Endoscopic biopsy diagnosis of acute gastrointestinal graft-versus-host disease: rectosigmoid biopsies are more sensitive than upper gastrointestinal biopsies.

OBJECTIVES: The diagnosis of gastrointestinal (GI) graft-versus-host disease (GVHD) is based upon histologic findings in endoscopic mucosal biopsy specimens. The portion of the GI tract with the highest diagnostic yield is a topic of debate. Our aim was to evaluate the sensitivity of simultaneous biopsy of the stomach, duodenum, and rectosigmoid in establishing the diagnosis of GI GVHD. METHODS: We identified 112 patients who had simultaneous endoscopic biopsies of the stomach, duodenum, and rectosigmoid within the first 100 days following allogeneic hematopoietic stem cell transplantation (HSCT). GVHD was defined histologically as the presence of gland apoptosis, not explained by other inflammatory or infectious etiologies. The patient was diagnosed with GI GVHD if at least one biopsy site was positive. RESULTS: Overall, 81% of the patients had GI GVHD. Of these, 66% had involvement at all three biopsy sites. Rectosigmoid biopsies had the highest sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing GI GVHD, at 95.6%, 100%, 100%, and 84%, respectively. The sensitivities of gastric and duodenal biopsies were 72.5% (P < 0.0001 vs rectosigmoid) and 79.2% (P = 0.0018), respectively. The negative predictive values of gastric and duodenal biopsies were 45.6% (P = 0.0039 vs rectosigmoid) and 52.5% (P = 0.0205), respectively. Rectosigmoid biopsies had a higher sensitivity and negative predictive value than biopsies at other sites whether the patient presented with diarrhea or nausea/vomiting. No association between the degree of mucosal injury and the presence of GVHD was found at any site. CONCLUSIONS: Biopsy of the rectosigmoid is the single best test for diagnosing GI GVHD.

Sentinel lymph node evaluation does not improve staging accuracy in colon cancer.

BACKGROUND: Lymph node involvement is an important prognostic factor in colorectal cancer. Sentinel lymph node (SLN) evaluation for assessing lymph node status in colorectal cancer remains controversial. Here we evaluated the sensitivity, predictive value, and accuracy of SLN evaluation for determining lymph node status in resectable colon cancer. METHODS: A prospective phase 2 cohort study of SLN evaluation in colon cancer was conducted from September 1998 to April 2006. Patients underwent resection and SLN mapping with 1% isosulfan blue and (m99)Tc sulfur colloid injection. SLNs were evaluated by hematoxylin and eosin (HE) staining and, if findings were negative, by additional thin HE sections and immunohistochemical (IHC) staining for pancytokeratin and MOC31. Overall survival for patients with IHC-positive disease was evaluated by Kaplan-Meier analysis and the log rank test. RESULTS: SLNs were identified in 119 (99%) of the 120 patients eligible for the study. Median number of SLNs identified was 4 (range, 0-13). Forty-nine patients (40%) had nodal metastases on HE. The SLN accurately identified nodal metastases in 29 (59%) of these 49 patients and was negative for metastases in 22 patients (41%). SLNs in eight patients (7%) were negative by HE but positive by IHC staining. Positive IHC status did not affect survival after a median follow-up of 33 months (P = .41). CONCLUSIONS: The low sensitivity and high false-negative rate of SLN evaluation does not support this technique for improving the accuracy of nodal staging for patients with colon cancer. The significance of IHC-positive SLNs remains uncertain.

Simplified staging for hepatocellular carcinoma.

