Protease inhibitors show promise in HIV infection.
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Antiviral Agents↗
Biomedical subjects
H Nelson
Publications and source records attributed to H Nelson.
Pulmonary metastases neutralization and tumor rejection by in vivo administration of beta glucan and bispecific antibody.
Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant beta glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with Cl-62 melanoma cells and immediately treated with i.p. beta glucan and/or anti-CD3 (500A2) x anti-p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with Cl-62 cells and 7 days later administered beta glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the beta glucan + BsAb group, as compared with controls, and with beta glucan alone. In the established tumor model, beta glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with beta glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and beta glucan alone. We conclude that T cells can be activated in vivo by beta glucan and retargeted with F(ab')2 BsAb.
Adjuvants, Immunologic↗
Sacropelvic resection and intraoperative electron irradiation in the management of recurrent anorectal cancer.
PURPOSE: To provide local control and palliation of pain, a multimodal ity approach, including external beam radiation therapy, surgical resection, and intraoperative electron irradiation (IOERT), has been used for patients with locally advanced anal or recurrent rectal cancers involving the sacrum. METHODS: Sixteen consecutive patients (11 males; 5 females; ages, 44-76) underwent surgical exploration, sacrectomy, and IOERT, between 1990 and 1994. RESULTS: Proximal extent of resection was S2-3 in four patients, S3-4 in five, and S4-5 in five. Two patients had resection of the anterior table of the sacrum. Margins were clear in 11, close in 3, and microscopically involved in 2 patients. Operative times ranged from 6 to 17 (median, 12.5) hours, and blood loss ranged from 300 to 12,600 (median, 3,350) ml. No operative deaths resulted. Major postoperative complications occurred in eight patients (50 percent): posterior wound infections and dehiscence, urinary leak, and ileal fistula. Five (31 percent) and 3 (19 percent) patients developed no or minor complications, respectively. Intensive Care Unit stay was one night for all patients, and overall hospital stay ranged from 11 to 30 (median, 16.5) days. Follow-up was available on all 16 patients. Kaplan-Meier survival was 68 percent at one year and 48 percent at two years. At the time of analysis, 9 of 16 patients were alive. Of the nine alive patients who responded to a questionnaire, eight reported a reduction in pain and improved quality of life postoperatively. CONCLUSIONS: Sacropelvic resection, in conjunction with IOERT, provides palliation and offers potential for cure in patients with locally advanced or recurrent anorectal cancer.
Adult↗
Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group.
UNLABELLED: This study was undertaken to determine the early experience of the embers of the COST Study Group with colorectal cancer treated by laparoscopic approaches. METHOD: A retrospective review was performed of all patients with colorectal cancer treated with laparoscopy by the COST Study Group before August 1994. Tumor site, stage, differentiation, procedure completion, presence of recurrence (local, distant, trocar site), and cause of death were analyzed. RESULTS: A total of 372 patients with adenocarcinoma of the colon and rectum were treated by laparoscopic approach between October 1991 and August 1994 (170 men and 192 women): right colectomy, 170; sigmoid colectomy, 55; low anterior resection, 56; abdominoperineal resection, 44; left colectomy, 22; colostomy, 8; total colectomy, 6; transverse colectomy, 7; exploration, 2. Conversion to an open procedure was required in 15.6 percent of cases. Operative mortality was 2 percent. Tumor characteristics were as follows: TNM state: I, 40 percent; II, 25 percent; III, 18 percent; IV, 17 percent; Differentiation: well-moderate, 88 percent; poor, 12 percent; carcinomatosis, 5 percent. Local (3.6 percent) and distant implantation occurred in four patients (1.1 percent). Only one of these patients died a cancer-related death (Stage III at 36 months). Cancer-related death rates increased with increasing stage of tumor: I, -4 percent; II, 17 percent; III, 31 percent; IV, 70 percent. CONCLUSION: A laparoscopic approach to colorectal cancer results in early outcome after treatment that is comparable with conventional therapy for colorectal cancer. A randomized trial is needed to compare long-term outcomes of open and laparoscopic approaches with colorectal cancer.
