Thermal ablation of hepatic malignancy: useful but still not optimal.

The mortality associated with primary and metastatic hepatic malignancies remains high because few patients are candidates for hepatic resection or transplantation. Resection is the most effective treatment for liver tumors but may be contraindicated by factors such as the tumor's location; hepatic transplantation can cure primary hepatocellular carcinoma and underlying cirrhosis, but a donor may not be immediately available. When resection or transplantation is not possible, thermal ablation is a reasonable therapeutic option. Effective destruction of tumors can be achieved with low recurrence rates and minimal complications or risk of death. In patients with primary hepatic malignancy, ablation treatment does not preclude subsequent transplantation. Although radiofrequency ablation is currently the most widely used thermal ablative technique for hepatic malignancy, microwave ablation is gaining popularity and eventually may prove to be more effective.

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins.

BACKGROUND: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. AIMS: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised disease. PATIENTS: Seventy patients who underwent curative resection for pancreatic ductal adenocarcinoma were evaluated. METHODS: All patients had surgical resection margins (pancreatic transection and retroperitoneal) that were histologically free of invasive cancer. DNA was extracted from these paraffin embedded surgical margins and assessed by quantitative real time polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. RESULTS: K-ras mutation was detected in histologically negative surgical margins of 37 of 70 (53%) patients. A significant difference in overall survival was demonstrated between patients with margins that were K-ras mutation positive compared with negative (median 15 v 55 months, respectively; p = 0.0008). By univariate and multivariate analyses, detection of K-ras mutation in the margins was a significant prognostic factor for poor survival (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95% CI 1.4-5.5), p = 0.004, respectively). CONCLUSIONS: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

Quality control issues in the management of colon cancer patients.

Quality assurance in colon cancer demands a multidisciplinary effort involving general practitioners, surgeons, radiologists, gastroenterologists, medical oncologists, and pathologists, among others. Maximal improvements in survival will result when colon cancer screening, diagnosis, staging, treatment and surveillance are optimized. We seek to identify those issues most relevant to the quality of care we provide our colon cancer patients.

Ultrastaging of early colon cancer using lymphatic mapping and molecular analysis.

Approximately one-third of node-negative colon cancers will recur, possibly due to understaging and inadequate pathological examination of lymph nodes (LNs). We evaluated the sensitivity, accuracy and feasibility of staging based on lymphatic mapping, focused examination, and molecular analysis of the sentinel node (SN) in patients with primary colorectal carcinoma. Between 1996 and 2000, 100 patients with colon carcinoma (CRC) underwent lymphatic mapping immediately after peritumoral injection of 1.0 cc of isosulphan blue dye. All LNs in the CRC specimen were examined by routine haematoxylin and eosin (H&E) staining. Sentinel nodes were examined by step serial sectioning, cytokeratin immunohistochemistry (CK-IHC) and/or reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in an attempt to identify occult micrometastatic disease. Lymphatic mapping was successful in 97% of the cases. There were 5 false-negative cases, predominately associated with T3/T4 tumours. Aberrant lymphatic drainage was identified in 8 patients (8%) altering the operative approach. 26 patients had H&E-positive LNs. In 74 patients who were node-negative by routine H&E, 18 (24%) had occult nodal micrometastases missed on routine H&E examination, but detected by focused analysis of the SN. RT-PCR analysis of the SN was performed in 40 patients, 26 of which were negative by H&E and CK-IHC. In 12/26 (46%) of these patients, there was additional evidence of micrometastatic disease. In this study, focused examination of the SN in conjunction with RT-PCR analysis identified micrometastatic disease in a significant number of node-negative patients. This may have important implications when selecting patients for adjuvant treatment protocols.

Hepatic cytoreduction followed by a novel long-acting somatostatin analog: a paradigm for intractable neuroendocrine tumors metastatic to the liver.

