Lymphatic spread patterns in young versus elderly patients with stage III colon cancer.

BACKGROUND: The anatomical pattern of lymph nodes spread differs between young (aged 45 years or younger) and elderly (aged 80 years or older) patients with stage III colon cancer and is poorly investigated. METHODS: Two groups of patients (young and elderly) with stage III colon cancer who underwent upfront extensive (D3) lymphadenectomy at eight Japanese centres between 1998 and 2018 were retrospectively analysed. The primary endpoint was the proportion of positive central lymph nodes. The lymph nodes spreading pattern and its prognostic impact on recurrence-free survival and overall survival in the two groups were also compared. RESULTS: Two hundred and ten young patients and 348 elderly patients were identified and compared. The total number of lymph nodes harvested and the total number of invaded lymph nodes were significantly higher in younger patients compared with elderly patients (median of 31.5 (3-151) versus 21 (3-116), P < 0.001 and median of 3 (1-21) versus 2 (1-25), P < 0.001 respectively). The proportion of positive central lymph nodes were higher in younger patients than in elderly patients (9.52% (95% c.i. 6.24 to 14.2%) versus 4.59% (95% c.i. 2.84 to 7.31%), P = 0.012). In multivariate models for recurrence-free survival, central lymph nodes invasion were identified as a poor prognostic factor in younger patients (HR 5.21 (95% c.i. 1.76 to 15.39)) but not in elderly patients (HR 1.73 (95% c.i. 0.80 to 3.76)). CONCLUSION: Young patients with stage III colon cancer have a higher risk of central lymph nodes invasion, suggesting a more aggressive disease biology. The presence of central lymph nodes invasion are associated with a worse outcome in young patients.

[Questionnaire Survey on the Timing of Comprehensive Genomic Profiling for Advanced Recurrent Colorectal Cancer and Its Impact on Patients].

BACKGROUNDS: Comprehensive genomic profiling(CGP)has been covered by health insurance since June 2019. However, the clinical impact of CGP on patients with metastatic colorectal cancer(mCRC)remains unclear. To date, there are very limited reports regarding patient-oriented outcomes of CGP in mCRC. PATIENTS: A questionnaire was completed by patients with mCRC who had already received their CGP results after April 2021. Eight questions were posed, covering the degree of satisfaction and timing when CGP was conducted. RESULTS: Of the 51 patients with mCRC who had received their CGP test results by August 2021 in our department, 21 patients responded to our questionnaire. In total 66.7% patients with mCRC answered "(very)satisfied"with the CGP testing. 28.6% of the patients already knew about CGP testing before their local doctors informed them. Except for 3 patients who did not answer, 47.6% and 9.5% of patients with mCRC"agreed"and "moderately agreed"with the timing of the CGP test. CONCLUSION: Although most patients with mCRC failed to access promising new treatment via CGP, approximately half of the patients answered that they were satisfied with the CGP testing. Conversely, a few patients already knew about CGP testing before it was proposed by their doctors. Thus, the provision of information at an early stage is necessary.

Anatomical Validation of Internal Iliac Vessels Assessed by Three-dimensional Angiographic Analysis.

Objectives: Anatomical understanding of the internal iliac vessels is important with the increasing frequency of minimally-invasive pelvic surgery. We aimed to investigate the branch patterns of internal iliac vessels, especially the veins. Methods: This study included 30 patients with 60 half-pelvises who underwent minimally-invasive pelvic surgery. Branch patterns were assessed on surgical videos with a multi-detector computed tomography-based three-dimensional simulation. Branch patterns of the superior gluteal artery and vein (SGA and SGV), inferior gluteal artery and vein (IGA and IGV), internal pudendal artery and vein (IPA and IPV), and obturator artery and vein (ObA and ObV) were investigated. Results: In the most frequent internal iliac vein (IIV) branch pattern, 67% of SGV branched from the IIV, 95% of the IGV branched from the IPV and 82% of the ObV branched from the IPV. According to Adachi's classification, 62% of IIVs were Type I and 33% Type IV. Although IIV branch patterns are heterogeneous, in individual patients with the most frequent branch patterns, good correlation (75-100%) of the branch patterns was observed between the internal iliac artery (IIA) and IIV, and between the right and left IIVs. Conclusions: This study clarified the branch patterns of IIV. In patients with the most frequent branch patterns, good correlation of the branch patterns was observed between the IIA and IIV, and between right and left IIV. We believe this helps secure the safety and standardization of minimally-invasive pelvic surgery.

Transanal Minimally Invasive Surgical Approach to Total Pelvic Exenteration.

