Clinicopathological features and prognosis of primary small bowel adenocarcinoma: a large multicenter analysis of the JSCCR database in Japan.

BACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.

Outcomes of Metastatic and Unresectable Small Bowel Adenocarcinoma in Japan According to the Treatment Strategy: A Nationwide Observational Study.

PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

Assessment of circulating microRNA specific for patients with familial adenomatous polyposis.

Circulating microRNAs (miRNAs) are considered promising biomarkers for diagnosis, prognosis, and treatment efficacy of diseases. However, usefulness of circulating miRNAs as biomarkers for hereditary gastrointestinal diseases have not been confirmed yet. We explored circulating miRNAs specific for patients with familial adenomatous polyposis (FAP) as a representative hereditary gastrointestinal disease. Next-generation sequencing (NGS) indicated that plasma miR-143-3p, miR-183-5p, and miR-885-5p were candidate biomarkers for five FAP patients compared to three healthy donors due to moderate copy number and significant difference. MiR-16-5p was considered as an internal control due to minimum difference in expression across FAP patients and healthy donors. Validation studies by real-time PCR showed that mean ratios of maximum expression and minimum expression were 2.2 for miR-143-3p/miR-16-5p, 3.4 for miR-143-3p/miR-103a-3p, 5.1 for miR-183-5p/miR-16-5p, and 4.9 for miR-885-5p/miR-16-5p by using the samples collected at different time points of eight FAP patients. MiR-143-3p/16-5p was further assessed using specimens from 16 FAP patients and 7 healthy donors. MiR-143-3p was upregulated in FAP patients compared to healthy donors (P = 0.04), but not significantly influenced by clinicopathological features. However, miR-143-3p expression in colonic tumors was rare for upregulation, although there was a significant difference by existence of desmoid tumors. MiR-143-3p transfection significantly inhibited colorectal cancer cell proliferation compared to control microRNA transfection. Our data suggested regulation of miR-143-3p expression differed by samples (plasma or colonic tumors) in most FAP patients. Upregulation of plasma miR-143-3p expression may be helpful for diagnosis of FAP, although suppressive effect on tumorigenesis seemed insufficient in FAP patients.

Sacrectomy for Recurrent Rectal Cancer Using the Transanal Total Mesorectum Excision Technique.

INTRODUCTION: In high sacrectomy, it is difficult to secure the lateral surgical margin and prevent severe postoperative complications. In this report, we present our unique surgical procedure using transanal total mesorectal excision for locally recurrent rectal cancer. TECHNIQUE: A 49-year-old woman was diagnosed with locally rerecurrent rectal cancer, which was located at the height of the S3 vertebra by preoperative imaging, and posterior pelvic exenteration concomitant with high sacrectomy below the S2 vertebra was planned. A multiaccess transperineal platform was placed to secure the lateral surgical margin using transperineal minimally invasive surgery during the perineal and sacral side procedure. Transperineal minimally invasive surgery has several clinical benefits over the conventional approach. For the perineal approach, a 2-team laparoscopic approach was performed. This surgical intervention with laparoscopic perineal assistance contributed to the completion of the dissection of the planned lateral surgical margin, such as the distal piriformis muscles and the sacrotuberous and sacrospinous ligaments, which are the most difficult areas to access in the lithotomy position. Regarding the sacral approach, it facilitated the dissection of the dorsal space of the sacrum; therefore, only a 7-cm transverse skin incision was required during sacrectomy. Small skin incisions and minimal dissection may reduce surgical site infections. RESULTS: The operative time was 933 minutes, with 80 mL of blood loss. There were no major complications, and pathologically confirmed curative resection was achieved. CONCLUSIONS: Our new technique utilizing transanal total mesorectum excision is feasible to secure the lateral surgical margin with minimal skin incision and dissection and may prevent severe postoperative complications.

Extended Total Mesorectal Excision Based on the Avascular Planes of the Retroperitoneum for Locally Advanced Rectal Cancer with Lateral Pelvic Sidewall Invasion.

