Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

TRIB3 Interacts With ß-Catenin and TCF4 to Increase Stem Cell Features of Colorectal Cancer Stem Cells and Tumorigenesis.

BACKGROUND & AIMS: Activation of Wnt signaling to ß-catenin contributes to the development of colorectal cancer (CRC). Expression of tribbles pseudo-kinase 3 (TRIB3) is increased in some colorectal tumors and associated with poor outcome. We investigated whether increased TRIB3 expression promotes stem cell features of CRC cells and tumor progression by interacting with the Wnt signaling pathway. METHODS: We performed studies with C57BL/6J-ApcMin/J mice injected with an adeno-associated virus vector that expresses a small hairpin RNA against Trib3 mRNA (ApcMin/J-Trib3KD) or a control vector (ApcMin/J-Ctrl). We created BALB/c mice that overexpress TRIB3 from an adeno-associated virus vector and mice with small hairpin RNA-mediated knockdown of ß-catenin. The mice were given azoxymethane followed by dextran sodium sulfate to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by histology, gene expression profiling, immunohistochemistry, and immunofluorescence. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-positive (LGR5Pos) and LGR5-negative (LGR5Neg) HCT-8 CRC cells, with or without knockdown or transgenic expression of TRIB3, were sorted and analyzed in sphere-formation assays. We derived organoids from human and mouse colorectal tumors to analyze the function of TRIB3 and test the effect of a peptide inhibitor. Wnt signaling to ß-catenin was analyzed in dual luciferase reporter, chromatin precipitation, immunofluorescence, and immunoblot assays. Proteins that interact with TRIB3 were identified by immunoprecipitation. CRC cell lines were grown in nude mice as xenograft tumors. RESULTS: At 10 weeks of age, more than half the ApcMin/J-Ctrl mice developed intestinal high-grade epithelial neoplasia, whereas ApcMin/J-Trib3KD mice had no intestinal polyps and normal histology. Colon tissues from ApcMin/J-Trib3KD mice expressed lower levels of genes regulated by ß-catenin and genes associated with cancer stem cells. Mice with overexpression of Trib3 developed more tumors after administration of azoxymethane and dextran sodium sulfate than BALB/c mice. Mice with knockdown of ß-catenin had a lower tumor burden after administration of azoxymethane and dextran sodium sulfate, regardless of Trib3 overexpression. Intestinal tissues from mice with overexpression of Trib3 and knockdown of ß-catenin did not have activation of Wnt signaling or expression of genes regulated by ß-catenin. LGR5Pos cells sorted from HCT-8 cells expressed higher levels of TRIB3 than LGR5Neg cells. CRC cells that overexpressed TRIB3 had higher levels of transcription by ß-catenin and formed larger spheroids than control CRC cells; knockdown of ß-catenin prevented the larger organoid size caused by TRIB3 overexpression. TRIB3 interacted physically with ß-catenin and transcription factor 4 (TCF4). TRIB3 overexpression increased, and TRIB3 knockdown decreased, recruitment of TCF4 and ß-catenin to the promoter region of genes regulated by Wnt. Activated ß-catenin increased expression of TRIB3, indicating a positive-feedback loop. A peptide (P2-T3A6) that bound ß-catenin disrupted its interaction with TRIB3 and TCF4. In primary CRC cells and HCT-8 cells, P2-T3A6 decreased expression of genes regulated by ß-catenin and genes associated with cancer stem cells and decreased cell viability and migration. Injection of C57BL/6J-ApcMin/J mice with P2-T3A6 decreased the number and size of tumor nodules and colon expression of genes regulated by ß-catenin. P2-T3A6 increased 5-fluorouracil-induced death of CRC cells and survival times of mice with xenograft tumors. CONCLUSION: TRIB3 interacts with ß-catenin and TCF4 in intestine cells to increase expression of genes associated with cancer stem cells. Knockdown of TRIB3 decreases colon neoplasia in mice, migration of CRC cells, and their growth as xenograft tumors in mice. Strategies to block TRIB3 activity might be developed for treatment of CRC.

ID1 expressing macrophages support cancer cell stemness and limit CD8+ T cell infiltration in colorectal cancer.