BACKGROUND: Total pelvic exenteration, a surgical procedure for patients with highly advanced primary and recurrent rectal cancer, is technically demanding. IMPACT OF INNOVATION: We report the utility of a transanal minimally invasive surgical approach to total pelvic exenteration. TECHNOLOGY MATERIALS AND METHODS: A 2-team approach with a laparoscopic transabdominal approach and transanal minimally invasive surgery was adopted. During the transabdominal approach in the pelvis, dissection was performed to remove the pelvic organs and visceral branches of the internal iliac vessels. The dissection goal via the transabdominal approach is the levator ani. During the transperineal approach, dissection is performed along the levator ani, and the tendinous arch of the levator ani is penetrated at the lateral side to achieve rendezvous between the 2 approaches. The levator ani is then dissected circumferentially, with identification of the internal pudendal vessels passing through the levator ani at the 4 o'clock and 8 o'clock positions, known as Alcock's canal. The anterior wall of Alcock's canal is formed by the coccygeus muscle and sacrospinous ligament, which are dissected by the transperineal approach to open Alcock's canal, thus obtaining a clear view of the internal pudendal vessels. On the anterior side, the urethra is divided with a laparoscopic linear stapler via the transperineal approach. PRELIMINARY RESULTS: Eight patients with rectal cancer underwent this procedure. The median (range) blood loss was 200 (120-1520) mL and operating time was 467 (321-833) minutes. Reoperation was performed in 1 internal hernia case; however, there were no mortalities, and there were no cases with severe complications or conversion to open surgery. CONCLUSIONS AND FUTURE DIRECTIONS: When performing total pelvic exenteration, transanal minimally invasive surgery offers direct visualization behind the tumor from the anal side and shows the deep pelvic structures, including the retroperitoneal space of the pelvic sidewall.

[Educational Project of Self-Removal of the Intravenous Central Venous Access Port Guided by Patients with Advanced Colorectal Cancer Instructed by a Nurse in the University Hospital].

BACKGROUND: Fluorouracil infusion for 46±5h from the central venous(CV)port is required for mFOLFOX6, FOLFIRI, and FOLFOXIRI in patients with advanced colorectal cancer(CRC), followed by self-removal of the needle by patients. At our hospital, outpatients were instructed for self-removal of the needle, but the results were unsatisfactory. Therefore, instructions for self-removal of the needle from the CV port have been initiated at the patient ward since April 2019, making use of a hospital stay of 3 days. PATIENTS: We retrospectively enrolled patients with chemotherapy-introduced advanced CRC from the CV port who received instructions for self-removal of the needle in the outpatient department and ward between January 2018 and December 2021. RESULTS: Of all patients with advanced CRC, 21 received instructions at the outpatient department(OP)while 67 at patient ward(PW). Incidences of successful self-removal of the needle without the aid of others were similar: 47% in OP and 52% in PW(p=0.80). However, after several additional instructions involving their families, it was higher in PW than in OP(97.0 vs 76.1%, p=0.005). Incidences of successful self-removal of the needle without the aid of others in those aged≥75/<75, and≥65/<65 years were 0%/61.1%, and 35.4%/67.5%, respectively. OP was as a risk factor for failed self-removal of the needle in the logistic regression analysis(odds ratio: 11.19, 95%CI: 1.86- 67.30). CONCLUSION: Repeated instructions involving patients' families during the hospital stay improved the incidence of successful self-removal of the needle. Involvement of patients' families from the beginning may effectively improve self- removal of the needle, particularly in the elderly patients with advanced CRC.

[Challenge of Skin Treatment Led by Nurses and Pharmacists for Advanced Colorectal Cancer Patients Treated with Anti-EGFR Antibodies].

Preemptive skin treatment led by nurses and pharmacists was started for patients with metastatic colorectal cancer (mCRC)who received anti-EGFR antibody treatment. Incidence of skin-related toxicities, amount of topical moisturizers used, and administered cycles of anti-EGFR antibody were retrospectively compared between a preemptive skin treatment group and a control group. Thirty-four mCRC patients before the introduction of preemptive skin treatment led by nurses and 23 mCRC patients treated with preemptive skin treatment led by nurses were evaluated. The incidence of 6- and 12- week Grade 2 or higher skin-related toxicity was 23.5% in the control group and 8.7% in the preemptive group(p=0.18), and 67.7% in the control group and 30.4% in the preemptive group(p=0.0076), respectively. Mean amounts of moisturizer used were both lower in the control group than in the preemptive group at both 6 weeks and 7-12 weeks(6 weeks; 275 g vs 550 g, p=0.036, 7-12 weeks; 575 g vs 1,175 g, p=0.013). However, the amount of topical steroid used was similar in both groups. Preemptive moisturizer skin treatment led by nurses and pharmacists may decrease the incidence of skin- related toxicity.

The impact of molecular profile on the lymphatic spread pattern in stage III colon 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.

[A Case of Curative Resection for Borderline-Resectable Locally Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy followed by Extended Surgery].

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.

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.

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.

[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.

[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.

[Radiofrequency Ablation Pulmonary Metastasis of Colorectal Cancer - Two Cases of Report].

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.