PURPOSE: The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) fails to stratify patients adequately with respect to prognosis. PATIENTS AND METHODS: The ability of the currently proposed tumor (T) categories to effectively stratify the survival of 557 patients who underwent complete resection for HCC at four centers was examined. Independent predictors of survival were combined into a new staging system. RESULTS: Using the current AJCC T classification, patients with T1 and T2 tumors had similar 5-year survivals (P =.6). In addition, the survival of patients with multiple bilobar tumors (T4) matched that of T3 patients (P =.5). Independent predictors of death were major vascular invasion (P <.001), microvascular invasion (P =.001), severe fibrosis/cirrhosis of the host liver (P =.001), multiple tumors (P =.007), and tumor size greater than 5 cm (P =.01). Based on our results, a simplified stratification is proposed: (a) patients with a single tumor and no microvascular invasion, (b) patients with a single tumor and microvascular invasion or multiple tumors, none more than 5 cm, and (c) patients with either multiple tumors, any more than 5 cm, or tumor with major vascular invasion (P <.001). Severe fibrosis/cirrhosis had a negative impact on survival within all categories. The survival of patients with lymph node involvement matched that of patients with major vascular invasion (P =.3). CONCLUSION: The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.

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.

Feasibility of a randomized trial of extended lymphadenectomy for pancreatic cancer.

HYPOTHESIS: The required sample size of a prospective randomized trial comparing standard pancreaticoduodenectomy with pancreaticoduodenectomy plus extended lymphadenectomy for pancreatic adenocarcinoma is prohibitively large, making such a trial infeasible. DESIGN: Retrospective cohort study. SETTING: Comprehensive cancer center. PATIENTS: We identified 158 patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma with separate pathologic analysis of second-echelon lymph nodes, defined as lymph nodes along the proximal hepatic artery and/or the great vessels. MAIN OUTCOME MEASURES: To estimate the sample size required for a randomized trial, we devised a biostatistical model with the following assumptions: extended lymphadenectomy can benefit only patients who (1) actually have disease removed from second-echelon nodes, (2) have microscopically negative (R0) primary tumor resection margins, and (3) do not have visceral metastatic (M0) disease. RESULTS: Seventy-six patients (48.1%) had negative first- and second-echelon lymph nodes, 65 (41.1%) had positive first-echelon and negative second-echelon lymph nodes, and 17 (10.8%) had positive first- and second-echelon lymph nodes. Patients with positive second-echelon lymph nodes had an R0 resection rate of 47.1%. At a median follow-up of 65.1 months, 4 patients with positive second-echelon lymph nodes were alive, but 3 had recurrent disease. This implies that only 1 patient (5.9%) with positive second-echelon lymph nodes may have had true M0 disease. Therefore, only 0.3% of patients (10.8% with positive second-echelon lymph nodes x 47.1% with R0 resection x 5.9% with M0 disease) may achieve a survival benefit from extended lymphadenectomy. A randomized trial of standard pancreaticoduodenectomy vs pancreaticoduodenectomy with extended lymphadenectomy would require 202 000 patients in each study arm to detect such a small difference. CONCLUSIONS: Definitive evaluation of the potential benefits of extended lymphadenectomy would require a prohibitively large sample size. Adequately powered randomized trials to address the potential benefit of extended lymphadenectomy are infeasible.

Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer.

PURPOSE: Multiple chromosome abnormalities, including gain of chromosome20q, have been detected frequently in human pancreatic cancers. Overexpression of the STK15/BTAK/Aurora A gene located on chromosome 20q13, which encodes a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation in multiple in vitro experimental systems. The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer. EXPERIMENTAL DESIGN: STK15 expression at both the mRNA and protein levels together with the copy number of STK15 gene was measured in nine pancreatic carcinoma cell lines: (a) HPAF-II; (b) Aspc-1; (c) Panc-1; (d) Panc-3; (e) Panc-28; (f) Panc-48; (g) HS766T; (h) MIAPaCa-2; and (i) BxPc3. STK15 protein expression was also examined in normal pancreatic tissues and tumors by Western blotting and immunohistochemistry. RESULTS: STK15 was overexpressed in all of the nine cell lines examined, but gene amplification was infrequent. Western Blot analysis of primary tumor tissues revealed 2-10 times overexpression of STK15 protein compared with normal adjacent tissues from pancreatic cancer patients. Concurrent overexpression of cdc20, an STK15-associated protein, and reduced expression of cdc25, a mitosis-activating protein phosphatase, were detected in the same tumor samples. Elevated STK15 protein expression was detected in 22 of 38 tumor sections (58%) from pancreatic cancer patients. The extent of STK15 expression was not significantly correlated with the size, degree of differentiation, and metastasis status of the tumors. CONCLUSIONS: These results show that STK15 is overexpressed in pancreatic tumors and carcinoma cell lines and suggest that overexpression of STK15 may play a role in pancreatic carcinogenesis.