INTRODUCTION: It has been considered difficult to achieve en bloc resection in cases of locally advanced rectal cancer with lateral pelvic sidewall invasion. The present study demonstrates a novel surgical procedure for these tumors. TECHNIQUE: There are 3 avascular planes of the retroperitoneum in the pelvic sidewall. Two visceral pelvic fasciae, namely the ureterohypogastric fascia and umbilical prevesical fascia, and the parietal pelvic fascia can be identified. In addition, the key structures of these fasciae, the ureter, umbilical artery, and external iliac vessels, can be identified transperitoneally before any dissection. Thus, these 3 avascular planes can be dissected without resorting to dissection of the retrorectal space. The key steps to this technique are: 1) after dissection from the side opposite to the site of tumor invasion to the dorsal side of the rectum, the avascular planes of the retroperitoneum among the 3 above-mentioned fasciae are dissected; and 2) the retrorectal space and pelvic sidewall space are connected by sharp dissection. RESULTS: Recognizing the 3 above-mentioned fasciae enables the dissection of the avascular planes of the pelvic sidewall, which helps to achieve en bloc dissection in cases of locally advanced rectal cancer with lateral pelvic sidewall invasion. CONCLUSION: The pelvic sidewall could be divided into 3 areas based on the visceral pelvic fasciae, which has helped to achieve en bloc dissection in cases of locally advanced rectal cancer with lateral pelvic sidewall invasion.

Combination of preoperative tumour markers and lymphovascular invasion with TNM staging as a cost and labour efficient subtyping of colorectal cancer.

Tumour-Node-Metastasis (TNM) staging of colorectal cancer (CRC) needs further classification for better treatment because of disease heterogeneity. Although molecular classifications which are expensive and laborious are under study, cost and labour efficient subtyping is desirable. We assessed the combinations of preoperative tumour marker (TM) elevation and tumour lymphovascular invasion (LVI) as a solution. We used the pooled data of 7151 colon cancer (CC) patients and 4620 rectal cancer (RC) patients who received curative surgery between 2004 and 2008 in Japan. The best-matched subtyping for predicting relapse-free survival (RFS) was statistically selected using the c-index and Akaike's information criterion. This subtyping (TM-LVI), which consisted of three categories by TM elevation status and severity of LVI status, was an independent prognostic factor for RFS of CC (stage IIa, IIIb, and IIIc) and RC (stage I, IIa, IIb, IIIa, and IIIb) and also for disease specific survival of CC (stage IIa, IIb, IIIb, and IIIc) and RC (all stage except for IIc). Although TM-LVI classified CRC patients into low and high recurrence risk groups, the application of adjuvant therapy was not accordance with the TM-LVI status. TM-LVI may be a cost and labour efficient subtyping of colorectal cancer for better treatment strategy.

Influence of chemoradiotherapy on nutritional status in locally advanced rectal cancer: Prospective multicenter study.

OBJECTIVE: The aim of this study was to investigate the influence of chemoradiotherapy (CRT) on nutritional status and the association between changes in nutritional status and clinical outcomes (treatment completion, adverse events, perioperative complications, and relapse-free survival [RFS]) in patients with locally advanced rectal cancer (LARC). METHODS: In this multicenter, phase II study, 41 patients with LARC underwent CRT for 5 wk, followed by a 6- to 8-wk interval before surgery. Body weight, body mass index (BMI), lean body mass, serum albumin, and prealbumin levels were measured before (pre-), during, and after CRT, and before surgery. Changes in these data and scores on the Malnutrition Universal Screening Tool (MUST) were calculated based on pre-CRT status. RESULTS: Twelve patients (29.3%) experienced body weight loss (BWL) ≥5% (defined as malnutrition) after CRT (P < 0.001) and before surgery (P = 0.035). Significant changes were seen in serum albumin levels and BMI during and after CRT (P < 0.001), and in MUST scores after CRT (P = 0.003) and before surgery (P = 0.035). Treatment completion was significantly associated with BWL (P = 0.028), MUST score (P = 0.013), and decreased serum albumin level (P = 0.001) after CRT. Regarding adverse events, MUST score before surgery (P = 0.009) and serum albumin level after CRT (P = 0.002) were significantly associated with diarrhea severity. Serum albumin level during CRT was associated with the onset of neutropenia (P = 0.005). No association was found between BWL and RFS. CONCLUSIONS: These findings suggest that malnutrition and changes in nutritional status are not only commonly observed after CRT, but also associated with treatment completion and adverse events.

