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Biomedical subjects

M W Arnold

Publications and source records attributed to M W Arnold.

At least 19 recordsLinked to original sources
PubMed1996

Intraoperative detection of occult colon cancer micrometastases using 125 I-radiolabled monoclonal antibody CC49.

BACKGROUND: The detection of locally-disseminated disease is one of the principal goals of oncologic surgery. For this study, a hand-held, gamma-detecting probe was used intraoperatively to assess the extent of colorectal carcinoma in patients previously injected with radiolabeled antibody to the TAG-72 antigen (CC49); this technique is known as Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH). RIGS-positive areas (i.e. those with increased signal over background) have previously been shown to contain carcinoma in a high proportion of cases. However, some RIGS-positive areas had no tumor detectable by clinical examination or routine histopathologic analysis. This study was undertaken to determine if the presence of occult metastases might account for this disparity. METHODS: A total of 57 regional lymph nodes (LN), resected from 16 patients with primary (9) or recurrent (7) colorectal carcinoma, were studied. The patients were injected with 125I labeled CC49 murine monoclonal antibody approximately 3 weeks prior to surgery. After routine histologic evaluation, the LN were analyzed for occult metastases; paraffin sections were cut at 5 levels (50 micron apart) and were examined by histology (hematoxylin and eosin stain [H & E]) and by immunohistochemistry (IHC) with a cocktail of monoclonal antibodies to cytokeratins. RESULTS: Fifty-seven LN were included in this study; 17 were H & E-positive (i.e., contained tumor by routine histologic examination [overt tumor]), while 40 LN were H & E-negative (i.e., no evidence of tumor after routine histologic examination). Thirty-nine LN were RIGS-positive, but only 14 of these were H & E-positive. Of the 25 RIGS-positive/H & E-negative LN, 10 (40%) demonstrated the presence of occult metastases after serial section/IHC analysis. Thus, a total of 27 LN contained metastatic carcinoma (17 overt, 10 occult); routine histologic analysis was able to identify tumor in only 17 of these 27 LN (63%), while the probe signaled the presence of tumor in 24 of these LN (89%). None of the RIGS-negative/H & E-negative LN were found to have occult metastases (0/15). Specific immunoreactivity with CC49 antibody was observed in 5 of 15 RIGS-positive/H & E-negative LN in which no tumor could be identified by any method (histopathology or IHC. CC49 immunoreactivity was not observed in 15 RIGS-negative/H & E-negative LN. CONCLUSIONS: The finding of a RIGS-positive LN had a significant association with the presence of tumor cells (P < 0.05). In this study, the RIGS procedure was more sensitive than clinical or histopathologic examination in detecting the regional spread of a tumor. Furthermore, in LN that showed no evidence of tumor by routine histopathologic examination, a positive RIGS reading was significantly associated with the presence of occult LN metastases (P < 0.01). This study is the first to demonstrate the detection of histologically occult tumor by a remote imaging device. RIGS assessment is a highly sensitive method for detecting occult tumor deposits, and may guide therapeutic intervention in patients with colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed1996

Peritoneal carcinomatosis and radioimmunoguided surgery.

The Radioimmunoguided Surgery (RIGS) system was developed, in part, to detect occult tumor in patients with recurrent colorectal cancer. Unfortunately, however, patients are sometimes found to have unresectable peritoneal metastasis. For these patients, intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) was used as a novel treatment method. Thirty-six intraperitoneal hyperthermic perfusions with MMC were given over the course of several studies. A preliminary study delineated two groups as possible candidates for this treatment: patients with pseudomyxoma peritonei and patients with peritoneal metastasis < 0.5 cm. Intraperitoneal hyperthermic perfusion (IPHP) was conducted for 1 hour after achieving an abdominal temperature of 41 degrees C. A dose of 30 mg MMC in 31 Plasmalyte was injected followed by a second 30 mg dose given at 30 minutes. Plasma pharmacokinetics of IPHP with MMC indicate an advantage in the range of 100-fold enhancement of exposure compared with delivery in plasma. The method was found to be safe when flow was observed and dosage decisions were made during perfusion according to flow. A clinical study group consisting of 15 patients underwent cytoreductive surgery followed by IPHP. The majority of them had either gastrointestinal or urologic anastomoses. There were no complications. In every patient the CEA level decreased after surgery and IPHP, with a median response of 6 months. RIGS technology aided in the selection of IPHP as a treatment choice by demonstrating the presence of an occult tumor burden in those patients whose traditional explorations were deceiving. This chapter includes technical details and suggestions for improving and modifying the use of IPHP.

