Mucin expression profile in Barrett's, dysplasia, adenocarcinoma sequence in the esophagus.

BACKGROUND: The molecular events that accompany the progression to adenocarcinoma (ADC) of the esophagus are poorly understood. Aberrant mucin receptor expression can contribute to increased cell growth and metastatic ability. AIM: The aim of this study was to establish a pattern for mucin (MUC) gene expression in the esophageal mucosa under normal and pathological conditions. SETTING: University Hospital Cancer Center Laboratory. Archived tissue samples studied in a retrospective fashion. MATERIALS AND METHODS: Tissue samples were obtained from the archives of patients with histological evidence of Barrett's esophagus (BE) progressing to ADC. Immunohistochemical analysis was performed using mouse monoclonal antibodies for MUC1, MUC2, MUC5AC, MUC6. Semiquantitative scoring of histological staining was performed using a linear scoring system: 0-staining absent; 1-staining in 0-25%; 2-staining in 25-50%; and 3-staining in 50-75% of the epithelium. The Binomial test was used to explore trends and differences in frequency of mucin expression along the pathological sequence. RESULTS: Only mild superficial staining of MUC1 was seen in normal squamous epithelium. MUC1 and MUC2 were uniformly expressed in all samples (7/7) of BE and dysplasia (P=0.008). MUC1 expression was upregulated (7/7) in progression to adenocarcinoma (P=0.008). The secretory mucins, MUC5AC and MUC6 showed a decrease in expression with progression from BE to dysplasia to ADC (P< 0.05). CONCLUSIONS: Downregulation of MUC5AC and MUC6 decreases mucosal protection against gastric acid. Increasing MUC1 expression is associated with progression from dysplasia to ADC. Upregulation of MUC2 reflects intestinal metaplasia in BE.

Phase I study of N-(phosphonacetyl)-L-aspartate with fluorouracil and with or without dipyridamole in patients with advanced cancer.

We conducted a combined biochemical modulation trial of N-(phosphonacetyl)-L-aspartate (PALA), dipyridamole (DP), and fluorouracil (5-FU) in patients with cancer. Eighty-eight patients with advanced cancer were entered into this Phase I trial. During the first part of the study, four doses of PALA (125, 250, 500, and 1000 mg/m2, administered on day 1) were evaluated to determine the PALA dose with maximal suppression of aspartate transcarbamylase (ATCase) activity that was clinically tolerable. Patients were randomized to receive DP (or no DP), 50 mg/m2, p.o. every 6 h on days 1-6, and all patients received 5-FU, 400 mg/m2, by bolus administration on days 2-5. Prior to and during therapy, WBCs were collected and assayed for ATCase activity. After the maximally tolerated PALA dose with 400 mg/m2 5-FU +/- 50 mg/m2 DP was defined, the 5-FU dose was escalated using the same administration schedule of 5-FU, PALA, and DP. The dose of 5-FU was escalated by 25% in each of the DP cohorts until dose-limiting toxicity was reached. ATCase activity was inhibited in a dose-dependent manner with PALA doses of 125, 250, 500, and 1000 mg/m2, resulting in 0, 13, 17, and 49% inhibition of ATCase activity. Only at the higher PALA doses (i.e., 500 and 1000 mg/m2) was ATCase activity suppressed during days 2-5, but the activity returned to pretreatment levels by day 15. Based on the clinical tolerance and significant suppression of ATCase activity, a PALA dose of 500 mg/m2 was selected for the 5-FU dose escalation phase. At a 5-FU dose of 625 mg/m2, dose-limiting toxicity (leukopenia, stomatitis, and diarrhea) occurred in both DP cohorts. We recommend that for this monthly treatment schedule, 500 mg/m2 PALA and 500 mg/m2 5-FU, with or without 50 mg/m2 DP, be used in subsequent Phase II trials.

Solar considerations in the development of cutaneous melanoma.