BACKGROUND: Optimal management of symptomatic neuroendocrine tumors that metastasize to the liver is controversial. We investigated aggressive hepatic cytoreduction and postoperative administration of octreotide long-acting release (LAR), a long-acting somatostatin analog. METHODS: Between December 1992 and August 2000, 31 patients underwent hepatic surgical cytoreduction (20 carcinoid, 10 islet cell, and 1 medullary). All patients had progressive symptoms refractory to conventional therapy. RESULTS: Hepatic cytoreduction (resection, cryosurgery, and/or radiofrequency ablation) eliminated symptoms in 27 patients (87%) and decreased secretion of hormones by an overall mean of 59%. When minor symptoms returned and/or hormonal levels increased during follow-up, adjuvant therapy was started. Ten patients received adjuvant octreotide LAR once a month, and 21 received other adjuvants. At a median postoperative follow-up of 26 months, 16 patients had progressive/recurrent disease, 13 had died of their disease, and 2 remained free of disease. Median symptom-free interval was 60 months (95% confidence interval, 48-72) with octreotide LAR and 16 months (95% confidence interval, 10-29) with other adjuvants (P = .0007). Two-year symptom-free survival rate was 100% with octreotide LAR and 33% with other adjuvants. CONCLUSIONS: Hepatic surgical cytoreduction can palliate progressive symptoms associated with liver metastases from intractable neuroendocrine tumors. Postoperative adjuvant therapy with octreotide LAR can prolong symptom-free survival.

Aberrant drainage and missed micrometastases: the value of lymphatic mapping and focused analysis of sentinel lymph nodes in gastrointestinal neoplasms.

Lymph node analysis is essential for staging gastrointestinal (GI) neoplasms. Our group has conducted several studies of intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) for the staging of GI neoplasms. LM is performed following injection of 0.5-1 ml of isosulfan blue dye, and blue-stained sentinel lymph nodes (SLNs) are analyzed by hematoxylin and eosin (H&E) staining, multiple sectioning, and cytokeratin immunohistochemistry. In feasibility trials, LM identified at least one SLN in 121 of 126 patients. Of the 58 cases with nodal metastasis, 50 (89%) had at least one positive SLN and 24 (42%) had nodal metastasis only in the SLN. In 25 cases, tumor deposits were identified by multiple sectioning (n = 8) or immunohistochemistry (n = 17) only. In 10 cases (8%), LM identified aberrant lymphatic drainage that altered the extent of the lymphadenectomy. Our cumulative experience indicates that focused analysis of the SLNs draining GI neoplasms can increase the detection of micrometastases and may improve selection of patients for adjuvant treatment.

Lymphatic mapping improves staging during laparoscopic colectomy for cancer.

BACKGROUND: Recently, lymphatic mapping (LM) of the sentinel lymph node (SN) has been coupled with ultrastaging methods to diagnose nodal micrometastases from colorectal cancer (CRC). We have developed a technique for LM at the time of laparoscopic colon resection (LCR). METHODS: Between August 1996 and February 2000, 11 patients with small early-stage CRC underwent laparoscopic LM and LCR. The primary tumor/polyp site was visualized through a colonoscope and either tattooed preoperatively with a carbon dye (India ink), or stained intraoperatively by peritumoral injection of isosulfan blue dye. Immediately after intraoperative injection of blue dye, efferent lymphatic channels were visualized through the laparoscope and followed to the SN. Each blue-stained SN was marked with a suture or clip. RESULTS: In all 11 cases, laparoscopic LM identified between one and three SN draining the primary tumor. LM added ~15-20 min to the operating time. The SN correctly reflected the nodal status of the entire specimen in all cases. In the one node-positive case, micrometastases were found only in an SN and only after cytokeratin immunohistochemistry (CK-IHC). In four cases, LM demonstrated unexpected primary lymphatic drainage that prompted an increase in the margins of resection. CONCLUSIONS: LM during laparoscopic colectomy for CRC may be useful to mark the primary tumor site and to demonstrate lymphatic drainage that can alter the margins of resection. Focused examination of SN identifies occult micrometastases that up-stage CRC.

Laparoscopic radiofrequency ablation of unresectable hepatic malignancies. A phase 2 trial.

