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Biomedical subjects

M Z Papa

Publications and source records attributed to M Z Papa.

At least 37 records · Page 2Linked to original sources

Avoiding diarrhea after subtotal colectomy with primary anastomosis in the treatment of colon cancer.

BACKGROUND: Subtotal colectomy has been criticized as causing increased frequency of stool passage, thus adding to the patients' morbidity. We review our experience with subtotal colectomy and determine the factors affecting postoperative diarrhea. STUDY DESIGN: One hundred thirty-six patients with colon cancer were treated by primary subtotal colectomy. Of these, 30 percent underwent an emergency resection; 15 percent, semi-emergency resection; and 55 percent, elective subtotal colectomy. There were 29 complications and 3 deaths. RESULTS: The incidence of complications was higher when the operation was carried out on an emergency or semi-emergency basis. In assessing the patients' increased postoperative stool frequency, there was no difference between the groups; but, the length of the remaining colon and the resected terminal ileum had a significant effect on postoperative diarrhea. If less than 10 cm of terminal ileum is resected and more than 10 cm of colon is left above the peritoneal reflection, there is a marked decrease in the incidence of diarrhea after subtotal colectomy. CONCLUSIONS: Subtotal colectomy is an acceptable treatment for left colonic carcinoma, electively as well as in emergency situations. Postoperative diarrhea can be minimized by attention to the length of small bowel and sigmoid that are resected.

Adult↗

Sphingomyelinase and ceramide suppress insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1.

The sphingomyelin pathway is a newly described signal transduction pathway mediating the action of several cytokines including tumor necrosis factor-alpha (TNF). TNF was recently shown to interfere with insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1). In this work we examined the possible effect of direct activation of the sphingomyelin pathway on insulin-induced tyrosine phosphorylation of IRS-1. Incubation of the insulin-sensitive rat hepatoma Fao cells with bacterial sphingomyelinase (SMase) that causes membrane hydrolysis of sphingomyelin led to a time- and dose-dependent decrease in insulin-induced tyrosine phosphorylation of IRS-1. The effect was apparent after 10 min of incubation and with a dose of 10 milliunits/ml SMase. It was not associated with a decrease in insulin receptor autophosphorylation. In addition, SMase treatment interrupted the association of the 85-kDa catalytic subunit of phosphatidylinositol 3-kinase with IRS-1. A similar impact on IRS-1 tyrosine phosphorylation was observed after addition of cell-permeable ceramide analogs (C2 and C6). Comparable changes in IRS-1 tyrosine phosphorylation and electrophoretic mobility were found after exposure of cells to either TNF, SMase, or ceramide. Our findings suggest that TNF may utilize the sphingomyelin pathway in its effect on the insulin-stimulated tyrosine phosphorylation of IRS-1.

Animals↗

Vascular complications of total abdominal perfusion and aortic stop-flow infusion.

During a 2 year period (1992-1993), 149 patients with advanced abdominal cancer underwent total abdominal ischemic perfusion (TAP) and stop-flow infusion (SFI) 159 times in an attempt to achieve palliation. These procedures and aortic stop-flow infusion require insertion of balloon catheters into the abdominal aorta and inferior vena cava by a transfemoral approach. Flow is arrested for 15 minutes, during which time chemotherapeutic agents are infused into the aorta, distal to the balloon occlusion. Femoral access is by a surgical incision. The passage of the catheters is guided by fluoroscopy. Some tumor response was observed in 35% of the patients. Ten patients had major vascular complications; two iliac artery aneurysms were lacerated and required emergency repair. There were two femoral artery false aneurysms that required surgical correction, one early and one late. Aortic dissection was detected in four patients, but these did not require surgical intervention. Two patients had thrombosis distal to the occluded vessel, both required surgical intervention. To reduce the incidence of these vascular complications we recommend: (1) a clinical and vascular laboratory evaluation before the procedure, and (2) angiography of normal flow in patients with underlying vascular disease.

Abdominal Neoplasms↗

The effect of anesthesia type on needle localization breast biopsy: another point of view.