Elimination of cancer stem cells (CSCs) and reinvigoration of antitumor immunity remain unmet challenges for cancer therapy. Tumor-associated macrophages (TAMs) constitute the prominant population of immune cells in tumor tissues, contributing to the formation of CSC niches and a suppressive immune microenvironment. Here, we report that high expression of inhibitor of differentiation 1 (ID1) in TAMs correlates with poor outcome in patients with colorectal cancer (CRC). ID1 expressing macrophages maintain cancer stemness and impede CD8+ T cell infiltration. Mechanistically, ID1 interacts with STAT1 to induce its cytoplasmic distribution and inhibits STAT1-mediated SerpinB2 and CCL4 transcription, two secretory factors responsible for cancer stemness inhibition and CD8+ T cell recruitment. Reducing ID1 expression ameliorates CRC progression and enhances tumor sensitivity to immunotherapy and chemotherapy. Collectively, our study highlights the pivotal role of ID1 in controlling the protumor phenotype of TAMs and paves the way for therapeutic targeting of ID1 in CRC.

TRIB3 reduces CD8+ T cell infiltration and induces immune evasion by repressing the STAT1-CXCL10 axis in colorectal cancer.

High CD8+ T cell infiltration in colorectal cancer (CRC) should suggest a favorable prognosis and a satisfactory response to immunotherapy; however, the vast majority of patients with CRC do not benefit from immunotherapy due to poor T cell infiltration. Therefore, a better understanding of the mechanisms for T cell exclusion from CRC tumors is needed. Tribbles homolog 3 (TRIB3) has been implicated as an oncoprotein, but its role in regulating antitumor immune responses has not been defined. Here, we demonstrated that TRIB3 inhibits CD8+ T cell infiltration in various CRC mouse models. We showed that TRIB3 was acetylated by acetyltransferase P300, which inhibited ubiquitination and subsequent proteasomal degradation of TRIB3. Ectopically expressed TRIB3 inhibited signal transducer and activator of transcription 1 (STAT1) activation and STAT1-mediated CXCL10 transcription by enhancing the epidermal growth factor receptor signaling pathway, causing a reduction in tumor-infiltrating T cells. Genetic ablation of Trib3 or pharmacological acceleration of TRIB3 degradation with a P300 inhibitor increased T cell recruitment and sensitized CRCs to immune checkpoint blockade therapy. These findings identified TRIB3 as a negative modulator of CD8+ T cell infiltration in CRCs, highlighting a potential therapeutic target for treating immunologically "cold" CRCs.

Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR).

PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy for unresectable rectal cancer (SUNRISE): interim analysis of a randomized phase II trial.

PURPOSE: The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis. METHODS AND MATERIALS: Patients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments. RESULTS: From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group. CONCLUSION: Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned.

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis.

BACKGROUND: Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy (NCRT). This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis. METHODS: In total, 1296 patients with NCRT or post-operative chemoradiotherapy (PCRT) were enrolled in this study between January 2008 and December 2015. Propensity score matching was used to correct for differences in baseline characteristics between the two groups. After propensity score matching, the metastasis pattern, including metastasis sites and timing, was compared and analyzed. RESULTS: After propensity score matching, there were 408 patients in the PCRT group and 245 patients in the NCRT group. NCRT significantly reduced local recurrence (4.1% vs. 10.3%, P = 0.004), but not distant metastases (28.2% vs. 27.9%, P = 0.924) compared with PCRT. In both the NCRT and PCRT groups, the most common metastasis site was the lung, followed by the liver. The NCRT group developed local recurrence and distant metastases later than the PCRT group (median time: 29.2 [18.8, 52.0] months vs. 18.7 [13.3, 30.0] months, Z = -2.342, P = 0.019; and 21.2 [12.2, 33.8] vs. 16.4 [9.3, 27.9] months, Z = -1.765, P = 0.035, respectively). The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group (39/114, 34.2%) and NCRT group (21/69, 30.4%). However, 20.3% (14/69) of the distant metastases appeared in the 3rd year in the NCRT group, while this number was only 13.2% (15/114) in the PCRT group. CONCLUSIONS: The predominant site of distant metastases was the lung, followed by the liver, for both the NCRT group and PCRT group. NCRT did not influence the predominant site of distant metastases, but the NCRT group developed local recurrence and distant metastases later than the PCRT group. The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.

Safety and efficacy of preoperative chemoradiotherapy in fit older patients with intermediate or locally advanced rectal cancer evaluated by comprehensive geriatric assessment: A planned interim analysis of a multicenter, phase II trial.

