Tumor budding

Tumor budding is defined as a single tumor cell or a cell cluster of up to 4 tumor cells, it is an independent predictor of lymph node metastasis in pT1 colorectal cancer and an independent predictor of survival in stage II colorectal cancer, and it should be taken into account along with other clinicopathologic factors in a multidisciplinary setting [1].

Tumor budding is counted on hematoxylin-eosin.

Intratumoral tumor budding in colorectal cancer has been shown to be related to lymph node metastasis and it should be included in guidelines/protocols for colorectal cancer reporting [1].

Tumor budding and tumor grade are not the same.

Tumor budding is graded according to its number in a microscopic field with a ×20 objective lens (0.785 mm²) in the hotspot. Tumors with less than five, five to nine, and 10 or more budding foci as classified as grades BD1, BD2, and BD3, respectively [2]. Category BD3 is subclassified as BD3a for tumors with 10 to 19 and BD3b for those with 20 or more budding foci in the hotspot (in a field of 0.785 mm²) at the invasive front [2].

Bibliographic references:

[1] Cho SJ, Kakar S. Tumor Budding in Colorectal Carcinoma: Translating a Morphologic Score Into Clinically Meaningful Results. Arch Pathol Lab Med. 2018;142(8):952-957. Available at: https://doi.org/10.5858/arpa.2018-0082-RA.

[2] Ueno H, et al. Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial. J Clin Oncol. 2019;37(22):1886-1894. Available at: https://doi.org/10.1200/JCO.18.02059.

Haggitt classification of colorectal polyps

Source: Bujanda L, et al. Malignant colorectal polyps. World J Gastroenterol. 2010;16(25):3103-3111. Available at: https://doi.org/10.3748/wjg.v16.i25.3103.

Narrow‐band imaging (NBI) International Colorectal Endoscopic (NICE) classification of colorectal tumors

WHO: World Health Organization.

Source: Sano Y, et al. Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team. Dig Endosc. 2016;28(5):526-533. Available at: https://doi.org/10.1111/den.12644.

ROVER (Radiation Oncology Virtual Education Rotation) GI (gastrointestinal)|GU (genitourinary) session

Regional lymph nodes in rectal cancer

Regional lymph nodes are located along the providing vessels of the rectum. The AJCC confines locoregional lymph node involvement to the following lymph nodes:

• sigmoid mesenteric;
• inferior mesenteric;
• superior rectal/hemorrhoidal;
• middle rectal/hemorrhoidal;
• inferior rectal/hemorrhoidal or mesorectal;
• perirectal;
• sacral promontory (Gerota's);
• lateral sacral;
• presacral;
• internal iliac.

Source: [1].

Lymph nodes outside of these areas are considered metastatic disease (M1) (for example, suspicious inguinal lymph nodes if the distal anal sphincter complex is involved) [1].

Coronal and axial drawings show the nodal stations relevant to anal and rectal cancers. Regional nodal stations are shown for anal cancers (blue-green) and rectal cancers (orange). Nodal stations considered metastatic for both anal and rectal cancer are shaded dark gray. Red and blue circles in the axial drawing are external and internal iliac arteries and veins.

Source: [2].

«Pelvic lymph nodes outside of the mesorectum — internal iliac, external iliac, obturator, and common iliac — are termed lateral pelvic lymph nodes (LPLNs). Rectal cancer with involved LPLNs is managed differently in the United States (US) compared to several countries in Asia. In the US, the AJCC defines only the internal iliac lymph nodes as regional, whereas external and common iliac lymph nodes are considered sites of metastatic disease. On the other hand, in Japan, all LPLNs are considered regional and patients are treated with curative intent [3-4]».

Differences in the understanding and management of LPLNs between the East and the West:

LLN = lateral lymph node; nCRT = neoadjuvant chemoradiotherapy; RT = radiotehrapy.