BACKGROUND: Efforts directed at early detection of breast cancer have resulted in an increased incidence of nonpalpable mammographic lesions that warrant excisional biopsy. The most common localization method is by use of the hook wire technique, or needle localization biopsy. Although much has been written about the localization technique, the impact of the method of anesthesia on the accuracy of the biopsy and especially on the completeness of the excision has not been clarified. PATIENTS AND METHODS: We studied 450 needle localization breast biopsies to determine whether the type of anesthesia (local versus general) influenced the accuracy and completeness of the biopsy. We compared 153 biopsies performed under local anesthesia to 297 done under general anesthesia. RESULTS: The use of local versus general anesthesia did not affect accuracy; however, it did determine the inability to achieve clean margins (27.6% versus 7.3%, respectively, P <0.02). It was more difficult to excise completely specimens located deeper than 3 cm in the breast, when the localizing needle travelled more than 3 cm, and when the lesions were of the microcalcification mammographic pattern. CONCLUSIONS: For lesions mammographically suspicious for malignancy, mainly those located deeper than 3 cm, general anesthesia is preferred.

Anesthesia, General↗

Regional hyperthermic perfusion with cisplatin following surgery for malignant melanoma of the extremities.

BACKGROUND: The study was undertaken to review our experience in the treatment of extremity melanoma with hyperthermic isolated limb perfusion (HILP), using cisplatin as the chemotherapeutic agent. We also evaluated the best timing for regional lymph node dissection in relation to the perfusion. PATIENTS AND METHODS: Sixty patients with advanced malignant melanoma of the limbs were treated with HILP used mainly as an adjuvant treatment. There were 56 lower- and 4 upper-limb HILPs. Cisplatin was used at a dose of 20 mg/L of limb volume. Temperature at the tumor site was 39 degrees C to 40 degrees C. Postoperative complications, disease-free period, and time to recurrence were recorded. RESULTS: There were no deaths related to the procedure. Forty-seven percent of the patients developed local complications; most complications were minor and resolved within 60 days. The local complication rate was higher when HILP was performed shortly after or simultaneously with regional lymph node dissection. None of the patients had systemic complications. Mean survival time from treatment was 87.2 months. Currently, 35 patients (58%) are alive and free of disease 52.7 +/- 22.5 months after HILP. Twelve patients (20%) are alive with recurrent disease, of which 5 recurred locally. The average time (+/- standard error of the mean) to recurrence was 24.5 +/- 13.8 months after perfusion. CONCLUSIONS: HILP with cisplatin is a relatively safe procedure, which seems to increase locoregional control of advanced malignant melanoma of the extremity. Separating the timing of lymph node dissection from HILP by 6 to 8 weeks reduces the complication rate.

Aged↗

A point scoring system for the clinical diagnosis of Buerger's disease.

INTRODUCTION: The literature on thromboangiitis obliterans (TAO, Buerger's disease) suffers from the lack of a unified method of establishing the diagnosis of the disease. The aim of this study was to test the application of a point scoring system (PSS) in the diagnosis of TAO. METHOD: Points are awarded for young age at onset, foot claudication, upper extremity involvement, superficial vein thrombosis and vasospastic phenomena. Atypical features detract points, and the resultant score classifies the diagnosis of TAO as being of low, medium or high probability. One hundred and seven patients diagnosed and classified according to our previous accepted criteria for TAO, were independently reclassified by the PSS, and the results of the two diagnostic processes were compared. RESULTS: Of the 107 patients diagnosed by our old criteria (OC) the diagnosis of TAO was rejected by the PSS in 20 patients. Of the remaining 87 patients the degree of certainty in the diagnosis (PSS vs. OC) was lower in 31 equal in 47 and higher only in nine. CONCLUSION: The proposed PSS is more discriminating than our OC. If this type of scoring system can be agreed upon the certainty in the diagnosis of TAO would be increased. Data collection would be improved, and the cause of clinical and basic research would be advanced.

Adult↗

Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1.

