Leyo Ruo

Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies.

Current approaches to adjuvant treatment after resection of gallbladder carcinoma (GBCA) and hilar cholangiocarcinoma (HCCA) are based on an incomplete understanding of the recurrence patterns of these diseases. Through an in‐depth analysis of the sites of initial recurrence after resection of GBCA and HCCA, the current study aimed to highlight differences in the biology of these tumors and to provide further insight for adjuvant therapeutic strategies.

Long-Term Prognostic Significance of Extent of Rectal Cancer Response to Preoperative Radiation and Chemotherapy

ObjectiveTo determine whether selected clinicopathologic factors, including the extent of pathologic response to preoperative radiation and chemotherapy (RT ± chemo), have an impact on long-term recurrence-free survival (RFS) in patients with locally advanced primary rectal cancer after optimal multimodality therapy. Summary Background DataAlthough complete pathologic response to preoperative RT ± chemo has been detected in up to 30% of rectal cancers, its significance on long-term outcome has not been widely reported. Previous retrospective studies evaluating clinical outcome in patients with complete or near-complete pathologic response documented good prognosis in this population but were limited by median follow-up in the range of 2 to 3 years. MethodsSixty-nine patients with locally advanced (T3–4 and/or N1) primary rectal cancer were prospectively identified. All were treated at one institution with preoperative RT to the pelvis (at least 4,500 cGy). Forty patients received concurrent preoperative 5-fluorouracil-based chemotherapy and 27 received both pre- and postoperative chemotherapy. Patients underwent resection 4 to 7 weeks after completion of RT. TNM stage, angiolymphatic or perineural invasion, and extent of response to preoperative RT ± chemo were determined by pathologic evaluation. Adverse pathologic features were defined as the presence of angiolymphatic and/or perineural invasion. RFS at 5 years was determined by the Kaplan-Meier method. ResultsWith a median follow-up of 69 months, 5-year RFS was 79%. RFS was significantly worse for patients with aggressive pathologic features and positive nodal status identified in the postirradiated surgical specimen. Risk ratios for RFS were 3.68 for the presence of aggressive pathologic features and 4.64 for node-positive rectal cancers. In patients with greater than 95% rectal cancer response to preoperative RT ± chemo, only one patient has died as a consequence of cancer, another has died of an unrelated cause, and the remainder were free of disease with a minimum follow-up of 47 months. ConclusionsThese data suggest that a marked response to preoperative RT ± chemo may be associated with good long-term outcome but was not predictive of RFS. The presence of poor histopathologic features and positive nodal status are the most important prognostic indicators after neoadjuvant therapy.

Operative Blood Loss Independently Predicts Recurrence and Survival After Resection of Hepatocellular Carcinoma

Objective:To determine if the degree of blood loss during resection of hepatocellular carcinoma (HCC) is predictive of recurrence and long-term survival. Background:Several studies have addressed the impact of blood transfusion on survival and recurrence after liver resection for HCC. However, the independent effect of intraoperative estimated blood loss (EBL) on oncologic outcome is unclear. Methods:From our prospective database, we identified 192 patients who had a partial hepatectomy for HCC from 1985 to 2002. Clinicopathologic predictors of EBL were identified using logistic regression. Overall survival (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were assessed using the Kaplan-Meier and Cox regression methods. Results:The median patient age was 64 (range, 19–86) and 66% were men. All patients had histologically proven HCC. The median follow-up time was 34 months (range, 1–297). Factors associated with increased EBL on multivariate analysis were male gender, vascular invasion, extent of hepatectomy, and operative time (P < 0.01). EBL and vascular invasion were independent predictors of OS and DSS. Only EBL was significantly associated with RFS on multivariate analysis (P = 0.02). Additionally, we found a significant inverse correlation between increasing levels of EBL and length of DSS (P = 0.01). Conclusions:The magnitude of EBL during HCC resection is related to biologic characteristics of the tumor as well as the extent of surgery. Increased intraoperative blood loss during HCC resection is an independent prognostic factor for tumor recurrence and death.

