Efficacy of Preoperative Combined 18-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography for Assessing Primary Rectal Cancer Response to Neoadjuvant Therapy

Purpose Efficacy of F-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) for determining neoadjuvant therapy response in rectal cancer is not well established. We sought to evaluate serial FDG-PET/CT for assessing tumor down-staging, percentage residual tumor, and complete response or microscopic disease with rectal cancer neoadjuvant therapy. Methods Patients with rectal cancer undergoing neoadjuvant therapy, definitive surgical resection, and FDG-PET/CT before and 4–6 weeks after neoadjuvant treatment were included. Tumors were evaluated pretreatment and on final pathology for size and stage. FDG-PET/CT parameters assessed were visual response score (VRS), standardized uptake value (SUV), PET-derived tumor volume (PETvol), CT-derived tumor volume (CTvol), and total lesion glycolysis (δTLG). Results Twenty-one rectal cancer patients over 3 years underwent neoadjuvant treatment, serial FDG-PET/CT, and resection. Complete response or microscopic disease (n = 7, 33%) was associated with higher ΔCTvol (AUC = 0.82, p = 0.004) and ΔSUV (AUC = 0.79, p = 0.01). Tumor down-staging (n = 14, 67%) was associated with greater ΔPETvol (AUC = 0.82, p < 0.001) and ΔSUV (AUC = 0.82, p < 0.001). Pathologic lymph node disease (n = 7, 33%) correlated with ΔCTvol (AUC = 0.75, p = 0.03) and ΔPETvol (AUC = 0.70, p = 0.08). Conclusion FDG-PET/CT parameters were best for assessing tumor down-staging and percentage of residual tumor after neoadjuvant treatment of rectal cancer and can potentially assist in treatment planning. This work was presented in the plenary session of the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract at the Digestive Disease Week in Los Angeles, CA on 24 May 2006.     

Neoadjuvant Chemotherapy and Radiation for Patients with Locally Unresectable Pancreatic Adenocarcinoma: Feasibility, Efficacy, and Survival

Abstract Background We evaluated the feasibility and efficacy of neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic cancer. Materials and Methods From October 2000 to August 2006, 245 patients with pancreatic adenocarcinoma underwent surgical exploration at our institution. Of these, 78 patients (32%) had undergone neoadjuvant therapy for initially unresectable disease, whereas the remaining patients (serving as the control group) were explored at presentation (n = 167). All neoadjuvant patients received gemcitabine-based chemotherapy, often in conjunction with docetaxal and capecitabine in a regimen called GTX (81%). Seventy-five percent of neoadjuvant patients also received preoperative abdominal radiation (5,040 rad). Results Neoadjuvant patients were younger than control-group patients (60.8 vs 66.2 years, respectively, p < 0.002). Seventy-six percent of neoadjuvant patients were resected as compared to 83% of control patients (NS). Concomitant vascular resection was required in 76% of neoadjuvant patients but only 20% of NS (p < 0.01). Complications were more frequent in the neoadjuvant group (44.1 vs 30.9%, p < 0.05), and mortality was higher (10.2 vs 2.9%, p < 0.03). Among the neoadjuvant patients, all but one of the deaths were in patients that underwent arterial reconstruction. Mortality for patients undergoing a standard pancreatectomy without vascular resection was 0.8% in this series. Of patients resected, negative margins were achieved in 84.7% of neoadjuvant patients and 72.7% of NS. Within the cohort of neoadjuvant patients, radiation significantly increased the complication rate (13.3 vs 54.6%, p < 0.006), but did not affect median survival (512 vs 729 days, NS). Median survival for patients who received neoadjuvant therapy (503 days) was longer than NS that were found to be unresectable at surgery (192 days, p < 0.001) and equivalent to NS that were resected (498 days). Conclusions Resection rate, margin status, and median survivals were equivalent when neoadjuvant patients were compared to patients considered resectable by traditional criteria, demonstrating equal efficacy. Surgical resection with venous reconstruction following neoadjuvant therapy for patients with locally advanced pancreatic cancer can be performed with acceptable morbidity and mortality. This approach extended the boundaries of surgical resection and greatly increased median survival for the “inoperable” patient with advanced pancreatic cancer. This work was presented at the American Hepato-Pancreato-Biliary Association Conference in Las Vegas, NV, April 2007.     

