Breast specimen orientation.

Lumpectomy specimens are commonly divided into six sides: superficial, deep, superior, inferior, medial, and lateral. Orienting stitches are placed on the specimen during surgery to allow reorientation by pathology. Despite those efforts, specimen disorientation may occur. The aim of this study was to assess the correlation in orientation between surgeons and pathologists. Lumpectomy specimens were routinely oriented. An additional Prolene suture was randomly placed by the surgeon on one side to be localized by pathology. The results were recorded and the disorientation rate calculated. Specimen size and presence of skin and/or muscle were also recorded. There were 122 lumpectomy specimens prospectively entered. Average specimen volume was 95.5 cm(3). Twenty-four specimens had segments of skin or muscle. The additional sutures were evenly divided between the six sides. The overall disorientation rate was 31.1% (95% confidence interval, 23.1-40.2).The side-specific disorientation rates were 43%, 40%, 35%, 29%, 28%, and 14% for the deep, superficial, lateral, medial, superior, and inferior surfaces, respectively (no statistical difference). Presence of skin or muscle on the specimen did not contribute to better orientation. Specimen volumes, however, were highly associated with orientation. Specimens of <20 cm(3) had a disorientation rate of 78%, while larger specimen had a disorientation rate of 20% (p < .001). Specimen orientation with stitches placed on two surfaces is associated with a high disorientation rate. Better orientation techniques are necessary to minimize the specimen disorientation.

Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.

Effects of mastectomy versus lumpectomy on emotional adjustment to breast cancer: a prospective study of the first year postsurgery.

PURPOSE: Procedure (mastectomy v lumpectomy) and choice of procedure were examined as predictors of adjustment to breast cancer in a prospective study of the experiences of the first year after surgery. PATIENTS AND METHODS: Breast cancer patients were interviewed the day before surgery, 10 days after surgery, and at the 3-month, 6-month, and 12-month follow-ups. Patients included 24 women who received mastectomy on strong recommendation, 24 who chose mastectomy for other reasons, and 15 who chose lumpectomy. Subjective well-being was assessed in terms of mood disturbance, perceived quality of life, life satisfaction, marital satisfaction, perceptions of social support, and self-rated adjustment. RESULTS: Surgical groups differed in well-being in only one respect: lumpectomy patients reported a higher-quality sex life at 6 and 12 months postsurgery than mastectomy patients. Choice of surgical procedure predicted higher levels of life satisfaction at 3 months. CONCLUSION: The lack of difference between surgical groups in areas other than sexual adjustment replicates previous findings, but extends them by (1) using a fully prospective design, (2) providing data on the period surrounding the surgery (as well as later periods), and (3) examining a broader range of indices of well-being than usual.

Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group.

PURPOSE: To assess the performance and the potential clinical impact of a new antibody imaging agent, CEA-Scan (Immunomedics Inc, Morris Plains, NJ), in 210 presurgical patients with advanced recurrent or metastatic colorectal carcinomas. METHODS: CEA-Scan, an anti-carcinoembryonic antigen (CEA) Fab antibody fragment labeled with technetium-99m-pertechnetate (99mTc), was injected intravenously (IV), and external scintigraphy was performed 2 to 5 and 18 to 24 hours later. Imaging with conventional diagnostic modalities (CDM) was also performed, and findings were confirmed by surgery and histology. RESULTS: The sensitivity of CEA-Scan was superior to that of CDM in the extrahepatic abdomen (55% v 32%; P = .007) and pelvis (69% v 48%; P = .005), and CEA-Scan findings complemented those of CDM in the liver. Among 122 patients with known disease, the positive predictive value was significantly higher when both modalities were positive (98%) compared with each alone (68% to 70%), potentially obviating the need for histologic confirmation when both tests are positive. Imaging accuracy also was significantly improved by adding CEA-Scan to CDM. In 88 patients with occult cancer, imaging accuracy was enhanced significantly by CEA-Scan combined with CDM (61% v 33%). Potential clinical benefit from CEA-Scan was demonstrated in 89 of 210 patients. Only two patients developed human antimouse antibodies (HAMA) to CEA-Scan after a single injection, and none of 19 assessable patients after two injections. CONCLUSION: CEA-Scan affords high-quality, same-day imaging, uses an inexpensive and readily available radio-nuclide, adds clinically significant information in assessing extent and location of disease in colorectal cancer patients, and only rarely induces a HAMA response.

A new CD44V3-containing isoform is involved in tumor cell growth and migration during human breast carcinoma progression.