Elective bowel resection for incurable stage IV colorectal cancer: prognostic variables for asymptomatic patients

BACKGROUND Surgical resection of primary colorectal cancer (CRC) in patients with stage IV disease at initial presentation remains controversial. Although bowel resection to manage symptoms such as bleeding, perforation, or obstruction has been advocated, management of asymptomatic patients has not been well defined. Patient-dependent factors (performance status, comorbid disease) and extent of distant metastases are among the considerations that impact on the decision to proceed with surgical management in asymptomatic stage IV CRC patients. We postulated that selected patients might benefit from elective resection of the asymptomatic primary CRC. The extent of distant metastases was objectively measured by several methods to identify potential prognostic variables that may help guide patient selection in this population. STUDY DESIGN We reviewed hospital and colorectal service databases for the years 1996 to 1999. Stage IV patients who had colorectal resections with gross residual metastatic disease were identified (n = 209). Among these 209 patients, 82 patients operated on for symptoms (obstruction, perforation, bleeding, or pain) were excluded, leaving 127 patients who underwent elective resection of their asymptomatic primary CRC. Over the same time period, 103 stage IV patients who did not undergo resection were identified. Data on patient characteristics and clinical management were collected. A radiologist performed an independent review of available CT scans to assess extent of liver disease. The chi-square test was used for analysis of categoric data and Students t-test for continuous variables. Survival was determined by the Kaplan-Meier method and distributions compared by the log rank test. Multivariate analysis was performed using Cox regression. RESULTS The resected group could be easily distinguished from the nonresected group by a higher frequency of right colon cancers (p = 0.03) and metastatic disease restricted to the liver (p = 0.02) or one other site apart from the primary tumor (p = 0.02). Resected patients had prolonged median (16 versus 9 months, p < 0.001) and 2-year (25% versus 6%, p < 0.001) survival compared with patients never resected. Univariate analysis identified three significant prognostic variables (number of distant sites involved, metastases to liver only, and volume of hepatic replacement by tumor) in the resected group. Volume of hepatic replacement was also a significant predictor of survival in Cox multivariate regression analysis (p = 0.01). Subsequent to resection of asymptomatic primary CRC, 26 patients (20%) developed postoperative complications. Median hospital stay was 6 days. Two patients (1.6%) died within 30 days of surgery. CONCLUSION Stage IV patients selected for elective palliative resection of asymptomatic primary colorectal cancers had substantial postoperative survival that was significantly better than those never having resection. Limited metastatic tumor burden and less extensive liver involvement were associated with better survival and a higher likelihood of benefit from elective bowel resection in asymptomatic patients with incurable stage IV CRC.

Resection of Hepatocellular Carcinoma in Patients Otherwise Eligible for Transplantation

Introduction The incidence of hepatocellular carcinoma (HCC) in the United States has increased 75% in the last decade. Liver transplantation is gaining acceptance for the treatment of early HCC, even in patients with adequate liver function. The objective of this study was to determine the long-term outcome of patients with early HCC who would have been candidates for transplantation but were treated instead with partial hepatectomy. Methods From August 1989 to November 2001, 611 patients with HCC were evaluated at our institution and entered into a prospective database. There were 180 (29%) patients who underwent partial hepatectomy, of whom 36 (20%) satisfied the currently accepted criteria for transplantation: 2 or 3 lesions each ≤ 3 cm in size or a solitary tumor ≤ 5 cm. Survival was determined by Kaplan-Meier analysis. Results Median tumor size was 3.5 (range, 1.8–5) cm and the median number of lesions was 1 (range, 1–3). Patients had pathologically confirmed cirrhosis of the liver in 78% (28/36) of cases, and 86% had normal liver function (Child class A). Perioperative morbidity was 25%, the median length of hospital stay was 8 (range, 4–24) days, and there was 1 (2.8%) perioperative death. At a median follow-up of 35 months for survivors, the 1-, 3-, and 5-year overall survival was 85%, 74%, and 69%, respectively, with a median survival of 71 months. The 5-year disease-free survival was 48% with a median of 52 months. Conclusions Partial hepatectomy in patients with early HCC who are otherwise eligible for transplantation can be performed with minimal morbidity and can achieve comparable 5-year survival to that reported for liver transplantation. Resection should be considered the standard therapy for patients with HCC who have adequate liver reserve.