Tumor necrosis factor-alpha (TNF) has been suggested to be the mediator of insulin resistance in infection, tumor cachexia, and obesity. We have previously shown that TNF diminishes insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). The current work examines potential mechanisms that mediate this event. TNF effect on IRS-1 in Fao hepatoma cells was not associated with a significant reduction in insulin receptor tyrosine kinase activity as measured in vitro but impaired the association of IRS-1 with phosphatidylinositol 3-kinase, localizing TNF impact to IRS-1. TNF did not increase protein-tyrosine phosphatase activity and protein-tyrosine phosphatase inhibition by vanadate did not change TNF effect on IRS-1 tyrosine phosphorylation, suggesting that protein-tyrosine phosphatases are not involved in this TNF effect. In contrast, TNF increased IRS-1 phosphorylation on serine residues, leading to a decrease in its electrophoretic mobility. TNF effect on IRS-1 tyrosine phosphorylation was not abolished by inhibiting protein kinase C using staurosporine, while inactivation of Ser/Thr phosphatases by calyculin A and okadaic acid mimicked it. Our data suggest that TNF induces serine phosphorylation of IRS-1 through inhibition of serine phosphatases or activation of serine kinases other than protein kinase C. This increased serine phosphorylation interferes with insulin-induced tyrosine phosphorylation of IRS-1 and impairs insulin action.

Alkaloids↗

Cardiac metastasis of liposarcoma.

The authors describe a retroperitoneal liposarcoma with secondary involvement of the left ventricle. Therapy has been disappointing, and is guided by the nature of the primary tumor, previous therapy, extent of metastatic spread, and feasibility of cardiac resection. In selected patients whose primary tumor is well-controlled and progressing slowly, with no evidence of widespread disease, resection of the cardiac metastases can be performed when technically feasible.

Echocardiography↗

Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates.

Tumor necrosis factor-alpha (TNF) has recently been shown to induce insulin resistance. We have examined the possible effect of TNF on the early events in insulin transmembrane signaling. Incubation of the insulin-sensitive rat hepatoma Fao cells with 5 nM TNF for 1 h led to a 65% decrease in insulin-induced tyrosine phosphorylation of both the insulin receptor beta-subunit and IRS-1, its major cytosolic substrate. TNF-induced impairment of tyrosine phosphorylation was maximal at 0.5 nM and was not accompanied by any reduction in insulin binding. Sixteen hours of TNF incubation led to further impairment in insulin-induced tyrosine phosphorylation of these proteins. Our findings suggest that TNF may exert its anti-insulin effect by interrupting the early insulin-stimulated tyrosine phosphorylation events, which are crucial to insulin transmembrane signaling.

Animals↗

Serum insulin-like growth factor-binding protein-2 (IGFBP-2) is increased and IGFBP-3 is decreased in patients with prostate cancer: correlation with serum prostate-specific antigen.

Insulin-like growth factors (IGFs) are potent mitogens that stimulate the growth of prostate cells. In serum, IGFs circulate bound to IGF-binding proteins (IGFBPs), which modulate their proliferative action. We studied the electrophoretic pattern of IGFBPs in the serum of patients with prostate cancer and in individuals with increased serum levels of prostate-specific antigen (PSA) in the absence of prostate malignancy. Serum IGFBP-2 was dramatically increased in patients with metastatic prostate cancer compared with healthy controls (23.83 +/- 6.93% vs. 2.95 +/- 0.52% of total serum IGFBPs; P < 0.02). A moderate rise in IGFBP-2 was also observed among patients with increased PSA without malignancy. In contrast, a decrease in serum IGFBP-3 was detected in most patients with metastatic prostate cancer (68.2 +/- 9.1% vs. 95.4 +/- 0.9% of total serum IGFBPs; P < 0.02) and was more pronounced in advanced cases. A highly significant correlation between serum IGFBP-2 and PSA levels was found (r = 0.62; P < 0.002), with a significant negative correlation between serum PSA and IGFBP-3 (r = -0.63; P < 0.002). We suggest that IGFBPs may be involved in growth modulation of prostate malignancy and that alterations in their serum levels may serve as a marker for prostate cancer.

Aged↗

Use of photodynamic therapy in the palliation of massive advanced rectal cancer. Phase I/II study.

Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm2). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications.

Adenocarcinoma↗

Comparative biodistribution and antibody-dependent cellular cytotoxicity of native and heavy chain chimeric antibody.

We have recently chimerized the heavy chain of the pan-carcinoma monoclonal antibody (mAb) B72.3. Studies were undertaken to compare the IgG1 chimeric antibody, B72.3-1-3 with native murine B72.3 (nB72.3). Using fluorescence-activated cell sorting analysis, B72.3-1-3 demonstrated specific binding to fresh LS174T tumor cells. Biodistribution of 131I B72.3-1-3 was similar to 131I nB72.3 in nude mice bearing LS174T xenografts. Peak radiolocalization indices were noted on day 6 for B72.3-1-3 and day 8 for nB72.3. Both antibodies were capable of imaging LS174T tumors by radioimmunoscintigraphy. Antibody-dependent cellular cytotoxicity of LS174T by human peripheral blood lymphocytes was tested in 8h 51Cr release assays. With either no antibody or nB72.3, lymphocytes were not capable of killing LS174T cells. However, B72.3-1-3 at a concentration of 5 and 50 micrograms/ml mediated significant lysis of tumor cells by human lymphocytes. These results suggest that chimeric antibodies retain their binding properties to tumor cells and display biodistribution patterns similar to their unmodified counterparts. Such modifications may reduce the deleterious human antimouse antibody response to murine mAbs as well as augment antibody-dependent cellular cytotoxicity of tumor cells by human effectors.

Animals↗

Is age an independent variable in the morbidity and mortality of patients with colorectal cancer? A prospective study.

The authors examine prospectively the results of a single surgeon (H.S.S.), using a computerized database to determine the effect of age on morbidity and mortality in the management of colorectal cancer. Computer input was performed by a nurse data manager (20 minutes per patient), and data retrieval required approximately 30 minutes of computer time. Between 1984 and 1989, 241 patients with primary colorectal cancer underwent operation. The average age was 67.9 years (range from 31 to 94 years). The authors compared 108 (44.8%) patients who were older than 70 years with 133 (55.2%) patients who were 70 years of age or younger. Rectal carcinoma was more common in the younger age group (41.3% v. 20.4%), but right-sided carcinoma was more common in the older age group (36.1% v. 19.6%, p less than 0.001). Bleeding was more frequent in the younger patients than in the older ones (51.9% v. 35.2%, p less than 0.01). There was no difference between the two groups in tumour staging, using the modified Dukes' classification. The overall mortality was 2.5% and morbidity was 39.4%, with no significant differences between the groups. The authors conclude that age should not be a determinant in consideration of operation for colorectal cancer and that a personal computerized database facilitates simple prospective studies.

Adult↗

Cyclic neutropenia with colonic perforation and nonhealing colocutaneous fistula.

Cyclic neutropenia is an hereditary disorder of white blood cells, characterized by profound neutropenic episodes approximately every three weeks. Septic complications are usually limited to cutaneous and oropharyngeal infections. A 4-year-old boy with known cyclic neutropenia was in shock with neutropenia, clostridial septicemia, and right lower quadrant peritonitis when he was admitted. At the time of laparotomy, inflammation of the cecum, with no gross perforation, was found; no resection or appendectomy was done. He subsequently developed a right lower quadrant abscess that was drained, resulting in a colocutaneous fistula. For the next 8 months his fistula persisted, with intermittent episodes of fever, increased fistula output, and abdominal pain during his neutropenic periods. Standard nonoperative approaches to healing the fistula failed (ie, elemental feeds, total parenteral nutrition, irrigations, antibiotics, and drains). Attempts to medically abolish his neutropenic episodes using lithium, gammaglobulin, and steroids also failed. Ultimately, he underwent an ileocecal resection with primary anastamosis; the operation was done immediately following a neutropenic episode, in order to allow adequate healing of his anastamosis before his next period of neutropenia. Postoperative course was satisfactory, and he remains well after 8 months follow-up. This case, and several similar previously reported cases, illustrate that cyclic neutropenia may present with serious surgical complications. They also underlines the important role that neutrophils play in the healing of enteric fistulae.