Adenocarcinoma↗
Curative reoperations for locally recurrent rectal cancer.
PURPOSE: Our aims were to determine the morbidity, survival and its influencing factors, and patterns of failure for patients who underwent further surgery with the hope of cure for locally recurrent rectal cancer. METHODS: Between January 1981 and December 1988, 224 patients with a preoperative diagnosis of recurrent rectal cancer underwent additional surgery at Mayo Medical Center in Rochester, Minnesota. Of these, 65 underwent further surgery with the hope of cure, i.e., no gross/microscopic residual disease at tumor margins after reoperation. Factors assessed included type of original operation, time interval between operation for primary tumor and initial operation for recurrence, symptom status, degree of fixation, types of reoperations for recurrence, and adjuvant therapy. RESULTS: None of the patients died within 30 days of reoperation. Seventeen complications requiring hospitalization and/or surgical procedure were observed in 14 patients. Extended operations (involving partial or complete removal of surrounding organs/structures) required more time to perform, a greater number of transfusions, and a longer hospital stay than more limited operations. Three-year, five-year, and median survival were 57, 34, and 44.7 months, respectively. Survival was greater after curative than after palliative resection (P < 0.001). Survival tended to be greater in females (P < 0.075) and in patients without pain (P < 0.065). Cumulative probability of local failure was 24, 41, and 47 percent at 1, 3, and 5 years, respectively. Cumulative risk of distant metastasis was 30, 51, and 62 percent at 1, 3, and 5 years, respectively. CONCLUSIONS: Our results indicate that complete excision of locally recurrent rectal cancer can provide a significant number of patients with long-term survival and can be accomplished safely in select patients.
Antimetabolites, Antineoplastic↗
Intraoperative electron and external beam irradiation with or without 5-fluorouracil and maximum surgical resection for previously unirradiated, locally recurrent colorectal cancer.
PURPOSE/OBJECTIVE: 1) Disease control and survival will be evaluated for treatment regimens containing intraoperative electron irradiation (IOERT) for locally recurrent, previously unirradiated colorectal cancers. 2) Various prognostic factors will be evaluated to determine whether they have an impact on disease control or survival. MATERIALS AND METHODS: From April 1981 through August 1995, 123 patients with previously unirradiated locally recurrent colorectal cancers received IOERT at our institution, usually as a supplement to external beam irradiation (EBRT) and maximum resection. All received EBRT with or without concomitant 5-fluorouracil-based chemotherapy. Forty-five Gy in 25 fractions was given to the tumor or tumor bed plus 3-cm to 5-cm margins in 121 of 123 patients and a boost of 5.4 to 9 Gy in 3 to 5 fractions to the tumor plus 2-cm margins. Maximum resection was performed before or after EBRT. IOERT doses ranged from 10 to 20 Gy in 119 of 123 patients, with dose dependent on resection margins (130 fields in 123 patients). Maintenance chemotherapy was given to only two patients. RESULTS: Disease relapse and survival were evaluated. Central failure (within the IOERT field) was documented in 13 of 123 patients (11 percent) with a five-year actuarial rate of 26 percent. Local relapse (in EBRT field) occurred in 24 patients (20 percent); five-year rate was 37 percent. Distant metastases occurred in 66 patients (54 percent); five-year rate was 72 percent. Median survival was 28 months, with overall survival at two, three, and five years of 62, 39, and 20 percent, respectively. Tolerance data suggest a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy, 2 of 29 or 7 percent; > or = 15 Gy, 19 of 101 or 19 percent; P = 0.12). Survival and disease control were analyzed as a function of potential prognostic factors. None of the prognostic factors had a significant impact on disease control or survival. Although there was a trend for reduction in local relapse rates with gross total vs. partial resection, this neither achieved statistical significance nor translated into improved survival. Patients with gross residual disease after maximum resection had three-year and five-year survival rates of 36 and 18 percent, respectively, which paralleled results for patients with gross total resection at 41 and 24 percent, respectively. CONCLUSION: Encouraging trends for improved local control with or without survival exist in separate locally recurrent colorectal IOERT analyses from our institution and other institutions. Therefore, continued evaluation of IOERT approaches seems warranted. Disease control within the IOERT and external fields is decreased when the surgeon is unable to accomplish a gross total resection. Therefore, it is reasonable to consistently add 5-fluorouracil or other dose modifiers during EBRT and to evaluate the use of dose modifiers in conjunction with IOERT (sensitizers and hyperthermia). In view of high systemic failure rates of > 50 percent in patients with locally recurrent disease, more routine use of systemic therapy is indicated as a component of IOERT-containing treatment regimens (use existent chemotherapy and/or develop effective immunotherapy and gene transfer therapy). Even with locally recurrent lesions, the aggressive multimodality approaches including IOERT have resulted in improved local control and long-term survival rates of 20 percent vs. an expected 5 percent with conventional techniques.