BACKGROUND: Radiofrequency ablation (RFA) of hepatic malignancies has been performed successfully via a percutaneous route or at laparotomy. We analyzed the efficacy and utility of laparoscopic intraoperative ultrasound and RFA in patients with unresectable hepatic malignancies. METHODS: Between November 1997 and November 1999, 27 patients with unresectable hepatic malignancies and no evidence of extrahepatic disease were entered in a phase 2 trial of laparoscopic intraoperative ultrasound and RFA. Real-time ultrasonography was used to guide RFA, and lesions were ablated at a temperature of 100 degrees C for 10 min. Overlapping ablations were performed for larger lesions. RESULTS: Additional tumors were identified in 10 (37%) of the 27 study patients by laparoscopy and laparoscopic intraoperative ultrasound despite extensive preoperative imaging. Radiofrequency ablation of 85 hepatic tumors yielded no mortality and only one case of postoperative bleeding. During a mean follow-up period of 14 months, four tumors (4.7%) locally recurred. Of the 27 patients, 11 (41%) remain free of disease at this writing; (22%) are alive with disease; and 10 (37%) have died with disease. CONCLUSION: Laparoscopic RFA and intraoperative ultrasound constitute a safe and accurate method for ablation of unresectable hepatic tumors.

CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer.

BACKGROUND: The immunogenicity of the polyvalent tumor cell vaccine CancerVax has been correlated with the survival of patients receiving active immunotherapy for melanoma. Because the various antigens expressed on the vaccine are common to colon adenocarcinoma cells, we examined the survival impact of immune responses elicited by CancerVax in patients with advanced colon cancer refractory to standard therapy. METHODS: Twenty-seven patients with American Joint Committee on Cancer (AJCC) stage IV colorectal adenocarcinoma were entered prospectively into the study. CancerVax was coadministered with bacille Calmette-Guerin (BCG) for the first 2 weeks of vaccine treatment. Blood was drawn at the start of therapy and every 2 weeks thereafter to measure serum titers of immunoglobulin (Ig)G and IgM against TA90 (a 90-kD immunogen common to colon cancer and CancerVax cells) and against purified protein derivative (PPD), a nontumor control antigen. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) reaction to vaccine cells and to PPD. Mean follow-up time was 17.5 months. RESULTS: There was a significant (P = .0001) increase in anti-TA90 IgG and IgM titers and in DTH response to vaccine cells. Humoral and skin responses to TA90 did not correlate with responses to PPD (P = .199 for IgM, P = .958 for IgG, and P = .149 for DTH). This suggests that these responses are not a manifestation of general immune competence. The median overall survival (OS) was 21.9 months for the entire group. Overall survival was higher among patients whose IgMTA90 titer was >800 (P = .003) or whose disease-free interval exceeded 12 months (P = .031). Multivariate Cox regression analysis-using age, sex, disease-free interval, disease status, extent of metastasis, humoral responses, and DTH responses-found only peak IgMTA90 titer to be a significant predictor of overall survival (P = .0365). CONCLUSIONS: CancerVax can induce measurable humoral and cellular immune responses to tumor-associated antigens in patients with advanced-stage colon cancer. These responses correlate with overall survival. This novel therapeutic regimen for patients with advanced colon cancer merits further investigation.

Repeat hepatic cryotherapy for metastatic colorectal cancer.

This study evaluated the risks and benefits of repeat hepatic cryotherapy for recurrent, unresectable hepatic metastases from colorectal carcinoma. Review of a prospective database identified 195 patients who underwent hepatic cryotherapy for metastatic colorectal carcinoma during a 7-year period. Of the 14 patients who underwent successful repeat cryotherapy for recurrences confined to the liver, 86% had Duke's stage D colorectal carcinoma at initial diagnosis. The median age of the 14 patients was 58 years (range 41 to 77 years). The median number of hepatic metastases was three at the first cryotherapy and two at the second cryotherapy. At a median follow-up of 71 months, the mean survival times from original diagnosis, first cryotherapy, and second cryotherapy were 53, 42, and 19 months, respectively. At the most recent follow-up, eight patients (57%) have died of their disease, four (29%) are alive with disease, and two (14%) have no evidence of disease. The mean interval between the first and second cryotherapies was 23 months. The complication rates after the first and second cryotherapies were 7% and 14%, respectively. One patient developed a wound dehiscence after the first cryotherapy. Following the second cryotherapy, one patient had a small bowel obstruction and another had a pleural effusion. There was no perioperative mortality. Repeat cryotherapy for recurrent, unresectable hepatic metastases from colorectal cancer is safe and improves survival. However, a prospective trial is needed to validate the efficacy of systemic therapy and to better define the indications for repeat hepatic cryotherapy.

