < 0.001) compared with age, sex, and primary T and N factors. The incidence of stomach cancer was the highest in EMs, followed by lung, breast, and prostate cancers. Multiple CRCs were evenly distributed throughout the right-side colon to the rectum.

Discussion/conclusion: SEMs were a strong poor prognostic factor for patients with stage I-III CRC. Patients with CRC, particularly those with SCRCs, should be surveyed for SEMs, especially for stomach and lung cancers.
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http://dx.doi.org/10.1159/000517271DOI Listing
July 2021

Analysis of the Positional Relationship Among the Operator, Camera, and Monitor: Overcoming the Difficulties of Mirror-image Conditions During Laparoscopic Surgery.

Surg Laparosc Endosc Percutan Tech 2021 Jun 23. Epub 2021 Jun 23.

Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.

Background: Although methods to overcome difficulties associated with mirror-image conditions have been investigated, the ideal spatial relationship among the operator line of sight, monitor location, and camera location remains unclear. Moreover, the best training method for improving laparoscopic surgical skills under varying operator line of sight, camera, and monitor positions is unknown. We aimed to investigate the role of laparoscopic training under mirror-image conditions in improving surgical efficiency and whether prior surgical experience affects such training.

Methods: This prospective study was conducted at the Department of Surgical Oncology, Tokyo University, Japan. Twenty-five surgeons participated. Novice (n=14), trained (n=7), and expert (n=4) participants performed the simulated task in a box trainer while varying the positional relationships among the surgeons, camera, and monitor. Five patterns were repeatedly performed 5 times per day for 4 days over 2 weeks.

Results: The most significant differences in terms of the time required to complete the task under mirror-image conditions among the 3 groups were on day 1 (novices: 185.8 s, trained: 79.7 s, and experts: 46.5 s, P=0.009). However, after 4 days of training, the corresponding times did not differ among the 3 groups (26.0, 30.7, and 23.1 s, respectively; P=0.415). Laparoscopic training was sufficiently effective under mirror-image conditions.

Conclusions: Mirror-image surgical conditions provided the most difficult setting, because surgeons and assistants often became disoriented, and task performance was most degraded. However, just 4 days of training was found to be sufficient to overcome the difficulties encountered while performing laparoscopic procedures under mirror-image conditions.
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http://dx.doi.org/10.1097/SLE.0000000000000955DOI Listing
June 2021

Ectopic decidua of the appendix: a case report.

Surg Case Rep 2021 May 11;7(1):117. Epub 2021 May 11.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Ectopic decidua is the presence of decidual tissue outside the uterus. Ectopic decidua of the appendix is a rare entity that can present with abdominal symptoms mimicking appendicitis. We report a case of a 39-year-old female patient at 27 weeks gestational age with a 2-day history of right lower quadrant abdominal pain.

Case Presentation: The patient was referred to our hospital with suspicion of either acute appendicitis or threatened rupture of the uterus, the latter of which was considered unlikely following close examination. Therefore, she underwent emergency appendectomy via laparotomy. Microscopic examination revealed decidual tissue with myxoid degeneration in the subserosal layer of the tip side of the appendix, without endometriosis, which was compatible with ectopic decidua (deciduosis).

Conclusions: Because it is extremely difficult to distinguish ectopic decidua of the appendix from acute appendicitis, even with various imaging modalities, we should be aware that ectopic decidua of the appendix is a differential diagnosis for acute appendicitis in pregnant women.
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http://dx.doi.org/10.1186/s40792-021-01204-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110666PMC
May 2021

Risk factors for non-reaching of ileal pouch to the anus in laparoscopic restorative proctocolectomy with handsewn anastomosis for ulcerative colitis.

Intest Res 2021 Mar 12. Epub 2021 Mar 12.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

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.
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http://dx.doi.org/10.5217/ir.2020.00158DOI Listing
March 2021

Establishing a novel method for assessing elasticity of internal anal sphincter using ultrasonic real-time tissue elastography.

ANZ J Surg 2021 06 12;91(6):E360-E366. Epub 2021 Apr 12.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/ans.16760DOI Listing
June 2021

Clinical significance of CD8 and FoxP3 tumor-infiltrating lymphocytes and MFG-E8 expression in lower rectal cancer with preoperative chemoradiotherapy.

Mol Clin Oncol 2021 May 5;14(5):87. Epub 2021 Mar 5.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

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.
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http://dx.doi.org/10.3892/mco.2021.2249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976375PMC
May 2021

Establishment of deformable three-dimensional printed models for laparoscopic right hemicolectomy in transverse colon cancer.

ANZ J Surg 2021 Jul 26;91(7-8):E493-E499. Epub 2021 Feb 26.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/ans.16659DOI Listing
July 2021

Epithelial-mesenchymal transition and metastatic ability of CD133 colorectal cancer stem-like cells under hypoxia.

Oncol Lett 2021 Jan 9;21(1):19. Epub 2020 Nov 9.

Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8655, Japan.