Antibiotics, Antineoplastic↗
PubMed1996

Intra-abdominal patterns of disease dissemination in colorectal cancer identified using radioimmunoguided surgery.

PURPOSE: Patterns of metastatic spread are difficult to determine with routine postoperative follow-up. This study was undertaken to evaluate two selected populations of colorectal cancer patients injected and screened with anti-tumor antibody. METHODS: Eighty-six evaluable patients with colorectal cancer underwent exploratory laparotomy with both traditional surgical exploration and radioimmunoguided surgery (RIGS) following injection of 125I-labeled CC49 monoclonal antibody. RIGS-positive tissue detectable with a handheld gamma-detecting probe was defined as tissue involved with the disease process. Comparisons were made between extent of disease using traditional exploration and extent using RIGS. RESULTS: In 41 patients with primary disease, traditional exploration detected 45 sites of disease (1.1 sites/patient) compared with 153 RIGS-positive sites (3.7 sites/patient). In 45 patients with recurrent disease, traditional exploration found 116 sites (2.6 sites/patient) vs. 184 RIGS-positive sites (4.1 sites/patient). Involvement by selected anatomic sites is shown below [Table: see text]. CONCLUSION: RIGS detected more tissue involved in disease process for all sites in both primary and recurrent disease except liver metastases. Areas with highest proportion of RIGS-positive tissue, the gastrohepatic ligament and celiac nodes, are rarely resected and are not pathologically examined. Positive RIGS localization of tumor antigen in these areas suggests more extensive dissemination of disease process.

Abdominal Neoplasms↗
PubMed1996

Radioimmunoguided surgery for colorectal cancer.

BACKGROUND: Operations for patients with colorectal cancer are based on traditions established by historical experience. Radioimmunoguided surgery (RIGS) provides new information that challenges these traditions. METHODS: Thirty-two patients with primary colorectal cancer underwent RIGS after being injected with anti-TAG-72 murine monoclonal antibody CC49 labeled with iodine-125. Sixteen of the patients had all gross tumor and RIGS-positive tissue removed (RIGS-negative group), and 16 had only traditional extirpation of the tumor because RIGS-positive tissue was too diffuse (RIGS-positive group). RESULTS: In the 16 patients having all RIGS-positive tissue removed, five had traditional regional en bloc resections and 11 had additional extraregional tissues resected. Identification of extraregional disease added two liver resections and 25 lymphadenectomies: 10 of the gastrohepatic ligament, five celia axis, six retroperitoneal, and four iliac. With a median follow-up of 37 months, survival in the RIGS-negative group is 100%. In 14 of 16 patients (87.5%) there is no evidence of disease. In the RIGS-positive group, follow-up shows 14 of 16 patients are dead and two are alive with disease (p < 0.0001). CONCLUSION: These results suggest that RIGS identifies patterns of disease dissemination different from those identified by traditional staging techniques. Removal of additional RIGS-positive tissues in nontraditional areas may improve survival.

Adult↗
PubMed1996

Intraperitoneal hyperthermic perfusion with mitomycin C for colorectal cancer with peritoneal metastases.