Impact of preoperative chemoradiotherapy using concurrent S-1 and CPT-11 on long-term clinical outcomes in locally advanced rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy regimens using a second drug for locally advanced rectal cancer are still under clinical investigation. AIM: To investigate the clinical outcomes of patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy using tegafur/gimeracil/oteracil (S-1) plus irinotecan (CPT-11). METHODS: This was a single-center retrospective study of 82 patients who underwent radical surgery for rectal cancer after chemoradiotherapy with S-1 (80 mg/m2/d), CPT-11 (60 mg/m2/d), and radiation (total 45 Gy) between 2009 and 2016. The median follow-up was 51 mo (range: 17-116 mo). RESULTS: Twenty-nine patients (35.4%) had T3 or T4 rectal cancer with mesorectal fascia invasion, 36 (43.9%) had extramural vascular invasion, 24 (29.8%) had N2 rectal cancer and eight (9.8%) had lateral lymph node swelling. The relative dose intensity was 90.1% for S-1 and 92.9% for CPT-11. Seventy-nine patients (96.3%) underwent R0 resection. With regard to pathological response, 13 patients (15.9%) had a pathological complete response and 52 (63.4%) a good response (tumor regression grade 2/3). The 5-year local recurrence-free survival, relapse-free survival and overall survival rates were 90.1%, 72.5% and 91.3%, respectively. We analyzed the risk factors for local recurrence-free survival by Cox regression analysis and none were detected. Previously described risk factors such as T4 stage, mesorectal fascia invasion or lateral lymph node swelling were not detected as negative factors for local recurrence-free survival. CONCLUSION: We demonstrated good compliance and favorable tumor regression in patients with locally advanced rectal cancer treated with preoperative S-1 and CPT-11.

A patient-derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma.

Basic and clinical studies on small bowel adenocarcinoma (SBA) are limited due to the rare nature of this cancer. We established a patient-derived xenograft (PDX) model from the tumor tissue of an advanced SBA patient with liver and peritoneal metastasis, and a cell line from the PDX. In the PDX model, compared to the control group, 5-fluorouracil (5-FU) treatment resulted in statistically significant tumor growth inhibition (TGI), while oxaliplatin (OHP) and irinotecan had no significant inhibitory effects. In combination with 5-FU, OHP showed the highest rate of TGI. The IC50 for OHP was significantly lower than those for paclitaxel, gemcitabine, and trifluorothymidine in the PDX-derived cell line when compared to in HT29, a colon cancer cell line. Genetic analysis of the patient tumor, PDX tumor, and the cell line demonstrated consistency in the microsatellite status and mutations in TP53, APC, HRAS, CSF1R, FGFR3, FLT3, PDGFRA, and RET genes. However, the PDX tumor alone had additional mutations, indicating that the PDX-derived cell line may support the unstable genetic status of the PDX. Our findings confirmed the effectiveness of the combination of OHP and 5-FU, which is a common treatment for advanced SBA and advanced colorectal cancer, in a preclinical model. This preclinical model of SBA can help in further understanding the biology of SBA.

Long-term clinical outcomes and follow-up status in Japanese patients with familial adenomatous polyposis after radical surgery: a descriptive, retrospective cohort study from a single institute.

PURPOSE: Data on long-term outcomes of familial adenomatous polyposis (FAP) are unclear in Japan because a nationwide registry system is lacking. We assessed overall survival, incidence of neoplasms, fecal incontinence, and postoperative follow-up status of patients with FAP treated surgically in our hospital. METHODS: In total, 154 patients with FAP who underwent radical surgery from 1981 to 2017 in our department were available for the questionnaire. Sixty-five patients, 36 of whom were followed at our hospital, were assessed using clinical records and the questionnaire. RESULTS: The median follow-up time was 187 months (interquartile range, 93.5-296 months). The median age at surgery was 36 years (range, 12-69 years). The 5-, 10-, 15-, and 20-year overall survival rate was 100%, 98%, 95%, and 89%, respectively. All five deaths were caused by diseases other than colorectal cancer. FAP-related neoplasms comprised 23 colorectal cancers, five duodenal cancers, three gastric cancers, five thyroid cancers, two ileal pouch cancers, and nine desmoid tumors. The incidence of desmoid tumors was significantly associated with the operation date. The duration from radical surgery to neoplasm onset significantly differed by neoplasm type. Forty-five of 54 patients (excluding those who died or underwent ileostomy) developed fecal incontinence (median Wexner score of 8). Surgical procedures involving hand-sewn sutures with rectal mucosal stripping were significantly associated with fecal incontinence and the Wexner score. Fifty-eight of the 60 surviving patients underwent follow-up examinations. CONCLUSION: Overall survival was favorable. Fecal incontinence depended on the surgical procedures. Most patients continued to receive follow-up examinations. TRIAL REGISTRATION: No. 3112 by Institutional Review Board of Hyogo College of Medicine.