Although CD133 is a representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia remains unclear. Therefore, the present study aimed to investigate the associations between CD133, the epithelial-mesenchymal transition and distant metastasis in colorectal cancer. CD133 and CD133 cells were isolated from a single colorectal cancer cell line LoVo, and their adhesive and migratory properties were compared under hypoxic conditions. Immunostaining analysis was performed to determine CD133 expression in clinical samples of primary tumors, as well as liver and peritoneal metastases. Under hypoxia, the expression levels of hypoxia-inducible factor (HIF)-1α and the epithelial-mesenchymal transition markers N-cadherin and vimentin were significantly higher in the CD133 compared with those in the CD133 cells. Furthermore, the migratory ability of the CD133 cells was higher compared with that of the CD133 cells under hypoxia. By contrast, the expression levels of β1 integrin were significantly lower in the CD133 cells under hypoxia compared with those in the CD133 cells. Immunohistochemical analysis of clinical samples revealed that the levels of CD133 expression in metastatic tissues from the liver were significantly higher compared with those in the corresponding primary tumors, whereas CD133 expression levels in peritoneal metastatic tissues were significantly lower compared with those in the corresponding primary tumors. In conclusion, compared with the CD133 cells, the CD133 colorectal cancer cells exhibited enhanced levels of HIF-1α expression and tumor cell migration during hypoxia. This was associated with an increased ability of epithelial-mesenchymal transition, possibly leading to the acquisition of an increased hematogenous metastatic potential and eventually resulting in liver metastasis. High β1 integrin expression levels in the CD133 cells under hypoxia may serve a key role in cell adhesion to the peritoneum, resulting in peritoneal metastasis.
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http://dx.doi.org/10.3892/ol.2020.12280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681219PMC
January 2021

Oncological Outcomes of Pathological T1 Lower Rectal Cancer Patients With or Without Preoperative Chemoradiotherapy.

In Vivo 2020 Nov-Dec;34(6):3559-3564

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: It remains unclear whether rectal cancers down-staged by preoperative chemoradiotherapy (CRT) have similar prognoses to those of the same stage without preoperative CRT. We compared prognoses of pT1 rectal cancer patients stratified by preoperative CRT.

Patients And Methods: We retrieved data of patients with pathological T1 rectal cancer between 2003 and 2020. Patients were divided into the "ypT1 group" who received preoperative CRT following surgery and the "pT1 group" who underwent surgery alone. Factors associated with relapse-free survival (RFS) were investigated.

Results: Among 86 patients, ypT1 and pT1 groups comprised 18 and 68 patients, respectively. There was no significant difference in RFS between the groups (p=0.19). Tumor location within 5 cm from the anal verge was associated with recurrence (hazard ratio: 0.13, p=0.034).

Conclusion: The prognosis of patients with ypT1 rectal cancer was similar to that of patients with pT1. Low tumor location was a poor prognostic factor.
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http://dx.doi.org/10.21873/invivo.12199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811633PMC
June 2021

Low preoperative maximum squeezing pressure evaluated by anorectal manometry is a risk factor for non-reversal of diverting stoma.

Langenbecks Arch Surg 2021 Feb 19;406(1):131-139. Epub 2020 Oct 19.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: A diverting stoma is created to prevent anastomotic leakage and related complications impairing sphincteric function in rectal surgery. However, diverting stoma may be left unclosed. This study is aimed to analyze preoperative factors including anorectal manometric data associated with diverting stoma non-reversal before rectal surgery. We also addressed complications related to diverting stoma in patients undergoing surgery for rectal malignant tumor.

Methods: A total of 203 patients with rectal malignant tumor who underwent sphincter-preserving surgery with diverting stoma were retrospectively evaluated. The risk factors for non-reversal of diverting stoma were identified by univariate and multivariate analyses. For these analyses, anorectal manometric data were measured before rectal surgery. The association between stoma-related complications and other clinicopathological features was also analyzed.

Results: During the median follow-up of 46.4 months, 24% (49 patients) did not undergo stoma reversal. Among parameters that were available before rectal surgery, age ≥ 75 years, albumin < 3.5 g/dl, tumor size ≥ 30 mm, tumor distance from the anal verge < 4 cm, and maximum squeezing pressure (MSP) < 130 mmHg measured by anorectal manometry (ARM) were independent factors associated with stoma non-reversal. The most common stoma-related complication was peristomal skin irritation (25%). Ileostomy was the only factor associated with peristomal skin irritation.

Conclusion: The current study demonstrated that low preoperative MSP evaluated by ARM, old age, hypoalbuminemia, and a large tumor close to the anus were predictive of diverting stoma non-reversal. Stoma site should be well deliberated when patients have the aforementioned risk factors for diverting stoma non-reversal.
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http://dx.doi.org/10.1007/s00423-020-02011-wDOI Listing
February 2021

Less intensive surveillance after radical surgery for stage I-III colorectal cancer by focusing on the doubling time of recurrence.

Surg Today 2021 Apr 15;51(4):550-560. Epub 2020 Sep 15.

Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: To propose a new and improved surveillance schedule for colorectal cancer (CRC) patients by focusing on the recurrence rate, resectability, and especially, the tumor doubling time (DT) of recurrent tumors.

Methods: The subjects of this retrospective review were 1774 consecutive patients who underwent radical surgery for stage I-III CRC between January, 2004 and December, 2015. We calculated the DT by measuring the tumor diameter using computed tomography (CT).

Results: The median DT for recurrences in the liver, lung, peritoneum, and other locations were 35, 72, 85, and 36 days, respectively, (p < 0.001) and tumor growth rates differed according to the organs where recurrence developed. Multiple linear regression analysis showed that the DT was strongly associated with the relapse-free interval from primary surgery (p < 0.001), and that the DT in patients with recurrence detected ≥ 3 years after primary surgery was longer by 151.1 days than that in patients with recurrence detected within 1 year after primary surgery. We proposed a less intensive surveillance, which achieved an average cost reduction of 32.5% compared with conventional surveillance in Japan.

Conclusion: We propose a new and more cost-efficient surveillance schedule for CRC surgery patients in the clinical setting.
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http://dx.doi.org/10.1007/s00595-020-02135-yDOI Listing
April 2021

Liver Injury Among Japanese Patients Treated Using Prophylactic Enoxaparin After Colorectal Surgery.

Dig Dis Sci 2021 08 5;66(8):2805-2815. Epub 2020 Sep 5.

Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

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.
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http://dx.doi.org/10.1007/s10620-020-06586-8DOI Listing
August 2021

Efficacy of intraperitoneally administered paclitaxel for colorectal cancer with peritoneal metastases.

Int J Colorectal Dis 2020 Oct 3;35(10):1945-1949. Epub 2020 Jun 3.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: Prognosis after peritoneal metastases in colorectal cancer is worse than that after lung or liver metastases. Previously, we demonstrated the safety of intraperitoneal (ip) administration of paclitaxel (PTX) combined with mFOLFOX6/CapeOX plus bevacizumab for colorectal cancer with peritoneal metastasis in a phase-I trial. Here, we evaluated the efficacy of this chemotherapy.

Methods: We enrolled six patients with histologically confirmed peritoneal metastases secondary to colorectal cancer. PTX was administered through a peritoneal access port, in combination with oxaliplatin-based systematic chemotherapy. Response rate, progression-free survival, 1-year survival rate, frequency of improvement in peritoneal cancer index (PCI), and cytology in peritoneal lavage were evaluated. This study was registered in the University Hospital Medical Information Network Clinical Trial Registry on July 1, 2016 (UNIN000022924).

Results: Three patients received the mFOLFOX6-bevacizumab regimen, whereas the other three received the CapeOX-bevacizumab regimen. The response rate was 25%. PCI score improved in 50% of the cases. Peritoneal lavage cytology that was positive in five patients before initiating the chemotherapy turned negative during chemotherapy in all patients. One-year survival rate was 100%, progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months.

Conclusion: The ip administration of PTX with systemic chemotherapy can potentially control peritoneal metastases in colorectal cancer.
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http://dx.doi.org/10.1007/s00384-020-03649-0DOI Listing
October 2020

Anastomotic bleeding following ileocolic end-to-side anastomosis using a circular stapler: incidence and risk factors.

Surg Today 2020 Nov 20;50(11):1368-1374. Epub 2020 May 20.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: To identify the incidence of and risk factors for postoperative bleeding after ileocolic end-to-side anastomosis using a circular stapler.

Methods: We analyzed, retrospectively, the risk factors for postoperative anastomotic bleeding in patients who underwent right-sided colectomy with end-to-side anastomosis done using a circular stapler during colon tumor surgery at our institute between January 2015 and March 2019.

Results: Anastomotic bleeding developed in 10 (3.6%) of the total 279 patients. Univariate analysis revealed that age ≥ 80 years (8.8% vs. 1.9%; P = 0.008) and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 1 (12.5% vs. 2.8%; P = 0.014) were significant risk factors for anastomotic bleeding. Postoperative anticoagulation therapy was not a risk factor for anastomotic bleeding. Multivariate analysis revealed that only age ≥ 80 years was an independent risk factor (odds ratio 4.12, 95% confidence interval 1.02-16.68, P = 0.047). Six of the ten patients with anastomotic bleeding were treated conservatively, three were treated by colonoscopic clipping, and one required surgery.

Conclusion: End-to-side anastomosis is safe and feasible, but must be performed carefully in the elderly, who are at higher risk of anastomotic bleeding.
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http://dx.doi.org/10.1007/s00595-020-02022-6DOI Listing
November 2020

Anal canal adenocarcinoma with pagetoid spread and inguinal lymph node metastasis treated with preoperative chemoradiotherapy: A case report.

Mol Clin Oncol 2020 Jun 16;12(6):529-532. Epub 2020 Mar 16.

Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8655, Japan.