BACKGROUND AND PURPOSE: Comprehensive geriatric assessment (CGA) is a diagnostic method to assess the physical and mental health status of older patients. The purpose of this study was to assess the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for intermediate or locally advanced rectal cancer in older people who were classified as "fit" by CGA. The interim analysis focusing on safety was reported here as the first part of this trial. METHODS AND MATERIALS: This is a single arm, multicenter, phase II trial. The eligible patients for this study were aged 70 years or above that fulfilled the standard of intermediate or locally advanced risk category, and met the standard of fit (SIOG1) evaluated by CGA. All patients received preCRT (50 Gy) with Raltitrexed (3 mg/m2 on d1 and d22). Qualitative and quantitative variables were described using descriptive statistics. The surgery adherence predicting was analyzed by multivariate logistic regression. RESULTS: Thirty-nine fit patients were enrolled. All patients except one finished radiotherapy without dose reduction. Thirty-two patients finished the prescribed Raltitrexed therapy as scheduled. A serious toxicity was observed in 12 patients (30.8%), and only six patients (15.4%) experienced non-hematological side effects. CONCLUSION: Overall, our results showed that preCRT was feasible and safe in older patients with rectal cancer who were evaluated as fit based on CGA, supporting the use of CGA to tailor oncological treatment and predict the tolerance of a specific therapy. Completing this trial as planned would provide further valuable insights.

The prognostic significance of the treatment response of regional lymph nodes and the refinement of the current TNM staging system in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.

The current TNM staging system uses the same category definitions for both rectal cancer patients with and without neoadjuvant chemoradiotherapy (NCRT). However, ypTNM stage, especially ypN stage does not predict patient survival after NCRT well. Whether tumor regression in lymph nodes (LRG) may improve the prediction has not been well studied. In total, 358 patients with rectal cancer who received NCRT followed by radical resection were recruited from 2004 to 2015, and the median follow-up time was 57.5 months. The main outcome measure was disease-free survival (DFS). In univariate analysis, factors associated with DFS were ypT stage, ypN stage, number of negative lymph nodes (NLN), lymph node ratio (LNR), tumor regression grade (TRG), M-TTRG (modified ypT stage by combining ypT stage and TRG), maximum LRG (LRGmax), sum score of LRG (LRGsum), LRG ratio (average value of LRGsum), and M-NLRG (modified ypN stage by combining LRGmax and LNR). In the multivariate Cox regression analysis, M-TTRG and M-NLRG (p < 0.001 and p = 0.030, respectively) were significantly associated with DFS. The estimated 5-year DFS rates were 86.6%, 60.3%, and 36.4% for patients with M-NLRG-0, M-NLRG-1, and M-NLRG-2, respectively (p < 0.001). A significant difference in survival was observed among patients with NCRT after incorporating TRG and LRG simultaneously into the current ypTNM staging system (p < 0.001). LRG was an important prognostic factor in rectal cancer patients treated with NCRT and could refine the ypTNM staging system. The modified ypTNM staging system in combination with LRGmax, LNR, and TRG could improve the DFS prediction in each subset of patients.

Risk factors for nonclosure of defunctioning stoma and stoma-related complications among low rectal cancer patients after sphincter-preserving surgery.

BACKGROUND: Defunctioning stoma is widely used to reduce anastomotic complications in rectal cancer surgery. However, the complications of stoma and stoma reversal surgery should not be underestimated. Furthermore, in some patients, stoma reversal failed. Here, we investigated the complications of defunctioning stoma surgery and subsequent reversal surgery and identify risk factors associated with the failure of getting stoma reversed. METHODS: In total, 154 patients who simultaneously underwent low anterior resection and defunctioning stoma were reviewed. Patients were divided into two groups according to whether their stoma got reversed or not. The reasons that patients received defunctioning stoma and experienced stoma-related complications and the risk factors for failing to get stoma reversed were analysed. RESULTS: The mean follow-up time was 47.54 (range 4.0-164.0) months. During follow-up, 19.5% of the patients suffered stoma-related long-term complications. Only 79 (51.3%) patients had their stomas reversed. The morbidity of complications after reversal surgery was 45.6%, and these mainly consisted of incision-related complications. Multivariate analyses showed that pre-treatment comorbidity (HR = 3.17, 95% CI 1.27-7.96, P = 0.014), postoperative TNM stage (HR = 2.55, 95% CI 1.05-6.18, P = 0.038), neoadjuvant therapy (HR = 2.75, 95% CI 1.07-7.05, P = 0.036), anastomosis-related complications (HR = 4.52, 95% CI 1.81-11.29, P = 0.001), and disease recurrence (HR = 24.83, 95% CI 2.90-213.06, P = 0.003) were significant independent risk factors for a defunctioning stoma to be permanent. CONCLUSIONS: Defunctioning stoma is an effective method to reduce symptomatic anastomotic leakage, but the stoma itself and its reversal procedure are associated with high morbidity of complications, and many defunctioning stomas eventually become permanent. Therefore, surgeons should carefully assess preoperatively and perform defunctioning stomas in very high risk patients. In addition, doctors should perform stoma reversal surgery more actively to prevent temporary stomas from becoming permanent.

