Effectiveness of positron emission tomography for predicting chemotherapy response in colorectal cancer liver metastases.

HYPOTHESIS: Chemotherapeutic agents may be able to convert unresectable colorectal hepatic metastasis to resectable disease, therefore changing the surgical options. The role of positron emission tomography (PET) for patients undergoing chemotherapy remains unclear. We hypothesize that recent chemotherapy treatment could result in false-negative PET results. DESIGN: Case-control study evaluating PET findings. SETTING: The University of Texas M. D. Anderson Cancer Center. PATIENTS: From May 1, 2006, through August 31, 2008, data for 224 consecutive patients were entered into a prospective database for evaluation of hepatic metastasis of colorectal carcinoma. One hundred thirty-eight patients underwent PET and conventional imaging (a combination of computed tomography, magnetic resonance imaging, and ultrasonography). All had oncologically sound colorectal operations. INTERVENTIONS: Liver resection or ablation for colorectal liver metastases. MAIN OUTCOME MEASURES: To determine the accuracy of PET scans to detect residual viable colorectal cancer liver metastases after a significant response to systemic chemotherapy. RESULTS: Patients with biopsy-proven disease underwent hepatic resection (120 patients [87.0%]), radiofrequency ablation (2 [1.4%]), or resection with radiofrequency ablation (7 [5.1%]). Nine patients (6.5%) had inoperable disease that was found intraoperatively. When performed within 4 weeks of chemotherapy, PET had a negative predictive value of 13.3% and a positive predictive value of 94.3%. The sensitivity was 89.9%, the specificity was 22.2%, and the accuracy was 85.5%. CONCLUSIONS: Positron emission tomography within 4 weeks of chemotherapy is not a useful test for evaluation of colorectal hepatic metastases. The high rate of false-negative results is likely due to metabolic inhibition caused by chemotherapeutic drugs. We recommend that physicians not use PET in patients recently completing chemotherapy; they should undergo the appropriate oncologic hepatic operation based on the high probability of viable malignant disease.

Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury.

Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer (CRC) in both the adjuvant treatment and metastatic disease settings. Significant improvements in outcomes have been achieved with oxaliplatin-based combinations in these settings when compared with administration of 5-fluorouracil alone. Pathologic evaluation of normal liver from patients undergoing neoadjuvant oxaliplatin treatment has identified histologic evidence of sinusoidal injury, although the effect of this finding on patient outcomes after hepatic resection appears to be minimal. This article describes the use of oxaliplatin-based chemotherapy in 6 patients with stage III or IV CRC who developed evidence of noncirrhotic portal hypertension. These patients developed complications of portal hypertension including esophageal or hemorrhoidal varices with bleeding, splenomegaly with associated thrombocytopenia, and ascites. In each case, oxaliplatin-induced hepatic sinusoidal injury was identified as the most likely factor contributing to the development of noncirrhotic portal hypertension. The literature on hepatic sinusoidal injury after oxaliplatin is reviewed and the proposed pathophysiology is discussed.

Borderline resectable pancreatic cancer: the importance of this emerging stage of disease.

BACKGROUND: Patients with borderline resectable pancreatic adenocarcinoma (PA) include those with localized disease who have tumor or patient characteristics that preclude immediate surgery. There is no optimal treatment schema for this distinct stage of disease, so the role of surgery is undefined. STUDY DESIGN: We defined patients with borderline resectable PA as fitting into one of three distinct groups. Group A comprised patients with tumor abutment of the visceral arteries or short-segment occlusion of the Superior Mesenteric Vein. In group B, patients had findings suggestive but not diagnostic of metastasis. Group C patients were of marginal performance status. Patients were treated initially with chemotherapy, chemoradiation, or both; those of sufficient performance status who completed preoperative therapy without disease progression were considered for surgery. RESULTS: Between October 1999 and August 2006, 160 (7%) of 2,454 patients with PA were classified as borderline resectable. Of these, 125 (78%) completed preoperative therapy and restaging, and 66 (41%) underwent pancreatectomy. Vascular resection was required in 18 (27%) of 66 patients, and 62 (94%) underwent a margin-negative pancreatectomy. A partial pathologic response to induction therapy (< 50% viable tumor) was seen in 37 (56%) of 66 patients. Median survival was 40 months for the 66 patients who completed all therapy and 13 months for the 94 patients who did not undergo pancreatectomy (p < 0.001). CONCLUSIONS: This is the first large report of borderline resectable PA and includes objective definitions for this stage of disease. Our neoadjuvant approach allowed for identification of the marked subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group.

Accuracy of preoperative imaging of hepatic tumors with helical computed tomography.