Resection of Hepatic Colorectal Metastases Involving the Caudate Lobe: Perioperative Outcome and Survival

Purpose: To examine clinical features and outcome of patients who underwent hepatic resection for colorectal liver metastases (LM) involving the caudate lobe. Patients and Methods: Consecutive patients who underwent hepatic resection for LM from May 1990 to September 2004 were analyzed from a multicenter database. Demographics, operative data, pathologic margin status, recurrence, and survival were analyzed. Results: Of 580 patients, 40 (7%) had LM involving the caudate. Six had isolated caudate LM and 34 had LM involving the caudate plus one or more other hepatic segments. Patients with caudate LM were more likely to have synchronous primary colorectal cancer (63% vs. 36%; P = 0.01), multiple LM (70% vs. 51%; P = 0.02) and required extended hepatic resection more often than patients with non-caudate LM (60% vs. 18%; P < 0.001). Only four patients with caudate LM underwent a vascular resection; three at first operation, one after recurrence of a resected caudate tumor. All had primary repair (vena cava, n = 3; portal vein, n = 1). Perioperative complications (43% vs. 28%) and 60-day operative mortality (0% vs. 1%) were similar (caudate vs. non-caudate LM, both P > 0.05). Pathological margins were positive in 15 (38%) patients with caudate LM and in 43 (8%) with non-caudate LM (P < 0.001). At a median follow-up of 40 months, 25 (64%) patients with caudate LM recurred compared with 219 (40%) patients with non-caudate LM (P = 0.01). Patients with caudate LM were more likely to have intrahepatic disease as a component of recurrence (caudate: 51% vs. non-caudate: 25%; P = 0.001). No patient recurred on the vena cava or portal vein. Patients with caudate LM had shorter 5-year disease-free and overall survival than patients with non-caudate LM (disease-free: 24% vs. 44%; P = 0.02; overall: 41% vs. 58%; P = 0.02). Conclusions: Patients who undergo hepatic resection for caudate LM often present with multiple hepatic tumors and tumors in proximity to the major hepatic veins. Extended hepatectomy is required in the majority, although vascular resection is not frequently necessary; when performed, primary repair is usually possible. Despite resection in this population of patients with multiple and bilateral tumors, and despite close-margin and positive-margin resection in a significant proportion, recurrence on the portal vein or vena cava was not observed, and long-term survival is accomplished (41% 5-year overall survival). These data were presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, Miami, Florida, March 12, 2006.     

Use of Positron Emission Tomography in Surgery Follow-Up of Esophageal Cancer

Introduction  Although the prognosis of patients with esophageal cancer has been improved by extended dissection, the incidence of recurrence still remains high. In esophageal cancer, positron emission tomography (PET) using ¹⁸F-fluorodeoxyglucose (FDG) already demonstrated to be useful for initial staging and monitoring response to therapy. This prospective study compared the ability of FDG-PET and conventional imaging to detect early recurrence of esophageal cancer after initial surgery in asymptomatic patients. Materials and Methods  Between October 2003 and September 2006, 41 patients with esophageal cancer were included in a prospective study after initial radical esophagectomy. FDG-PET, thoracoabdominal computed tomography (CT), abdominal ultrasonography, and endoscopy were performed every 6 months after initial treatment. Results and Discussion  Twenty-three patients had recurrent disease (56%), mostly within the first 6 months after surgery (70%). Despite two false-positive scans due to postoperative changes, FDG-PET was more accurate than CT (91% vs. 81%, p = 0.02) for the detection of recurrence with a sensitivity of 100% (vs. 65%), a specificity of 85% (vs. 91%), and a negative predictive value of 100% on a patient-by-patient-based analysis. For the detection of locoregional recurrence, FDG-PET was more accurate than CT (96.2% vs. 88.9%). FDG-PET was also more accurate than CT for the detection of distant metastases (92.5% vs. 84.9%), especially when involving either bones (100%) or liver (98.1%). A lower sensitivity of FDG-PET (57%) for the early detection of small lung metastases did not affect patient management (accuracy = 92.5%). Conclusion  FDG-PET appears to be very useful for the systematic follow-up of asymptomatic patients after esophagectomy with an initial scan performed 6 months after surgery. Presented at the Forty-sixth Annual Meeting of The European Society of Nuclear Medicine, Athens, Greece, September 30–October 4, 2006 (oral presentation).     

Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific. Presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, March 11, Miami, Florida.     

Radiofrequency Ablation vs. Resection for Hepatic Colorectal Metastasis: Therapeutically Equivalent?

Introduction  The role of ablation for hepatic colorectal metastases (HCM) continues to evolve as ablation technology changes and systemic chemotherapy improves. Our aim was to evaluate the therapeutic efficacy of radiofrequency ablation (RFA) of HCM compared to surgical resection. Methods  A retrospective review of our 1,105 patient prospective hepatic database from August 1995 to July 2007 identified 192 patients with only hepatic resection or only ablation for HCM. Results  Patients who underwent RFA were similar to resection patients based on a similar Fong score (1.8 vs. 2.1 p = 0.28), presence of extrahepatic disease (15% vs. 9% p = 0.19), mean number of hepatic lesions (2.8 vs. 2.1 p = 0.14), and prior chemotherapy (67% vs. 60% p = 0.33). Median time to recurrence was shorter with ablation than resection (12.2 vs. 31.1 months; p < 0.001). Recurrence at the ablation–resection site was more common with ablation than resection occurring 17% vs. 2% (p ≤ 0.001) of the time, respectively. Distant recurrence in the liver was also more common with ablation occurring in 33% of patients vs. 14% for resection (p = 0.002). Conclusions  Surgical resection is associated with a lower chance of recurrence and a longer disease-free interval than RFA and should remain the treatment of choice in resectable HCM.     

Chemotherapy-Induced Normalization of FDG Uptake by Colorectal Liver Metastases Does Not Usually Indicate Complete Pathologic Response

Dramatic responses are being observed in colorectal cancer liver metastases treated with newer chemotherapeutic regimens. These have been associated with normalization of [¹⁸F]fluoro-2-deoxy-d-glucose (FDG) uptake (complete metabolic response) on follow-up Positron Emission Tomography with [¹⁸F]fluoro-2-deoxy-d-glucose (FDG-PET) scans in some patients. It is unclear how often complete metabolic response is indicative of complete tumor destruction. We analyzed a subset of patients who had neoadjuvant chemotherapy for hepatic metastases from colorectal adenocarcinoma. Inclusion criteria were: (1) FDG-avid hepatic lesions before initiation of chemotherapy; (2) complete metabolic response of the same lesions after chemotherapy; and (3) histopathologic examination of hepatic lesions. Complete pathologic response was defined as no histologically identifiable viable tumor. Fourteen patients fit the inclusion criteria. All had synchronous, hepatic-only colorectal metastases. On microscopic examination, complete pathologic response to the neoadjuvant regimen was found in only 5 of 34 lesions (15%) and in only 3 of the 14 patients (21%). Seven lesions had complete metabolic response and disappeared on computed tomography (CT); of these, six still contained viable tumor. We conclude that complete metabolic response on FDG-PET after neoadjuvant chemotherapy is an unreliable indicator of complete pathologic response. Therefore, currently, curative resection of liver metastases in these patients should not be deferred on the basis of FDG-PET findings. Presented at the 2007 Annual Meeting of the American Hepato–Pancreato–Biliary Association, April 19–22, 2007, Las Vegas, Nevada.     