On the basis of these considerations, the possible action spectrum for melanoma can be narrowed considerably, but not confined to any one solar emission band. The physical factors discussed eliminate all but UV, visible, and NIR radiation as possible solar agents. Ionizing radiation fits neither the epidemiologic data nor first-order physical considerations. Wavelengths longer than the NIR wavelengths, although they could conceivably account for the occurrence of melanoma under clothed parts of the body, carry so little energy that they are probably unimportant. Epidemiologic evidence regarding the effects of skin pigment favors UV or visible radiation. A distinction between these two components is not obvious; UV-C and UV-B photons carry greater energy and are more likely to induce biochemical cutaneous effects, but the total flux in the UV-A and visible radiations is far greater. That UV-B radiation may play a role in melanoma is supported; at the same time, one cannot exclude the possibility that the action spectrum for melanoma is, instead, the UV-A, the visible, or even the NIR portion of the sunlight spectrum. The strong differential effect of altitude on the transmission of light of different wavelengths might serve as an important discriminating variable. If solar UV radiation is implicated in the development of melanoma, then altitude should emerge as a significant factor in epidemiologic studies. If visible or IR radiation is the active agent, then differences on the basis of altitude should be small or negligible. Intrinsic solar variations that follow the annual sunspot number appear inadequate in either the UV or the visible band to account directly for the apparent 11-year modulation of melanoma incidence found in some registries. Secondary atmospheric effects brought about by the action of solar UV changes on the ozone layer may be adequate to explain a weak 11-year modulation in melanoma incidence, although continuous measurements of UV-B flux made at sites in the United States through a full solar cycle have shown no such effect. Nor do these early measurements reveal the long-term increase in UV-B intensity expected from the destruction of stratospheric ozone by industrial pollutants over the last 10 years.

Detection of colorectal cancer K-ras mutations using a simplified oligonucleotide ligation assay.

It has been suggested that some mutations in codons 12 and 13 of the K-ras gene are associated with the progression of colorectal adenomas to carcinomas. The aim of this study was to develop a rapid, colorimetric assay for K-ras point mutations commonly associated with colorectal cancer. K-ras exon 1 was amplified from colorectal tumor DNA and K-ras activating mutations detected using an oligonucleotide ligation assay (OLA) in combination with immunological and colorimetric detection. Using the OLA with oligonucleotides specific to individual K-ras mutations, 6 (of 17 total colorectal adenomas/carcinomas) were found to have K-ras mutations. The assay could detect as little as 10% mutant allele. A simplified OLA designed to test for either the presence (+) or absence (-) of any of the K-ras activating mutations was developed. The assay was further streamlined by use of a dipstick methodology for colorimetric development. If required, assay sensitivity can be increased by the use of the recently described EDNA-ELCA detection system. The simplified (+/-) mutation OLA in combination with a dipstick or EDNA-ELCA detection system provides a rapid, sensitive assay for K-ras point mutations suitable for use as part of the clinical assessment of colorectal cancer.

Minimal-access surgery for staging of malignant melanoma.

OBJECTIVE: To develop a simple, minimally invasive technique of determining whether regional node metastasis has occurred in patients with melanoma. SETTING: Teaching hospital tertiary care and private practice settings. PATIENTS: Between February 1993 and October 1994, 121 patients with invasive malignant melanoma and clinically negative lymph nodes were enrolled in this clinical trial. DESIGN: Consecutive sample clinical trial. Within 24 hours prior to lymph node resection, a radioactive tracer was injected into the dermis around the site of the primary melanoma. Forty-four patients also had blue dye injected immediately prior to surgical resection. Measurement of radioactivity in the lymph nodes and surgical localization were made using a handheld gamma detector. Radiolabeled nodes were selectively removed with the least dissection possible. In patients with pathologically positive radiolabeled nodes, regional lymphadenectomy was performed. OUTCOME MEASURES: Successful identification of radiolabeled sentinel lymph nodes, correlation of radiolabeling with injection of blue dye, and regional node recurrence rate. RESULTS: Surgeons successfully resected the radiolabeled sentinel lymph nodes in 118 (98%) of 121 patients. One hundred percent of blue-stained lymph nodes were successfully radiolabeled. Fifteen patients had pathologically positive sentinel lymph nodes. In 10 patients, the sentinel node was the only node with metastasis. Two systemic and one regional node recurrences occurred during a mean follow-up of 220 days. CONCLUSIONS: Selective gamma probe-guided resection of the radiolabeled sentinel lymph node is possible in over 95% of patients with melanoma. This technique offers a simple and reliable method of staging of regional lymph nodes in these patients without performing a regional lymphadenectomy.