Adult↗
111In-CYT-103 scanning in recurrent colorectal cancer--does it affect standard management?
PURPOSE: In a blinded fashion, radiolabeled B72.3 was investigated in operative cases of recurrent colorectal cancer to determine if diagnostic accuracy would be improved to ultimately maximize curability and minimize interventional morbidities. METHODS: Study patients underwent conventional evaluation including history, physical examination, abdominal/pelvic computed tomographic scan (CT), colon examination, and carcinoembryonic antigen (CEA) determination, with select magnetic resonance imaging and ultrasonographic imaging as indicated. Murine monoclonal antibody B72.3 was labeled with indium-111 (111In-CYT-103 provided by Cytogen) and scans obtained at 48 hours and, selectively, at 72 and 96 hours. Unlike previous studies, the operating surgeon was blinded to 111In-CYT-103 abdominal scan results until surgical exploration was complete. RESULTS: Of 15 study patients (10 male; 5 female), average age was 57 years, and average CEA was 10 ng/ml (with eight elevated CEA levels). A single patient did not undergo surgery because of presence of pulmonary metastases identified on CT scan but not identified on a 111In-CYT-103 scan. Laparotomies included resection and intraoperative radiation (10), resection alone (1), and biopsy only (3). CT and 111In-CYT-103 scans were compared with operative findings. CT scans had an accuracy and positive predictive value of 47 and 100 percent, respectively, whereas those of 111In-CYT-103 scan were 60 and 82 percent, respectively. Contribution of the scan to diagnosis and management was graded by the surgeon as no effect (67 percent), beneficial effect (13 percent), or negative effect (20 percent). CONCLUSIONS: 111In-CYT-103 was more accurate compared with CT scan, but when value of the scan was examined with respect to its potential contribution to patient management, it was beneficial in only 13 percent of patients. Further refinements may enhance the value of antibody imaging techniques.
Adenocarcinoma↗
Wound recurrence following conventional treatment of colorectal cancer. A rare but perhaps underestimated problem.
UNLABELLED: Reports of trocar and extraction site tumor recurrences following laparoscopic colectomy raise concern that such recurrences may be occurring more frequently with laparoscopic compared with open colectomy. Contemporary data on the incidence of incisional recurrence following open colectomy, in the age of adjuvant therapies, are not available. PURPOSE: This study was undertaken to examine the incidence and clinical features of wound recurrence in current prospective trials including 1,711 patients with primary adenocarcinoma of the colon or rectum treated for cure. METHODS: Files of all patients with recurrence (n = 623) were reviewed. Each site of recurrence was recorded separately. All patients have been followed prospectively, and 3-year and 4-year data are mature on 100 and 70 percent, respectively. Stage at diagnosis was B2 in 344 patients and C in 1,367 patients (> 4 nodes positive in 346 patients). RESULTS: Recurrence was identified in 623 patients (36.4 percent) and occurred at a mean of 1.5 years following primary treatment. Eleven patients (0.6 percent) had documented incisional recurrences (9 abdominal wound, 1 perineal wound, and 1 stoma wound). Only four were diagnosed clinically, and the remaining seven were diagnosed incidentally at reoperation. Of 11 patients with incisional wound recurrences, 2 had primary Stage B2 and 9 had primary Stage C disease. Nine of 11 patients were found to have multiple sites of recurrence at time of recurrence. At a mean follow-up of 1.8 years after recurrence, 3 of 11 patients are alive with disease, although 8 have died because of disease. CONCLUSIONS: Incisional recurrence is uncommon, although likely underestimated, following conventional treatment of colorectal carcinoma. Its occurrence is usually a harbinger of diffuse intra-abdominal disease. These data may provide useful information for investigations of laparoscopic approaches to colon cancer.