BACKGROUND: Intraperitoneal (i.p.) metastases pose a special problem for surgical treatment because of their multiplicity and microscopic size. This study was designed to examine the feasibility and safety of i.p. hyperthermic perfusion (IPHP) with mitomycin C (MMC) for treating recurrent colorectal cancer. METHODS: Fifteen patients with metastatic colon cancer were treated. All patients underwent cytoreductive procedures leaving only residual i.p. metastases < 1 cm in diameter. All patients had received prior systemic chemotherapy, but their disease had progressed. Intraperitoneal chemotherapy was administered through three large catheters (28 French) using a closed system of two pumps, a heat exchanger, and two filters. After the patient's abdominal temperature reached 41 degrees C, 45-60 mg of MMC was circulated intraperitoneally for 1 h. RESULTS: The majority of patients had various anastomoses: small bowel (n = 11), large bowel (n = 5), and urologic (n = 5). No anastomotic complications occurred in any of the patients. One patient experienced severe systemic MMC toxicity, which caused cytopenia and respiratory depression. In all patients the carcinoembryonic antigen (CEA) level decreased after surgery and IPHP. Median follow-up was 10 months, and recurrence was defined as an elevation in CEA level. Disease recurred in three patients within 5 months, and disease recurred in seven other patients over the next 3 months; one patient remains clinically free of disease after 8 months. CONCLUSION: Our data suggest that IPHP is a safe palliative method of treatment for patients with peritoneal carcinomatosis. The median patient response duration of 6 months may warrant consideration of a repeat IPHP procedure at that time.

Antibiotics, Antineoplastic↗
PubMed1995

The significance of intraoperative periportal lymph node metastasis identification in patients with colorectal carcinoma.

BACKGROUND: Nine patients who underwent Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH) procedures for colorectal cancer were found to have disease recurrence in the periportal area. This led to a retrospective study to determine whether periportal lymph node involvement could have been predicted intraoperatively for these patients. METHODS: One hundred twenty-four patients underwent second-look RIGS for recurrent colon and rectal cancer from 1986 to 1992. The monoclonal antibody (MAb) B72.3 was administered as the carrier agent to 87 patients and the CC49 second-generation MAb was administered to 37 patients. Both MAbs were radiolabeled with Iodine-125. RESULTS: Periportal lymph nodes with RIGS-positive tissue were found in 47 (38%) patients, hematoxylin and eosin-positive lymph nodes were found in 13 of 47, and in further immunohistochemical studies performed for 31 of the remaining 34 patients, positive lymph nodes were found in 8, resulting in an incidence of 48% (21/44). A critical review of the nine patients' charts who later presented with a tumor mass in the periportal area demonstrated intraoperative gamma-detecting probe counts in ratios three to five times that of the normal adjacent tissues in the periportal area at the time of first exploration. Probe-directed biopsy was reported to be histologically negative for tumor in these patients, and, thus, the surgeon proceeded assuming the periportal area to be negative. A retrospective study of the periportal lymph nodes of these patients using cytokeratin immunohistochemical analysis identified tumor in five (56%). CONCLUSIONS: These findings suggest that the RIGS system may be a valuable method of intraoperative prediction and detection of periportal lymph node metastasis.

Antibodies, Monoclonal↗
PubMed1995

Radioimmunoguided surgery in primary colorectal carcinoma: an intraoperative prognostic tool and adjuvant to traditional staging.

BACKGROUND: The prognostic value of traditional staging classification for colorectal cancer has changed little since Dukes created the first staging scheme. Some patients with known metastatic disease are long-term survivors, while other patients with local disease die early. New intraoperative cancer detection technology, the radioimmunoguided surgery (RIGS) system, is being studied as a tool to aid in prediction of patient outcome. PATIENTS AND METHODS: Thirty-one patients with primary colorectal cancer were injected with the monoclonal antibody CC49, which was radiolabeled with iodine 125 (125I). A hand-held gamma-detecting probe was used at surgery to detect the radiolabeled antibody. Patients were classified as to the presence or absence of 125I-CC49-positive residual tissue at the close of surgery. Patient survival was analyzed. RESULTS: Follow-up ranged from 30 to 54 months. Survival of 11 stage I or II patients was longer than in 20 stage III or IV patients (P = 0.019). All 14 patients cleared of RIGS-positive tissue were alive at last follow-up, while 15 of 17 RIGS-positive patients died of their disease (P < 0.0001). CONCLUSIONS: The RIGS system used during surgery provides the surgeon with immediate prognostic information on patients with colorectal cancer and supplements traditional pathologic staging.

Adult↗
PubMed1995

Pilot study evaluating the intraoperative localization of radiolabeled monoclonal antibody CC83 in patients with metastatic colorectal carcinoma.

