Search

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.

A 55-year-old man was referred for surgery after colonoscopy revealed type 3 advanced lower rectal cancer in the lower rectum. CT and MRI scan showed no distant metastasis but on the left side of the rectum, there was a 34×30 mm large mass suspicious of lymph node metastasis, which had left-sided wall pelvic fascia invasion. We performed preoperative chemoradiotherapy(CRT)to ensure a secure surgical margin. As a result, the tumor volume was reduced and robot-assisted rectal amputation and bilateral lateral lymph node dissection were performed using a combined transperineal speculum approach. The pathological results showed that circumferential resection margin of 3 mm was secured. The lymph nodes on the left side of the rectum were mostly fibrotic and the tumor component had almost disappeared. Preoperative CRT is useful for securing the surgical margin. The multidisciplinary treatment including extended surgery enabled the curative resection of even highly advanced rectal cancer.

The anatomical spread of lymph node (LN) metastasis is of practical importance in the surgical management of colon cancer (CC). We examined the effect of KRAS, BRAF, and microsatellite instability (MSI) on LN count and anatomical spread pattern in stage III CC. We determined KRAS, BRAF, and MSI status from stage III CC patients. Biomarker status was correlated with LN count and anatomical spread pattern, which was classified as sequential or skipped. Relapse‐free survival (RFS) was estimated using Kaplan‐Meier method, and correlations were assessed using log‐rank and Cox regression analyses. We analyzed 369 stage III CC patients. The proportion of KRAS mutant (mt), BRAF mt, and MSI‐high (H) were 44.2% (163/344), 6.8% (25/344), and 6.8% (25/344), respectively. The mean number of metastatic LN was higher in microsatellite‐stable (MSS) compared with MSI patients (3.5 vs. 2.7, P = .0406), although no differences were observed in accordance with KRAS or BRAF status. Interestingly, patients with BRAF mt and MSI‐H were less likely to harbor skipped metastatic LN (9.3% vs 20% and 4% vs 10.5% compared with BRAF wild‐type (wt) and MSS, respectively), but KRAS status did not predict anatomical spread pattern. Patients with KRAS wt and MSI‐H showed superior RFS compared with KRAS mt and MSS patients, respectively, whereas BRAF status did not affect RFS. Differences exist in the anatomical pattern of invaded LN in accordance with the molecular status of stage III CC. Patients with MSI‐H CC have less invaded and skipped LN, suggesting that a tailored surgical approach is possible., The association of KRAS/BRAF/MSI with invaded lymphatic spread pattern in colon cancer was assessed. The anatomical pattern of invaded LN varies in accordance with the molecular status, which may affect the outcome in stage III colon cancer.

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. 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. 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. Overall survival was favorable. Fecal incontinence depended on the surgical procedures. Most patients continued to receive follow-up examinations. No. 3112 by Institutional Review Board of Hyogo College of Medicine

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.

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.

Case 1: 63-year-old woman received abdominoperineal resection with lateral lymph node dissection for rectal cancer in 2008. After adjuvant chemotherapy, she suffered from lung metastasis and received partial pneumonectomy in 2012. However, chemotherapy was performed again for lung metastasis and mediastinal lymph nodes in 2013. Radiofrequency ablation (RFA)was performed to lung metastasis in 2016 due to ineffectiveness of chemotherapy. Case 2: 81-year-old man received Hartmann's procedure for rectal cancer with lung and liver metastasis in 2012. After 6 months of chemotherapy, liver partial resection and pulmonary partial resection were performed. In spite of additional chemotherapy, He received partial pneumonectomy in 2013. In 2014, he restart chemotherapy due to lung metastasis. In 2016, he received RFA for lung metastasis because of ineffectiveness of chemotherapy. After that, he received g-knife for brain metastasis. He is going to receive RFA for another lung metastasis.

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.

Background: Combination oxaliplatin and capecitabine therapy is recommended to treat advanced small bowel adenocarcinoma (SBA). However, SBA is rare, and limited preclinical studies and randomized clinical trials have been conducted. Methods: A patient-derived xenograft (PDX) was established from an advanced SBA patient with liver metastasis and peritoneal metastasis. Growth inhibition by oxaliplatin, irinotecan, 5-fluorouracil (5-FU), and 5-FU in combination with oxaliplatin, irinotecan, or paclitaxel was assessed using the PDX. Drug sensitivity against oxaliplatin, irinotecan, 5-FU, and paclitaxel was assessed using SBA cells from the PDX. The patient’s clinicopathological and genetic features were compared with the PDX to evaluate it as a preclinical model. Results: 5-FU, but not oxaliplatin and irinotecan showed statistically significant growth inhibition compared to control group (P = 0.0024). Among the combination treatment with 5-FU, oxaliplatin showed the highest tumor growth inhibition rate of 0.84 or 1.1, which was 0.46 for irinotecan and 0.49 for paclitaxel, respectively. IC50 of SBA cells was significantly lower against oxaliplatin and higher against paclitaxel compared with colon cancer cell line HT29. These results corresponded to the clinical response to FOLFOX (folinic acid+5-FU+oxaliplatin) and FOLFIRI (folinic acid+5-FU+irinotecan). PDX pathological and genetic features resembled those of the patient. Conclusions: We established a preclinical model comprising the PDX from SBA and SBA cells from the PDX. This model showed that the combination of oxaliplatin and 5-FU was a reasonable standard therapy for advanced SBA. A preclinical model comprising PDX and tumor cells from PDX seems to be useful for rare tumors including SBA. Citation Format: Tomoki Yamano, Jihyung Song, Kei Kimura, Akihito Babaya, Michiko Hamanaka, Kozo Kataoka, Naohito Beppu, Masafumi Noda, Masataka Ikeda, Naohiro Tomita. A patient-derived xenograft model demonstarates the effectiveness of combined oxaliplatin and 5-fluorouracil for advanced small bowel adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1053.