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Annals of Surgical Oncology [journal]
- Radical Surgery with Total Mesorectal Excision in Patients with T1 Rectal Cancer. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 21.
Radical resection with total mesorectal excision (TME) is the accepted standard of care for most rectal cancers. However, T1 rectal cancers may be at low risk for metastases and are therefore treatable with local resection. The aim of our study was to investigate whether the identification of these patients is possible through existing selection criteria.Between 2001 and 2012, radical resection with TME was performed in 68 patients with a histologically confirmed T1 adenocarcinoma of the rectum. Each patient was staged preoperatively as lymph node negative. Patients at low risk to metastasize were defined as proposed by Hermanek and Gall (Int J Colorectal Dis 1(2):79-84, 1986), Kikuchi et al. (Dis Colon Rectum 38(12):1286-1295, 1995) and Hase et al. (Dis Colon Rectum 38(1):19-26, 1995) Postoperative morbidity, mortality, and oncological outcome were analyzed.Despite nodal negative staging, 9 of 68 patients (13 %) were node positive. Following the proposal of Hermanek and Gall, Kikuchi et al., and Hase et al., 14 % (5/37), 12 % (3/26), and 16 % (6/38) of patients, respectively, with low-risk tumors had lymph node metastases. In the univariate analysis, none of the investigated parameters could predict lymph node metastases. Following radical resection, none of the patients, regardless of nodal involvement, developed a recurrence.Preoperative diagnostics regarding lymphatic tumor propagation and histomorphological assessment of tumor samples as predictors of lymph node metastasis are unreliable. Following radical resection with TME, the oncological outcome of node-positive patients with T1 rectal adenocarcinoma is comparable with that of lymph node-negative patients. Considering the lymph node metastases rate, a local excision should always be complemented with additional therapy.
- Laparoscopic Versus Open Surgery for Colorectal Cancer in Elderly Patients: A Multicenter Matched Case-Control Study. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 21.
The safety of laparoscopic surgery (LAP) in elderly patients with colorectal cancer has not been demonstrated. The aim of this study was to compare the outcomes of LAP and open surgery (OP) and estimate the feasibility of LAP in colorectal cancer patients aged ≥80 years.We conducted a propensity scoring matched case-control study of colon and rectal cancer patients aged ≥80 years using data from 41 hospitals between 2003 and 2007. A total of 1,526 colon cancer patients and 282 rectal cancer patients underwent surgery and were included in the analysis. The primary end point was 3-year overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and postoperative complications.LAP and OP were compared in 804 colon cancer patients (402 pairs) and 114 rectal cancer patients (57 pairs) after all covariates were balanced, and no significant differences were observed, except for tumor size in colon cancer. OS, DFS, and CSS did not differ between the groups for either colon cancer (P = 0.916, 0.968, and 0.799, respectively) or rectal cancer (P = 0.765, 0.519, and 0.950, respectively). In colon cancer cases, LAP was associated with fewer morbidities than was OP (24.9 vs. 36.3 %, P < 0.001); no such difference was observed for rectal cancer patients (47.4 vs. 40.4 %, P = 0.450).LAP is an acceptable alternative to OP in elderly patients with colorectal cancer.
- Nerve-Guided Laparoscopic Total Mesorectal Excision for Distal Rectal Cancer. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 21.