Source: [5]

Bibliographic references:

[1] van Loenhout R, Zijta F, Lahaye M, Beets-Tan R, Smithuis R. The Radiology Assistant: Rectal Cancer - MR staging 2.0 [Internet]. Radiologyassistant.nl. 2015 [cited 2019 May 28]. Available from: http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-staging-20.html#in565b4b37b539c.
[2] Matalon SA, et al. Anorectal Cancer: Critical Anatomic and Staging Distinctions That Affect Use of Radiation Therapy. Radiographics. 2015 Nov-Dec;35(7):2090-107. Available at: https://doi.org/10.1148/rg.2015150037.
[3] Akiyoshi T, et al. Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease? Ann Surg. 2012 Jun;255(6):1129-34. Available at: https://doi.org/10.1097/SLA.0b013e3182565d9d.
[4] Yahya JB, et al. Does a fine line exist between regional and metastatic pelvic lymph nodes in rectal cancer-striking discordance between national guidelines and treatment recommendations by US radiation oncologists. J Gastrointest Oncol. 2018 Jun;9(3):441-447. Available at: https://doi.org/10.21037/jgo.2018.02.05.
[5] Radjindrin A, Shanmugam V. Does Lateral Pelvic Lymph node matters in rectal cancer. Glob Surg. 2018;4(4):1-3. Available at: https://doi.org/10.15761/GOS.1000196.

Anorectal anatomy

«Note the anal crypts and glands; 90 percent of anorectal fistulas originate in a cryptoglandular abscess. Also note the relationship of the crypts and glands to the internal and external sphincters.»

Source: UpToDate [Internet]. Uptodate.com. 2019 [cited 2019 May 26]. Available from: https://www.uptodate.com/contents/image?imageKey=SURG%2F72874&topicKey=SURG%2F17127&search=rectum&source=outline_link&selectedTitle=1~150.

«The anal canal is 2.5 to 3.5 cm long and begins superiorly where the rectal ampulla is narrowed by the puborectalis sling (the levator ani muscle, which is palpable as the anorectal ring). It ends at the intersphincteric groove. Externally, the anal canal is surrounded by the internal and external anal sphincter muscles.

The superior half of the anal canal contains a series of longitudinal ridges called the anal columns (of Morgagni), which extend from the anorectal junction superiorly to the anal valves inferiorly. The anal valves form an irregular line called the dentate (or pectinate) line (colored purple in the diagram), which is an important anatomical landmark. The portions of the anal canal superior and inferior to it have different origins of arterial supply, nerve innervation, venous/lymphatic drainage, and epithelial lining.

The anal canal is internally lined with mucous membrane above the dentate line and anoderm below it. The upper portion of the anoderm (anal verge) consists of smooth, hairless skin; the lower portion of the anoderm (perianal skin) contains pigmented skin containing hair follicles and glands.»

Source: UpToDate [Internet]. Uptodate.com. 2019 [cited 2019 May 26]. Available from: https://www.uptodate.com/contents/image?imageKey=ONC%2F62539&topicKey=ONC%2F106743&search=rectal%20cancer&source=outline_link&selectedTitle=1~150.

Rectal division

Division of the upper, middle, and lower rectum [1]:

Image adapted from Surgical Anatomy of the Colon, Rectum, and Anus [Internet]. Abdominal Key. 2017 [cited 2019 May 29]. Available from: https://abdominalkey.com/surgical-anatomy-of-the-colon-rectum-and-anus/.

Measurement of rectal cancer with respect to the reference level and method:

Source: Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479–516. Available at: https://doi.org/10.1093/annonc/mds236.

«The rectum extends from the anorectal junction to the sigmoid. The rectosigmoid junction is arbitrarily defined as 15 cm above the anorectal angle. A tumor more than 15 cm above the anorectal angle is regarded and treated as a sigmoid tumor. Rectal cancer can be divided into:

- Low rectal cancer: distal border is 0-5 cm from the anorectal angle;

- Mid rectal cancer: distal border is 5-10 cm from the anorectal angle;
- High rectal cancer: distal border is 10-15 cm from the anorectal angle.»

Source: The Radiology Assistant: Rectal Cancer - MR staging 2.0 [Internet]. Radiologyassistant.nl. 2015 [cited 2019 May 26]. Available from: http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-staging-20.html.

Bibliographic references:

[1] UpToDate [Internet]. Uptodate.com. 2019 [cited 2019 May 26]. Available from: https://www.uptodate.com/contents/image?imageKey=SURG%2F107991&topicKey=SURG%2F17127&search=rectum%20anatomy&source=outline_link&selectedTitle=1~150.

Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience

Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience: Hypo-fractionated radiotherapy and stereotactic body radiotherapy are viable options for treatment of oligometastases. A prodrug of mitomycin-C is under clinical testing as a pegylated liposomal formulation (Promitil) with an improved safety profile over mitomycin-C. Promitil was offered to two patients with oligometastases from colorectal cancer as radiosensitizer. Each derived durable clinical benefit from Promitil administered immediately prior to and following irradiation. Transient toxicity to normal tissues of moderate to severe degree was observed. Promitil appears to have potential clinical value in this setting.