Is unplanned return to the operating room a useful quality indicator in general surgery?

HYPOTHESIS: To test our hypothesis that unplanned return to the operating room (OR) is a useful quality indicator, we examined how often and for what reasons patients go back to the OR in a broad-based general surgery practice. DESIGN AND SETTING: Prospective cohort study at a rural tertiary care center. PATIENTS: Consecutive series of 3044 patients undergoing general surgery procedures in the OR between September 1, 1998, and March 31, 2000. Information about all postoperative adverse events occurring before discharge or within 30 days (whichever was longer) was collected prospectively. Unplanned return to the OR was defined as any secondary procedure required for a complication resulting directly or indirectly from the index operation. MAIN OUTCOME MEASURES: Unplanned return to the OR, mortality, and hospital charges. RESULTS: Overall, 107 (3.5%) had an unplanned return to the OR. A relatively small number of inpatient procedures accounted for a disproportionate share of unplanned reoperations, including colon resection (18% of total reoperations), renal transplant (9%), gastric bypass (6%), and pancreatic resection (6%). As expected, hospital charges were markedly higher for patients with unplanned returns to the OR. Reoperation was also associated with higher mortality rates; statistically significant increases were noted for pancreatic resection (33% vs 3.7%; P =.04), esophagogastrectomy (100% vs 4.2%; P =.002), and laparoscopic Nissen fundoplication (50% vs 0%; P =.01). Overall, 91 reoperations (85%) were for complications occurring at the original surgical site, including those related to an anastomosis (n = 16), surgical wound (n = 21), infection (n = 16), bleeding (n = 12), and other (n = 26). CONCLUSIONS: Unplanned returns to the OR occur across a broad spectrum of general surgical procedures and carry significant implications. Because they most often reflect problems related to the procedure itself, reoperation rates may be useful for monitoring quality across hospitals and for identifying opportunities for quality improvement locally.

Parathyroid adenoma and gastric carcinoma as manifestations of Cowden's disease.

Cowden's disease is a well-described clinical syndrome, the primary symptoms of which are orocutaneous hamartomas and disseminated gastrointestinal polyposis. In general, the gastrointestinal polyps are benign, and the incidence of malignant transformation is believed to be low. Other associated manifestations of Cowden's disease include breast cancer and thyroid disease (benign and malignant). A patient with previously unrecognized Cowden's disease underwent upper gastrointestinal endoscopy for surveillance of hyperplastic gastric polyps, and a gastric carcinoma in situ was detected. During the course of follow-up the patient was found to have primary hyperparathyroidism resulting from a parathyroid adenoma. Although several benign proliferative and malignant conditions are associated with Cowden's disease, neither parathyroid adenoma nor gastric carcinoma has been reported previously.

Proliferation-associated nucleolar antigen P120: a prognostic marker in node-negative breast cancer.

BACKGROUND: P120 is a nucleolar proliferation antigen found in rapidly dividing cells and in a variety of malignancies. METHODS: Our purpose was to determine whether P120 expression is a prognostic factor for patients with node-negative breast cancer by testing pathologic material from 90 patients for P120 immunoreactivity, histologic grade, and estrogen receptors. RESULTS: P120 was detected in 52 of the 90 specimens (58%). Node-negative cancer patients with tumors that did not express the P120 antigen had a significantly better overall survival rate than node-negative cancer patients with tumors that did express P120 (92% vs 69%; p = 0.035). Histologic studies indicated that 36 tumors were grade I, 28 were grade II, and 26 were grade III. The presence of P120 correlated significantly with the nuclear grade of the tumor: 73% of grade III tumors, 64% of grade II tumors, and 42% of grade I tumors stained positive for P120 (p = 0.033). The correlation between nuclear grade and overall survival rate was also significant (grade 1, 94%; grade II, 79%; grade III, 58%); (p = 0.003). No significant correlation was found between P120 expression and estrogen receptors. Multivariate analysis shows that P120 expression and histologic grade together are the strongest predictors of survival. CONCLUSIONS: The biologic marker P120 may play an important role in determining which patients with node-negative cancer will benefit most from adjuvant therapy.

Improved survival with adjuvant immunotherapy after surgical resection in a murine model.

BACKGROUND: Adoptive immunotherapy has met with limited success in the treatment of bulky metastatic disease. The purpose of this study was to determine whether lymphocytes stimulated in vitro could improve survival when given as an adjuvant to surgical resection in animals harboring microscopic metastatic disease. METHODS: Lymphocytes from nodes draining the primary tumor (DLN lymphocytes) were stimulated in vitro with phorbol 12,13-dibutyrate and ionomycin and used as adjuvant immunotherapy after surgical resection of the primary tumor. Mice with advanced P-815 footpad tumors and disseminated microscopic metastases underwent amputation of the tumor-bearing extremity and were randomized to various adjuvant treatments. RESULTS: Mice treated with adjuvant immunotherapy using stimulated DLN lymphocytes demonstrated significantly improved survival, showing that DLN lymphocytes stimulated in vitro can abrogate metastases that are invading multiple organs simultaneously. Mice successfully treated with adjuvant immunotherapy demonstrated long-term (80 days) in vivo antitumor activity by rejecting subsequent tumor challenge. In addition, stimulated DLN lymphocytes provided in vivo antitumor activity to naive mice. CONCLUSIONS: Adjuvant immunotherapy after resection in the face of residual microscopic tumor burden may prove to be a useful application of adoptive immunotherapy.