CD44 isoforms belong to a family of cell adhesion molecules expressed on the cell surface of many tumor cells during human breast cancer progression. In this study we have analyzed the expression of CD44v3-containing isoforms [containing heparan sulfate addition sites for growth factor binding] in primary breast tumors, axillary nodal metastases and normal breast tissue. Using reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot, cloning, nucleotide sequencing and RT-in situ-PCR analyses, we have found that at least two CD44v3-containing isoforms, including one new species of CD44v2,deltav3-10 (deltav3 defined as a v3 exon lacking the first 24 base pairs) and another previously reported CD44v3,8-10 are preferentially expressed in human primary breast tumor and axillary nodal metastases but not in normal breast tissues. These finding suggest that these CD44v3-containing isoforms are closely associated with breast cancer metastasis.

Reversal of cyclosporine-induced mortality with a synthetic polymeric immunostimulant in a murine model of fecal peritonitis.

We have been investigating the effects of a synthetic immunostimulative polymer known as copovithane (Cpv). This agent appears to enhance humoral immunity in untreated and cyclosporine-immunosuppressed mice and is nontoxic in rodents and man. The purpose of this study was to determine whether cyclosporine (CsA) is deleterious to survival in a murine cecal ligation, puncture, and excision (CLPE) model of fecal peritonitis, and--if so--whether this effect could be ameliorated by Cpv without interfering with skin allograft acceptance. Cpv significantly prolongs survival in the CLPE model; the optimal dose for this effect was found to be 100 mg/kg. CsA was found to have a significant and deleterious effect on survival at several dosage levels when administrated 48 and 24 hr before cecal ligation, and immediately before and 16 hr after cecal ligation. Using a dose of CsA sufficient for skin allograft acceptance and the same schedule of administration outlined above, Cpv 100 mg/kg was administered 48 hr prior to cecal ligation. Mice treated with CsA plus Cpv had significantly longer survival than mice treated with CsA alone; furthermore, the survival of CsA-plus-Cpv-treated animals was not significantly different from that of saline-treated controls. Acceptance and survival of H-2 incompatible skin allografts in mice treated with CsA were not affected by Cpv 100 mg/kg/week. We conclude that CsA-induced mortality in the CLPE model can be abrogated by Cpv without adversely affecting skin allograft survival. It may eventually be possible to reduce the incidence of septic complications in clinical allotransplantation by prophylactically administering Cpv to patients on CsA immunosuppression.

Somatostatin receptor expression in Hürthle cell cancer of the thyroid.

Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.

Preoperative scintigraphy and operative probe scintimetry of colorectal carcinoma using technetium-99m-88BV59.

UNLABELLED: We report a pilot study of radioimmunoscintigraphy (RIS) and operative gamma probe scintimetry (OPS) using a 99mTc-labeled anti-cytokeratin human monoclonal antibody (MAb) (99mTc-88BV59) in patients with newly diagnosed, recurrent or metastatic colorectal cancer. METHODS: Twelve presurgical patients with biopsy- or contrast radiographic-proven colorectal cancer or recurrent colorectal carcinoma were studied. After chest roentgenography and abdominopelvic CT, 99mTc-88BV59 was administered intravenously, planar and SPECT external imaging was performed 3 to 6 hr after injection and planar imaging was performed 18 to 24 hr after injection. Surgery was performed immediately after late planar imaging. OPS of a standardized list of sites to document background radiation activity and of tumor sites, resection margins and tumor beds was performed. RESULTS: The patients had 23 histologically proven tumor sites. Overall sensitivity for CT, planar RIS, SPECT, surgery and OPS was 43%, 61%, 78%, 96% and 91%, respectively. SPECT was superior to CT for imaging extrahepatic abdominal and pelvic disease. OPS detected all liver and extrahepatic abdominal tumor sites and correctly predicted histological tumor-free margins and tumor beds in all cases. OPS did not identify tumor deposits that the surgeon could neither see nor feel. No patient demonstrated human anti-human immune responsiveness 1 and 3 mo after 99mTc-88BV59 infusion. CONCLUSION: Technetium-99m-88BV59 is a safe, effective radioimmunoconjugate for colorectal cancer imaging, with superior sensitivity as compared to CT.

Sentinel lymph node localization in early breast cancer.

METHODS: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection. RESULTS: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies. CONCLUSION: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.

Abdominal surgery in patients undergoing long-term peritoneal dialysis.