Response to Neoadjuvant Chemotherapy Does Not Predict Overall Survival for Patients With Synchronous Colorectal Hepatic Metastases

Objective  We investigated the relation between response to neoadjuvant chemotherapy and overall survival (OS) in patients with colorectal liver metastases (CLM). Background  It has previously been reported that patients with synchronous CLM whose disease progresses while receiving neoadjuvant chemotherapy or who do not receive neoadjuvant chemotherapy experience worse survival than patients whose disease responds to neoadjuvant chemotherapy. Methods  By means of a prospectively maintained surgical database, between 1995 and 2003, we identified 111 patients with a synchronous CLM who received neoadjuvant chemotherapy before hepatic resection. The disease of all 111 patients was deemed resectable, and patients underwent hepatic resection with curative intent. Results  The median OS after liver resection was 62 months, with a median follow-up of 63 months. Median OS was similar between the three study groups classified by response to neoadjuvant chemotherapy (complete or partial response, 58 months; stable disease, 65 months; and disease progression, 61 months; P = .98). By univariate analysis, carcinoembryonic antigen level after liver resection of <5 ng/dL, size of metastatic lesion of ≤5 cm, lymph node–negative primary tumor, and disease-negative margins were associated with improved survival. Patients in the disease progression group had more positive margins and metastases >5 cm in size than patients in the complete or partial response group and the stable disease group. Patients whose tumor progressed but who received postoperative hepatic arterial infusion had a trend toward improved survival compared with those who did not receive hepatic arterial infusion (70% vs. 50% at 3 years, permutation log rank test P = .12). Conclusions  Response to neoadjuvant chemotherapy did not correlate with OS even after controlling for margins, stage of primary tumor, and postoperative carcinoembryonic antigen level. Postoperative salvage treatment may have helped the survival of some patients.     

Survival of Patients with Synchronous and Metachronous Colorectal Liver Metastases—is there a Difference?

Background  The aim of this study was to compare outcomes in patients with synchronous and metachronous colorectal liver metastases, with special emphasis on prognostic determinants. Study design  We analyzed prospectively collected data on 101 patients with synchronous metastases (group A) who were treated surgically during the time period from April 1998 to December 2006 in regard to overall and disease-free survival, impact of chemotherapy, as well as several serum parameters. A group of patients with metachronous colorectal liver metastases (group B) was considered for baseline comparison. Results  Twenty-three patients in group A received only an explorative laparotomy. Surgical treatment included right hepatectomy (n = 7), left hepatectomy (n = 5), right trisectionectomy (n = 10), left trisectionectomy (n = 1), left lateral resection (n = 11), and sectionectomy (n = 44). Thirty-day mortality was 3%. Morbidity was observed in 10% of the patients. One-, 3-, and 5-year overall survival rates for synchronous metastases were 86%, 68%, and 47%, respectively. The corresponding rates for metachronous metastases were 94%, 68%, and 39% (p > 0.05). Disease free survival was 74%, 42%, and 33% in group A versus 84%, 62%, and 13% in group B (p = 0.28). There was no difference in survival between patients receiving neoadjuvant chemotherapy and no chemotherapy (p > 0.05). Out of all serum parameters, carcinoembryonic antigen levels were a negative predictor for overall and disease-free survival only. Conclusions  Patients with synchronous colorectal liver metastases had a similar 5-year overall and disease-free survival, which corresponds to patients with metachronous metastases. The impact of neoadjuvant chemotherapy in patients with synchronous metastases needs to be further clarified.     

Analysis of Anal Sphincter Preservation Rate According to Tumor Level and Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients

The anal sphincter preservation rate (ASPR) according to tumor level and neoadjuvant chemoradiotherpy (CRT) has not been fully evaluated. Therefore, the aim of this study was to evaluate the correlation between the tumor level, neoadjuvant CRT, and the ASPR in rectal cancer patients. We studied 544 patients (tumor level, 0–6 cm) who underwent curative resection for rectal cancer between 1991 and 2005. Patients were divided six into groups according to tumor level over 1-cm intervals, and the ASPR was evaluated in patients with and without neoadjuvant CRT according to tumor level. Sphincter preservation surgery was performed in 191 patients, and 86 patents underwent neoadjuvant CRT. The overall ASPR was 43.0% (37/86) in patients with neoadjuvant CRT and 33.6% (154/458) in patients without neoadjuvant CRT (P = 0.094). In an analysis according to tumor level, the ASPR was 0.0 vs 0.0% in ≤1 cm, 0.0 vs 2.1% in 1 ≤ 2 cm (P = 0.589), 11.8 vs 16.8% in 2 ≤ 3 cm (P = 0.599), 55.6 vs 20.2% in 3 ≤ 4 cm (P = 0.001), 57.7 vs 45.9% in 4 ≤ 5 cm (P = 0.227), and 66.7 vs 69.5% in 5 ≤ 6 cm (P = 0.827). Neoadjuvant CRT did not increase the ASPR in tumor level within ≤6 cm. However, for the tumor level (3 ≤ 4 cm), neoadjuvant CRT significantly increased the ASPR. Presented at the 20th Annual meeting of International Society for Digestive Surgery in Rome, Italy, November 29–December 2, 2006 (oral presentation in Grassi Prize Session).     