Perianal Paget's disease is a rare condition, which is not usually accompanied by cancer. Here, a case of anal canal carcinoma with pagetoid spread and inguinal lymph node metastasis, which exhibited a significant response to preoperative chemoradiotherapy (CRT), is presented. A 58-year-old woman was admitted to The University of Tokyo Hospital with a complaint of discomfort around the anus. Physical examination revealed an erythematous inflamed skin lesion in the perianal region and a tumor of 15 mm in diameter detected on palpation in the left inguinal region, which was diagnosed as metastatic adenocarcinoma by excisional biopsy. Colonoscopy revealed moderately differentiated adenocarcinoma of 15 mm in diameter in the anal canal. Skin biopsy of the perianal region revealed an infiltration of pagetoid cells, which were positive for cytokeratin 7, and negative for cytokeratin 20 and gross cystic disease fluid protein 15. Based on these results, the patient was diagnosed as having anal canal adenocarcinoma with pagetoid spread. The patient received preoperative CRT including the bilateral inguinal region. After CRT, robotic-assisted laparoscopic abdominoperineal resection was performed. The macroscopic findings of the surgical specimen confirmed the formation of a scar as a result of the preoperative CRT. Microscopic examination of the anal tumor revealed no residual carcinoma or lymph node metastasis. In conclusion, this case may suggest the potential applicability of preoperative CRT for the local control of anal canal carcinoma with pagetoid spread.
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http://dx.doi.org/10.3892/mco.2020.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179386PMC
June 2020

Upfront Surgery for Small Intestinal Non-Hodgkin's Lymphoma.

Anticancer Res 2020 Apr;40(4):2373-2377

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: The clinical significance of surgery for secondary small intestinal non-Hodgkin's lymphomas (NHL) remains unknown. This study aimed to investigate the efficacy of resection for both primary and secondary small intestinal NHL.

Patients And Methods: Twenty patients with small intestinal lymphoma who underwent surgical resection at our Institute between 2009 and 2017 were retrospectively evaluated. The clinicopathological and surgery-related factors were reviewed. We also analyzed their surgical outcomes such as postoperative complications, perforation rate, and overall survival (OS).

Results: In total, 13 (65%) and 7 (35%) patients had primary and secondary lymphomas, respectively. A total of 70% of patients were diagnosed with aggressive-type lymphomas. A total of 15 (75%) patients had Lugano system stage IV. Only one (5%) patient experienced postoperative grade II deep vein thrombosis and pulmonary embolism. The 3-year OS rate after surgery was 59.6%.

Conclusion: Surgical resection prior to chemotherapy is a feasible and safe therapeutic strategy for small intestinal NHL.
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http://dx.doi.org/10.21873/anticanres.14206DOI Listing
April 2020

The Influence of Neoadjuvant Chemoradiation for Middle and Lower Rectal Cancer on Anorectal Function.

Anticancer Res 2020 Apr;40(4):2199-2208

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: To date, there is no clear understanding whether preoperative long-course chemoradiotherapy combined with surgery for rectal cancer is detrimental to anorectal function. The purpose of this study was to clarify the influence of preoperative chemoradiotherapy and surgery for middle and lower rectal cancer on postoperative anorectal function.

Patients And Methods: Data of 113 patients with middle or lower rectal cancer treated with preoperative chemoradiotherapy plus surgery or surgery alone between January 2013 and December 2016 were analyzed. A total of 84 and 29 patients underwent low anterior resection and intersphincteric resection, respectively. In patients with T3 or deeper and with any N stage cancer below peritoneal reflection, surgery plus lateral lymph node dissection or preoperative radiation (total: 50.4 Gy/28 fractions) to the pelvis with chemoradiotherapy plus surgery was treated. Anorectal function was assessed prior to treatment and 6 and 12 months postoperatively. Specifically, maximum resting pressure and maximum squeezing pressures were measured. The Wexner score was recorded prior to treatment and 12 months postoperatively.

Results: maximum resting pressure and maximum squeezing pressure decreased post-surgery in both groups. Maximum resting pressure and maximum squeezing pressure at 12 months and the Wexner score at 12 months post-surgery were comparable among patients treated with chemoradiotherapy plus surgery and those treated with surgery alone.

Conclusion: Preoperative chemoradiotherapy did not clearly impair postoperative anorectal function in patients who underwent low anterior resection and intersphincteric resection.
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http://dx.doi.org/10.21873/anticanres.14181DOI Listing
April 2020

Risk factors and therapeutic significance of inguinal lymph node metastasis in advanced lower rectal cancer.

Int J Colorectal Dis 2020 Apr 3;35(4):655-664. Epub 2020 Feb 3.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: This study aimed to clarify predictors and therapeutic significance of inguinal lymph node metastasis (ILNM) in patients with rectal cancer.

Methods: Patients with rectal adenocarcinoma invading the anal canal who underwent curative surgery between 2003 and 2019 were retrospectively reviewed. Synchronous and metachronous lymph node (LN) metastasis were collectively defined as final nodal metastasis (f-LNM). Factors associated with f-LNM were analyzed. Moreover, the "modified therapeutic value index," defined by multiplication of the frequency of f-LNM by the 5-year overall survival rate for patients who received treatment for f-LNM, was calculated for each LN area.