BACKGROUND: CC83, a second-generation monoclonal antibody (MAb) against tumor-associated glycoprotein TAG-72 has been shown to have a higher affinity constant than the anti-TAG MAbs CC49 and B72.3. Clinical studies have shown the effectiveness of both CC49 and B72.3 radiolabeled MAbs in localizing colorectal carcinoma with a hand-held gamma-detecting probe during operation. This current study was designed to assess the safety and tumor-binding ability of radiolabeled CC83 MAb in this setting. METHODS: Seventeen patients with recurrent colorectal cancer underwent intravenous injection with CC83 MAb radiolabeled with iodine 125 (2.0 mCi125I/0.2 mg CC83 MAb). Exploratory laparotomy was carried out 21 to 28 days after injection, consisting of a thorough traditional exploration followed by a survey with a hand-held gamma-detecting probe. All traditionally suspicious and probe-positive tissue was either biopsied or resected and subsequently examined for the presence of carcinoma by using routine histochemical staining techniques. RESULTS: Thirty-two sites were identified as suspicious for cancer by traditional surgical exploration and 39 through intraoperative survey with a hand-held gamma-detecting probe in the seventeen patients completing the study. Biopsy or resection yielded 27 tumor sites when tissue was evaluated by using routine hematoxylin-eosin staining. All 27 tumor sites were localized by the radiolabeled CC83 MAb, whereas 12 additional sites were RIGS positive but hematoxylin-eosin negative, resulting in a sensitivity and positive predictive value of 100% and 69%, respectively. Traditional methods of exploration detected 23 of 27 tumor sites (85% sensitivity), and nine false-positive sites were recorded (72% positive predictive value). Occult tumor was found by using CC83 MAb in four (15%) of 27 sites, altering the surgical plan in three patients. CONCLUSIONS: This initial study indicates that CC83 MAb, when used with RIGS, is safe and sensitive in detecting recurrent intraabdominal colorectal cancer.

Adult↗
PubMed1995

Radioimmunoguided Surgery system improves survival for patients with recurrent colorectal cancer.

BACKGROUND: Advanced colorectal cancer is fatal. No systemic therapies have resulted in increased patient survival. METHODS: One hundred thirty-one patients with recurrent colorectal cancer enrolled in two prospective nonrandomized studies using Radioimmunoguided Surgery (RIGS) system from May 1986 to April 1992 have been analyzed. Eighty-six patients were injected with the anti-tumor-associated glycoprotein (TAG) antibody B72.3, and 45 patients were injected with the second-generation anti-TAG monoclonal antibody CC49. Both monoclonal antibodies were radiolabeled with iodine 125. Both traditional and RIGS explorations were used to determine resectability. Follow-up was a minimum of 28 months. RESULTS: Forty-nine (37.4%) of the 131 patients underwent a curative resection. Twenty-seven of the patients (55%) are alive 2 to 8 years after operation. The cancers of the remaining 82 patients were unresectable, and only two patients (2%) are alive. In this unresectable group alternative intraoperative therapeutic methods (intraoperative radiation therapy, intraperitoneal hyperthermic perfusion, hepatic lines, and brachytherapy) were tried in 11 patients with two survivors. There were no survivors in 18 patients whose cancers were found to be traditionally resectable but unresectable with RIGS or in the 53 patients whose cancers were clearly unresectable by traditional exploration. Patients selected for curative resection had significantly increased survival (p < 0.0001). CONCLUSIONS: As an intraoperative tool RIGS significantly improves the selection of patients for curative resection.

Adenocarcinoma↗
PubMed1994

PEG ileus. A preventable complication.

Percutaneous endoscopic gastrostomy (PEG) tube placement is an established procedure in the nutritional management of patients. There are numerous reports in the literature describing the techniques for placing PEG tubes. However, there are few reports that discuss the proper methods for removing these devices and the complications that may result from incorrectly removing a PEG tube. An increasing number of patients with PEG tubes are being cared for by individuals who are not familiar with these devices and their proper method of removal. The use of an incorrect method to remove a PEG tube may result in significant morbidity to the patient. We report a case of bowel obstruction resulting from the incorrect removal of a PEG tube that required laparotomy. To prevent similar complications, PEG tubes should be removed using the appropriate method by individuals familiar with the device.

