Transfusion-associated graft versus host disease in the immunocompetent patient: an ongoing problem.

Transfusion associated-graft versus host disease (TA-GVHD) is a rare complication of blood transfusion. It carries a very high mortality rate. Although the phenomenon has been well described in immunocompromised patients, this review focuses on the immunocompetent host. Cases of TA-GVHD continue to be reported following a variety of surgical procedures, especially cardiac procedures requiring cardiopulmonary bypass. Additional risk factors for TA-GVHD include blood component transfusion in populations with limited genetic diversity, the use of directed donations from family members, and the transfusion of fresh blood. As there is no effective treatment, the focus is on prevention.

Analytic review: Interleukin-6 in surgery, trauma, and critical care: part I: basic science.

A variety of cytokines play a role in the response to an inflammatory stimulus. The interleukin-6 (IL-6)-type cytokines are released in response to tissue injury or an inflammatory stimulus. They act locally and systemically to generate a variety of physiologic responses, principal among them is the acute phase response. The IL-6 type cytokines demonstrate pleiotropy and redundancy of actions. This is made possible by the distinctive characteristics of the IL-6 receptor complex, which contains an ubiquitous subunit that is shared by most IL-6-type cytokines, as well as a cytokine-specific subunit.

Interleukin-6 in surgery, trauma, and critical care part II: clinical implications.

A variety of cytokines play a role in the inflammatory response. Interleukin-6 (IL-6)-type cytokines are released in response to tissue injury or an inflammatory stimulus, and act locally and systemically to generate a variety of physiologic responses. Interleukin-6 concentrations are elevated after surgery, trauma, and critical illness. The magnitude of IL-6 elevation correlates with the extent of tissue trauma/injury severity. Furthermore, there is an association between IL-6 elevation and adverse outcome. Interleukin-6 levels can also be used to stratify patients for therapeutic intervention.

Regional treatment of colorectal liver metastasis.

Compared to systemic chemotherapy, intraarterial administration of tumoricidal agents with or without systemic chemotherapy in the treatment of nonresectable metastatic colorectal cancer is associated with superior response rate. The time-to-hepatic progression is also increased but the effect on overall survival is variable. When combined with other treatment modalities the number of patients who benefit from the treatment increases. In a subgroup of patients with resectable disease, hepatic artery infusion of chemotherapy as adjuvant therapy may be beneficial. Progression of the disease, hepatic and systemic toxicity, and complexity of the surgical aspects of the treatment limit the routine use of this treatment modality.

Thermoablation of colorectal liver metastasis.

Thermoablation is a local therapy that is effective in in situ destruction of colorectal liver metastasis while preserving surrounding normal liver tissue. It is less invasive compared to surgery, easy to use, and can be repeated. The therapy provides local control of unresectable disease and is an alternative therapy for small resectable lesions in patients with insufficient hepatic reserve after resection or coexistent comorbid conditions. It can artificially increase the resection margin thus increasing the number of patient candidate for resection. When used in conjunction with liver resection it clears the liver of multiple lesions that are surgically inaccessible or unresectable. Main limitations of the treatment are local recurrence of the disease, treatment-related complications, and questionable impact on patient. Outcome of therapy can be improved when used as part of multimodality treatment.

Ulcerative colitis and cancer.

Patients with ulcerative colitis (UC) are at an increased risk for the development of colorectal cancer (CRC). Unlike sporadic CRC, the cancer in UC patients arises from a focal or multifocal dysplastic mucosa in areas of inflammation. The clinical features of UC-associated cancer are similar to those found in patients with hereditary non-polyposis colorectal cancer. As with other varieties of CRC, UC-associated cancer exhibits a variety of genetic and molecular changes/abnormalities. These abnormalities are however clustered in areas of mucosae with histological abnormalities. The magnitude and timing of these changes are however significantly different. Surveillance and identification of patients at risk for cancer are a challenging problem.

Should total number of lymph nodes be used as a quality of care measure for stage III colon cancer?