Peritoneal carcinomatosis with urachal signet-cell adenocarcinoma.

Urachal adenocarcinoma is an uncommon clinicopathologic entity associated with a dismal prognosis. We report a case of peritoneal carcinomatosis from urachal adenocarcinoma (signet cell type) treated with cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC). Prior to treatment, disease had progressed with systemic chemotherapy. The patient remained free of symptomatic peritoneal disease or local recurrence but eventually died 23 months after IPHC and 31 months after diagnosis due to widespread bone metastases.

Invasive cutaneous melanoma in elderly patients.

Clinical and pathologic variables were compared between "older" (greater than or equal to 70 years) and "younger" (30 to 39 years) patients with primary invasive cutaneous melanoma. Older patients had more nodular melanomas and acral lentiginous melanomas (58%); superficial spreading melanomas predominated in younger patients (74%). Mean tumor thickness was greater in the older patients (3.95 vs 2.02 mm). Invasive levels 2 and 3 occurred more often in younger patients (41.1% vs 13%); level 5 occurred more often in older patients (30.4% vs 5.3%). Microscopic ulceration occurred more often in older (46.4%) than in younger patients (19.4%). Older patients classified as clinical stage I at presentation or with primary lesions 1.50- to 3.00-mm thick had poorer survival. Younger women survived longer than younger men; this was not true of older patients. The elderly patients with cutaneous melanoma were more likely to have poor prognostic features and thus more likely to die from melanoma than the younger patients.

Complications of heated intraperitioneal chemotherapy and strategies for prevention.

Heated intraperitoneal chemotherapy is a potentially useful strategy for therapy of peritoneal carcinomatosis in adult patients, and we have found it to be associated with an acceptable complication rate. Careful perioperative management is critical, and we have presented our current experience guidelines for management and overview of complications.

Quality of life after intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal carcinomatosis.

AIMS: This study assessed the functional status and quality of life (QOL) of patients with disseminated peritoneal cancer (DPC) before and after cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (IPHC). METHODS: Patients with confirmed or suspected diagnosis of gastro-intestinal cancer including stomach, pancreas, hepatobiliary and colorectal cancer with peritoneal implants were enrolled in the study. Sixty-four patients completed the Functional Assessment of Cancer Therapy-Colon (FACT-C) scale and several other instruments at baseline. Forty-eight, 40, 39 and 31 patients were assessed at approximately 2 weeks post-surgery, and 3, 6 and 12 months respectively. RESULTS: There was a significant overall effect on the physical (P=0.0025), emotional (P<0.0001) and functional well-being (P=0.0044) subscales and the FACT-C (P=0.0076). Physical and functional well-being scores decreased at post-surgery follow-up and increased relative to baseline at 3, 6 and 12 months. Nineteen per cent, 46%, 59% and 74% of patients resumed greater than 50% of their normal activities post-operatively at 3, 6 and 12 months respectively. A percentage of patients reported depressive symptoms: baseline (28%), post-operatively (33%), 3 months (23%), 6 months (21%) and 12 months (29%). CONCLUSIONS: Cytoreductive surgery followed by IPHC was well tolerated. Most patients returned to baseline or better levels of functioning within 3 months post-treatment.

Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study.

Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.

Localization of regional lymph nodes in melanomas of the head and neck.