Agranulocytosis↗

Surgical morbidity in patients with systemic lupus erythematosus.

Thirty-six surgical procedures were performed on 29 patients with systemic lupus erythematosus (SLE). Nineteen cases involved active lupus at the time of surgery and 11 were performed on an emergent basis. Most patients had multiple organ involvement and were on some form of systemic therapy at the time of surgery. Thirty-seven postoperative complications were confined to 20 of these cases. Comparing this complicated group with the remaining 16 uncomplicated cases, the patients in the former group had a higher mean dose of steroid preoperatively, more organ involvement by SLE, and more frequent renal involvement; a higher percentage of the cases in this group were emergent rather than elective. The majority of factors examined failed to show predictive value in the outcome of surgery in lupus patients. We conclude that surgical complications are frequent in SLE patients and have identified four factors predictive of increased morbidity.

Adolescent↗

Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors.

We have evaluated the effects of chemotherapeutic agents on the toxicity and antitumor benefit of therapy of established murine tumors by high-dose interleukin 2 (IL-2). Cyclophosphamide (Cy), doxorubicin, and bischloroethylnitrosourea were given to normal mice prior to IL-2 administration to test the effects of these agents on IL-2-induced toxicity. Cy at doses of 100 mg/kg and 150 mg/kg completely protected mice from a 100% lethal dose of IL-2, and doses of 50 mg/kg and 150 mg/kg allowed the administration of a median of 4.5 and 10.0 more doses of IL-2, respectively, before death from IL-2 toxicity occurred. Doxorubicin at 8 mg/kg and bischloroethylnitrosourea at 20 mg/kg did not impact on toxicity in IL-2-treated mice. In mice bearing pulmonary metastases of the weakly immunogenic MCA-105 sarcoma, IL-2 increased median survival time from 33 (no IL-2) to greater than 60 days for all doses of IL-2 tested when combined with a single injection of Cy at 75 mg/kg (P less than 0.002). Increasing doses of either Cy or IL-2 produced increasing benefits on survival which were always greater than either treatment alone. These effects of Cy and IL-2 were also seen in mice bearing the nonimmunogenic MCA-101 sarcoma and a murine adenocarcinoma (MCA-38). Doxorubicin and bischloroethylnitrosourea did not consistently enhance the effects of IL-2 treatment. Cy appears to reduce the yield of in vivo generated lymphokine-activated killer cells, but these lymphokine-activated killer cells are still lytic for fresh tumor targets in vitro. Thus, the mechanism of this synergy does not appear to involve stimulation of lymphokine-activated killer cell activity, but may in part involve reduction of tumor burden by the chemotherapeutic agent, an increase in susceptibility of tumor to cellular immune lysis, and/or a decrease in suppressor cell activity mediated by the chemotherapy.

Animals↗

Intra-abdominal extrahepatic disease in patients with colorectal hepatic metastases.

The resection of hepatic metastases in patients with extrahepatic disease is of no proven benefit. Preoperative identification of extrahepatic disease may prevent unnecessary laparotomy. Preoperative evaluation including physical examination, computed tomography of the abdomen, full lung tomography or chest-computed tomography, and radionuclide bone scanning identified extrahepatic metastases, most commonly in the lung, in 25 of 132 patients with purported isolated liver metastases. Of 107 patients with negative staging evaluations, intra-abdominal extrahepatic metastases were found in 26 percent (28 of 107) at laparotomy, most commonly in portal and celiac lymph nodes. The presence of extrahepatic disease correlated with greater than 25 percent hepatic replacement by tumor, presence of symptoms, and Dukes' C primary lesions; however, none was predictive. We were unable to develop a model to preoperatively predict the presence of intra-abdominal extrahepatic disease. The authors recommend a preoperative evaluation including physical examination, and computed tomographic scans of the abdomen and chest. A bone scan is required only in patients with symptoms referable to bone. Despite a negative preoperative evaluation, however, a considerable proportion of patients with colorectal hepatic metastases will have extrahepatic disease at the time of abdominal exploration.

Abdominal Neoplasms↗