Results: A total of 145 patients were enrolled (16 patients with f-ILNM). To predict f-ILNM, the cutoff of the inguinal lymph node (ILN) diameter of 8.5 mm gave an area under the curve of 0.889. Dentate line involvement (odds ratio 33.4) and ILN larger than the cutoff of 8 mm (odds ratio 11.9) were independently associated with f-ILNM. The modified therapeutic value indices of the inguinal, lateral pelvic, and mesorectal LNs in the entire population were 6.1, 8.2, and 20.3 points, respectively. In patients with dentate line invasion by cancer, the index of the ILN increased to 11.7 points. In patients with an ILN > 8 mm, the index further increased to 21.1 points.

Conclusion: Dentate line involvement and ILN > 8 mm predicted the development of ILNM in patients with rectal cancer invading the anal canal. Treatment of the ILN should be considered for patients with the above predictors given the significant therapeutic outcomes.
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http://dx.doi.org/10.1007/s00384-020-03520-2DOI Listing
April 2020

Metastatic role of mammalian target of rapamycin signaling activation by chemoradiotherapy in advanced rectal cancer.

Cancer Sci 2020 Apr 22;111(4):1291-1302. Epub 2020 Feb 22.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Postoperative distant metastasis dramatically affects rectal cancer patients who have undergone neoadjuvant chemoradiotherapy (NACRT). Here, we clarified the association between NACRT-mediated mammalian target of rapamycin (mTOR) signaling pathway activation and rectal cancer metastatic potential. We performed immunohistochemistry for phosphorylated mTOR (p-mTOR) and phosphorylated S6 (p-S6) on surgical specimen blocks from 98 rectal cancer patients after NACRT (cohort 1) and 80 colorectal cancer patients without NACRT (cohort 2). In addition, we investigated the association between mTOR pathway activity, affected by irradiation, and the migration ability of colorectal cancer cells in vitro. Based on the results of the clinical study, p-mTOR was significantly overexpressed in cohort 1 (with NACRT) as compared to levels in cohort 2 (without NACRT) (P < .001). High p-mTOR and p-S6 levels correlated with the development of distant metastasis only in cohort 1. Specifically, high p-S6 expression (HR 4.51, P = .002) and high pathological T-stage (HR 3.73, P = .020) after NACRT were independent predictors of the development of distant metastasis. In vitro, p-S6 levels and migration ability increased after irradiation in SW480 cells (TP53 mutation-type) but decreased in LoVo cells (TP53 wild-type), suggesting that irradiation modulates mTOR signaling and migration through cell type-dependent mechanisms. We next assessed the expression level of p53 by immunostaining in cohort 1 and demonstrated that p-S6 was overexpressed in samples with high p53 expression as compared to levels in samples with low p53 expression (P = .008). In conclusion, p-S6 levels after NACRT correlate with postoperative distant metastasis in rectal cancer patients, suggesting that chemoradiotherapy might modulate the mTOR signaling pathway, promoting metastasis.
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http://dx.doi.org/10.1111/cas.14332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156826PMC
April 2020

Assessment of the Changes in Mitochondrial Gene Polymorphism in Ulcerative Colitis and the Etiology of Ulcerative Colitis-associated Colorectal Cancer.

Anticancer Res 2020 Jan;40(1):101-107

Department of Surgical Oncology, the University of Tokyo, Tokyo, Japan.

Background: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer.

Materials And Methods: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared.

Results: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC.

Conclusion: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer.
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http://dx.doi.org/10.21873/anticanres.13931DOI Listing
January 2020

Postoperative chemotherapy is associated with prognosis of stage IV colorectal cancer treated with preoperative chemotherapy/chemoradiotherapy and curative resection.

Int J Colorectal Dis 2020 Jan 5;35(1):177-180. Epub 2019 Dec 5.

Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: Advances in systemic chemotherapy have increased the resectability in colorectal cancer (CRC) associated with metastases even if it was initially unresectable. However, what determines the prognosis of stage IV CRC patients treated by preoperative therapy and surgery remains unclear. We attempted to identify prognostic factors in such CRC patients.

Methods: We reviewed stage IV CRC patients who underwent curative resection between December 2007 and May 2019. The patients who underwent conversion chemotherapy for initially unresectable disease and those who received neoadjuvant chemotherapy (NAC) for resectable synchronous metastases or neoadjuvant chemoradiotherapy (NACRT) for advanced lower rectal cancer with resectable metastases were included. Recurrence-free survival (RFS) and overall survival (OS) were examined by multivariate analyses using Cox proportional hazard models. The RFS and OS curves were analyzed according to postoperative adjuvant chemotherapy (AC).

Results: Among 70 patients who underwent curative surgery (34 men, mean age: 60 years old), 33 had initially unresectable disease, 23 received NAC, and 14 NACRT. By multivariate analyses, AC was an independent predictor for improved RFS and OS (hazard ratio = 0.29, p = 0.0002, and hazard ratio = 0.37, p = 0.025). Patients treated with AC showed improved RFS and OS than those without AC (2-year RFS rate = 30% vs 19%, p = 0.031, and 3-year OS rate = 87% vs 67%, p = 0.045).