OBJECTIVES: To study the efficacy of gamma-probe radiolocalization of the first draining (sentinel) lymph node (SLN) in stage N0 melanoma of the head and neck and to evaluate its potential role in the staging and treatment of this disease. DESIGN: Gamma-probe radiolocalization, a new alternative to blue-dye lymphatic mapping, uses a scintillation (gamma) probe to identify radiolabeled SLNs. In a consecutive sample clinical trial, gamma-probe radiolocalization of the SLN is compared with lymphoscintigraphy and blue-dye lymphatic mapping. Follow-ups ranged from 1.7 years to 4 years, with a mean follow-up of 2.5 years. SETTING: Tertiary and private care teaching hospital. PATIENTS: Between June 1993 and November 1995, 23 patients with stage N0 intermediate-thickness melanoma of the head and neck were enrolled in this volunteer sample. INTERVENTIONS: Twenty-four hours prior to surgery, a radioactive tracer was intradermally injected around the circumference of a primary melanoma. Twelve patients also had blue dye injected just prior to surgical resection. Using a handheld gamma probe, radiolabeled lymph nodes were identified and selectively removed with minimal dissection. In patients with nodes with histologic evidence of metastases, a regional lymphadenectomy was performed. MAIN OUTCOME MEASURES: The successful identification of radiolabeled SLNs, the correlation of SLN radiolabeling to lymphoscintigraphy and blue-dye mapping, and the long-term development of regional metastases. RESULTS: Surgeons successfully resected the radiolabeled SLNs in 22 (96%) of 23 patients. The success rate of blue-dye lymphatic mapping was 8 (75%) of 12 patients and lymphoscintigraphy was 20 (91%) of 22 patients. One hundred percent of blue-stained lymph nodes were radiolabeled. The one patient in whom no SLN could be identified developed regional disease at 17 months. CONCLUSIONS: Gamma-probe radiolocalization and resection of the radiolabeled SLN is a simple and reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.

Sentinel lymphadenectomy in the management of primary cutaneous malignant melanoma. An update.

The management of lymph nodes in melanoma patients who have no clinical evidence of nodal disease has changed dramatically with the development of selective lymph node biopsy. This procedure localizes the node in a regional basin most likely to contain a metastasis (the sentinel node) and averts the morbidity of unnecessary elective node dissection. This update reviews the rationale for this procedure and describes the methodology used by the surgeon and the pathologist. A progress report highlights the promise and limitation of this procedure. Sentinel node biopsy is currently the standard for staging select groups of melanoma patients, but the field is rapidly evolving and may eventually be surpassed by even newer molecular diagnostic techniques.

Metastatic head and neck cancer to the percutaneous endoscopic gastrostomy exit site: a case report and review of the literature.

Percutaneous endoscopic gastrostomy (PEG) is a relatively safe procedure and is an important supportive treatment adjunct for patients with head and neck cancer. We report a case in which squamous cell carcinoma of the larynx implanted at a PEG exit site. This was resected for cure. In this case, and in five others reviewed in the literature, the PEG placement method was the "pull" technique. It is unknown whether other methods of PEG placement may reduce metastatic implants at the PEG exit site, but the possibility of this complication must be considered.

Hemangiopericytoma: an unusual cause of upper gastrointestinal hemorrhage.

Hemangiopericytomas, first described in 1942, are rare, highly vascular neoplasms that arise from capillary pericytes. They are seen most commonly as a painless mass arising from the lower extremity but can also originate in the pelvic retroperitoneum and on the head, neck, chest, and abdomen. An unusual case is reported here of a patient presenting with recurrent massive upper gastrointestinal (GI) bleeding in whom a large hemangiopericytoma was found arising in the perisplenic soft tissues. Precedence exists in the literature for the association of hemangiopericytoma with GI bleeding. In prior reports, however, a mural origin of the tumor and subsequent bleeding into the GI lumen was demonstrated. In the case presented here, marked dilatation of the gastric and splenic vessels was noted, but there was no direct pathologic involvement of the stomach wall. It is proposed that superficial gastric erosions combined with the tumor-associated increased vascularity within the stomach wall led to recurrent major bleeding. Diagnosis of these tumors roentgenographically is nonspecific, but angiography is helpful. Morphological characteristics allow accurate histopathological diagnosis and provide prognostic information. The treatment of choice remains wide surgical excision, with the addition of radiation or chemotherapy in selected cases.