Hypermethylation of Corticotropin Releasing Hormone Receptor-2 Gene in Ulcerative Colitis Associated Colorectal Cancer.

BACKGROUND/AIM: The difficulty of early diagnosis of colitis associated colorectal cancer (CACRC) due to colonic mucosal changes in long-standing ulcerative colitis (UC) patients is often experienced in daily clinical practice. Noninvasive objective monitoring for cancer development is advantageous for optimizing treatment strategies in UC patients. We aimed to examine the epigenetic alterations occurring in CACRC, focusing on DNA hypermethylation of CpG islands. MATERIALS AND METHODS: The level of DNA methylation in CpG cites was compared between CACRC and the counterpart non-tumorous mucosa using Infinium HumanMethylation 450K BeadChip. RESULTS: Our subjects included 3 males and 3 females (median age, 49.5 years). The 450K CpG site DNA methylation microarray revealed that the difference in ß value (level of hypermethylation) was the highest for corcicotropin releasing hormone receptor 2 (CRHR2) between CACRC and counterpart non-tumorous mucosa. CONCLUSION: Detection of hypermethylation of CRHR2 may be promising for cancer screening in UC patients.

Splicing modulator FR901464 is a potential agent for colorectal cancer in combination therapy.

FR901464 (FR) was first described as an anticancer drug and later identified as a modulator of splicing factor 3B subunit 1 (SF3B1). Although the effectiveness of splicing modulators has been investigated in colorectal cancer (CRC) cells, their usefulness in animal experiments has not been confirmed. The association of SF3B1 with CRC progression and the influence of FR on transcriptional activity in CRC has not been fully elucidated. FR showed strong cytotoxicity against CRC cell lines, SF3B1-mutated cancer cell lines, and human fibroblasts with IC50 values less than 1 ng/ml. FR-resistant clones derived from HCT116, DLD1, Lovo, and CT26 cells showed IC50 values greater than 100 ng/ml. SF3B1 sequencing demonstrated low frequencies of SF3B1 mutations in CRC and mutations in codon 1074 of exon 22 in all FR-resistant clones. Unlike hematological malignancies, SF3B1 expression was not associated with CRC progression. Although FR showed significant growth inhibition in a xenograft model of RKO cells, severe toxicity was also induced. These data indicated CRC might be a suitable target of FR unless toxicity occurs. Microarray analysis and real-time quantitative PCR demonstrated downregulation of genes associated with Fanconi anemia (BRCA1 and BRCA2) and 28 driver oncogenes. These data suggested combination treatment of FR with other anticancer drugs whose sensitivity is associated with genes affected by FR treatment. Combination treatment with PARP1 inhibitor olaparib, whose sensitivity was enhanced by BRCA 1/2 deficiency, showed synergistic effects in CRC cells. Our data indicates the potential of FR in combination therapy rather than monotherapy for CRC treatment.

UGT1A1 polymorphisms in rectal cancer associated with the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan.

The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3-T4, N0-N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m2 per day tegafur/gimeracil/oteracil (S-1; days 1-5, 8-12, 22-26, and 29-33), 60 mg/m2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Six to eight weeks after completing chemoradiotherapy, total mesorectal excision was carried out. Patients with UGT1A1 polymorphisms were divided into WT (n = 26), heterozygous (n = 15), and homozygous (n = 5) groups, the latter including double heterozygosities. We evaluated associations between clinical characteristics, including UGT1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. Incidence rates of grade 3+ neutropenia and diarrhea were 17.0% and 30.4%, respectively. Relative dose intensity was 89.3%. Pathological complete response rate (grade 3) was 26.1%, and the good response (grade 2/3) rate was 84.8%. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT1A1 polymorphism is a predictive factor to determine the clinical efficacy of preoperative chemoradiotherapy and hematological toxicity induced by chemoradiotherapy using irinotecan in locally advanced rectal cancer patients.

Evaluation of appropriate follow-up after curative surgery for patients with colorectal cancer using time to recurrence and survival after recurrence: a retrospective multicenter study.