Echogenic Appearance of Colorectal Liver Metastases on Intraoperative Ultrasonography is Associated with Survival After Hepatic Resection

Survival after resection of colorectal liver metastases has traditionally been associated with clinicopathologic factors. We sought to investigate whether echogenicity of colorectal liver metastasis as assessed by intraoperative ultrasound (IOUS) was a prognostic factor after hepatic resection. Prospective data on tumor IOUS appearance were collected in 84 patients who underwent hepatic resection for colorectal liver metastasis. Images were digitally recorded, blindly reviewed, and scored for echogenicity (hypo-, iso-, or hyperechoic). The median tumor number was 1 and the median tumor size was 5.0 cm. At the time of surgery, the IOUS appearance of the colorectal liver metastases were hypoechoic in 35 (41.7%) patients, isoechoic in 37 (44.0%) patients, and hyperechoic in 12 (14.3%) patients. Traditional clinicopathologic prognostic factors were similarly distributed among the three echogenicity groups (all p > 0.05). Patients with a hypoechoic lesion had a significantly shorter median survival (30.2 months) compared with patients who had either an isoechoic (53.2 months) or hyperechoic (42.3 months) lesion (p = 0.005). The 5-year survival after hepatic resection of colorectal liver metastasis was also associated with the echogenic appearance of the lesion (hypoechoic 14.4 vs isoechoic 37.4 vs hyperechoic 46.2%) (p < 0.05). Intraoperative ultrasound echogenicity should be considered a prognostic factor after hepatic resection of metastatic colorectal cancer. This study was presented at the 47th annual meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, CA, USA, 22 May 2006.     

Long-term outcome after multivisceral and tumor/vascular resection in patients with soft tissue sarcoma

Background/Aims  Soft tissue sarcomas (STS) are rare tumors. General treatment is difficult while multimodality treatment strategies are more and more common. In these strategies, surgical resection of the primary tumor is essential to achieve local control of the tumor. In certain cases, complex resections (CR) including multivisceral and/or vascular resection are needed to achieve resection with tumor-free margins. In this study, we evaluated retrospectively the overall prognosis, morbidity, and mortality of patients treated for STS at our university hospital. Patients/Methods  Between 1992 and 2000, 24 of 154 patients with STS received multivisceral resection and four of 154 underwent vascular resection. To determine the influence of CR on overall prognosis, we compared n = 19 patients after CR with a matched control group after simple tumor resection (SR). To determine surgical morbidity and mortality the whole study group was used (n = 154, SR n = 126, CR n = 28). Results  The median follow up for all patients was 6.89 years (mean 5.64 years SD 4.3) with no difference between the groups (CR vs SR: 5.4 SD 4.8 vs 5.9 SD 3.9 years; p = 0.711). Patients receiving CR had a similar overall prognosis (mean survival 9.9 years), morbidity (10.7%) and mortality (0%) compared to patients with SR (mean survival 8.5 years; morbidity 10.3%; mortality 3.96%). Conclusions  Multivisceral resection and/or vascular resection with tumor-free margins can be achieved with the same overall prognosis, same morbidity and mortality as SR. This has to be taken into account when evaluating the treatment strategy in patients with STS.     