Aged↗
PubMed1993

Role of carcinoembryonic antigen in predicting resectability of recurrent colorectal cancer.

The reported low resectability rate for patients with recurrent colorectal cancer who have carcinoembryonic antigen (CEA) levels > 11 has led us to perform this study. One hundred twenty-four patients who underwent Radioimmunoguided Surgery (RIGS) procedures for recurrent colorectal cancer from 1986 to the present were studied. In surgery, all patients underwent a traditional exploration followed by survey with a hand-held, gamma-detecting probe to detect preinjected radiolabeled monoclonal antibodies attached to cancer cells. Sites of metastases included: 72 liver (58.1 percent), 23 pelvis (18.5 percent), 15 distant lymph nodes (12.1 percent), 2 anastomotic (1.6 percent), and 12 other sites (9.7 percent). The resectability rate was 43.5 percent (54 patients). The mean preoperative CEA level for patients with resectable disease was significantly lower than for patients with unresectable disease (P = 0.017): unresectable--mean, 87.1; SD, 141.0; minimum, 0.3; maximum, 501; resectable--mean, 36.6; SD, 59.3; minimum, 0.3; maximum, 329. The CEA level for patients with liver metastasis did not vary significantly from those patients without metastasis: 70 vs. 58.2 (P = 0.58). Those patients with resectable liver tumors had lower mean CEA levels than those with unresectable liver, approaching significance: 41.6 vs. 91.9 (P = 0.065). Other metastatic sites had a mean CEA level of: pelvic, 72.6; distant lymph nodes, 47.8; anastomotic, 2.7; and other sites, 53.8. These data suggest that there is a significant difference between the preoperative CEA level of the resectable and unresectable recurrent colorectal cancer patients, but the large standard deviation does not justify abandonment of exploration for any CEA level.

Antibodies, Monoclonal↗
PubMed1993

Adjuvant treatment for rectal cancer: current status.

Surgery is still the cornerstone of curative treatment for rectal cancer. A combination of postoperative radiation and chemotherapy is the preferred adjuvant treatment for TNM stages II and III rectal cancer. Although studies combining 5-fluorouracil (5-FU) and the investigational agent semustine (methyl-CCNU) with radiation showed some survival benefit, preliminary results of recent studies suggest that radiation with 5-FU alone is an effective substitute. Preoperative radiation treatment has several advantages over postoperative radiotherapy. The major disadvantage, that tumors may be downstaged, preventing exact evaluation of treatment results, may be overcome by using rectal ultrasound for preoperative staging. Another promising treatment is preoperative radiation combined with 5-FU as a radiosensitizer and for possible increased systemic effect. Studies are needed to find a better, less toxic radiosensitizer, to explore new chemotherapy combinations with 5-FU (such as levamisole), and to define the proper dose sequence and integration.

Combined Modality Therapy↗
PubMed1992

Intraoperative detection of colorectal cancer with radioimmunoguided surgery and CC49, a second-generation monoclonal antibody.

Radioimmunoguided surgery (RIGS) has been employed intraoperatively in cases of colorectal cancer to assess the extent of local tumor spread and metastatic disease. This technique uses radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens, and a hand-held gamma-detection probe to detect the radiolabel fixed to tumor tissue. Recently introduced is an MAb directed against tumor-associated glycoprotein (anti-TAG), CC49. Sixty patients were entered into the initial study. Eighteen of 21 (86%) primary tumors were localized by the CC49 MAb and the gamma-detecting probe. Twenty-nine of 30 (97%) recurrent tumors were localized. Antibody dose did not affect localization. Specimens were divided into tissue types I through IV, based on antibody localization and hematoxylin and eosin (H&E) staining: type I, RIGS (-) and histologically (-); type II, RIGS (-) and histologically (+); type III, RIGS (+) and histologically (-); type IV, RIGS (+) and histologically (+). Type IV tissue were further classified by whether they were grossly apparent, IVa, or grossly inapparent, IVb (occult). Occult tumor found by RIGS and confirmed by H&E staining (type IV) had localization ratios similar to RIGS-positive, histology-negative tissue (type III). Traditionally found cancer (type IV) had significantly higher ratios. In 12 of 24 patients (50%) with primary tumors and 14 of 30 patients (47%) with recurrent tumors, RIGS with CC49 altered the planned operative procedure. Radioimmunoguided surgery with CC49 provides useful, immediate intraoperative information not available by other techniques.

