Adequate Margins to Prevent Local Re-recurrence of Rectal Cancer: Viewpoint of Pathological Findings

Patients and Methods

Patients' characteristics. The study included 110 LRRC patients who had previously undergone curative resection for rectal cancer at the Department of Gastroenterological Surgery at the Aichi Cancer Center Hospital in Nagoya, Japan, between January 1981 and December 2012. This was study a retrospective study. At our Hospital, this procedure is equivalent to obtaining permission from our ethics committee on human research in the event of a retrospective study (Aichi Cancer Center Ethics Committee).

Previously, radical dissection of all primary regional lymph nodes and TME were performed in all cases. No cancer cells were observed in the CRM in any of the cases. There was a median period of 679 days (range=238-2949 days) from the date of resection of the primary lesion to resection of local recurrence. The median follow-up period was 685 days (range=64-5197 days).

In almost all cases, a preoperative diagnosis for LRRC was performed by computed tomography (CT)-guided fine-needle aspiration biopsy. However, when acquisition of the biopsy was impossible, the preoperative diagnosis was performed by CT, magnetic resonance imaging, or positron emission tomography (PET). Distant recurrences were analyzed by CT or PET.

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Figure 1.

Continuous development is defined as ‘Expanding type’ (left). Discontinuous tumor development is defined as ‘Infiltrating type’ (right).

Our indications for surgical treatment of LRRC were the proximal sacral invasion until the level of the S1-S2 junction, and no invasion to the pelvic sidewall, iliac vessels, or sciatic notch (8). If unresectable distant recurrences were recognized and contraindicative, operative treatment was contraindicated. No patients diagnosed with resectable recurrence were treated with preoperative chemoradiation. The surgical procedures performed were LR, LAR, APR, APRS, TPE, and TPES.

After surgery for LRRC, 31 patients received adjuvant chemotherapy only, with oral 5-fluorouracil, 5’-doxifluridine, carmofur, xelox, or uracil-tegafur with leucovorin being the most common, for approximately 6 to 12 months. A further 21 patients were treated with adjuvant radiation only. Finally, 20 patients were treated with adjuvant chemoradiotherapy (9, 10, 11).

We conducted a review of patient hospital records to obtain clinicopathological information such as gender, age (median=58 years), primary lesion-related factors (histological type of primary lesion, lymphatic invasion, venous invasion, and presence or absence of lymph node metastasis), and recurrent lesion-related factors (surgical procedure and pre-carcinoembryonic antigen, and pre-CEA). Pre-CEA was calculated from data collected within one or two months before resection of the recurrent lesion.

Primary rectal adenocarcinomas were graded mainly based on their glandular appearance and were classified as well-, moderately, or poorly-differentiated, according to the World Health Organization histopathological classification for colon and rectum tumors (11) and the Japanese Classification of Colorectal Carcinomas (12). The histological type of the primary lesion was classified into two groups, well- and moderately-differentiated (‘W/M’) and those other than W/M (‘Others’).

The histological type of the central lesion of recurrence was classified into two groups, the ‘Expanding type’ (continuous development of the main tumor) and ‘Infiltrating type’ (discontinuous tumor development with mesenteric implants, and lymphatic, venous, and perineural invasion) (Figure 1).

The CRM of recurrence (radial margin), defined as the minimal distance (x) from the greatest depth of tumor invasion to the denuded surface, was estimated by microscopy (median, 2,000 μm) and classified into three groups, ‘R1’ (x=0 μm), ‘R0 shortness’ (0 μm <x<2,000 μm), and ‘R0 longness’ (x ≥2,000 μm) (Figure 2).

The histological change from the primary lesion to the recurrent lesion was classified into three groups, ‘No change pattern’, a change from W/M to an expanding type; ‘Change pattern’, a change from W/M to an infiltrating type, and ‘Other pattern’, a change from any type but W/M to an infiltrating type.

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Figure 2.

CRM of recurrence, the minimal distance (x) from the greatest depth of tumor invasion divided by the denuded surface. The left image depicts ‘R0 short’ (0 μm <x<2,000 μm) and the right image, ‘R1’ (x=0 μm).

Statistical analysis. Univariate and multivariate stepwise logistic regression analyses were performed to identify factors influencing local re-recurrence-free survival, re-recurrence-free survival, and overall survival. The log-rank test was used to evaluate differences in local re-recurrence-free survival, re-recurrence-free survival, and overall survival rates between groups. Statistical significance was set at p<0.05.