Validation of lymphatic mapping in colorectal cancer: in vivo, ex vivo, and laparoscopic techniques.

BACKGROUND: The use of lymphatic mapping (LM) is being investigated to improve the staging of colorectal cancer (CRC) and thereby identify patients who might benefit from adjuvant chemotherapy. This study evaluated in vivo, laparoscopic, and ex vivo approaches for the ultrastaging of CRC. METHODS: Seventy-five CRC patients were enrolled in a study of LM with peritumoral injection of isosulfan blue dye. LM was undertaken during open colon resection (OCR) in 64 patients, during laparoscopic colon resection (LCR) in 9 patients, and after specimen removal (ex vivo) in 2 patients. Ex vivo LM was also undertaken in 6 patients after unsuccessful in vivo LM. All nodes were examined by hematoxylin and eosin (H&E) staining; in addition, sentinel lymph nodes (SNs) were multisectioned and examined by immunohistochemical staining with cytokeratin (CK-IHC). RESULTS: At least one SN was identified in 72 patients (96%). In vivo LM identified SNs in 56 of 64 (88%) patients undergoing OCR and in 9 of 9 (100%) patients undergoing LCR. Ex vivo LM was undertaken as the initial mapping procedure in 2 cases of intraperitoneal colon cancer and after in vivo LM had failed in 6 cases of extraperitoneal rectal carcinoma; an SN was identified in 7 of the 8 cases. Focused examination of the SN correctly predicted nodal status in 53 of 56 OCR cases, 9 of 9 LCR cases, and 6 of 7 ex vivo cases. Multiple sections and CK-IHC identified occult micrometastases in 13 patients (17%), representing 10 OCR, 1 LCR, and 2 ex vivo cases. CONCLUSIONS: LM of drainage from a primary CRC can be accurately performed in vivo during OCR or LCR. Ex vivo LM can be applied when in vivo techniques are unsuccessful and may be useful for rectal tumors. During LCR, colonoscopic injection can be used to mark the primary tumor and define the lymphatic drainage so that adequate resection margins are obtained. These LM techniques improve staging accuracy in CRC.

Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial.

PURPOSE: Approximately 30% of patients with American Joint Committee on Cancer stage I or II colorectal cancer (CRC) develop systemic disease. We hypothesized that multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of sentinel lymph nodes (SNs) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis. PATIENTS AND METHODS: In a multi-institutional study, 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection. Each dye-stained SN was tagged, and the tumor and regional nodes were resected en bloc. All lymph nodes were examined by conventional hematoxylin and eosin (HE) staining. In addition, each SN was cut into multiple sections for cytokeratin immunohistochemical (CK-IHC) staining and for RT-PCR and electrochemiluminescent detection of three markers: beta-chain human chorionic gonadotropin, hepatocyte growth factor receptor, and universal melanoma-associated antigen. Whenever possible, RT-PCR assay was also performed on primary tumor tissue. The detection sensitivity of individual markers was 10(-3) to 10(-4) microg of RNA and one to five tumor cells in 10(7) lymphocytes of healthy donors. RESULTS: One to three SNs were identified in each patient. An average of 15 nodes were removed from each CRC specimen. No nonsentinel (untagged) node contained evidence of tumor if all tagged (sentinel) nodes in the same specimen were histopathology tumor-negative. HE staining of SNs identified tumor in 10 patients (25%), and CK-IHC of SNs identified occult micrometastases in four patients (10%) whose SNs were negative by HE. Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC, 12 (46%) had positive RT-PCR results. The number of markers expressed in each SN correlated (P <.04) with the T stage of the primary tumor. There was 79% concordance in marker expression for the respective pairs (n = 38) of primary tumor and histopathologically positive SNs, and 86% (12 of 14) concordance between RT-PCR positive and histopathologically positive SNs. CONCLUSION: Identification and focused examination of the SN is a novel method of staging CRC. CK-IHC and RT-PCR identified occult micrometastases in 53% of patients whose SNs were negative by conventional staging techniques. These ultrasensitive assays of the SN can identify patients who may be at high risk for recurrence of CRC and therefore are more likely to benefit from systemic adjuvant therapy.

Radiofrequency ablation of unresectable hepatic malignancies: lessons learned.