INTRODUCTION: The follow-up schedule for colorectal cancer patients after curative surgery is inconsistent among the guidelines. Evaluation of time to recurrence (TTR) and survival after recurrence (SAR) may provide evidence for appropriate follow-up. METHODS: We assessed 3039 colon cancer (CC) and 1953 rectal cancer (RC) patients who underwent curative surgery between 2007 and 2008. We evaluated the pre- and post-recurrent clinicopathological factors associated with TTR and SAR in each stage of CC and RC. RESULTS: The recurrence rates of stages I, II, and III were 1.2%, 13.1%, and 26.3%, respectively, for CC, and 8.4%, 20.0%, and 30.4%, respectively, for RC. In CC patients, high carcinoembryonic antigen (CEA) level and lymphovascular invasion were independent predictors of short TTR. In RC patients, metastatic factors (liver metastasis in stage III) and venous invasion (stage III) were independent predictors of short TTR. The prognostic factors of SAR were age (stage II CC and stage III RC), female gender (stage III RC), high CEA level (stage II RC), histological type (stage III CRC), nodal status (stage III CC), recurrence within 1 year (stage III RC), M1b recurrence (stage II CRC), local recurrence (stage II CC), and no surgical resection after recurrence (stage II and III CRC). CONCLUSIONS: The follow-up schedule for stage I should be different from that for the other stages. We recommend that intensive follow-up is appropriate in stage III CC patients with undifferentiated adenocarcinoma or N2 nodal status, stage II RC patients with high preoperative CEA level, and stage III RC patients.

Genomic landscape of colitis-associated cancer indicates the impact of chronic inflammation and its stratification by mutations in the Wnt signaling.

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, known as colitis-associated cancer (CAC). It is still unclear what driver mutations are caused by chronic inflammation and lead to CAC development. To get insight into this issue, we investigated somatic alterations in CAC. We performed exome sequencing of 22 fresh CACs and targeted sequencing of 43 genes on 90 archive specimens from Japanese CAC patients, of which 58 were ulcerative colitis (UC) and 32 were Crohn's disease (CD). Consistently with the previous reports, TP53 was commonly mutated (66%) whereas APC, KRAS and SMAD4 were mutated less frequently (16%, 11% and 11%, respectively). Mucinous CD-CACs in the anus, an Asian-specific subtype of CD-CAC, had less somatic mutations in our target genes. We also found that RNF43, a negative regulator of the Wnt signaling, was somatically mutated in a significant fraction of CACs (10 of 90; 11%). Two lines of evidence indicated that somatic mutations of RNF43 were related to chronic inflammation. First, somatic mutations of RNF43 were significantly associated with longer duration of IBD. Second, clinico-pathological features suggested many of the APC-mutated CACs were actually sporadic colorectal cancer whereas RNF43-mutated CACs did not have this tendency. RNA-Seq analysis showed that RNF43-mutated CACs had elevated expression of c-Myc and its target genes, suggesting that RNF43 is a bona fide driver of CAC development. This study provides evidence that somatic mutation of RNF43 is the driver genetic alteration that links chronic inflammation and cancer development in about 10% of CACs.

[Two Cases of CT-Guided Radiofrequency Ablation Therapy for Pelvic Recurrence from Rectal Cancer].

We experienced 2 cases of pelvic recurrence from rectal cancer. These patients received radiofrequency ablation(RFA) therapy. Case 1 was a 76-year-old man who underwent intersphincteric resection for lower rectal cancer in October 2013. In May 2015, the patient received systemic chemotherapy for multiple lung metastases and pelvic local recurrence. In January 2017, RFA was performed to reduce the pain of the pelvic recurrence. Immediately after RFA, the pain markedly reduced, and 2 months after treatment, the patient discontinued his pain therapy. Case 2 was a 48-year-old man who underwent Hartmann 's procedure for ulcerative colitis with rectal cancer in November 2011. In July 2012, we performed abdominoperineal resection for rectal cancer that developed in the remnant rectum. In November 2012, he received systemic chemotherapy for multiple lung metastases and pelvic recurrence. In addition, we performed stereotactic radiotherapy(SRT)for the pelvic recurrence. In May 2016, because he developed bilateral hydronephrosis and painful pelvic recurrence, we performed bilateral nephrostomy and RFA for the painful pelvic recurrence. After RFA, pain reduced, but he developed a pelvic abscess that was treated by CT-guided drainage. He underwent complete ablation for the recurrent pelvic mass 2 years after RFA but died of exacerbation of multiple lung metastases. CT-guided RFA for painful pelvic recurrence from rectal cancer can be considered a feasible and effective treatment to reduce pain.