Urogenital dysfunctions are well-recognized problems after rectal cancer surgery and are often due to autonomic nerve damage. Although following holy planes during total mesorectal excision (TME) reduces the possibility of damage to the autonomic nerve fibers, these could still be affected in some critical areas.1 (,) 2 To improve the quality of surgery and prevent nerve damage, accurate intraoperative anatomical orientation of autonomic nerve is essential.3 Thanks to advancement of the high-definition laparoscopic technology, even the finest nerve fibers deep in the pelvic cavity can be identified through illumination and magnification.4 We aim to present a surgical technique of using the autonomic nerves as landmarks to guide laparoscopic TME for distal rectal cancer, with the purpose of preventing autonomic nerve damage to the largest extent.The video describes the technique of performing nerve-guided laparoscopic TME in a 50-year-old man with a rectal cancer (7 cm from anal verge). Preoperative staging by endorectal ultrasound and pelvic magnetic resonance imaging is stage I rectal cancer (cT2N0M0). Five trocars (two 12 mm and three 5 mm) are used. All procedures are performed with conventional laparoscopic instruments. The sigmoid colon is mobilized using a medial approach. The superior hypogastric plexus lies just posterior to the inferior mesenteric artery (IMA) are clearly identified and protected. Then the root of the IMA is ligated and cut. The left Toldt space is dissected, followed by complete mobilization of the sigmoid colon. The superior hypogastric plexus nerve fibers combine to a strong pair of hypogastric nerves as they enter the pelvic cavity, and can be clearly identified when the mesorectum is lifted. Then the mesorectum is separated from the hypogastric nerves by sliding down along the nerves. Dissection of the mesorectum is continued in the loose areolar plane along the midline down to the sacrococcygeal junction. Then the mesorectum is dissected laterally from posterior midline up to 9 o'clock on the left and to 3 o'clock on the right side. The splanchnic nerves can be identified as they swing from the sacrum and straight into the pelvic plexus. The peritoneum is dissected in an arc line about 0.5 cm above the line of rectovesical pouch. After the anterior side of the rectum is mobilized, the mesorectum is dissected along the seminal vesicles downward and sideward to the lateral margin. The neurovascular bundle of Walsh at the anterolateral side of the rectum is clearly identified and protected. The mobilization of the mesorectum ceases at the tendinous arch of levator ani. Then the rectum is only fixed to the pelvic side wall by its lateral ligaments, which are consisted by rectal branch of the inferior pelvic plexus and vessels. Thus care should be taken to cut only those rectal nerve fibers, leaving the inferior pelvic plexus intact. The mesorectum is divided 5 cm distal to the lesion with one firing of an endoscopic stapler. The specimen is extracted through a 3 cm transumbilical laparotomy. End-to-end anastomosis using a circular stapler is performed intra-abdominally.There were no intraoperative complications. The operating time was 160 min. Blood loss was 20 mL. The patient underwent an uneventful recovery and was discharged home on postoperative day 6. Final pathology was pT2N0M0. At 6-month follow-up, the patient had no urogenital dysfunctions.Nerve-guided laparoscopic total mesorectal excision for distal rectal cancer is safe and feasible. This technique should be considered whenever possible as a means to prevent autonomic nerve damage and subsequent loss of urogenital function.
- Prokineticin 1 Protein Expression is a Useful New Prognostic Factor for Human Sporadic Colorectal Cancer. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 21.
Hematogenous metastasis, regarded as closely related to angiogenic growth factors, is associated with colorectal cancer prognosis. The angiogenic growth factor prokineticin 1 (PROK1) has been cloned from endocrine cells. However, its protein expression in human malignant tumors has not been studied. The current study established the anti-PROK1 monoclonal antibody (mAb) and examined the relationship between the expression of PROK1 protein and human colorectal cancer.The expression of PROK1 protein was assessed in 620 resected sporadic colorectal cancer tissue samples by immunohistochemical staining with in-house-developed human PROK1 mAb to investigate the relationship of PROK1 expression to clinicopathologic factors, recurrence, and survival rate and to evaluate its prognostic significance.The expression of PROK1 protein was detected in 36 % (223/620) of human primary colorectal cancer lesions but no in the healthy mucosa adjacent to the colorectal cancer lesions. According to the clinicopathologic examinations, the frequency of positive PROK1 expression was significantly higher in cases with serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, liver metastasis, hematogenous metastasis, and higher stage disease. The recurrence rate and prognosis for patients with PROK1 expression-positive lesions were significantly worse. In the Cox proportional hazard model, PROK1 expression was an independent prognostic factor.The expression of PROK1 protein was identified for the first time as a new prognostic factor in colorectal cancer.