Radiofrequency ablation (RFA) is increasingly used for the local destruction of unresectable hepatic malignancies. Relative contraindications include tumors in proximity to vital structures that may be injured by RFA and lesions whose size exceeds the ablation capabilities of the probe system employed. Given current technology, we believe that RFA should be cautiously utilized for lesions greater than 5 cm in diameter. Open (celiotomy) and laparoscopic approaches to RFA allow intraoperative ultrasonography, which may demonstrate occult hepatic disease. In addition, RFA performed via celiotomy can be accompanied by resection or cryosurgical ablation, and isolation of the liver from adjacent organs. Percutaneous RFA should be reserved for patients who cannot undergo general anesthesia, those with recurrent or progressive lesions, and those with smaller lesions sufficiently isolated from adjacent organs. Complications may be minimized when these approaches are selectively applied.

Solid and papillary epithelial neoplasms of the pancreas: aggressive resection for cure.

Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women. We retrospectively reviewed our experience with pancreatic neoplasms from 1986 to the present and identified nine patients with SPENP. All nine patients were female with a mean age of 32 years (range 16-66). All patients presented with gastrointestinal complaints including pain, mass, dyspepsia, or bloating and were subsequently diagnosed with a tumor of the pancreas by CT scan. All patients underwent surgical resection. Two patients had tumors located in the head of the pancreas and underwent a pancreaticoduodenectomy. The remainder had tumors located in the tail of the pancreas and underwent distal pancreatectomy. Pathology demonstrated solid and papillary or solid and cystic pseudopapillary neoplasm of the pancreas. Three tumors were positive for both vimentin and alpha-1 antitrypsin on immunohistochemical studies, and three were positive for neuron-specific enolase. All nine patients underwent curative resection and are alive without any evidence of recurrence with a mean follow-up of 5.4 years. SPENP is considered to be a low-grade malignancy with an excellent prognosis. Prompt diagnosis and surgical resection can result in cure.

Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5-fluorouracil.

Most colorectal cancers metastatic to the liver are resistant to chemotherapy and are not amenable to surgical resection. This study evaluated our 6-year experience (July 1992-July 1998) in treating patients with unresectable hepatic colorectal metastases refractory to systemic 5-fluorouracil (5-FU). One hundred fifty-three patients underwent cryosurgical ablation (CSA) of 5-FU-resistant hepatic metastases. The patients then received either hepatic arterial floxuridine (FUDR), systemic CPT-11, or no postoperative adjuvant chemotherapy. Number, size, and location of hepatic metastases, carcinoembryonic antigen (CEA) levels, and type of postoperative treatment were analyzed. One to 15 lesions were frozen (median number, 3; median size, 6 cm), for a total of 73 synchronous and 80 metachronous lesions. Overall median survival was 28.4 months from the date of diagnosis of liver metastases and 16.1 months from the time of CSA. After cryosurgery alone, median survival was 13 months, which was significantly shorter than the post-CSA survival of 23.6 months with adjuvant CPT-11 and 21.2 months with hepatic FUDR (P = 0.007). Predictors of survival included preoperative CEA, postoperative reduction in CEA, and adjuvant chemotherapy (P < 0.05). Neither size, number of lesions, nor tumor location impacted survival. At a median follow-up of 13 months, 67% of patients have recurred (35% hepatic, 16% extrahepatic, and 49% both). Twenty percent of the recurrences were in the lobe of the CSA site. The 25 patients who underwent a second CSA had a median survival of 28.4 months from CSA and 40 months from the date of diagnosis of liver metastases. These data indicate that CSA offers an effective alternative for unresectable patients resistant to 5-FU. Systemic CPT-11 or regional FUDR may further prolong survival after CSA.

Focused examination of sentinel lymph nodes upstages early colorectal carcinoma.