OBJECTIVE: To assess whether TNODS is an independent prognostic factor after adjusting for the lymph node ratio (LNR). SUMMARY BACKGROUND DATA: The medical literature has suggested that the TNODS is associated with better survival in stage II and III colon cancer. Thus TNODS was endorsed as a quality measure for patient care by American College of Surgeons, National Quality Forum. There is, however, little biologic rationale to support this linkage. METHODS: : A total of 24,477 stage III colon cancer patients were identified from Surveillance, Epidemiology, and End Results cancer registry and categorized into 4 groups, LNR1 to LNR4, according to LNR interval: <0.07, 0.07 to 0.25, 0.25 to 0.50, and >0.50. Patients were also stratified according to TNODS into high TNODS (> or = 12) and low TNODS (<12) groups. The method of Kaplan-Meier was used to estimate the 5-year survival and the log-rank test was used to test the survival difference among the different groups. RESULTS: Patients with high TNODS have better survival compared with those with low TNODS (5-year survival 51.0% vs. 45.0%, P < 0.0001). However, after stratifying by LNR status, there was no significant survival difference between patients with high TNODS and those with low TNODS within strata LNR2 (5-year survival 56.3% vs. 56.0%, P = 0.26). Ironically, patients with high TNODS had significantly worse survival than those with low TNODS within strata LNR3 (5-year survival 41.2% vs. 47.4%, P = 0.0009) and LNR 4 (5-year survival 22.0% vs. 32.1%, P < 0.0001). CONCLUSIONS: The previously reported prognostic effect of TNODS on node-positive colon cancer was confounded by LNR. This observation calls into question the use of TNODS as a quality measure for colon cancer patients' care.

Lymph node ratio: role in the staging of node-positive colon cancer.

BACKGROUND: Recent literature has shown that lymph node ratio (LNR) is superior to the number of positive lymph nodes (pLNs) in predicting the prognosis in several malignances other than colon cancer. We hypothesize that LNR may play a similar role in stage III colon cancer. METHODS: We included 24,477 stage III colon cancer cases from the Surveillance, Epidemiology, and End Results cancer registry. Patients were categorized into four groups, LNR1 to 4, according to cutoff points 1/14, 0.25, and 0.50. Kaplan-Meier and Cox proportional hazard model were used to evaluate the prognostic effect and estimate the relative risk (RR) and 95% confidence interval (CI) of LNR. RESULTS: The 5-year survival for patients with stage IIIA, IIIB, and IIIC was 71.3%, 51.7%, and 34.0%, respectively (P < .0001). There was no survival difference among LNR1 to LNR4 for stage IIIA patients. In stage IIIB patients, the 5-year survival for those with LNR1 to LNR4 was 63.5%, 54.7%, 44.4%, and 34.2%, respectively (P < .0001). In stage IIIC patients, the 5-year survival for those with LNR2 to LNR4 was 49.6%, 41.7%, and 25.2%, respectively (P < .0001). LNR is an independent predictor of survival after adjusting patient's age, tumor size, tumor grade, race, number of pLNs, and total number of LNs harvested. (RR 2.30, 95% CI 2.08-2.55). CONCLUSION: Patients with stage IIIB and IIIC colon cancer represent a heterogeneous group of patients with the majority either overstaged or understaged. LNR is a more accurate prognostic method for stage III colon cancer patients. We propose an algorithm to incorporate LNR into current AJCC staging system.

Large gaps of midline abdominal incisions and their management.

The operative management of midline full-thickness abdominal wall gaps is difficult, often requires several surgical procedures and is associated with significant short- and long-term complications. A rectus abdominis-posterior sheath (RAPS) flap with skin grafting provides a tension-free one-step repair which was used in three patients successfully with midline abdominal wall (including the skin) gaps who had multiple previous operations related to intra-abdominal malignancy. No complications occurred in these patients in relation to this procedure.

Modified anterior compartment resection of the thigh.

For large soft tissue sarcomas of the anterior thigh, an anterior compartment resection is often performed. This may leave the patient with the inability to extend the knee. In our practice, we find that it is usually possible to preserve one of the heads of the quadriceps, usually the vastus medialis, with intact innervation, and thus preserve significant extension function of the knee joint, while the requirements for a radical oncologic procedure are being met. The modified anterior compartment resection preserves one or more heads of the quadriceps and requires a thorough knowledge of the course and distribution of the branches of the femoral nerve from the level of the inguinal ligament to their termination at the individual heads of the quadriceps femoris.

Solitary papillary breast carcinoma metastasis to the large bowel presenting as primary colon carcinoma: case report and review of the literature.