Nineteen patients undergoing long-term peritoneal dialysis (LTPD) required abdominal operations--11 elective and 8 emergency. The preoperative hemoglobin level was 9.0 +/- 2.6 gm/dl, and the serum albumin was 28.8 +/- 4.9 gm/L. There was one death in the elective group (an inguinal herniorrhaphy) and four deaths in the emergency group (three spontaneous colonic perforations and one strangulated ventral hernia). Wound complications occurred in five patients. To obtain an indication of nutritional status of patients on intermittent LTPD and high-protein diets, 17 in-center patients underwent nutritional assessment, and deficiencies in delayed hypersensitivity skin testing and total lymphocyte counts were prevalent. Wounds require secure, watertight closure to prevent dialysis leakage. In elective abdominal surgery, LTPD should be carried out shortly preoperatively to delay dialysis for a few days after operation and to decrease defective platelet function. Preoperative transfusion for anemia is generally unnecessary. Drains should be avoided or removed before resumption of LTPD. Abdominal wall hernias should be repaired electively. Constipation should be avoided. Marked protein loss accompanies peritonitis. In certain instances, transfer to hemodialysis is indicated.

Effect of radiofrequency hyperthermia and chemotherapy on primary and secondary hepatic malignancies when used with metronidazole.

Hyperthermia is selectively toxic to neoplastic tissue. Since August 1981, 357 patients with incurable tumors in various body areas have been treated with chemotherapy and radiofrequency hyperthermia (RFHT) with adjuvant metronidazole at this center. Of this group, the cases of 102 patients with hepatic tumors are reported here. Patients received one to ten treatment courses, each course consisting of two to five daily RFHT sessions. Systemic temperature rose 0.6 +/- 0.3 degrees C during treatment, and tumor core temperature (measured by percutaneous transhepatic thermistor) reached 39.5 +/- 1.2 degrees C in 38 monitored patients. Results have been encouraging; in particular, among 15 patients with newly diagnosed colorectal metastases limited to the liver (and as yet untreated for their secondary disease), there has been objective partial tumor regression in 66.7%. Side effects have been few. Skin burns and subcutaneous fat necrosis were seen in 3.9% and 13.7% of patients, respectively. Tumor temperature is difficult to measure reliably and does not correlate with machine power or tumor response. A phase III trial is currently underway to determine the efficacy of RFHT and chemotherapy for patients with hepatic metastases from colorectal adenocarcinoma.

Segmental mastectomy without radiotherapy for T1 and small T2 breast carcinomas.

We describe 111 patients with invasive breast cancer treated by segmental mastectomy at the University of Miami (Fla) since 1975. Postoperative adjuvant radiotherapy was recommended as optional rather than mandatory to 64 of these patients based on small (2.5 cm or less) primary tumor size, adequate resection margins, no lymphatic or vascular invasion within the segmental mastectomy specimen, and minimal associated in situ cancer. Fifty-one of these patients elected to forego postoperative adjuvant radiotherapy. At 72 months median follow-up, relapse occurred in the ipsilateral breast in three patients who elected to forego postoperative adjuvant radiotherapy (6% by Kaplan-Meier analysis). Retrospective pathologic review revealed that tumor grade may also be important in determining whether postoperative adjuvant radiotherapy is necessary following segmental mastectomy. These data suggest that postoperative adjuvant radiotherapy may not be required in every patient treated by segmental mastectomy. Further studies to define which patients can be spared the inconvenience, expense, and potential morbidity of postoperative adjuvant radiotherapy are warranted.

Total axillary lymphadenectomy in the management of breast cancer.

The optimal extent of axillary dissection in patients with breast cancer remains unclear. We report 278 total axillary lymphadenectomies (levels I, II, and III and Rotter's [interpectoral] nodes) that were performed in 264 closely followed up private patients. There have been no axillary recurrences to date (mean follow-up, 50 months). If only level I and II nodes had been removed, the false-negative staging error would have been only 2.6%. However, 29 (31.5%) of 92 pathological node-positive axillae contained apical and/or Rotter's metastases. The incidence of complications was comparable with that reported for partial lymphadenectomy. Arm lymphedema developed in 6% of nonirradiated patients; postoperative radiotherapy and gross nodal disease were significant risk factors for lymphedema. Total axillary lymphadenectomy largely prevents axillary, recurrence, eliminates the small staging error inherent in partial lymphadenectomy, and has acceptable morbidity, provided radiotherapy to the regional nodal areas is avoided.

Radical surgery for extensive rectal cancer: is it worthwhile?