Increased apoptosis in metastatic human colonic adenocarcinomas.

Recent work suggests that apoptosis is disrupted during the progression of many solid tumors. Isogenic metastatic colon adenocarcinoma cells displayed significantly higher levels of staurosporine-induced apoptosis compared to their nonmetastatic counterparts in vitro. In addition, analysis of 15 matched primary tumors and liver metastases demonstrated that the levels of apoptosis were significantly higher in the metastases, and this increased cell death was associated with significantly lower levels of Bcl-2 protein expression. Our data demonstrate that the molecular events associated with acquisition of the metastatic phenotype sensitize colon cancer cells to some pro-apoptotic stimuli.

Chemoradiation for adenocarcinoma of the anus.

PURPOSE: To assess the efficacy and limitations of definitive chemoradiation for adenocarcinoma of the anal canal and to propose a treatment strategy that addresses the limitations of treatment. METHODS AND MATERIALS: Between 1976 and 1998, 16 patients with localized adenocarcinoma of the anal canal were treated with radiotherapy with or without chemotherapy with curative intent. Available histologic slides were reviewed for evidence of primary adenocarcinoma of anal duct origin. The treatment results for these patients were compared with those of a group of patients with epidermoid histologic features who were all treated with definitive chemoradiation (55 Gy with concurrent 5-fluorouracil and cisplatin, n = 92) between 1989 and 1998. The hospital records were reviewed for all patients. Patients with epidermoid carcinoma presented with more advanced primary tumors (42% vs. 19% Stage T3 or greater). All adenocarcinoma patients were treated with radiotherapy (median dose 55 Gy): 11 received concurrent 5-fluorouracil-based chemotherapy and 5 received radiotherapy alone. The initial surgical procedures included abdominoperineal resection, excisional biopsies (n = 5), and local excision (n = 1). Abdominoperineal resection was performed as salvage therapy after local recurrence in 5 patients. The Kaplan-Meier method was used to calculate 5-year actuarial pelvic control, distant disease control, disease-free survival, and overall survival. The median follow-up was 45 months (range 5-196) for patients with adenocarcinoma and 44 months (range 9-115) for patients with epidermoid histologic features. RESULTS: Both local and distant recurrence rates were significantly greater in the adenocarcinoma patients. Of 16 patients with adenocarcinoma, 7 (5-year actuarial rate 54%) had recurrence at the primary site compared with 16 (5-year actuarial rate 18%) of 92 patients with epidermoid histologic features (p = 0.004). Distant disease developed in more patients with adenocarcinoma (5-year actuarial rate 66%) than in patients with epidermoid carcinoma (5-year actuarial rate 10%, p <0.001). The 5-year actuarial disease-free survival and overall survival rate for adenocarcinoma patients was 19% and 64%, respectively, compared with 77% (p <0.0001) and 85% (p = 0.017) for those with epidermoid carcinoma. CONCLUSION: Patients with localized adenocarcinoma of the anus treated with definitive chemoradiation had high rates of pelvic failure and distant metastasis compared with comparably staged patients with epidermoid histologic features treated similarly. On the basis of these limitations, we recommend preoperative chemoradiation followed by abdominoperineal resection to maximize pelvic disease control and consideration of adjuvant chemotherapy to address the problem of micrometastatic disease.

Prognostic histologic indicators of curatively resected hepatocellular carcinomas: a multi-institutional analysis of 425 patients with definition of a histologic prognostic index.