Breast carcinoma has the potential for widespread dissemination. Spread to the lower gastrointestinal tract is infrequent, often multifocal, occurs in association with spread to other sites, and most commonly develops from lobular carcinoma. Solitary colorectal metastasis as the first and sole manifestation of spread is a rare occurrence and can be confused with primary intestinal malignancy. We present a case of metastatic papillary breast carcinoma presenting as a perforated primary colon cancer. Identity of the lesion was confirmed by direct histologic comparison of the resected tumor with prior breast specimen, cytokeratin expression, and the presence of estrogen receptors.

Cutdowns for totally implantable access ports to central veins.

For insertion of totally implantable access ports, with the catheter end in the superior vena cava, the percutaneous (Seldinger) technique is commonly used. Of cutdowns, the cephalic vein cutdown is the most popular one (success rate about 80%), followed by the external jugular vein cutdown. Our preliminary experience suggests that internal jugular vein and basilic vein cutdowns have the anatomic features to prove both of them superior to the cephalic vein cutdown.

Transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) refers to a clinical syndrome of acute lung injury that occurs in a temporal relationship with the transfusion of blood products. Because of the difficulty in making its diagnosis, TRALI is often underreported. Three not necessarily mutually exclusive hypotheses have been described to explain its etiogenesis: antibody mediated, non-antibody mediated, and two hit mechanisms. Treatment is primarily supportive and includes supplemental oxygen. Diuretics are generally not indicated, as hypovolemia should be avoided. Compared with many other forms of acute lung injury, including the acute respiratory distress syndrome, TRALI is generally transient, reverses spontaneously, and carries a better prognosis. A variety of prevention strategies have been proposed, ranging from restrictive transfusion strategies to using plasma derived only from males.

The prognostic superiority of log odds of positive lymph nodes in stage III colon cancer.

BACKGROUND: Literature showed that lymph node ratio (LNR) and total number of lymph nodes (TNODS) are independent prognostic factors in node-positive colon cancer. Our study assesses the prognostic superiority of the log odds of positive lymph nodes (LODDS) in the same patient population. MATERIAL AND METHODS: A total of 24,477 stage III colon cancer cases from the SEER registry were reviewed. Patients were categorized based on LNR into LNR1 to LNR4, according to cutoff points 0.07, 0.25, and 0.50, and based on LODDS into LODDS1 to LODDS5, according to cutoff points -2.2, -1.1, 0, and 1.1. The relative risk (RR), and 95% confidence interval (CI) were evaluated using the method of Kaplan-Meier and Cox model. RESULTS: Patients with LNR4 could be classified into LODDS4 (61.4%) and LODDS5 (38.4%). The survival in these two groups was significantly different (5-year survival, 33.5% vs. 23.3%, p < 0.0001). Univariate analysis showed that the higher LNR (RR = 3.45, 95% CI = 3.26-3.66) or low TNODS (RR = 0.99, 95% CI = 0.986-0.99) was significantly associated with poor survival. However, after adjusting for LODDS status, the association did not appear to be significant (LNR, RR = 0.90, 95% CI = 0.65-1.24, p = 0.52; TNODS, RR = 1.001, 95% CI = 0.997-1.005, p = 0.54). CONCLUSION: Colon cancer patients with LNR4 disease represent a heterogeneous group. The previously reported prognostic association of TNODS and LNR and outcome of stage III disease were confounded by LODDS.

What is new in cytokine research related to trauma/critical care.

Cytokines are low molecular weight proteins whose production can be modified by various insults. They have the potential to modify cellular responses to these insults. Recent years have seen a plethora of research in cytokine biology in trauma and critical care.

Gene expression profiles of late colonic Crohn's disease.

To determine the genetic program mediating and maintaining the change from susceptibility to Crohn's disease (CD) to ongoing tissue destruction and loss of function, we utilized Affymetrix HG U95 AV2 Gene Chips and analyzed unpooled surgical CD colon specimens from adult patients. Using the patient as his own genetic filter we examined involved versus uninvolved adjacent areas, comparing results within one individual and then performing analysis comparing results between four individuals. Our results interrogated twice as many genes than the previous studies that used pooled unmatched specimens. We identified a limited set of nine genes upregulated in all four patients, and one gene (PTN) as downregulated. Several of the genes, including DEFA6, PAP, REG1A, REG1B, and phospholipase A2 had been implicated in previous studies, supporting their key role in CD. In 3 of 4 patients, 24 genes were upregulated in diseased areas, including DEFA5, IL-8, MMP-1, S100 calcium binding protein, and MGSA. Additional new candidate genes were identified, including DMT1, SERPINA1, GW112, and iNOS. The use of the unpooled samples allowed the detection of significant interindividual differences in expression of many other genes, supporting disease heterogeneity in CD. Results with select genes were confirmed with RT-PCR studies, as well as on biopsy samples from pediatric patients. We have determined a common profile of "late" CD, and also demonstrated the potential variability, suggesting possible differences in etiology, triggers, and the need for more individualized management. Additional studies to investigate protein expression of these candidate genes should be undertaken.