In a small proportion of patients with extensive primary or locally recurrent rectal cancer, disease remains confined to the pelvis for a prolonged period. Symptoms are highly prejudicial to quality of life and often refractory to treatment short of extirpative surgery. Cure requires en bloc excision of all involved pelvic viscera with tumor-free margins. The pelvic exenterations (PE) are the most radical operations for rectal cancer. PE carries a high risk of perioperative morbidity and mortality, and has profound functional, psychological, and psychosexual implications for patients. Careful preoperative counseling regarding surgical risks and the impact of PE on body function and image is indispensable; the patient's consent must be truly informed. Patients with major medical or psychiatric/emotional comorbidity and those who are mentally incompetent are not candidates. Tenesmus and central pelvic/perineal pain are amenable to PE whereas radicular pain is not; sciatica and lower extremity lymphedema portend unresectability. Extrapelvic disease should be excluded preoperatively. While invaded sacrum can be resected en bloc with involved viscera (sacropelvic exenteration), fixity of tumor to the pelvic sidewall(s) in nonirradiated patients almost invariably implies unresectability. Other contraindications to PE include invasion of the proximal (S1 or higher) lumbosacral spine or lumbosacral plexus/sciatic nerves, ureteric obstruction proximal to the ureterovesical junctions, and encasement of the external or common iliac vessels by tumor. PE for advanced primary rectal carcinoma yields 5-year survival of over 40%; when performed for recurrent disease, long-term salvage rates are not as high. While radical surgery is rarely indicated for palliation, PE in carefully selected (good performance status and life expectancy, complete excision of all gross disease) incurable patients results in abrogation of disabling symptoms and reasonable intervals of high-quality survival.

Metastasectomy as a cytoreductive strategy for treatment of isolated pulmonary and hepatic metastases from breast cancer.

The authors sought to examine the utility of resection in conjunction with adjuvant chemotherapy for treatment of metastases from breast cancer isolated to the liver or lungs. Limitations of regional therapy were examined and potential agents for systemic therapy were reviewed. As resection of metastases is a controversial therapeutic approach, no clinical trials are available for review. Rather, evidence for a potential role for surgery rests on retrospective studies of small series of patients. Technical advances have rendered resection of liver and lung metastases safe. Long-term results as reported by other investigators support the role of metastasectomy in selected patients. The site of failure following ablation of liver metastases is usually in the liver. Following resection of lung metastases, nonpulmonary and disseminated recurrences are most common. Adjuvant therapy with docetaxel or any other agent or combination with significant activity against visceral metastases might potentiate long-term results.

How coping mediates the effect of optimism on distress: a study of women with early stage breast cancer.

At diagnosis, 59 breast cancer patients reported on their overall optimism about life; 1 day presurgery, 10 days postsurgery, and at 3-, 6-, and 12-month follow-ups, they reported their recent coping responses and distress levels. Optimism related inversely to distress at each point, even controlling for prior distress. Acceptance, positive reframing, and use of religion were the most common coping reactions; denial and behavioral disengagement were the least common reactions. Acceptance and the use of humor prospectively predicted lower distress; denial and disengagement predicted more distress. Path analyses suggested that several coping reactions played mediating roles in the effect of optimism on distress. Discussion centers on the role of various coping reactions in the process of adjustment, the mechanisms by which dispositional optimism versus pessimism appears to operate, third variable issues, and applied implications.

Breast cancer: management of the opposite breast.

Women who have or had cancer in one breast are at especially high risk for developing cancer in the contralateral breast. Other risk factors for second primary breast tumors include age, the use of radiation in treating the index cancer, and pathological characteristics of the original cancer. Management approaches range from close clinical and mammographic surveillance only to immediate prophylactic contralateral mastectomy. Routine and selective biopsy of the opposite breast at the time of treatment of the initial cancer have their proponents. The authors discuss these methods and the effect of a second cancer on overall prognosis.

High-fat diets suppress CD3 and CD25 expression on the surface of murine lymphocytes.

To determine the effects of dietary fats on surface antigen expression, we tested the effects of amount and type of dietary fat on murine lymphocytes. Mice were fed diets with 12 en%, 23 en%, or 47 en% fat containing coconut, olive, safflower, or linseed oil. After 2 wk of ad libitum feeding, the mice were killed and splenic lymphocytes were harvested. Lymphocytes were incubated with fluorescent-tagged monoclonal antibodies and assayed for mean and total surface expression using flow cytometry. Our results show that high-fat (47 en%) diets suppress expression of CD3 and CD25 antigens. We also found that linseed-oil diets suppress expression of CD11a but enhance expression of CD25 antigens. Both CD3 and CD25 are critical for lymphocyte activation, and we conclude that immunosuppression associated with high-fat diets may be associated with suppression of these surface antigens.

Does a radiation dose-response relation exist concerning survival of patients who have soft-tissue sarcomas of the extremities? Radiation dose-response relation for soft-tissue sarcomas.

This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.

Pseudotumor cerebri.

Pseudotumor cerebri is a clinical syndrome in which signs and, sometimes, symptoms of raised intracranial pressure are present but in which mental and neurological function are unaffected. Therefore, the diagnosis is reached after mass and other structural causes of raised pressure have been excluded. Many causes of pseudotumor have been suggested, not all of them well documented. Pathogenesis, however, includes cerebral edema, increased cerebral blood volume, and decreased cerebro spinal fluid (CSF) absorption. Except for the risk of vision in a minority of cases, the prognosis is excellent.