Prospective evaluation of selective lymph node biopsy for cutaneous malignant melanoma.

Some patients presenting with cutaneous malignant melanoma without palpable adenopathy have regional metastatic disease. We have applied the technique of gamma probe-directed selective lymph node biopsy and used the results to direct further therapy. The results of a prospective nonrandomized clinical study are presented. Between November 1993 and December 1996, 63 patients with a diagnosis of primary cutaneous malignant melanoma underwent lymphoscintigraphy with technetium sulfur colloid followed by gamma probe-guided lymph node biopsy. There were 32 (51%) women and 31 (49%) men with a mean age of 51.1 years (median, 50; range, 13-87). Mean Breslow thickness was 2.13 mm (range, 0.5-15.0 mm; median, 1.56 mm). Primary locations were head and neck in 8 (13%), trunk in 24 (38%), upper extremity in 13 (21%), and lower extremity in 18 (29%). Selective lymph node biopsy was done on an outpatient basis with local anesthesia in 49 cases (78%) and in the operating room with general anesthetic in 14 patients (22%). One lymph node site was biopsied in 46 patients (73%), two sites in 16 (25%), and three in 1 (2%), for a total of 81 selective lymph node biopsy sites, mean 1.29 per patient. The mean number of labeled lymph nodes removed per site per patient was 1.64 (range, 1-5). Seroma or infection occurred in 6 patients (10%). Micrometastatic disease was identified in nine selective lymph node biopsy sites in eight patients. Of eight patients undergoing lymph node dissection, 5 (63%) had no additional pathological lymph node involvement. With a mean follow-up of 579 days from selective lymph node biopsy (median, 594; range, 36-1157), 59 (94%) have no evidence of disease. Three patients have died, 2 with systemic disease (475 and 1149 days) and 1 from a myocardial infarction (380 days). No patient has failed with regional-only recurrence. Gamma probe-directed selective lymph node biopsy is a straightforward procedure that can be done in the outpatient setting and facilitates management of patients with cutaneous malignant melanoma.

Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of gastrointestinal origin.

No standard effective treatment exists for peritoneal carcinomatosis of gastrointestinal origin. The pharmacokinetic advantage of intraperitoneal chemotherapy and the synergy of heat and certain anticancer agents have prompted researchers to investigate intraperitoneal hyperthermic chemotherapy in treating disseminated peritoneal cancers. We have conducted a large Phase II trial to determine the safety and efficacy of aggressive cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC) in treating peritoneal carcinomatosis of gastrointestinal origin. Patients with disseminated peritoneal carcinomatosis of gastrointestinal origin with or without malignant ascites were eligible. After aggressive surgical debulking, patients were administered a 2-hour heated (40.5 degrees C) intraperitoneal perfusion with mitomycin C. The major response variable monitored was overall survival. Patients were assessed for toxicity after IPHC administration using the National Cancer Institute Common Toxicity Criteria. Eighty-four patients with peritoneal carcinomatosis of gastrointestinal origin were evaluated for survival and toxicity (colon, n = 38; appendix, n = 22; stomach, n = 19; other gastrointestinal, n = 5). Thirty-nine (46%) patients had malignant ascites at the time of therapy. The operative mortality (30-day) was 6 per cent. Hematologic toxicity was the most common toxicity but was of mild to moderate severity (7 and 4% of patients had grade 3/4 white blood cell or platelet toxicity, respectively). The overall median survival was 14.3 months. The median survival of patients with peritoneal carcinomatosis of appendiceal, colorectal, and gastric origins were 31.1+, 14.6, and 10.1 months, respectively. Significant differences in median survival were seen in patients without and with malignant ascites (27.7 vs 7.6 months; P = 0.0004) and R0/R1 (complete gross tumor resection) versus R2 (gross residual tumor) surgical resection status (28.5+ vs 10.8 months, P = 0.0002). These data suggest that aggressive cytoreductive surgery with IPHC using mitomycin C is safe and effective in treating peritoneal carcinomatosis of gastrointestinal origin. Additional studies and broader applications of this treatment are encouraged.