Prospective assessment of primary rectal cancer response to preoperative radiation and chemotherapy using 18-fluorodeoxyglucose positron emission tomography

PURPOSE: The purpose of this prospective study was to determine the ability of fluorine-18 fluorodeoxyglucose positron emission tomography to assess extent of pathologically confirmed rectal cancer response to preoperative radiation and 5-fluorouracil-based chemotherapy. METHODS: Patients with primary rectal cancer deemed eligible for preoperative radiation and 5-fluorouracil-based chemotherapy because of a clinically bulky or tethered tumor or endorectal ultrasound evidence of T3 and/or N1 were prospectively enrolled. Positron emission tomography and CT scans were obtained before preoperative radiation and 5-fluorouracil-based chemotherapy (5,040 cGy to the pelvis and 2 cycles of bolus 5-fluorouracil with leucovorin) and repeated four to five weeks after completion of radiation and 5-fluorouracil-based chemotherapy. In addition to routine pathologic staging, detailed assessment of rectal cancer response to preoperative radiation and 5-fluorouracil-based chemotherapy was performed independently by two pathologists. Positron emission tomography parameters studied included conventional measures such as standardized uptake value (average and maximum), positron emission tomography-derived tumor volume (size), and two novel parameters: visual response score and change in total lesion glycolysis. RESULTS: Of 21 patients enrolled, prospective data (pretreatment and posttreatment positron emission tomography, and complete pathologic assessment) were available on 15 patients. All 15 demonstrated pathologic response to preoperative radiation and 5-fluorouracil-based chemotherapy. This was confirmed in 100 percent of the cases by positron emission tomography compared with 78 percent (7/9) by CT. In addition, one positron emission tomography parameter (visual response score) accurately estimated the extent of pathologic response in 60 percent (9/15) of cases compared with 22 percent (2/9) of cases with CT. CONCLUSIONS: This pilot study demonstrates that fluorine-18 fluorodeoxyglucose positron emission tomography imaging adds incremental information to the preoperative assessment of patients with rectal cancer. However, further studies in a larger series of patients are needed to verify these findings and to determine the value of fluorine-18 fluorodeoxyglucose positron emission tomography in a preoperative strategy aimed at identifying patients suitable for sphincter-preserving rectal cancer surgery.

Patterns of Morphologic Alteration in Residual Rectal Carcinoma Following Preoperative Chemoradiation and their Association with Long-term Outcome

Preoperative radiation (RT) and chemotherapy improve outcome in patients with locally advanced rectal adenocarcinoma and, therefore, have been used increasingly in patient management. The histopathologic alterations in postirradiated rectal adenocarcinoma and their prognostic significance have not been fully characterized. In this study, detailed analyses of morphologic alterations of stromal and tumor cells were performed in a series of 66 posttreatment rectal carcinomas, and the pathologic findings were correlated with long-term outcome. All tumors were locally advanced, with a bulky and/or tethered tumor or endorectal ultrasound or magnetic resonance imaging evidence of T3-4 and / or N1 disease. All patients were treated at one institution with preoperative RT to the pelvis (at least 4500 cGy) with or without concurrent 5-fluorouracil (5-FU)-based chemotherapy 4 to 7 weeks prior to surgical resection. Pathologic assessment showed some treatment response in all patients. Nine patients (13.4%) had complete response, and 8 (11.9%) had near-complete response (> 95% of the tumor replaced by fibroinflammatory tissue). Salient morphologic features included marked fibrosis with or without prominent inflammatory cells replacing neoplastic glands; lack of active tumor necrosis; increased mucin production and mucin pools; marked cytoplasmic eosinophilia, often in combination with marked nuclear atypia but without active mitoses in tumor cells showing treatment effect; endocrine tumor phenotype; and retention of mucosal adenoma in the presence of tumor regression within the bowel wall. With a median follow-up of 69 months, the estimated 5-year recurrence-free survival (RFS) for the entire group was 79%. By univariate analysis, the residual tumor stage (P < 0.05) and reduction of pretreatment T stage (P = 0.002) significantly correlated with RFS, as did pN stage (P = 0.002) and lymphovascular invasion (P = 0.008). The extent of treatment response did not correlate with RFS (P = 0.4). However, patients with a treatment response ≥ 95% seemed to fare better than those with a treatment response <95% (marginally significant difference in RFS, P = 0.057). Univariate and multivariate analyses identified the following morphologic patterns that were significantly associated with a reduced RFS independent of other risk factors: a fibrotic-type stromal response with minimal inflammatory infiltrates (P = 0.001) and absence of surface ulceration (P = 0.026). Our study represents the first detailed morphologic assessment of rectal carcinomas that have been subjected to long course preoperative RT and chemotherapy. Our results demonstrate distinct morphologic features in treated rectal carcinomas that are prognostically relevant.

