Right-sided CRC invading duodenum and/or pancreas is a rare condition [6, 23, 25], and only a few studies have reported adjacent-organ resection [4, 6, 7, 14–16, 25–29]. In our study, among 2269 patients with primary right-sided CRC who underwent radical RC screened, only 19 patients (12 men and 7 women) underwent en bloc RHCPD for LARCC with direct infiltration into the duodenum and/or pancreas. The patients who underwent duodenal resection with correction by direct suture or pedicled ileal flap were excluded because of the poor outcome and high rate of morbidity and mortality . LARCC once confirmed during the operation, all adhesions between tumor and adjacent organs should be considered as malignant invasion due to 33–84% malignant invasion on pathologic examination [4, 15] and should not be separated as there exist a risk of tumor recurrence rate of 90–100% [9, 10]. In our study, en bloc resection was performed, and adhesions were verified as malignant only after histopathologic examination.
Right-sided CRC invading duodenum and/or pancreas was considered to have poor outcomes and unresectable in the earlier days. However, recent studies have reported a promising prognosis, with a 5-year survival rate ranging from 21–55% in patients with LARCC invading adjacent organs undergoing en bloc multivisceral resection [4, 5, 12, 15, 19]. Similarly, in our study, all the patients who underwent curative RHCPD achieved good outcomes, with 1-, 3-, and 5-year OS rate of 88.2%, 65.9%, and 57.6%, whereas DFS rates of 71.6%, 56.4%, and 56.4% respectively. Comparatively higher OS rate in our study is probably because of the fact that even though all the patients were staged T4b, regional lymph node dissemination of the cancer may not be that advanced because only 5 out of 19 patients were lymph node positive (N2a and N1b). In addition, some colon cancers exhibits locally aggressive invasion instead of distant spread [4, 15, 27, 29]. According to the previous reports, 25–60% of right colon carcinoma that invaded the adjacent duodenum or pancreas do not have lymph node metastasis [4, 6, 15, 27, 29]. Furthermore, Saiura et al reported significantly longer survival in patients with node-negative status than node-positive patients . Similarly, in our study, the survival of patients with node-positive had short survival (< 3 years) at the time of last follow-up Meanwhile, the 3- and 5-year OS of 14 patients with N0 were 88.9% and 77.8%, respectively, among them 4 patients survived for > 5 years. In subsequent univariate and multivariate analysis, regional lymph node dissemination was significant prognostic factor for poor survival.
Furthermore, based on the KM curve analysis, OS was significantly better in patients with well- or moderately differentiated tumor compared with patients with poorly differentiated tumor. This is probably because of the fact that the histologic type of tumor may affect the lymph node metastasis and prognosis in patients with LARCC as reported by a retrospective study conducted by Saiura et al 2008. The rate of lymph node metastasis was significantly higher in well-differentiated adenocarcinoma than mucinous or poorly differentiated adenocarcinoma in LARCC (P = 0.015) . In our study, only 1 patient (6.7%) with moderately differentiated adenocarcinoma had node-positive status, whereas all the patients with poorly differentiation adenocarcinoma had node-positive status, and the 3-year OS rates of the 2 groups (well- or moderately differentiated tumor vs. poorly differentiation adenocarcinoma) were 82.1% versus 0%.
Molecular markers such as K-Ras, N-Ras, B-Raf, HER2, and MSI play a significant role in the disease prognosis in CRC, and hence, analysis of these biomarkers helps in facilitating proper treatment to the needy patients . In our study, all the patients in MSI-H status survived for > 3 years, while 3-year OS of patients in MSS status was only 35.0% (P = 0.047). OS did not differ significantly between K-Ras mutant and wild-type (P = 0.888), BRAF V600E mutant and wild-type tumors (P = 0.771) nor Her-2 (P = 0.635). Hence, only MSI was the significant prognostic factor affecting survival.
In FOxTROT trial, preoperative chemotherapy has resulted in significant downstaging of tumor in patients with locally advanced colon cancer compared to postoperative chemotherapy (P = 0.04) . Another retrospective study by Arredondo et al. has also shown tumor downstaging (62.5%), R0 resection (100%), and a promising prognosis (median OS of 31 months) in locally advanced colon cancer patients treated with preoperative chemotherapy . Similarly, in our study, the 3-year OS rates was greater in the preoperative and postoperative chemotherapy group (100% and 77.8%) compared with no perioperative chemotherapy group (25.0%). However, these finding need to be confirmed by considering studies with large sample size.
There are several limitations associated with the present study. First, the number of LARCC patients with invasion of duodenum and/or pancreas is low, and hence, the number of participants is small in this study. Large-scale studies may produce more reliable results. Second, the chemotherapy regimens varied among patients. In the era of advanced chemotherapy, administering the same regimen for a long-term study seems formidable. However, the present study also has several strengths such as this study gathered the largest number of patients, and all the clinical information and follow-up were proved to be accurate. Moreover, histologic-genetic examination was performed in detail, and we were able to build a bridge between the preoperative clinical evidence with histologic-genetic findings and prognosis.