Sentinel lymph node mapping for carcinoma of the colon: a pilot study.

Sentinel lymph node (SLN) mapping has evolved into the standard of care for melanoma and may replace routine node dissection in the treatment of breast cancer. There are few data evaluating sentinel node mapping in patients with cancer of the colon. This trial represents our initial experience with SLN mapping for carcinoma of the colon. SLN mapping was performed in 22 patients most of whom had biopsy-proven adenocarcinoma of the colon. One milliliter of isosulfan blue was injected with a 25-gauge needle into the subserosa at four sites around the edge of the palpable tumor. The SLN was identified visually and excised. A standard lymphadenectomy was then performed. The SLN was analyzed with standard hematoxylin and eosin evaluation. Immunohistochemical techniques for carcinoembryonic antigen and cytokeratin (Imm) were performed if the H&E was negative. The mapping added approximately 5 minutes to the total operative time and no adverse reactions to the dye occurred. A SLN was identified in 20 of 22 cases. In cases with negative lymph nodes the SLN was predictive of all the regional nodes by both H&E and Imm (14 of 14). In patients with positive lymph nodes the SLN was predictive in all cases (six of six). In one case the only node with disease was the SLN, and in this case the diease was identified by only Imm; thus this patient was upstaged. SLN mapping is feasible and safe and can readily be performed in patients with colonic cancer. In conjunction with SLN mapping, Imm techniques may upstage a subset of patients likely to be at increased risk for metastatic disease. Consequently SLN mapping of colon cancer should be evaluated in large prospective trials.

Treatment and prevention of malignant ascites associated with disseminated intraperitoneal malignancies by aggressive combined-modality therapy.

No satisfactory treatment exists to treat or prevent malignant ascites secondary to nonovarian intraperitoneal (IP) disseminated malignancies. A Phase I/II clinical trial combining radical cytoreductive surgery (CS) and IP hyperthermic chemotherapy (IPHC) with mitomycin C is presented. Between December 9, 1992 and July 31, 1995, 39 patients (pts) were explored for IP cancer. Five pts with known liver metastases were excluded, leaving 34 pts (15 female, 19 male) of median age 53 (range, 17-76). The majority of pts had disseminated IP cancers of gastrointestinal origin (80%). Prior therapy included the following: chemotherapy, 20 pts (59%); surgery, 29 pts (85%); and radiation, 2 pts (6%). Following CS, IPHC with mitomycin C was done. At surgery, 12 pts (35.3%) had frank ascites, and 12 pts (35.3%) had positive IP cytology without ascites. The median hospital stay was 9 days (range, 5-65) with no 30-day mortality. Complications for 36 treatments included: thrombocytopenia Eastern Cooperative Oncology Group grade 3 or 4, two cases (5.6%); neutropenia requiring granulocyte colony-stimulating factor, seven cases (19.4%); sepsis, four cases (11.1%); bowel leak, two cases (5.6%); and serous wound leak, two cases (5.6%). Ascites correlated with worse resection status (P = 0.025). Ascites was controlled in 9 of 12 (75.0%) pts, with failures at 1, 4, and 14 months (median follow-up, 7.5 months). No cytology-positive ascites-negative pts developed clinical ascites (median follow-up, 9.4 months). The median survival time in pts with ascites was 10.1 months versus 32.7 for patients without ascites (P = 0.013). For the entire study population, the 1- and 2-year survival rates were 74.6 and 48.5 per cent, respectively (median follow-up, 18.2 months). In this study, malignant ascites was controlled in 75 per cent of cases and prevented in all pts with positive IP cytology. CS plus IPHC appears to be relatively well tolerated and may be effective for the treatment and prevention of malignant ascites.