- Robotic Versus Laparoscopic Intersphincteric Resection for Low Rectal Cancer: Comparison of the Operative, Oncological, and Functional Outcomes. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 18.
Robotic surgery was developed to overcome the limitations of laparoscopic surgery and is increasingly used to treat low rectal cancer. In this study, we compared the operative, oncological, and functional outcomes of low rectal cancer patients who underwent robotic or laparoscopic intersphincteric resection (ISR).Prospectively collected data from low rectal cancer patients who underwent laparoscopic or robotic ISR between September 2006 and August 2011 were retrospectively compared. The functional outcomes of patients followed up for ≥12 months after ileostomy closure were evaluated via questionnaire.Forty-four and 26 patients underwent robotic and laparoscopic ISR, respectively. The robotic group patients had a higher body mass index (BMI; 21.42 ± 3.13 vs. 24.13 ± 3.33 kg/m(2); p = 0.001), more advanced clinical N stage (p = 0.029), lower cancer location (3.71 ± 0.89 vs. 3.24 ± 0.78 cm; p = 0.023), more frequent chemoradiotherapy (26.9 vs. 54.5 %; p = 0.025), and longer operation time (286.77 ± 51.46 vs. 316.43 ± 65.11 min; p = 0.038). However, no intergroup differences were observed in the pathological details (except the number of retrieved lymph nodes), postoperative morbidity, 3-year overall survival, recurrence-free survival (RFS), local RFS, and functional outcomes.Robotic and laparoscopic ISR yielded similar operative, oncological, and functional outcomes in patients with low rectal cancer, despite differences in unfavorable outcome-affecting factors, including BMI, clinical N stage, cancer location, and chemoradiotherapy frequency. A randomized trial will provide more solid methodology for investigating the potential benefits of robotic ISR.
- A Novel Animal Model for Locally Advanced Breast Cancer. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 18.
Locally advanced breast cancer (LABC) poses complex management issues due to failure of response to chemotherapy and progression to local complications such as skin erosion, superinfection, and lymphedema. Most cell line and animal models are not adequate to study LABC.A patient-derived xenograft (IOWA-1T) from a patient with LABC was characterized for expression profile, short tandem repeat profile, oncogenic mutations, xenograft growth, and response to therapy.Short tandem repeat profile authenticated the cell line as derived from a human woman. The primary tumor and derived xenografts were weakly estrogen receptor alpha positive (<5 %), progesterone receptor negative, and HER2 nonamplified. Expression array profile compared to MCF-7 and BT-549 cell lines indicate that IOWA-1T was more closely related to basal breast cancer. IOWA-1T harbors a homozygous R248Q mutation of the TP53 gene; in vitro invasion assay was comparable to BT-549 and greater than MCF-7. IOWA-1T xenografts developed palpable tumors in 9.6 ± 1.6 days, compared to 49 ± 13 days for parallel experiments with BT-20 cells (p < 0.002). Tumor xenografts became locally advanced, growing to >2 cm in 21.6 ± 2 days, characterized by skin erosion necessitating euthanasia. The SUMO inhibitor anacardic acid inhibited the outgrowth of IOWA-1T xenografts, while doxorubicin had no effect on tumorigenesis.IOWA-1T is a novel cell line with an expression pattern consistent with basal breast cancer. Xenografts recapitulated LABC and provide a novel model for testing therapeutic drugs that may be effective in cases resistant to conventional chemotherapy.
- Pulmonary Metastasectomy in Colorectal Cancer Patients with Previously Resected Liver Metastasis: Pooled Analysis. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 18.
Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited.We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis.Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006).PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.
- Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 18.