Adult↗
PubMed1992

Radioimmunoguided surgery challenges traditional decision making in patients with primary colorectal cancer.

BACKGROUND: Initial experience with the radioimmunoguided surgery system (RIGS) has been found to impact on decision making in patients with recurrent colorectal cancers. Reported here is experience with RIGS-influenced therapeutic decisions in patients with primary colorectal cancer. METHODS: Thirty-six evaluable patients with primary cancers were injected with the second-generation anti-tumor-associated glycoprotein antibody CC49 labeled with 1 to 2 mCi iodine 125. Pharmacokinetic determination and precordial counts were obtained after injection and weekly until levels were less than 20 counts/2 sec. At surgery abdominal and pelvic explorations were performed, first traditionally by inspection and palpation and then with the hand-held, gamma-detecting probe. RIGS-positive tissue was considered cancerous and removed if possible. RESULTS: Thirty patients (83%) had positive antibody localization at surgery. Of those patients with localization, in 24 (80%) additional information was obtained at the time of surgery. In 11 patients (34%) staging changes were made as a result of RIGS exploration. New findings resulted in operative changes in nine patients (25%). Eleven (30%) of the original 36 patients became eligible for adjuvant chemotherapy based on current recommendations because of RIGS findings. CONCLUSIONS: In conclusion, the RIGS system provides immediate staging information that impacts on therapeutic interventions, challenging the adequacy of traditional procedures alone for primary colorectal cancer exploration.

Colonic Neoplasms↗
PubMed1992

Early postlaparotomy percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is a relatively new procedure, the indications for which are evolving. We have recently attempted PEG placement in 19 patients during the early postlaparotomy period (less than 14 days) for initiating enteral feedings or providing decompression of the gastrointestinal tract. All patients had unexpected postoperative complications, including neurologic catastrophe, recurrent obstruction of the small intestine, acute respiratory failure, enterocutaneous fistula or poor oral intake. Of 19 attempts, PEG placement was successful in 18 patients (94.7 per cent). There were no major complications; two minor complications (exit site infection) were associated with catheter placement. All PEG placed for enteral feedings were successfully used for nutritional support, and gastrointestinal decompression was accomplished in seven of eight patients requiring PEG. The results of this study demonstrate that PEG is technically feasible, safe and effective in the early postlaparotomy period in high-risk patients with complicated postoperative courses and the need for long term enteral access.

Adult↗
PubMed1991

Abdominal colon and rectal operations in the elderly.

Sixty-seven abdominal operations for colon and rectal disorders were performed on 56 patients 80 years of age or older from January 1, 1984 to June 30, 1989. Nine patients required multiple operations. Sixty-two procedures (92 percent) were performed on patients in their ninth decade; two operations were performed on patients 95 years of age or older. Forty-five patients (80 percent) were operated upon for carcinoma. Operations included segmental colectomy (33 patients), low anterior resection (12 patients), total abdominal colectomy (3 patients) and abdominoperineal resection (2 patients). Forty patients were classified as ASA Class III; the majority were monitored in the surgical intensive care unit for a mean of 2.84 days. Thirty patients were monitored with arterial catheters and 21 with central invasive monitoring. Operative mortality was 7 percent (4 patients). Two patients died from diffuse carcinomatosis; one patient had a fatal myocardial infarction. The final death occurred from multisystem organ failure following anastomotic dehiscence. Twenty-seven operations were performed without postoperative complications; 18 operations were followed by a single minor complication. The average hospital stay was 18.96 days. All patients were admitted from home. Thirty-three returned home postoperatively; 16 were discharged to an extended care facility. In conclusion, elderly patients with colon and rectal disorders can be operated upon with acceptable morbidity and mortality. Age alone should not interdict surgical therapy.

Abdomen↗