Multiagent Chemotherapy for Isolated Colorectal Liver Metastases: A Single-centered Retrospective Study

Background  Few studies identifying variables associated with prognosis after resection of colorectal liver metastases (CLM) account for treatment with multiagent chemotherapy (fluoropyrmidines with irinotecan, oxaliplatin, bevacizumab, and/or cetuximab). The objective of this retrospective study was to determine the effect of multiagent chemotherapy on long-term survival after resection of CLM. Methods  Demographics, clinicopathologic tumor characteristics, treatments, and long-term outcomes were reviewed. Results  From 1996 to 2006, 230 patients underwent resection of CLM. Treatment strategies before and after resection included fluoropyrimidine monotherapy (n = 34 and n = 39), multiagent chemotherapy (n = 81 and n = 73), and observation (n = 115 and n = 118). Prehepatectomy treatment strategy was not associated with overall survival. Actuarial 4-year survival was 63%, 39%, and 40% for patients treated with multiagent chemotherapy, fluoropyrimidine monotherapy, and observation after hepatectomy, p = 0.06. Posthepatectomy multiagent chemotherapy (p = 0.04, HR 0.52 [0.27–1.03]), duration of posthepatectomy chemotherapy treatment of 2 months or longer (p = 0.05, HR 0.49 [0.25–0.99]), carcino-embryonic antigen level >10 ng/mL (p = 0.03, HR 2.09, 95% CI [1.32–3.32]), and node positive primary tumor (p = 0.002, HR 1.79 [1.06–3.02]) were associated with overall survival in multivariate analysis. Conclusions  The association of posthepatectomy multiagent chemotherapy with overall survival in this retrospective study indicates the need for prospective randomized trials comparing multiagent chemotherapy and fluoropyrimidine monotherapy for CLM.     

Chemotherapy Has Also an Effect on Primary Tumor in Colon Carcinoma

Background  This study characterizes the histological effect of chemotherapy (CT) on primary colonic tumors. Methods  Between 2000 and 2006, 38 patients with stage IV colon cancer underwent resection of the primary, after chemotherapy (CT group, n = 16) or without preoperative CT (control group, n = 22). For all primary tumors, histological analysis included: fibrosis, acellular necrosis, acellular mucin pools, lymphoplasmacytic infiltration, and changes at tumor surface. Tumor regression grade (TRG) was determined by the amount of residual tumor cells and was graded from 1 to 5. Results  No patient had complete histological response. Major histological tumor regression (TRG2) was observed in 70% of patients treated by CT and none of the not treated patients (P < 0.0001). Fibrosis, acellular necrosis, and surface changes were significantly increased in the CT group. TRG in the primary was comparable to the TRG in the corresponding liver metastases for 7/9 patients who underwent both colonic and hepatic resection after CT. Conclusion  CT induces major histological response in 70% of colon cancers. Response to CT in the primary and the corresponding liver metastases are correlated. These results support a policy of initial CT management for stage IV colon cancer and may warrant future studies of neoadjuvant CT in locally advanced colon carcinomas.     

Systemic Chemotherapy and Two-Stage Hepatectomy for Extensive Bilateral Colorectal Liver Metastases: Perioperative Safety and Survival

Background Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy. Methods From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two-stage hepatectomy were retrospectively analyzed (1998–2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated. Results One- (group I) and two-stage(group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1–20) and seven (range 2–20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS). Conclusions Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes. Presented at the Society for Surgery of the Alimentary Tract 48th Annual Meeting, May 2007, Washington, DC.     

Combined [<Superscript>18</Superscript>F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Detection of Recurrent, <Superscript>131</Superscript>I-Negative Thyroid Cancer