Despite growing information on the clinical behavior of hepatocellular carcinoma, the histologic features associated with survival are not well characterized. Clinical and pathologic data on 425 patients who underwent complete resection for hepatocellular carcinoma were reviewed. Six microscopic features, namely, microvascular invasion, nuclear pleomorphism, mitosis, tumor architecture, growth interface, and tumor necrosis, were examined. Independent predictors of survival were identified and combined into a simple prognostic index. By univariate analysis, microvascular invasion, seen in 51.3% of patients (p <0.001), nuclear grade 3, present in 42% of the cases (p <0.001), and mitosis (p <0.008) were significant predictors of poor survival. Hepatocellular carcinoma with a compact growth pattern had a better prognosis as compared with macrotrabecular (p = 0.014) and acinar (p = 0.051) patterns. By multiple regression analysis, only microvascular invasion (p <0.001) and nuclear grade 3 (p = 0.008) were independent predictors of poor survival. The predictive values of microvascular invasion and nuclear grade allowed the construction of a hepatocellular prognostic index (HPI) whereby HPI = (microvascular invasion status x 0.459) + (nuclear grade x 0.287), with microvascular invasion either absent (0) or present (1) and nuclear grade scored as 1, 2, or 3. Using a cut-off of 0.746 (corresponding to at least nuclear grade 2 with microvascular invasion), two groups could be segregated: fair prognosis (HPI < or = 0.746), with a 50% survival of 5.06 years, and poor prognosis (HPI >0.746) with a 50% survival of 2.71 years (p <0.001). HPI was more discriminating than Edmondson grade, with Edmondson II hepatocellular carcinomas dispersed in both fair and poor prognosis groups. Microvascular invasion and nuclear grade 3 emerge as strong prognostic indicators, and their combination provides adequate prognostic stratification. Practically, hepatocellular carcinoma can be stratified in two groups with regard to prognosis: 1) fair prognosis group (nuclear grade 1 with or without microvascular invasion and nuclear grade 2 without microvascular invasion), and 2) poor prognosis (nuclear grade 2 with microvascular invasion and nuclear grade 3 with or without microvascular invasion). The combination of these histologic parameters provides adequate prognostic stratification.

Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head.

PURPOSE: We conducted a phase II trial to assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy (PD) for stage I/II pancreatic adenocarcinoma. PATIENTS AND METHODS: Eligible patients with pancreatic head/uncinate process adenocarcinoma and radiographically defined potentially resectable disease received chemoradiation with 7 weekly intravenous (IV) infusions of gemcitabine (400 mg/m(2) IV over 30 minutes) plus radiation therapy (30 Gy in 10 fractions over 2 weeks). Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and, in the absence of disease progression, were taken to surgery. RESULTS: The study enrolled 86 patients. At the time of restaging, disease progression or a decline in performance status precluded 13 patients from surgery. Seventy-three (85%) of 86 patients were taken to surgery, extrapancreatic disease was found in nine, and 64 (74%) of 86 underwent a successful PD. Median overall survival (86 patients) was 22.7 months with a 27% 5-year survival. Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients (P < .001). The 5-year survival for those who did and did not undergo PD was 36% and 0%, respectively. CONCLUSION: Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets: patients likely to benefit from PD (n = 64) and those in whom surgery would be unlikely to provide clinical benefit (n = 22). Furthermore, the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer.

The significance of neuroendocrine differentiation in adenocarcinoma of the esophagus and esophagogastric junction after preoperative chemoradiation.

BACKGROUND: Esophageal and esophagogastric junction (EGJ) adenocarcinomas frequently have neuroendocrine (NE) differentiation, but the significance of NE differentiation in patients who have undergone preoperative chemoradiation and resection remains unclear. METHODS: The authors evaluated the presence of NE differentiation in esophageal and EGJ adenocarcinomas by immunohistochemistry for chromogranin A and synaptophysin and evaluated the clinical significance of NE differentiation in 83 patients (10 patients who had a complete tumor response and 73 patients who had residual tumor in resection specimens) who received preoperative chemoradiation. RESULTS: Of 73 patients who had residual tumor after preoperative treatment, 52% showed NE differentiation. The proportion of tumor cells with NE differentiation had increased from 6% +/- 18% in pretreatment biopsy specimens to 47% +/- 42% (P = .00003) in posttreatment resection specimens in 30 patients who had paired pretreatment biopsy and resection specimens available. Disease-free survival (P = .002) and overall survival (P = .006) were significantly better in patients who had a complete tumor response than in patients who had residual tumor. Among patients who had residual tumor after preoperative chemoradiation, disease-free survival (P = .03) and overall survival (P = .045) were significantly better in patients who had residual tumor without NE differentiation than in patients who had residual tumor with NE differentiation. In multivariate analysis, the presence of NE differentiation in residual tumor was a prognostic factor for worse disease-free survival (P = .02) independent of pathologic stage and extent of residual tumor. CONCLUSIONS: The results from this study suggested that tumor cells with NE differentiation were more resistant to neoadjuvant chemoradiation in patients with esophageal and EGJ adenocarcinomas. The presence of NE differentiation in residual tumor was associated with poor survival after preoperative neoadjuvant therapy.