Approximately 30 per cent of patients with early colorectal carcinoma (CRC) develop systemic disease. A subgroup of these patients may harbor occult micrometastatic disease and might benefit from adjuvant chemotherapy. We investigated sentinel lymph node (SLN) mapping and focused pathologic examination of the SLN as a means of detecting nodal micrometastases. Between 1996 and 2000 SLN mapping was performed in 50 consecutive patients undergoing colectomy for CRC. All lymph nodes in the resection specimen were examined via routine hematoxylin and eosin (H&E) staining. In addition multiple sections of each SLN were examined via both H&E and cytokeratin immunohistochemistry. At least one SLN was identified in 47 patients (94%). In seven patients (14%) SLN mapping identified aberrant drainage that altered the planned resection. The SLN(s) correctly predicted nodal basin status in 44 of 47 (94%) cases; there were three falsely negative SLNs. Sixteen cases had positive SLNs by conventional H&E staining. An additional 10 (20%) cases were upstaged by a focused examination of the SLNs. Micrometastases were identified in three cases by H&E staining of multiple sections of the SLN and in seven only by cytokeratin immunohistochemistry. In nine cases the SLN was the only node containing tumor cells. In this study, SLN mapping demonstrated aberrant nodal drainage patterns that altered the surgical resection in patients with CRC. Focused examination of SLNs may detect micrometastases missed by conventional techniques and thereby identify patients who might benefit from adjuvant therapy.

Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications.

BACKGROUND: Radiofrequency ablation (RFA) is increasingly used for the local destruction of unresectable hepatic malignancies. There is little information on its optimal approach or potential complications. METHODS: Since late 1997, we have undertaken 91 RFA procedures to ablate 231 unresectable primary or metastatic liver tumors in 84 patients. RFA was performed via celiotomy (n = 39), laparoscopy (n = 27), or a percutaneous approach (n = 25). Patients were followed with spiral computed tomographic (CT) scans at 1 to 2 weeks postprocedure and then every 3 months for 2 years. RESULTS: Intraoperative ultrasound (IOUS) detected intrahepatic disease not evident on the preoperative scans of 25 of 66 patients (38%) undergoing RFA via celiotomy or laparoscopy. In 38 of 84 patients (45%), RFA was combined with resection or cryosurgical ablation (CSA), or both. RFA was used to treat an average of 2.8 lesions per patient, and the median size of treated lesions was 2 cm (range, 0.3-9 cm). The average hospital stay was 3.6 days overall (1.8 days for percutaneous and laparoscopic cases). Ten patients underwent a second RFA procedure (sequential ablations) and, in one case, a third RFA procedure for large (one patient), progressive (seven patients), and/or recurrent (three patients) lesions. Seven (8%) patients had complications: one skin burn; one postoperative hemorrhage; two simple hepatic abscesses; one hepatic abscess associated with diaphragmatic heat necrosis following sequential percutaneous ablations of a large lesion; one postoperative myocardial infarction; and one liver failure. There were three deaths, one (1%) of which was directly related to the RFA procedure. Three of the complications, including one RFA-related death, occurred after percutaneous RFA. At a median follow-up of 9 months (range, 1-27 months), 15 patients (18%) had recurrences at an RFA site, and 36 patients (43%) remained clinically free of disease. CONCLUSIONS: Celiotomy or laparoscopic approaches are preferred for RFA because they allow IOUS, which may demonstrate occult hepatic disease. Operative RFA also allows concomitant resection, CSA, or placement of a hepatic artery infusion pump, and isolation of the liver from adjacent organs. Percutaneous RFA should be reserved for patients at high risk for anesthesia, those with recurrent or progressive lesions, and those with smaller lesions sufficiently isolated from adjacent organs. Complications may be minimized when these approaches are applied selectively.

Lymphatic mapping and focused analysis of sentinel lymph nodes upstage gastrointestinal neoplasms.

BACKGROUND: Lymph node analysis is essential for staging gastrointestinal (GI) neoplasms. Intraoperative lymphatic mapping and sentinel lymphadenectomy were originally described for melanoma but have not yet been investigated for most GI neoplasms. HYPOTHESES: (1) Lymphatic mapping and sentinel lymphadenectomy is feasible in GI neoplasms, (2) the sentinel node (SN) status reflects the regional node status, and (3) focused analysis of the SN improves staging accuracy. DESIGN: Prospective patient series. PATIENTS AND METHODS: Lymphatic mapping was performed in 65 patients with GI neoplasms by injecting 0.5 to 1 mL of isosulfan blue dye around the periphery of the neoplasm. Blue-stained SNs were analyzed by hematoxylin-eosin staining, multiple sectioning, and cytokeratin immunohistochemistry. RESULTS: Lymphatic mapping identified at least 1 SN in 62 patients (95%). Of the 36 cases with nodal metastasis, 32 (89%) had at least 1 positive SN and 15 (42%) had nodal metastasis only in the SN. In 11 cases, tumor deposits were identified by multiple sectioning (n = 2) or immunohistochemistry (n = 9) only. In 5 cases (8%), lymphatic mapping identified aberrant lymphatic drainage that altered the extent of the lymphadenectomy. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy are feasible in GI neoplasms and identify aberrant lymphatic drainage. The SN status accurately reflects the regional node status. Focused analysis of the SN increases the detection of micrometastases and may improve selection of patients for adjuvant treatment.