Influence of age and comorbidity on prognosis and application of adjuvant chemotherapy in elderly Japanese patients with colorectal cancer: A retrospective multicentre study.

BACKGROUND: Adjuvant therapy for colorectal cancer (CRC) in patients aged ≥75 years is supported by inadequate evidence, although such patients are increasing in number worldwide. PATIENTS AND METHODS: We assessed the influence of age and comorbidities on the prognosis of CRC in elderly patients using pooled data by the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. In total, 4598 patients (3304 with colon cancer and 1294 with rectal cancer) who underwent curative surgery from 2004 to 2006 were analysed with respect to age, Charlson comorbidity score (CS), tumour marker positivity, adjuvant therapy and prognosis. RESULTS: The number of patients aged <64, 65-74 and >75 years was 2007 (44%), 1614 (35%) and 977 (21%), respectively. Tumour location, tumour marker positivity, clinical stage, performance of adjuvant therapy, CS and overall survival (OS) were significantly different among these age groups (P < 0.0001). Among patients aged ≥75 years with stage III CRC, 35% with colon cancer and 21% with rectal cancer received adjuvant therapy; these proportions were much lower than those in younger patients. Application of adjuvant therapy was dependent on the CS in patients aged ≤74 years, but not in older patients. Sex, the carcinoembryonic antigen concentration and adjuvant therapy were significantly associated with OS in elderly patients with stage III CRC. CONCLUSION: Age and comorbidities worsened the OS of patients with CRC who underwent curative surgery. However, patients aged ≥75 years were undertreated regardless of their CS despite the possibility of OS improvement by adjuvant therapy.

[A Case of Cecal Cancer with Para-Aortic Lymph Node Metastasis and Peritoneum Dissemination Treated with Curative Resection after mFOLFOX6 plus Panitumumab Chemotherapy].

A 67-year-old woman was diagnosed with cecal cancer, para-aortic lymph node metastasis, peritoneum dissemination, and left breast cancer. We administered mFOLFOX6 plus panitumumab for cecal cancer and an aromatase inhibitor for her breast cancer. She received 7 courses of systemic chemotherapy and showed a partial response. She additionally received 5 courses of mFOLFOX6 plus panitumumab. We performed ileocecal resection, sigmoidectomy, right oophorectomy, dissection of the para-aortic lymph nodes, and peritoneal dissemination. The histopathological findings revealed adenocarcinoma, ypT3, ypN0, ycM0, ypStage II (therapeutic effect Grade 2). One month later, she underwent an enforced left breast segmental resection and sentinel lymph node biopsy(0/2). The results of the pathological examination indicated no residual cancers (therapeutic effect Grade 3). The patient is now in good health and was administered S-1 as an outpatient.

[Two Cases of Achieving a Pathological Complete Response via Hepatic Arterial Infusion Chemotherapy for Liver-Limited and Unresectable Liver Metastases from Colorectal Cancer with RAS Mutations].

We had 2 cases of liver-limited and unresectable liver metastases from colorectal cancer with RAS mutations. These patients received hepatic arterial infusion chemotherapy(HAI), finally achieving pCR. Case 1 was a 76-year-old female with rectosigmoid cancer and multiple liver metastases. We underwent anterior resection for primary lesion. After surgery, the patient had received first-line and second-line systemic chemotherapy for the multiple liver metastases. The patient achieved SD and had Grade 3 neutropenia. We then performed HAI as third-line chemotherapy and we therefore underwent hepatectomy. The results of the pathological examination after hepatectomy pCR and is currently alive without cancer recurrence for 61 months. Case 2 was a 53-year-old male with sigmoid colon cancer and multiple liver metastases. We underwent sigmoidectomy with laparoscopic assistance. Three months after surgery, we underwent resection of the lateral segment of the liver under laparoscopy. This patient had cancer recurrence in the remnant liver at 6 months after surgery and had received first-line systemic chemotherapy. The patient had Grade 3 neutropenia after 1 course of chemotherapy and showed no improvement. We then performed HAI as second-line chemotherapy, and we therefore underwent hepatectomy. The results of the pathological examination after hepatectomy were pCR and he is currently alive without cancer recurrence for 30 months.