BACKGROUND: The accuracy of preoperative computed tomography (CT) scans in the era of modern imaging techniques with helical, high-resolution CT has not been adequately assessed. We reviewed the data from our departmental prospective database with the hypothesis that intraoperative ultrasonography (IOUS) still detects more hepatic tumors than are evident on preoperative helical CT scans. METHODS: All patients who underwent surgical resection and/or radiofrequency ablation of primary or metastatic hepatic tumors between January 2001 and July 2002 were included in the review. All patients had preoperative helical CT imaging followed by hepatic IOUS. The number of malignant lesions and evidence of local disease identified by the preoperative CT scan versus IOUS and surgical exploration were compared. RESULTS: In this time period, 250 patients underwent surgical resection and/or radiofrequency ablation of hepatic tumors. In 67 (27%) of these patients, IOUS identified more hepatic tumors than were seen on preoperative helical CT scan. In eight patients (3%), CT underestimated local extension of the disease into the diaphragm. The incidence of inaccurate preoperative prediction of the extent of disease increased significantly with a greater number of hepatic tumors. CONCLUSIONS: IOUS identified additional hepatic tumors in 27% of patients who underwent hepatic resection after state-of-the-art preoperative CT imaging. This study provides evidence that IOUS remains an essential part of the complete assessment of hepatic malignancies in patients who receive surgical treatment.

Early and late complications after radiofrequency ablation of malignant liver tumors in 608 patients.

BACKGROUND: Radiofrequency ablation (RFA) has become a common treatment of patients with unresectable primary and secondary hepatic malignancies. We performed this prospective analysis to determine early (within 30 days) and late (more than 30 days after) complication rates associated with hepatic tumor RFA. METHODS: All patients treated between January 1, 1996 and June 30, 2002 with RFA for hepatic malignancies were entered into a prospective database. Patients were evaluated during RFA treatment, throughout the immediate post RFA course, and then every 3 months after RFA to assess for the development of treatment-related complications. RESULTS: A total of 608 patients, 345 men (56.7%) and 263 women (43.3%), with a median age of 58 years (range 18-85 years) underwent RFA of 1225 malignant liver tumors. Open intraoperative RFA was performed in 382 patients (62.8%), while percutaneous RFA was performed in 226 (37.2%). The treatment-related mortality rate was 0.5%. Early complications developed in 43 patients (7.1%). Early complications were more likely to occur in patients treated with open RFA (33 [8.6%] of 382 patients) compared with percutaneous RFA (10 [4.4%] 226 patients, P < 0.01), and in patients with cirrhosis (25 [12.9%] complications in 194 patients) compared with noncirrhotic patients (31 [7.5%] complications in 414 patients, P < 0.05). Late complications arose in 15 patients (2.4%) with no difference in incidence between open and percutaneous RFA treatment. The combined overall early and late complication rate was 9.5%. CONCLUSIONS: Hepatic tumor RFA can be performed with low mortality and morbidity rates. Though relatively rare, late complications can develop and physicians performing hepatic RFA must be cognizant of these delayed treatment-related problems.

Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma.

PURPOSE: Because cirrhosis is extremely common in hepatocellular carcinoma (HCC) in the United States, and it precludes the use of several chemotherapy agents, this phase II trial of fluorouracil (FU) and recombinant interferon alfa-2b (rIFNalpha2b) in HCC was launched with the assumption that it could be tolerated by cirrhotics. PATIENTS AND METHODS: Forty-three patients with HCC (34), and fibrolamellar HCC (FLHCC; nine) were treated with continuous intravenous (IV) FU (200 mg/m2/d x 21 every 28 days) and subcutaneous (SC) rIFNalpha2b (4 million U/m2) three times weekly. Survival was determined in all 43 patients, and response could be assessed in 28 HCC and 8 FLHCC patients. RESULTS: The median ages of the patients were 63.5 and 19 years among HCC and FLHCC patients, respectively. Liver cirrhosis was present among 71% of HCC patients but among none of the FLHCC patients. Nine of 36 (25%; four of 28 [14%] HCC patients; five of eight [62.5%] FLHCC patients) patients in which a response could be assessed had a complete response (CR; one patient with FLHCC and no patients with HCC) or partial response (PR; eight patients [four HCC and four FLHCC patients]). Four HCC patients underwent resection, and two had a histologic CR; one HCC patient with a PR underwent orthotopic liver transplantation. One FLHCC patient also underwent resection without clear margins. Overall median survival was 19.5 months (95% confidence interval [CI], 11.2 to 27.8 months); median survival was 15.5 months (95% CI, 8.5 to 22.5 months) among HCC patients, and that of FLHCC patients was 23.1 months (95% CI, 10.3 to 35.9 months). Overall grade 3 or 4 toxicity included stomatitis (32.6%), fatigue (4.7%), and hematologic toxicity (9.3%). CONCLUSION: Continuous IV FU and thrice-weekly SC rIFNalpha2b are an effective treatment, especially for FLHCC, and may have a neoadjuvant role in this disease. This regimen has activity in HCC and can be tolerated even by cirrhotic patients.

Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy.

BACKGROUND: Our institution has previously demonstrated a survival advantage conferred by preoperative neoadjuvant therapy for locally advanced rectal cancers. We now report our results using transanal excision as definitive surgical therapy in a selected group of patients who experienced significant downstaging of T3 rectal cancers after neoadjuvant therapy. STUDY DESIGN: Seventy-four patients diagnosed with locally advanced (T3) rectal cancers were treated with neoadjuvant chemoradiotherapy. After neoadjuvant therapy, 11 (14.9%) patients who had significant downstaging of their tumors were selected to undergo transanal excision of their residual rectal cancers. Intraoperative cryostat evaluation was used to confirm negative margin status, and all patients were subsequently followed with routine endoscopy, transrectal ultrasonography, and digital rectal examinations. RESULTS: Tumors were located between 1 cm and 7 cm from the anal verge (mean 4.3 +/- 0.6 cm), and were located in lateral, anterior, and posterior positions. Mean followup was 55.2 +/- 8.9 months (median 47.9 months). Imaging studies using CT, MRI, transrectal ultrasonography, or combination demonstrated suspicious lymph nodes in three patients. After neoadjuvant therapy, these lymph nodes were no longer demonstrated in two patients. There were no local recurrences, nodal metastases, or operative mortalities. One patient (9%) developed distant metastases (pulmonary nodules), and remains alive 30 months after transanal excision. One patient (9%) experienced sphincter laxity, which was successfully repaired, and is now asymptomatic. One patient (9%) developed postoperative urgency that resolved spontaneously. CONCLUSIONS: In patients who have initial bulky (T3) lesions, and experience significant downstaging after neoadjuvant chemoradiotherapy, transanal excision appears to be a safe and effective treatment, preserving sphincter function and avoiding laparotomy.

Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation.

Microvascular invasion affects survival after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). We sought to identify preoperative predictors of microvascular invasion in patients with HCC who were candidates for OLT. A cohort of 245 patients who underwent resection for HCC and fulfilled the criteria for OLT (i.e., single tumors < or =5 cm or no more than three tumors < or =3 cm) were identified from a multi-institutional database. Thirty-three percent of the patients had pathologic evidence of microvascular invasion. Thirty percent of patients with single tumors and 47% with multiple tumors had microvascular invasion (P = 0.04). Only 25% of patients with tumors smaller than < or =2 cm had microvascular invasion, compared to 31% and 50% with tumors greater than 2 to 4 cm or larger than 4 cm, respectively (P = 0.01). Tumor grade was highly correlated with microvascular invasion: 12% of patients with well-differentiated tumors had microvascular invasion, compared to 29% and 50% with moderately or poorly differentiated tumors, respectively (P < 0.001). The independent predictors of microvascular invasion were tumor size greater than 4 cm (odds ratio [OR], 3.0, 95% confidence interval [CI ], 1.2 to 7.1), and high tumor grade (OR, 6.3; 95% CI, 2.0 to 19.9). Tumor size and grade are strong predictors of microvascular invasion. A tumor biopsy with pathologic grading at the time of pretransplantation ablative therapy could improve selection of patients with HCC for OLT.

Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome.

PURPOSE: To evaluate the toxicity of a preoperative regimen of paclitaxel and concurrent external-beam radiation therapy, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 30 Gy external-beam radiation therapy and concomitant weekly 3-hour infusions of paclitaxel (60 mg/m(2)). Radiographic restaging was performed 4 to 6 weeks after chemoradiation, and patients with localized disease underwent pancreatectomy with EB-IORT. RESULTS: Thirty-five patients completed chemoradiation; 16 (46%) experienced grade 3 toxicity. Four patients (11%) required hospitalization for dehydration due to grade 3 nausea and vomiting. Twenty (80%) of 25 patients who underwent surgery underwent pancreatectomy; EB-IORT was used in 13 patients. There were no histologic complete responses to preoperative therapy; 21% of specimens demonstrated more than 50% nonviable cells (grade 2b treatment effect). With a median follow-up period of 46 months, the 3-year overall survival rate with chemoradiation and pancreatectomy was 28%. CONCLUSION: Preoperative paclitaxel-based concurrent chemoradiation is feasible. The toxicity of this regimen seems greater than that with fluorouracil. The histologic responses and survival are similar, suggesting no advantages to paclitaxel-based preoperative treatment.

Liver imaging. A surgeon's perspective.

Advances in the diagnosis and treatment of liver lesions have improved therapy for a broad range of clinical conditions, many of which could not be effectively treated in the recent past. These advances are the result of better surgical techniques as well as diagnostic imaging. This article discusses the anatomy of the liver and the clinical evaluation of patients with liver lesions. Common benign and malignant liver lesions are presented with radiologic characteristics and treatment options.