Respiratory distress syndrome: principles and current therapy.

Acute respiratory distress syndrome (ARDS) describes a clinicopathologic disease process that occurs in association with a variety of clinical situations. The severity and outcome of this syndrome varies. Prolonged hospital stay, significant early morbidity and mortality, and long-term pulmonary parenchymal changes that result in reduced, often debilitating, pulmonary functions, typify the outcome of severe form of ARDS. Treatment is supportive with ventilatory assistance and adjunctive use of supplemental oxygen and end expiratory airway pressure (PEEP). Oxygen therapy and PEEP, though dramatically improve lung mechanics and oxygenation, are not innocuous and may adversely affect cardiovascular function and even induce pulmonary parenchymal injury. Over the years a variety of "lung protective" treatment modalities have been introduced and proved as effective and safe in the treatment of this syndrome

Free interferon-alpha/beta receptors in the circulation of patients with adenocarcinoma.

BACKGROUND: Many viral and neoplastic diseases are resistant to interferon-alpha/beta (IFN-alpha/beta) therapy or develop resistance during the course of IFN treatment. In patients with viral diseases, the authors identified four IFN inhibitors, of which the most important, most likely is a free IFN receptor of type 1 appearing in the circulation that captures and neutralizes IFN-alpha/beta. METHODS: Ninety-one cancer patients and 25 healthy individuals were studied. Free circulating IFN receptor-alpha/beta type 1 was studied. The patients were ages 35-75 years. The diagnoses were 24 cases of colon carcinoma, 7 cases of prostate carcinoma, 16 cases of breast carcinoma, 8 cases of ovarian carcinoma, 9 cases of uterine carcinoma, 5 cases of lung carcinoma, 3 cases of astrocytoma, 4 cases of transitional cell carcinoma of the bladder, 1 case of osteosarcoma, 3 cases of multiple myeloma, 4 cases of Hodgkin disease, 2 cases of non-Hodgkin lymphoma, 3 cases of myelodysplastic syndrome, and 2 disseminated tumors of unknown origin. RESULTS: All patients were found to have increased free IFN receptor-alpha/beta type 1 in the circulation, with the highest levels reported in patients with adenocarcinoma. CONCLUSIONS: High IFN inhibitory activity in patients with cancer may be a significant factor in their increased susceptibility to progressive disease, infectious complications, and resistance to IFN therapy. Ongoing studies are being performed with the objective of overcoming this inhibitory activity.

Embolization as cause of bowel ischemia after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: We investigated the incidence, cause, and outcome of large bowel and small bowel ischemia after endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Medical records for all patients undergoing endovascular AAA repair from December 1999 to December 2003 were reviewed. The incidence, cause, and outcome of clinically detected postoperative bowel ischemia were analyzed. RESULTS: Seven hundred two endovascular AAA repairs were performed. In 10 patients (1.4%) acute bowel ischemia developed. Six of these patients sustained concurrent small bowel necrosis, and the remaining 4 had isolated colon ischemia. Seven patients underwent exploratory laparotomy. In 6 of these bowel resection was performed, and in 1 patient the ischemic bowel was unsalvageable. Of the 6 patients with small and large bowel ischemia, 4 had segmental or patchy necrosis, which was separated by normal-appearing intestine, and 1 had extensive ischemia that involved most of the small bowel and the entire colon, with pathologic evidence of microembolization. Three patients had preoperative occlusion of the inferior mesenteric artery. One had unilateral and 1 had bilateral hypogastric artery interruption. Five of the 6 patients with small bowel ischemia had thrombus or atheroma in the proximal aneurysmal necks. All patients with isolated colon ischemia survived. All 6 patients with concurrent small bowel ischemia died. CONCLUSION: The total incidence of clinically evident bowel ischemia after endovascular AAA repair is similar to that after open surgery. However, small bowel ischemia occurs more commonly in patients with endovascular repair, and is associated with extremely high mortality. The direct pathologic evidence and the patterns of segmental, skipped, or patchy ischemia in most patients imply that microembolization has an important role.