Conclusion: Because of its association with improved prognosis, AC should be considered for stage IV CRC patients after curative resection regardless of initial resectability status and preoperative therapy.
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http://dx.doi.org/10.1007/s00384-019-03461-5DOI Listing
January 2020

Accelerated perineural invasion in colitis-associated cancer: A retrospective cohort study.

Medicine (Baltimore) 2019 Oct;98(42):e17570

Department of Surgical Oncology.

Perineural invasion (PNI) is a prognostic factor in patients with colorectal cancer. Neurotrophic factors, molecular determinants of PNI, are altered in their expression levels in patients with ulcerative colitis. In this study, we evaluated the frequency of PNI in colitis-associated cancer (CAC) and sporadic cancer.We retrospectively reviewed 778 colorectal cancers with pathological T3-T4 in 761 patients all of whom were surgically resected without preoperative treatment. The lesions were classified into either CAC or sporadic cancer based on the clinical information. Clinicopathological findings including PNI were compared between CACs and sporadic cancers. Moreover, we analyzed the risk factors for positive PNI by multivariate analysis using a logistic regression model.Ten of the cancers (1.3%) were diagnosed as CACs, and the remaining 768 as sporadic cancers. CACs were characterized by being nonobstructive and predominantly located in the rectum. The CACs had a larger size and more frequent undifferentiated histology than sporadic cancers. PNI was observed more frequently in CACs (90%) than in sporadic cancers without obstruction (45%, P = .007). On multivariate analysis, CAC was one of the significant factors associated with PNI (odds ratio: 9.05, P = .040).Our results suggest that CAC was more likely to exhibit PNI than sporadic colorectal cancer.
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http://dx.doi.org/10.1097/MD.0000000000017570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824779PMC
October 2019

Management of isolated para-aortic lymph node recurrence of colorectal cancer.

Surg Today 2020 Sep 29;50(9):947-954. Epub 2019 Aug 29.

Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Isolated para-aortic lymph node recurrence (PALNR) after curative surgery for colorectal cancer (CRC) is rare and its optimal management is not defined clearly. This review investigates the best outcomes among published studies on the management of PALNR in the field of CRC. We searched the PubMed database for studies reporting on the management of isolated PALNR in CRC, published in English or Japanese from January, 2000 to December, 2018. Studies including patients with other metastases were excluded. A total of 24 retrospective studies including 227 patients with PALNR were evaluated. The 3-year overall survival (OS) ranged from 60 to 100%, with a median OS of 34-80 months for patients who underwent PALNR dissection, and 14-42 months for patients who received non-surgical treatment. No surgery-related mortality was reported and the incidence of surgical, mainly low-grade, complications ranged from 33 to 52%. The predictors of improved survival outcome included R0 resection margins. Dissection for PALNR from CRC is considered a feasible treatment option that may yield a better prognosis than non-surgical treatment alone. Preoperative chemotherapy or CRT should be considered for their potential benefits, including a reduction in cancer volume and improved R0 resection rates.
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http://dx.doi.org/10.1007/s00595-019-01872-zDOI Listing
September 2020

The influence of pulmonary comorbidities on treatment choice and short-term surgical outcomes among elderly patients with colorectal cancer.

Int J Colorectal Dis 2019 Aug 28;34(8):1497-1501. Epub 2019 Jun 28.

Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: Most elderly patients with colorectal cancer have comorbidities and reduced functional reserve, which may increase their risks of postoperative morbidity and mortality, and subsequently influence the treatment choice. Therefore, this study aimed to investigate the treatment choice and compare laparoscopic and open surgery in this setting.

Methods: This retrospective study evaluated 118 patients with colorectal cancer (≥ 85 years old between January 2007 and February 2018) to determine the influence of comorbidities on treatment choice, as well as the safety and feasibility of laparoscopic surgery for these patients.

Results: The patients included 42 men (35.6%) and 106 patients (89.8%) with comorbidities. The treatments were curative resection for 90 patients and palliative surgery for 16 patients, including 5 cases of colostomy/ileostomy because of the difficulty of primary cancer resection, pneumonia, or pulmonary hypertension. Twelve patients received non-surgical treatment, including 7 patients with decreased respiratory function because of chronic obstructive pulmonary disease or pneumonia. Forty-three patients underwent open curative resection and 47 patients underwent laparoscopic curative resection, which was associated with a significantly shorter hospital stay (14 days vs. 19days, P < 0.01), a lower morbidity rate (17.0% vs. 37.2%, P = 0.035), and less blood loss (10 mL vs. 140 mL, P < 0.01). One patient in each group died during the postoperative period because of worsened pre-existing pneumonia.