Colorectal carcinoma (CRC) represents a group of histopathologically and molecularly heterogeneous diseases, which may contain signet-ring cell component and/or mucinous component to a varying extent under pathology assessment. However, little is known about the prognostic significance of those components, independent of various tumor molecular features.Utilizing a molecular pathological epidemiology database of 1,336 rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study, we examined patient survival according to the proportion of signet-ring cell and mucinous components in CRCs. Cox proportional hazards models were used to compute hazard ratio (HR) for mortality, adjusting for potential confounders including stage, microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations.Compared to CRC without signet-ring cell component, 1-50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 1.40 [95 % confidence interval (CI) 1.02-1.93], and >50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 4.53 (95 % CI 2.53-8.12) (P trend < 0.0001). Compared to CRC without mucinous component, neither 1-50 % mucinous component (multivariate HR 1.04; 95 % CI 0.81-1.33) nor >50 % mucinous component (multivariate HR 0.82; 95 % CI 0.54-1.23) was significantly associated with CRC-specific mortality (P trend < 0.57).Even a minor (50 % or less) signet-ring cell component in CRC was associated with higher patient mortality, independent of various tumor molecular and other clinicopathological features. In contrast, mucinous component was not associated with mortality in CRC patients.
- Aggressive Therapeutic Strategies Improve the Survival of Hepatocellular Carcinoma Patients with Performance Status 1 or 2: A Propensity Score Analysis. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 18.
Targeted therapy or chemotherapy is suggested as standard treatment for hepatocellular carcinoma (HCC) patients with performance status (PS) 1-2 according to the Barcelona Clinic Liver Cancer (BCLC) system. The underlying rationales have not been fully studied.This study enrolled 2,620 HCC patients. One-to-one matched pairs between HCC patients receiving aggressive anti-HCC treatments (resection, transplantation, ablation, and transarterial chemoembolization) and those receiving targeted therapy or chemotherapy or best supportive care were generated by using the propensity score with a matching model. Survival analysis was performed with the Kaplan-Meier method and the log-rank test. Mortality risk was calculated with the Cox proportional hazards model.Of 793 patients with PS 1-2, 64 % received aggressive anti-HCC treatments against the suggestion of the BCLC system. The patients receiving aggressive anti-HCC treatments had significantly milder cirrhosis, a smaller tumor burden, and better long-term survival than the patients undergoing targeted therapy or chemotherapy or best supportive care (all p < 0.05). With the use of propensity scores, 166 pairs of matched HCC patients with PS 1-2 were selected from different treatment groups. After matching, patients were comparable in age, gender, severity of cirrhosis, tumor burden, and prevalence of diabetes mellitus (all p > 0.05) at baseline. In the propensity score model, patients with PS 1-2 undergoing aggressive anti-HCC treatments had significantly better long-term survival (p < 0.0001). The adjusted hazard ratio of the choice for targeted therapy or chemotherapy or best supportive care to the choice for aggressive anti-HCC treatments was 2.028 (p < 0.0001).According to the findings, HCC patients with PS 1-2 should consider aggressive anticancer treatments if no contraindication is noted. Adjustment of the BCLC treatment allocation is needed to enhance its prognostic accuracy.
- Patients with Invasive Lobular Breast Cancer Are Less Likely to Undergo Breast-Conserving Surgery: A Population Based Study in The Netherlands. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Oct 17.
The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC).Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the NCR. All patients underwent BCS or primary mastectomy without neoadjuvant treatment and proportions per year were calculated. Logistic regression analysis with adjustment for period, age, nodal status and tumor size was performed to determine the impact of histology on the likelihood of undergoing BCS.A total of 152,574 patients underwent surgery in the period between 1990 and 2010, of which 89 % had IDC and 11 % had ILC. In the group of IDC with pT1 and pT2 tumors combined, 54 % underwent BCS compared with 43 % of patients with ILC (p < 0.0001). The proportion of patients with IDC treated by BCS increased from 46 % in 1990 to 62 % in 2010. The BCS rate among ILC patients increased from 39 % in 1990 to 48 % in 2010. Patients with ILC were less likely to undergo BCS compared with patients with IDC (odds ratio 0.69; 95 % confidence interval 0.66-0.71).The incidence of BCS for patients with IDC or ILC is rising in The Netherlands. However, the increase of BCS is less explicit in patients with ILC, with a higher chance of undergoing mastectomy compared with patients with IDC.