TA90-IC, a new marker for advanced colon cancer.

BACKGROUND: Although carcinoembryonic antigen (CEA) is the most frequently used marker for colon cancer, it is elevated in only 70% of patients with advanced disease and in even fewer patients with earlier stages of disease. We previously identified a 90-kDa glycoprotein, TA90, which is present in serum in the form of circulating immune complexes. TA90 is found in a variety of solid neoplasms but rarely in healthy controls (3.2%). We hypothesized that this new tumor-associated antigen may be a useful marker for colon cancer. METHODS: Serum samples from 59 patients with known colon adenocarcinoma were analyzed for the presence of CEA and TA90. Fifty-one (86%) patients had distant metastases; the remaining patients had clinically localized primary colon cancer. A murine monoclonal antibody-based enzyme-linked immunosorbent assay was used to measure concentrations of TA90-specific circulating immune complexes (TA90-IC). A positive value was defined as an optical density of more than 0.410 at 405 nm. Forty-seven (80%) of the 59 patients had serum samples for TA90 and CEA drawn at the same time. RESULTS: TA90-IC concentrations were elevated more frequently than CEA concentrations (82.9% vs. 70.2%; P = .134). The combination of both markers identified more patients with colon carcinoma than did either marker alone (93.6%; P < .001). CONCLUSIONS: Concomitant use of TA90-IC and CEA identified 93.6% of patients with advanced colon cancer. The role of TA90-IC in screening and monitoring progression of earlier disease deserves further investigation.

Cryosurgical ablation and radiofrequency ablation for unresectable hepatic malignant neoplasms: a proposed algorithm.

BACKGROUND: Thermal ablation of unresectable hepatic tumors can be achieved by cryosurgical ablation (CSA) or radiofrequency ablation (RFA). The relative advantages and disadvantages of each technique have not yet been determined. HYPOTHESIS: Radiofrequency ablation of malignant hepatic neoplasms can be performed safely, but is currently limited by size. Cryosurgical ablation, while associated with higher morbidity, is more effective for larger unresectable hepatic malignant neoplasms. DESIGN: Retrospective analysis of prospective patient database. PATIENTS AND METHODS: Between July 1992 and September 1999, 308 patients with liver tumors not amenable to curative surgical resection were treated with CSA and/or RFA (percutaneous, laparoscopic, celiotomy). No patient had preoperative evidence of extrahepatic disease. All patients underwent laparoscopy with intraoperative ultrasound if technically possible. Both RFA and CSA were performed under ultrasound guidance. Resection, as an adjunctive procedure, was combined with ablation in certain patients. RESULTS: Laparoscopy identified extrahepatic disease in 12% of patients, and intraoperative hepatic ultrasound identified additional lesions in 33% of patients, despite extensive preoperative imaging. Radiofrequency ablation alone or combined with resection or CSA resulted in reduced blood loss (P<.05), thrombocytopenia (P<.05), and shorter hospital stay compared with CSA alone (P<.05). Median ablation times for lesions greater than 3 cm were 60 minutes with RFA and 15 minutes with CSA (P<.001). Local recurrence rates for lesions greater than 3 cm were also greater with RFA (38% vs 17%). CONCLUSIONS: Laparoscopy and intraoperative ultrasound are essential in staging patients with hepatic malignant neoplasms. Radiofrequency ablation when combined with CSA reduces the morbidity of multiple freezes. Although RFA is safer than CSA and can be performed via different approaches (percutaneously, laparoscopically, or at celiotomy), it is limited by tumor size (<3 cm). Percutaneous RFA should be considered in high-risk patients or those with small local recurrences.