[Clinical results and prognostic analysis of local excision in lower rectal cancer].

OBJECTIVE: To analyze the results and the prognosis of local excision of lower rectal cancer, and investigate the proper indication of local excision for cure purpose. METHODS: The clinicopathological data of 76 patients with lower rectal cancer treated from February 1985 to October 2007 were analyzed. RESULTS: Sixty-nine patients received transanal excision, 6 cases received trans-sacral excision and 1 case received trans-vaginal excision. Among the cases, 48 cases were ranged as T1 phase, 25 cases as T2, 3 cases as T3. The operation complication rate was 7.9%, and the 30-day mortality rate post operation was 0. The local recurrence rate was 22.4% and the overall 5 year survival rate was 84.5%. The local recurrence was significantly related with T stage and resection margin status. The survival was significantly related with mucinous adenocarcinoma, resection margin status and lymphovascular invasion; and the resection margin and lymphovascular invasion was the independent factors affecting survival. CONCLUSION: Local excision was safe in early stage lower rectal cancer. Careful patient selection is the key of the operation. The proper indication of local excision is T1-2 without high risk factors (high histopathological grade, presence of lymphatic or vascular invasion, mucinous adenocarcinoma); and the cases with T2 phase tumor should undergo chemoradiotherapy after local excision.

[Outcome of surgical therapy for liver metastasis of colorectal cancer: analysis of 75 cases].

OBJECTIVE: To explore the strategy to improve the long term survival of liver metastasis of colorectal cancer after surgical treatment. METHODS: The clinical data of 75 patients with liver metastasis of colorectal cancer, 43 males and 32 females, aged 51.4, who received hepatectomy between January 1981 and November 2005, were analyzed. RESULTS: The primary tumor site was colon in 39 cases, and rectum in 36 cases. Liver metastasis was synchronous in 59 patients, and metachronous in 16 patients. 45 patients received simultaneous liver and colorectal resection, 29 patients received metachronous resection, and 1 patient did not receive primary rectal cancer resection. The operative complication rate and the mortality were 16% (12/75) and 1.33% (1/75) respectively. The overall 1- 3-, and 5-year survival rates were 86.7%, 35.5%, and 22.2% respectively, and the median survival time was 25 months. There were residual tumors in 35 patients. The 1-, 3-, and 5-year survival rates of the residual tumor group were 80.6%, 5.4%, and 5.4% respectively, all significantly lower than those of the radical resection group (91.6%, 58.1%, and 34.9% respectively, and the median survival time of the residual tumor group was 18 months, significantly shorter than that of the radical resection group (38 months) (all P = 0.000). CONCLUSION: Surgical resection of liver metastasis of colorectal cancer significantly prolongs the survival time, and resection of all liver deposits and the extrahepatic disease is the most important factor influencing survival.

[Simultaneous liver and colorectal resection for synchronous colorectal liver metastasis].

OBJECTIVE: To investigate the safety and long term outcome of simultaneous liver and colorectal resection for synchronous colorectal liver metastasis. METHODS: Forty-three synchronous colorectal liver metastasis patients who received simultaneous colectomy and hepatectomy between May 1981 and November 2005 were analyzed retrospectively. RESULTS: The group included 21 male patients and 22 female patients, with the median age of 52 years. The overall median operative time was 180 minutes, 30 cases received blood transfusion, and the median volume was 800 ml. The median hospital stay was 15 days. The morbidity and mortality was 18.6% and 2.3%, respectively. The overall median survival time was 25 months, 5-year survival rate was 19.1%. The survival of patients underwent R0 resection were substantially better (median survival time 48 months, 5-year survival rate 33.8%) than that of the patients who did not undergo R0 resection (20 months, 7.6%) (P = 0.002). CONCLUSIONS: Simultaneous liver and colorectal resection is safe and effective for synchronous colorectal liver metastasis. Furthermore, simultaneous R0 resection should be the optimal surgery for the resectable cases.

[Clinicopathological features and surgical treatment of familial adenomatous polyposis].