Prospective trial for the treatment of malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare and often rapidly fatal disease with median survival of 5 to 12 months for untreated cases and 16 months reported after multimodality treatment. We report a prospective clinical treatment study using cytoreductive surgery combined with intraoperative intraperitoneal heated chemotherapy (IPHC) perfusion using mitomycin C for MPM. Twelve patients (11 male with a mean age 51 years) were treated. Seven patients presented with bulky disease and seven with ascites. All underwent exploratory laparotomy with histologically confirmed diagnosis of MPM. Surgical debulking as feasible was performed. Complete gross tumor removal was possible in only one patient. Cytoreduction was followed by a 2-hour closed low-volume IPHC using mitomycin C. One patient died 50 days postoperatively from complications relating to small bowel perforation. Hematologic toxicity of the procedure was minimal. Ascites was controlled in all patients and permanently in 86 per cent of patients presenting with ascites. To date median survival is 34.2 months with median follow-up of 45.2 months. One patient was re-explored for ventral hernia 2 years post-IPHC, had negative peritoneal biopsies, and remains disease-free at 5 years. Given the dismal prognosis associated with MPM the results of treatment with cytoreductive surgery combined with IPHC perfusion are encouraging. The rarity of MPM makes appropriately powered prospective randomized trials unlikely. Therefore, we now offer this approach off protocol; however, further study of this combined modality therapy is warranted.

Virchow's node revisited. Analysis with clinicopathologic correlation of 152 fine-needle aspiration biopsies of supraclavicular lymph nodes.

OBJECTIVE: The left supraclavicular lymph node (Virchow's node) may be involved by metastatic malignancies, including those of abdominal or pelvic origin. Almost all previous studies have been based on examination of surgically sampled tissue or postmortem examination. To our knowledge, there has not been a study for nearly 40 years addressing the metastatic pattern to the left supraclavicular lymph node. Furthermore, there has been no study comparing left with right supraclavicular lymph node metastasis or the utilization of fine-needle aspiration biopsy to samples these sites. DESIGN: A retrospective review of 152 fine-needle aspiration biopsies of supraclavicular lymph nodes was performed, and the neoplasms were grouped into six diagnostic categories from five primary regions. RESULTS: The patients ranged in age from 2 years to 94 years (average, 55 years) and consisted of 66 males and 83 females. Three patients were biopsied twice. Of the 152 fine-needle aspirations, 87 (57.2%) were of the left supraclavicular lymph node and 65 (42.8%) of the right supraclavicular lymph node. Of the 96 biopsies positive for malignancy, 58 (60.4%) were biopsies of the left and 38 (39.6%) were of the right supraclavicular lymph nodes. Sixteen of 19 pelvic tumors and all six primary abdominal malignancies metastasized to the left supraclavicular lymph node. Thorax, breast, and head and neck malignancies showed no differences in metastatic patterns to the right and left supraclavicular lymph nodes. Ten patients (10.4% of positive nodes) had a diagnosis of non-Hodgkin's lymphoma, leukemia, or Hodgkin's disease. Six patients (7.1% of positive nodes) had a metastasis of unknown primary site, and 19 cases (19.8%) had acute or chronic inflammation; seven of the latter cases demonstrated acid-fast bacilli in the aspirated smears. CONCLUSIONS: Fine-needle aspiration biopsy is an excellent initial procedure in the workup of an enlarged supraclavicular lymph node. Our study confirmed that malignancies originating in the pelvis or abdomen were significantly more likely to metastasize to the left supraclavicular lymph node and that the primary site and types of malignancies that involved the left supraclavicular lymph node were different from those involving the right supraclavicular lymph node.