Prospective study correlating P120 antigen expression with established prognostic factors in breast cancer.

P120 is a nucleolar proliferation antigen found in rapidly dividing cells and a variety of malignancies. Previous retrospective studies have demonstrated that, when detected in human breast cancer, P120 is associated with a poorer prognosis. To determine whether P120 expression correlates with other prognostic factors in breast cancer, we prospectively analysed pathologic and clinical data from 61 patients. P120 was detected in 40 of the 61 specimens (66%). No significant correlation existed between P120 expression and either tumour size or hormone receptors. A significant correlation was found between P120 expression and histological grade, degree of aneuploidy, S-phase fraction, degree of nodal involvement, and stage of disease. P120 is a biological marker indicative of tumour aggressiveness and may play an important role in determining which patients would most benefit from adjuvant therapy.

Perforated gastric and duodenal ulcer: an analysis of prognostic factors.

A review of patients treated operatively for perforated ulcer was undertaken to determine factors that independently predict mortality and morbidity. From 1980 to 1989 84 patients were treated with operative mortality and morbidity rates of 18 and 37 per cent, respectively. Patients with gastric ulcer were significantly older and were more likely to have concomitant medical problems, to use steroids, and be hospitalized at time of their perforation. They also had a higher perioperative mortality rate when compared to patients with gastroduodenal ulcers (P < 0.05 for each). Patients treated with definitive operation (n = 51) had a significantly lower recurrent ulcer rate when compared to an equivalent group treated with simple closure (n = 33) (mean follow-up, 47 months). Multivariate analysis confirmed a patient's likelihood of complication or death could be predicted using three variables (P < 0.03); age greater than 42 years, hospitalization at time of perforation, concomitant medical illness. While the relative distribution of these three factors in patients with gastric versus peptic ulcers appears to account for the difference in outcome between these two groups, the distribution of these factors between patients treated with patch closure and definitive operation was not significantly different. Patient outcome from operation for perforated ulcer is dependent on preoperative conditions and appears to be independent of surgical procedure performed. There was no benefit to simple closure of a perforated ulcer. Definitive procedures of perforated ulcers are associated with lower ulcer recurrence and therefore are advocated to treat perforation.

Phorbol dibutyrate and ionomycin improve murine effector cell cytotoxicity.

Simultaneous protein kinase C stimulation with phorbol 12,13-dibutyrate (PDBU) and calcium mobilization with ionomycin (Io) trigger cellular events leading to expression of proliferation-associated genes in human lymphocytes. The effect of a 16-hr exposure to PDBU and Io on the growth and cytotoxic activity of murine splenocytes and tumor-infiltrating lymphocytes (TIL) cocultured with interleukin-2 (IL-2) was studied. PDBU + Io increased the number of cytotoxic effector cells that could be generated in lymphokine-activated killer cells (LAK) cultures (40-fold) and to a lesser extent in TIL (10-fold). DNA synthesis of TIL increased significantly when exposed to PDBU + Io. Also, TIL stimulated with PDBU + Io demonstrated in vitro tumor-specific lytic activity significantly greater than that of control TIL (500 lytic units vs 50). The cell-surface phenotype of TIL treated with PDBU + Io was identical to that of control TIL (> 95% CD-3+, CD-4-, CD-8+). Results of adoptive immunotherapy using splenocytes stimulated by PDBU + Io and cultured in IL-2 were identical to those achieved when standard LAK cultures were used. However, treatment using TIL stimulated by PDBU + Io led to a significant reduction in the number of pulmonary nodules compared to standard TIL. In addition, PDBU + Io-stimulated TIL maintained significant in vivo activity without the need for systemic IL-2 administration. Pharmacologic manipulation of cytotoxic precursor cells is a useful strategy for improving the generation of murine cytotoxic effector cells. By using PDBU + Io, cytotoxic lymphocytes could be generated with improved in vitro and in vivo activity.

Management of mammographic indeterminate lesions. First place winner of the Conrad Jobst Award in the Gold Medal paper competition.