Intraductal papillary mucinous neoplasms of the pancreas: effect of invasion and pancreatic margin status on recurrence and survival.

BACKGROUND: The natural history and prognosis for patients with intraductal papillary mucinous neoplasms (IPMN) with and without invasion remain poorly defined. This study evaluated the outcome after pancreatectomy for IPMN according to the pancreatic transection margin status and the presence or absence of invasive carcinoma. METHODS: Data from a prospective pancreatic tumor database and medical records were reviewed for all patients who underwent pancreatic resection for IPMN at our institution between July 1990 and July 2003. Surgical specimens were re-reviewed by a single pathologist. RESULTS: IPMN was diagnosed in 35 (26%) of 137 patients who underwent pancreatic resection for cystic neoplasms. Invasive IPMN was confirmed in 13 (37%) of 35 patients. Noninvasive IPMN was found in 22 (63%) of 35 patients; pathology re-review changed the original diagnosis from invasive to noninvasive IPMN in 6 patients. Noninvasive IPMN was found at the final pancreatic margin in eight patients; none developed recurrent disease at a median follow-up of 34 months. Recurrent disease was identified in 7 (58%) of 13 patients with invasive IPMN and in none with noninvasive IPMN. The median overall survival was 22.9 and 84.9 months in patients with invasive and noninvasive IPMN, respectively (P=.0009). CONCLUSIONS: Distinction between invasive and noninvasive IPMN is essential in estimating prognosis and determining the need for adjuvant therapy and the frequency of follow-up surveillance. Noninvasive IPMN, even if present at the pancreatic margin, was not associated with recurrent disease. In contrast, invasive IPMN was associated with early recurrence and short survival.

Leiomyosarcoma of the esophagus metastatic to the eyelid: a clinicopathologic report.

PURPOSE: To report a case of gastrointestinal sarcoma with leiomyosarcomatous differentiation metastatic to the eyelid. METHODS: Clinical data including a comprehensive ophthalmologic examination, histologic findings, a bone scan, and hospital records were reviewed. RESULTS: A 56-year-old woman with a history of esophageal cancer had a rapidly growing lesion on her right upper eyelid that was initially treated as a chalazion. A biopsy specimen of the lesion was consistent with a gastrointestinal sarcoma with leiomyosarcomatous differentiation. The esophageal tumor was reclassified after histopathologic evaluation of the eyelid specimen. Bony metastasis developed soon after excision of the eyelid lesion. The patient died 3 months after proper diagnosis of the eyelid lesion. CONCLUSIONS: This is a rare case of a metastatic leiomyosarcoma of the eyelid. To our knowledge, only two other cases of eyelid leiomyosarcoma have been described in the literature. The importance of correct histopathologic diagnosis of eyelid lesions is underscored in this case report.

Detection of small pancreatic tumors with multiphasic helical CT.

OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of helical CT in the detection of adenocarcinomas of the pancreas measuring 2 cm or smaller at pathologic examination. MATERIALS AND METHODS: Thin-section triple phase (20, 40, and 70 sec after the start of injection) contrast-enhanced helical CT scans of the abdomen in 18 patients with a pancreatic carcinoma that was 2 cm or smaller and 18 patients with a normal pancreas were retrospectively reviewed by two senior radiologists who specialized in oncologic abdominal imaging. Discrepancies were resolved by consensus. The observers were unaware of the clinical information. CT scans were evaluated for the presence of a pancreatic mass, bile, and pancreatic duct stricture. The location and size of tumors as determined on CT were compared with pathologic findings. The CT results were also compared with the prospective CT interpretations derived from the radiology reports and with the endoscopic sonographic reports when available. RESULTS: The sensitivity of thin-section triple-phase helical CT in the detection of small pancreatic masses was 77%, and the specificity was 100% for the two experienced observers. The sensitivity and specificity were 72% and 100%, respectively, for the prospective interpretations done by 10 observers. There was no correlation between the tumor size at pathology and the CT measurements. CONCLUSION: Thin-section contrast-enhanced helical CT is sensitive and highly specific for the detection of pancreatic tumors measuring 2 cm or smaller. Improvement in the detection rate of this technique compared with previous techniques lies in the optimization of parenchymal enhancement during the pancreatic phase and the decrease in slice thickness.

Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation.

In this study, we evaluated the influence of nonmyeloablative and ablative conditioning regimens on the occurrence of acute and chronic graft-versus-host disease (GVHD). One hundred thirty-seven patients undergoing matched-related sibling transplantations received the same GVHD prophylaxis. Myeloablative regimens included intravenous busulfan/cyclophosphamide (n=45) and fludarabine/melphalan (n=29). Patients in the nonmyeloablative group (n=63) received fludarabine/idarubicin/cytarabine, cisplatin/fludarabine/idarubicin, and fludarabine/cyclophosphamide. The actuarial rate of grade II to IV acute GVHD was significantly higher (hazard ratio, 3.6; 95% confidence interval, 1.5-8.8) in patients receiving ablative regimens (36%) compared with the nonmyeloablative group (12%). The cumulative incidence of chronic GVHD was higher in the ablative group (40%) compared with the nonmyeloablative group (14%). The rates were comparable within the first 200 days and were significantly higher in the ablative group beyond day 200 (hazard ratio, 5.2; 95% confidence interval, 1.2-23.2). Nonrelapse and GVHD-related mortality were relatively low in both groups. The use of the described nonmyeloablative preparative regimens was associated with a reduced incidence of grade II to IV acute GVHD and chronic GVHD compared with the busulfan/cyclophosphamide and fludarabine/melphalan transplant regimens. It is interesting to note that nonrelapse mortality with nonmyeloablative regimens in older and more debilitated patients was low (14%) and comparable to that achieved with standard high-dose regimens in younger patients.

A prospective evaluation of radiocolloid and immunohistochemical staining in colon carcinoma lymphatic mapping.

BACKGROUND: Although the utility of lymphatic mapping (LM) and sentinel lymph node (SLN) biopsy in patients with melanoma and breast carcinoma has been well documented, this same is not true for patients with colon carcinoma. The authors previously reported a high false-negative rate for SLN biopsy in patients with colon carcinoma using isosulfan blue dye alone. The objective of the current study was to determine whether radiocolloid would increase the sensitivity of LM/SLN biopsy in patients with colon carcinoma. METHODS: The authors performed LM on 57 patients with colon carcinoma using both isosulfan blue dye and radiocolloid. The SLN(s) were identified by either their blue color or by increased radioactivity. The SLNs then underwent both routine histologic sectioning and immunohistochemical (IHC) staining for cytokeratins. RESULTS: An SLN was identified in 56 patients (98%). Radiocolloid was able to identify only 1 additional positive SLN (9%). Overall, it was found that the disease had metastasized to the lymph nodes in 22 patients, even though there was no evidence of disease in the SLN(s) in 11 of those 22 patients on routine histologic sectioning (false-negative rate, 50%; sensitivity, 50%). In five patients, IHC of the SLN was the only indicator of metastatic disease. The inclusion of IHC-positive SLNs in these calculations would decrease the false-negative rate to 17% and would increase the sensitivity of SLN biopsy to 83%. CONCLUSIONS: In the current study, the addition of radiocolloid did not increase the sensitivity of detection of positive SLN(s) compared with the use of isosulfan blue dye alone. IHC of the SLN potentially may increase the sensitivity of LM and reduce the false-negative rate. However, the long-term prognostic significance of IHC in patients with colon carcinoma remains controversial.