Background Whole-body ¹³¹I scintigraphy (WBS) and serial thyroglobulin measurement (Tg) are standard methods for detecting thyroid cancer recurrence after total/near total thyroidectomy and ¹³¹I ablation. Some patients develop elevated Tg (Tg-positive) or there is clinical suspicion of recurrence, but WBS are negative (WBS-negative). This may reflect non-iodine-avid recurrence or metastasis. In 2002, the Centers for Medicare and Medicaid Services (CMS) approved positron emission tomography with [¹⁸F]fluorodeoxyglucose (FDG-PET) for Tg-positive/WBS-negative patients with follicular-cell-origin thyroid cancer. Limited data are available regarding the performance of combined FDG-PET/computed tomography (FDG-PET/CT) for detecting recurrent thyroid cancer in WBS-neg patients. Methods This retrospective review of prospectively collected data analyzed 65 patients who had FDG-PET/CT for suspected thyroid cancer recurrence (April 1998–August 2006). Patients were WBS-negative but were suspected to have recurrence based on Tg levels or clinical grounds. Suspected FDG-PET/CT abnormalities were reported as benign or malignant. Lesions were ultimately declared benign or malignant by surgical pathology or clinical outcome (disease progression). Results Of 65 patients who underwent FDG-PET/CT, 47 had positive FDG-PET/CT. Of the positive FDG-PET/CT, 43 studies were true positives, with 21 (49%) confirmed pathologically by surgical resection. The four false positives (3/4 confirmed pathologically) included an infundibular cyst, an inflamed supraclavicular cyst, pneumonitis, and degenerative disc disease. Of the 18 FDG-PET/CT studies that were negative, 17 were true negatives and one was a false negative (metastatic papillary carcinoma). Thus, FDG-PET/CT demonstrated a patient-based sensitivity of 98%, specificity of 81%, positive predictive value of 91%, and negative predictive value of 94%. Conclusions FDG-PET/CT is useful for detecting thyroid cancer recurrence in WBS-negative patients, and can assist decision making.     

Improved Staging With Pretreatment Positron Emission Tomography/Computed Tomography in Low Rectal Cancer

Background ¹⁸F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT) are widely accepted in the evaluation for metastatic or recurrent rectal cancer. Only spiral CT and transrectal ultrasonography (TRUS) are routinely used in the initial evaluation of primary rectal cancer. We wished to determine whether PET/CT could provide additional information in patients undergoing standard evaluation for primary rectal cancer. Methods Thirty-seven patients (mean age, 58 years; range, 26–90 years) with a previously untreated rectal cancer underwent TRUS or magnetic resonance imaging, spiral CT, and FDG-PET/CT. The tumor location (low, ≤6 cm; mid, 7–10 cm; or high, ≥10 cm) and carcinoembryonic antigen level were recorded. Discordant findings between spiral CT and FDG-PET/CT were confirmed by histological analysis or imaging follow-up. Results FDG-PET/CT identified discordant findings in 14 patients (38%), and this resulted in upstaging of 7 patients (50%) and downstaging of 3 patients (21%). Although node-positive disease on TRUS/magnetic resonance imaging was associated with discordant FDG-PET/CT findings, this was not statistically significant. Discordant PET/CT findings were significantly more common in patients with a low rectal cancer than in those with mid or high rectal cancer (13 vs. 1; P = .0027). The most common discordant finding was lymph node metastasis (n = 7; 50%). Histological confirmation of discordant FDG-PET/CT findings was performed in seven patients, and in no case did FDG-PET/CT prove to be inaccurate. Discordant PET/CT findings resulted in a deviation in the proposed treatment plan in 27% of patients (n = 10). Conclusions FDG-PET/CT frequently yields additional staging information in patients with low rectal cancer. Improved accuracy of pretreatment imaging with FDG-PET/CT will allow for more appropriate stage-specific therapy. Presented at the Annual Meeting of the Society of Surgical Oncology, Atlanta, Georgia, March 3–6, 2005.     

A Decision Analysis Model Identifies the Interval of Efficacy for Transarterial Chemoembolization (TACE) in Cirrhotic Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation

Introduction For liver transplant candidates with hepatocellular carcinoma (HCC), the ability of neoadjuvant transarterial chemoembolization (TACE) to improve outcomes remains unproven. The objective of our study was to determine if there was a specific time interval where neoadjuvant TACE would decrease the number of HCC patients removed from the pretransplant waitlist. Materials and Methods A decision model was developed to simulate a randomized trial of neoadjuvant treatment with TACE vs. no TACE in 600 virtual patients with HCC and cirrhosis. Transition probabilities for TACE morbidity (1 ± 1%), TACE response rates (30 ± 20%), and disease progression (7 ± 7% per month) were assigned by systematic review of the literature (18 reports). Sensitivity analyses were performed to determine time thresholds where TACE would decrease the number of delisted patients. Results TACE treatment had statistical benefit at waitlist time breakpoints of 4 and 9 months (P < 0.05). When waitlist times were less than 4 months, waitlist attrition was similar (20% vs. 34%, P = 0.08). When waitlist times exceed 9 months, waitlist dropout rates re-equilibrated (33% vs. 46%, P = 0.06). Review of the current literature determined that only those studies reporting on patients with waitlist times between 4 and 9 months found a benefit to neoadjuvant TACE. Conclusions This analysis indicates that the benefit of neoadjuvant TACE may be limited to those patients transplanted from 4 to 9 months from first TACE. These data may help transplant programs to tailor TACE treatments based on predicted waitlist times to achieve optimal resource utilization and improved organ allocation efficiency. Presented at the 7th World Congress of the International Hepato Pancreato Biliary Association Meeting, September 6, 2006, Edinburgh, Scotland.     

Endoscopic Ultrasound and Computed Tomography Predictors of Pancreatic Cancer Resectability

Introduction This study investigates the ability of endoscopic ultrasound (EUS) and computed tomography (CT) to predict a margin negative (R0) resection and the need for venous resection in patients undergoing pancreaticoduodenectomy (PD). Methods Patients with pancreatic head adenocarcinoma undergoing surgery with intent to resect during the last 5 years were identified. EUS and CT data on vascular involvement were collected. Preoperative imaging was compared to intraoperative findings and final pathology. Contingency table analysis using Fisher’s exact test identified imaging features of EUS and CT associated with unresectability and positive margins. Results Seventy-six patients met study criteria. Forty-seven (62%) underwent potentially curative PD. The R0 resection rate was 70%. There were 16 unresectable patients because of locally advanced disease. Venous involvement >180° and arterial involvement >90° by CT had 100% positive predictive value for failure to achieve R0 resection (p < .01). If patients with prestudy biliary stents were excluded, EUS venous abutment or invasion also predicted R0 failure (p = .02). Combined but not individual EUS and CT findings were predictive of need for vein resection. Conclusions Pancreas protocol CT imaging appears to be a better predictor of resectability compared to EUS. EUS accuracy is affected by the presence of biliary stents. This article was presented at SSAT, Washington DC, May 2007.     

Prognostic Factors and Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Background  The aim of this study was to determine prognostic factors for survival after resection of pancreatic adenocarcinoma (PC) and to compare outcomes after surgery alone versus surgery plus adjuvant therapy. Methods  We performed a retrospective review of 219 patients who underwent pancreaticoduodenectomy for PC with curative intent between 1995 and 2007. Data were collected prospectively. Postoperative adjuvant chemoradiation therapy (CRT) consisted of fluorouracil or gemcitabine-based chemotherapy; the median radiation dose was 45 Gy. Results  The 3- and 5-year overall survival (OS) rates were 24.3% and 14.2%, respectively. Median OS was 14.0 months [95% confidence interval (CI), 12–16 months]. Patients with metastatic lymph nodes experienced improved median survival (16 vs 10 months; P < 0.001) and 3-year OS (3-year OS 28% vs 8%) after adjuvant CRT compared with those who had no CRT. Patients who underwent non-curative resection had the same effect (median OS, 13 vs 8 months; P = 0.037). Lymph node metastasis and non-curative resection showed no significance on multivariate analysis. Poor differentiation [risk ratio (RR) = 2.10; P < 0.001] and tumor size >3 cm (RR = 1.57; P = 0.018) were found to be adverse prognostic factors; adjuvant CRT had borderline significance (RR = 0.70; P = 0.087). Conclusions  Adjuvant CRT benefited a subset of patients with resected PC, particularly those with lymph node metastasis and those undergoing non-curative resection. Multivariate analysis demonstrated that patients with tumors larger than 3 cm and poor differentiation had poor prognosis.