Prognostic Implications of the Distribution of Lymph Node Metastases in Rectal Cancer After Neoadjuvant Chemoradiotherapy

PURPOSE After preoperative chemoradiotherapy of rectal cancer, the number of retrievable and metastatic lymph nodes is decreased. The current TNM classification is based on number and not location of lymph node metastases and may understage disease after chemoradiotherapy. The aim of this study was to examine the prognostic significance of location of involved lymph nodes in rectal cancer patients after preoperative chemoradiotherapy. PATIENTS AND METHODS We prospectively examined whole-mount specimens from 121 patients with uT3-4 and/or N+ rectal cancer who received preoperative chemoradiotherapy followed by resection. Location of involved lymph nodes was compared with median number of lymph nodes involved as well as presence of distant metastasis at presentation. RESULTS Lymph node metastases were detected in 37 patients (31%). Thirteen patients with lymph node involvement along major supplying vessels (proximal lymph node metastases) had a significantly higher rate of distant metastatic disease at time of surgery than patients without proximal lymph node involvement (P < .001); median number of lymph nodes involved was two for patients with proximal lymph node metastases and 1.5 for patients with mesorectal lymph node involvement alone. CONCLUSION Our data suggest that, after preoperative chemoradiotherapy, proximal lymph node involvement is associated with a high incidence of metastatic disease at time of surgery. Because the median number of involved lymph nodes is low after preoperative chemoradiotherapy, the TNM staging system may not provide an accurate assessment of metastatic disease. Therefore, the ypTNM staging system should incorporate distribution as well as number of lymph node metastases after preoperative chemoradiotherapy for rectal cancer.

Major 20th-century advancements in the management of rectal cancer

ConclusionsAt the beginning of the century, rectal cancer was a deadly disease treated simply by perineal excision. With advances in pathologic staging, preoperative assessment, surgical technique, and CMT made in the last century, we have witnessed improved oncologic and functional results after treatment of rectal cancer. As we look to the future, the use of molecular markers may help identify patients with node-negative disease yet aggressive biology in need of adjuvant therapy. It is also anticipated that improvements in various imaging modalities may better select patients for local procedures or preoperative adjuvant therapy. Further-more, ongoing progress in our understanding of pelvic anatomy and neurophysiology should improve preservation of both genitourinary and sphincter function.

Long-term follow-up of patients with familial adenomatous polyposis undergoing pancreaticoduodenal surgery

Adenomatous polyps and adenocarcinomas of the periampullary region are the most common upper gastrointestinal neoplasms encountered in familial adenomatous polyposis (FAP) patients. Tumors arising from the liver, biliary tract, and pancreas have also been reported. The purpose of this study was to review the clinical outcome of FAP patients after pancreaticoduodenal surgery for periampullary neoplasms. Of the 61 individuals participating in our prospective FAP registry, 8 underwent surgical resection of periampullary neoplasms between 1987 and 1998. The charts of these individuals were reviewed for clinical indications, type of pancreaticoduodenal surgery, postoperative complications, and outcome. Of the 8 patients identified, 7 had pancreaticoduodenectomy and 1 had duodenotomy with ampullectomy. The indications for surgery were periampullary cancer (3), severe dysplasia within a duodenal villous tumor (4), and solid-pseudopapillary tumor of the pancreas (1). At the time of pancreaticoduodenal surgery, patients ranged in age from 29–65 years, and all but one had undergone colorectal surgery, on average 16 years beforehand. Pancreatic ascites after a pylorus-sparing pancreaticoduodenectomy was the only surgical complication. At a median follow-up of 70.5 months (range 37–162), 2 patients had died, neither from their periampullary neoplasm. The patient treated by local excision subsequently developed gastric cancer arising from a polyp and went on to gastrectomy. Another patient developed confluent benign jejunal adenomas just beyond the gastroenteric anastomosis almost 12 years after pancreaticoduodenectomy for severe dysplasia of a duodenal villous adenoma. Pancreaticoduodenectomy is a safe and appropriate surgical option for FAP patients with duodenal villous tumors containing severe dysplasia or carcinoma. Postoperative morbidity was minimal and there was no perioperative mortality. Good long-term prognosis can be expected in completely resected patients although subsequent proliferative and/or neoplastic lesions may still be detected in the gastrointestinal tract with prolonged follow-up.