Conclusion: Laparoscopic surgery was safer and less invasive than open surgery for colorectal cancer among ≥ 85-year-old patients. Pulmonary comorbidities affected the choice of non-curative surgery and may be related to the risk of postoperative mortality.
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http://dx.doi.org/10.1007/s00384-019-03336-9DOI Listing
August 2019

Cecal cancer with essential thrombocythemia treated by laparoscopic ileocecal resection: a case report.

Surg Case Rep 2019 Jun 21;5(1):101. Epub 2019 Jun 21.

Department of Surgical Oncology, Faculty of Medical Sciences, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by thrombocytosis and a propensity for both thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Here, we report a case of colorectal cancer in an ET patient treated using laparoscopic ileocecal resection.

Case Presentation: A 40-year-old woman was admitted to our hospital after presenting with liver dysfunction. She had been previously diagnosed with ET; aspirin and anagrelide had been prescribed. Subsequent examination at our hospital revealed cecal cancer. Distant metastasis was absent; laparoscopic ileocecal resection was performed. Anagrelide was discontinued only on the surgery day. She was discharged on the seventh postoperative day without thrombosis or hemorrhage. However, when capecitabine and oxaliplatin were administered as adjuvant chemotherapy with continued anagrelide administration, she experienced hepatic dysfunction and thrombocytopenia; thus, anagrelide was discontinued. Five days later, her platelet count recovered. Subsequently, anagrelide and aspirin administration was resumed, without any adjuvant chemotherapy. Her liver function normalized gradually in 4 months. One-year post operation, she is well without tumor recurrence or new metastasis.

Conclusions: To our knowledge, this is the first report of laparoscopic colectomy performed on an ET patient receiving anagrelide. Our report shows that complications such as bleeding or thrombosis can be avoided by anagrelide administration. Contrastingly, thrombocytopenia due to anagrelide intake should be considered when chemotherapy that could cause bone marrow suppression is administered.
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http://dx.doi.org/10.1186/s40792-019-0660-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588662PMC
June 2019

Laparoscopic surgery in rectal cancer patients taking anti-thrombotic therapy.

Minim Invasive Ther Allied Technol 2020 Aug 22;29(4):202-209. Epub 2019 May 22.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Several previous studies have shown that laparoscopic resection of rectal cancer is a feasible option. However, its safety and efficacy in patients receiving long-term anti-thrombotic therapy (AT) remain unclear. We retrospectively reviewed 364 patients who underwent elective resection for rectal cancer via a laparoscopic approach between 2007 and 2018 in our institute. Patients were classified according to the long-term use of AT. AT was interrupted perioperatively with or without heparin bridging therapy in all anti-thrombotic users. Clinicopathological factors and surgical outcomes were analyzed between patient groups. Thirty-two patients (9%) receiving AT were older and had lower albumin and hemoglobin levels than those not receiving AT (the non-AT group), and were predominantly male. Estimated blood loss and operative time in the AT group (median: 50 mL and 294 min) did not differ from those in the non-AT group (median: 20 mL and 295 min). There were no intergroup differences in the frequencies of other postoperative complications and oncological outcomes. Our results at the very least can support that laparoscopic surgery for rectal cancer is a safe and feasible option for patients taking long-term AT discontinued perioperatively.
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http://dx.doi.org/10.1080/13645706.2019.1619583DOI Listing
August 2020

The component changes of lysophospholipid mediators in colorectal cancer.

Tumour Biol 2019 May;41(5):1010428319848616

1 Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate lysophospholipid levels in colorectal cancer tissues to identify lysophospholipids, the levels of which change specifically in colorectal cancers. We used liquid chromatography-tandem mass spectrometry to measure lysophospholipid levels in cancerous and normal tissues from 11 surgical specimens of sigmoid colon cancers, since recent advances in this field have improved detection sensitivities for lysophospholipids. Our results indicate that, in colon cancer tissues, levels of lysophosphatidylinositol and lysophosphatidylserine were significantly higher ( p = 0.025 and p = 0.01, respectively), whereas levels of lysophosphatidic acid were significantly lower ( p = 0.0019) than in normal tissues. Although levels of lysophosphatidylglycerol were higher in colon cancer tissues than in normal tissues, this difference was not found to be significant ( p = 0.11). Fatty acid analysis further showed that 18:0 lysophosphatidylinositol and 18:0 lysophosphatidylserine were the predominant species of lysophospholipids in colon cancer tissues. These components may be potentially involved in colorectal carcinogenesis.
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http://dx.doi.org/10.1177/1010428319848616DOI Listing
May 2019

The combination of temsirolimus and chloroquine increases radiosensitivity in colorectal cancer cells.

Oncol Rep 2019 Jul 23;42(1):377-385. Epub 2019 Apr 23.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo 113‑8655, Japan.