The positive predictive value of mammography in nonpalpable malignancy, only 20 to 25 per cent, could be improved with better mammographic criteria for lesions not requiring biopsy. The outcomes of 89 patients with indeterminate lesions were reviewed to determine whether these lesions could be managed safely by observation rather than biopsy. Indeterminate lesions were defined as 1) tightly clustered, nonlinear calcifications (> 5 within 1 cm of tissue); 2) dominant, well-circumscribed soft-tissue masses (< or = 1 cm2); or 3) asymmetric density. Lesions not immediately undergoing biopsy were followed with frequent-interval mammography. Twenty-two lesions (26%) underwent immediate biopsy, and 2 of these demonstrated carcinoma in situ with microinvasion. Sixty-seven lesions (74%) were observed (median follow-up, 34 months), and 2 (2.5%) proved to be malignant, for an overall malignancy rate of 4.5 per cent. All malignancies were stage I, and the patients remain alive with no evidence of disease (average follow-up, 24 months). Sixty patients were spared unnecessary biopsy, decreasing potential wire-directed biopsies by 25 per cent. The positive predictive value of mammography increased from 21 to 32 per cent over the period. Indeterminate lesions can be safely followed with frequent ipsilateral mammography, reserving biopsy for lesions that progress. Management schemes such as this one can be used to decrease the number of negative wire-directed biopsies.

Phorbol dibutyrate plus ionomycin improves the generation of cytotoxic T cells from draining lymph nodes of patients with advanced head and neck cancer.

Fifty-one cervical nodes from 19 patients with advanced head and neck cancer were stimulated with phorbol dibutyrate and ionomycin (PDBu + Io) to determine the effect of such stimulation on the generation of cytotoxic T cells and whether this stimulation could bypass the need for autologous tumor stimulation. Lymphocytes stimulated with PDBu + Io demonstrated a sixfold greater in vitro expansion and significantly increased DNA synthesis. Whereas fresh lymphocytes displayed no cytotoxicity, stimulation with PDBu + Io and culture in interleukin-2 (IL-2) led to significant cytotoxicity equivalent to that of lymphocytes stimulated with autologous tumor and IL-2. T cells with the greatest cytotoxicity were generated from patients with nodal metastases. In patients with stage IV tumors, effector cells demonstrating greater lysis of natural killer-resistant targets (Daudi cells) were associated with higher rates of recurrence (50% versus 12%, respectively, p < 0.001). Stimulation with PDBu + Io augments growth and proliferation of lymphocytes from draining lymph nodes and preserves cytotoxicity without the need for autologous tumor. Excluding the need for antigenic stimulation by autologous tumor may prove useful in adoptive immunotherapy procedures.

Management of local recurrence in well-differentiated thyroid carcinoma.

Local recurrence of well-differentiated thyroid carcinoma has a reported mortality approaching 50%. The University of Kentucky experience was reviewed to determine whether aggressive surveillance and treatment with reoperation and/or I-131 ablation increased survival following recurrence. Records of 66 consecutive patients with well-differentiated thyroid carcinoma treated at the University of Kentucky Medical Center (1980-1989) were reviewed. Forty-nine cases of papillary carcinoma and 17 cases of follicular carcinoma were studied; median follow-up was 68 months. At presentation, patients with follicular carcinoma were older (48 versus 35 years; P less than 0.05) and more frequently had metastatic disease (17% versus 2%, P less than 0.05). Fifty-eight (88%) patients were alive and disease-free at last follow-up. Fifteen patients (24%) had developed recurrent disease; median time to recurrence was 24 months. Multivariate regression examined the variables of age, sex, histology, tumor size, cervical adenopathy, capsular and vascular invasion, multicentricity, and surgical procedure. While distant metastases affected actuarial survival, no factor independently predicted local recurrence. In six patients with local recurrence, nonpalpable disease was detected by I-131 scan. All were treated with ablation and remain disease-free (mean follow-up 42 months). Eight patients with local recurrence presented with palpable lesions; seven underwent surgery. While two patients developed repeated local recurrences, the other five remain disease-free (mean follow-up 52 months). Early detection and aggressive treatment of local recurrence improve survival in patients with well-differentiated thyroid carcinoma. To facilitate use of I-131, we advise total thyroidectomy for patients with well-differentiated thyroid carcinoma.

Gastric carcinoma metastatic to the breast.

A patient with signet ring adenocarcinoma of the stomach with metastatic disease to the breast treated at our institution is presented and added to the 14 cases reported in the literature. A review of the common clinical features and possible mechanisms of metastases is given. While the majority of patients present with symptoms referable to their gastric malignancy, the patient in this case initially sought treatment because of her breast mass. Metastatic deposits within the breast may be difficult to distinguish from primary breast carcinoma. For this reason, immunohistochemistry utilizing carcinoembryonic antigen (CEA), C-ERB B-2, and gross cystic protein were used in this case to confirm an extramammary source. In order to prevent unnecessary breast surgery and provide proper treatment of the gastric primary, the patient's complete clinical presentation must be used to guide diagnostic evaluation.

Extracellular ascorbic acid increases in striatum following systemic amphetamine.

Push-pull perfusion of the anterior striatum was performed in freely moving rats which were administered 4 mg/kg d-amphetamine sulfate. Ascorbic acid was measured in the perfusate using high performance liquid chromatography with electrochemical detection. Increased extracellular ascorbic acid resulted from the amphetamine, lasting over a period of two hours. The time course of the increase corresponded to the increased oxidation current measured by intrastriatal chonoamperometry under equivalent conditions.