OBJECTIVE: To investigate the clinicopathological features and surgical treatment of familial adenomatous polyposis (FAP). METHODS: The clinical data of 51 patients with FAP, 29 males and 22 females, aged 36.6 (17-67), hospitalized Sep 1980-Dec 2005 were analyzed. RESULTS: Twenty-nine patients had family history of FAP and 7 of them were discovered during screened because of family history. The main clinical manifestations included rectal bleeding or bloody stool, diarrhea, abdominal pain, and general discomfort in the abdomen. Synchronous malignant changes were found in 28 patients while hospitalized. The incidence of colorectal cancer was 54.9%. The average age of those with colorectal cancer was 40.5 and the age of those without colorectal cancer was 31.9. 81.8% of the colorectal cancers occurred on the rectum and sigmoid colon. Different types of proctocolectomy were performed on 50 patients, and one patient received only pelvic radiotherapy. The follow-up rate was 74.5%. Only 27.5% of the patients received regular surveillance. Colorectal cancer was found in 8 patients after the first operation. So far 17 patients died. CONCLUSIONS: There were no specific clinical manifestations for FAP. Colonoscopy is the most important diagnostic procedure. Surgical treatment should be given as soon as possible. The specific operation type should be based on the individual aspects of patients. Life-time surveillance and follow-up are very important.

Advances for achieving a pathological complete response for rectal cancer after neoadjuvant therapy.

Neoadjuvant therapy has become the standard of care for locally advanced mid-low rectal cancer. Pathological complete response (pCR) can be achieved in 12%-38% of patients. Patients with pCR have the most favorable long-term outcomes. Intensifying neoadjuvant therapy and extending the interval between termination of neoadjuvant treatment and surgery may increase the pCR rate. Growing evidence has raised the issue of whether local excision or observation rather than radical surgery is an alternative for patients who achieve a clinical complete response after neoadjuvant therapy. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for pCR of rectal cancer in the modern era.

Clinicopathological and prognostic features of hepatoid adenocarcinoma of the stomach.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric carcinoma, which has its unique clinicopathological features and poorer prognosis than that of the ordinary gastric adenocarcinoma. At present, there is still a lack of understanding about this disease. The current study aimed to summarize and discuss the clinical, pathological, immunohistochemical, and prognostic features of this disease. METHODS: A total of 20 patients of HAS were retrospectively studied. All the patients were treated in Cancer Hospital of Chinese Academy of Medical Sciences between March 1998 and October 2009. Statistical analysis, including the Kaplan-Meier method, log-rank test and Cox model, were performed by the SPSS 15.0 software. RESULTS: Seventeen patients (85%) had at least 1 lymph node metastases; 17 patients (85%) received postoperative immunohistochemical examinations, with an alpha-fetoprotein (AFP) positive rate of 94.1% (16/17); 14 patients had distant metastases (including 12 liver metastases, 1 lung metastasis, and 1 celiac widespread metastases), and one simultaneously had anastomotic recurrence and liver metastases. The overall survival time was 2 - 99 months (median: 12.0 months). The 3-year survival rate of the 20 patients was 17.2%. The 3-year survival rate of patients with complete hepatocyte-like regions and those with both hepatocellular carcinoma and adenocarcinoma regions was 20.0% and 17.5%, respectively (P = 0.361). The survival difference among the radical surgery group, palliative surgery group and no surgery group was statistically significant (P = 0.022). The Kaplan-Meier method and log-rank test showed that surgery, pTNM stages, and adjuvant chemotherapy were associated with prognosis (P < 0.05). The Cox model only confirmed that the pTNM stages and adjuvant chemotherapy had statistical significance for the prognosis of HAS (P < 0.05) due to the limited cases. CONCLUSIONS: HAS is a special type of gastric carcinoma and has a poor prognosis. The pTNM stage is an independent risk factor for HAS. Multidisciplinary therapy, including surgery and chemotherapy, may improve the prognosis of HAS.

Wide local excision could be considered as the initial treatment of primary anorectal malignant melanoma.

BACKGROUND: Anorectal malignant melanoma was a rare disease with extremely poor prognosis. The aim of this study was to explore the clinical characteristic, diagnosis and treatment strategies of anorectal malignant melanoma. METHODS: The data of 57 patients with anorectal malignant melanoma was collected and retrospectively analyzed. RESULTS: Rectal bleeding and anal mass were found to be common symptoms of anorectal malignant melanoma. The preoperative diagnosis rate of anorectal malignant melanoma was 48.6%. The overall 3-year and 5-year survival rate was 38.0% and 21.3% respectively. The 3-year survival rates of stage I and II patients were 63.0% and 16.7% respectively (P = 0.000), and the 5-year survival rates were 33.3% and 11.1% (P = 0.001), which both had significant statistic differences. The 3-year survival rate of patients undergone abdmoninoperineal resection and patients undergone wide local excision were 36.7% and 53.0% respectively (P = 0.280), while the 5-year survival rate were 24.1% and 23.1% (P = 0.642), which both had no significant statistic differences. CONCLUSIONS: This study identified no survival advantage to abdominoperineal resection in treatment of anorectal malignant melanoma, and we propose that wide local excision could be considered as the initial treatment of choice.