The PI3K/AKT/mTOR pathway and autophagy are known to play important roles in cancer radioresistance. The aim of the present study was to investigate whether the combination of temsirolimus (TEM), an mTOR inhibitor, and chloroquine (CQ), an autophagy inhibitor, can increase radiosensitivity in colorectal cancer (CRC) cells. The efficacies of TEM and/or CQ as radiosensitizers were examined using clonogenic assays in CRC cell lines SW480 and HT‑29. The expression levels of the phosphorylated isoforms of S6 and 4E‑BP1, downstream proteins of mTOR, as well as the expression levels of p62 and LC3, autophagy‑related proteins, were assessed by western blot analysis. The formation of acidic organelles was detected in acridine orange‑stained cells. Apoptosis and caspase activity were assessed using flow cytometry. The results revealed that ionizing radiation (IR) activated the downstream proteins of mTOR and induced autophagy. In the clonogenic assays, neither TEM nor CQ influenced the efficacy of IR, whereas their combination significantly increased the dose‑dependent efficacy of IR. TEM inhibited phosphorylation of the downstream proteins of mTOR and induced autophagy. CQ inhibited autophagy in the late phase and did not influence the downstream proteins of mTOR. TEM and CQ inhibited both the phosphorylation of downstream proteins of mTOR and autophagy. Cell death analysis revealed that the combination of TEM and CQ strongly induced apoptosis in cells exposed to IR. In conclusion, the combination of TEM and CQ increased radiosensitivity in CRC cells through co‑inhibition of mTOR and autophagy.
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http://dx.doi.org/10.3892/or.2019.7134DOI Listing
July 2019

Adjuvant chemotherapy improves prognosis of resectable stage IV colorectal cancer: a comparative study using inverse probability of treatment weighting.

Ther Adv Med Oncol 2019 16;11:1758835919838960. Epub 2019 Apr 16.

Department of Thoracic Surgery, The University of Tokyo, Tokyo, Japan.

Background: Adjuvant chemotherapy (AC) is known to be beneficial for stage III colorectal cancer (CRC). In contrast, only a few studies have reported the survival benefits of AC for stage IV CRC after curative surgery.

Methods: We identified 155 CRC patients with various organ metastases who underwent curative surgery in our hospital between 2003 and 2017. Clinicopathological parameters and postoperative AC were reviewed. Multivariate analyses were performed to identify prognostic factors. Moreover, the effects of AC on recurrence-free survival (RFS) and overall survival (OS) were analyzed using inverse probability of treatment weighting.

Results: The cohort comprised 94 males and 61 females, with a mean age of 63 years. AC was administered to 57% of patients who underwent surgery between 2003 and 2010 and 76% between 2011 and 2017 ( = 0.015). AC was more likely administered to patients with a good performance status, high preoperative albumin level, regional node and peritoneal metastases, and no intraoperative blood transfusion. Multivariate analyses identified AC as a significant prognostic factors for RFS and OS [hazard ratio (HR): 1.86, = 0.003, and 2.66, = 0.002, respectively]. After adjusting for different backgrounds, 5-year RFS and OS rates were higher in patients receiving AC (27% and 67%) than in those without AC (14% and 46%, < 0.0001 and = 0.0005). Subgroup analyses showed that AC significantly improved RFS in node-negative patients (HR: 2.16, = 0.029), and RFS and OS in node-positive patients (HR: 2.03, < 0.0001, and 2.02, = 0.001, respectively).

Conclusion: AC can be discussed with resectable stage IV CRC patients because of its significant survival-improving effects.
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http://dx.doi.org/10.1177/1758835919838960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469283PMC
April 2019

Association between KRAS G13D mutations and anastomotic recurrence in colorectal cancer: Two case reports.

Medicine (Baltimore) 2019 Mar;98(12):e14781

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Rationale: The prevalence of anastomotic recurrence (AR) in colorectal cancer (CRC) after resection of the primary tumor (PT) is 5% to 14%. However, no association has been observed between specific somatic genetic alterations and AR. Such associations may shed light on the mechanism of AR.

Patient Concerns: We experienced 2 patients with AR of CRC. The first patient was a 42-year-old woman who underwent resection of an AR of rectal cancer 2 times within 19 months after resection of the PT. The second patient was a 77-year-old woman who underwent resection of an AR of ascending colon cancer twice within 38 months after resection of the PT.

Diagnosis: Both cases were diagnosed as repetitive AR.

Interventions: Loss of heterozygosity analysis, microsatellite instability (MSI) study of 9 microsatellite loci, and mutational analysis of KRAS, BRAF, APC, TP53, and SMAD4 were performed.

Outcomes: All the lesions, except 1, harbored mutations in APC, KRAS, and TP53, without MSI, after neoadjuvant chemoradiotherapy. The APC, KRAS, and TP53 mutations were pathogenic or likely pathogenic in the PTs and ARs. Both women harbored the same KRAS G13D mutation, which accounts for 8% of all KRAS mutations in sporadic CRC s. The probability of the incidental occurrence of KRAS G13D mutations in both cases is 0.64%, provided that the mutations were independent of AR.

Lessons: Our findings may shed light on the mechanism of AR in CRC, namely, that the PT harbored the same mutations as the AR and the lesions in both cases harbored the KRAS G13D mutation.
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http://dx.doi.org/10.1097/MD.0000000000014781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709076PMC
March 2019
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