Aged↗
Detection of colorectal polyps by computed tomographic colography: feasibility of a novel technique.
BACKGROUND & AIMS: Computed tomographic colography (CTC) represents a novel technique for colorectal polyp detection. A prospective study was undertaken to determine the optimal CTC scanning parameters based on an artificial colon model and to assess the feasibility of CTC to detect clinically significant colorectal polyps. METHODS: A colon model was scanned by helical computed tomography at multiple parameters. Reformatted two-dimensional and three-dimensional images were then graded for polyp detection and image quality. Subsequently, 10 patients with known colon polyps underwent CTC immediately before colonoscopy. The number of polyps detected by two radiologists using CTC were compared with colonoscopy results that served as the gold standard. RESULTS: The optimal scanning parameters in the colon model were 5-mm collimation, 5 mm/s table speed, and 1-mm reconstruction interval. Ten patients had 30 polyps (range, 0.2-2.0 cm) by colonscopy, and all polyps > or = 0.5 cm were adenomas. Polyp detection by CTC for both observers was 100% (5 of 5) > or = 1 cm, 71% (5 of 7) between 0.5 and 0.9 cm, and 11%-28% (2-5 of 18) < 0.5 cm. CONCLUSIONS: Based on this small, unblinded pilot study, CTC is feasible for colorectal polyp detection > or = 0.5 cm in diameter.
Aged↗
Short external loops as potential substrate binding site of gamma-aminobutyric acid transporters.
While the gamma-aminobutyric acid (GABA) transporter GAT1 exclusively transports GABA, GAT2, -3, and -4 also transport beta-alanine. Cross-mutations in the external loops IV, V, and VI among the various GABA transporters were performed by site-directed mutagenesis. The affinity of GABA transport as well as inhibitor sensitivity of the modified transporters was analyzed. Kinetic analysis revealed that a cross-mutation in which loop IV of GAT1 was modified to resemble GAT4 resulted in increased affinity to GABA from Km = 8.7 to 2.0 microM without changing the Vmax. A cross-mutation in loop VI, which swapped the amino acid sequence of GAT2 for GAT1, decreased the affinity to GABA (Km, 35 microM). These results suggest that loops IV and VI contribute to the binding affinity of GABA transporters. A substitution of three amino acids in loop V of GAT1 by the corresponding sequence of GAT3 resulted in beta-alanine sensitivity of its GABA uptake activity. These three amino acids in loop V seem to participate in the beta-alanine binding domain of GAT3. It is suggested that those three external loops (IV, V, and VI) form a pocket in which the substrate binds to the GABA transporters.
Amino Acid Sequence↗
FDA advised to license three anti-HIV agents.
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Adult↗
Anti-CD3 x anti-tumor F(ab')2 bifunctional antibody activates and retargets tumor-infiltrating lymphocytes.
Bifunctional Abs (BFA) with specificity for the TCR/CD3 complex of T cells and tumor Ag can bridge T lymphocytes and tumor cells and, thereby, trigger activation events. The ability of intact and F(ab')2 anti-CD3 (500A2) x anti-p97 (96.5) BFA to induce activation of T lymphocytes in the presence of murine melanoma tumor cells (CL-62) expressing human melanoma-associated Ag (p97) was investigated in vitro and in vivo. Intact and F(ab')2 BFA induced significant proliferation of T lymphocytes in the presence of p97+ tumor cells. Incubation of splenocytes with intact or F(ab')2 BFA and p97+ tumor cells increased BFA-mediated cytotoxicity against relevant tumor cells. Intact BFA, in contrast to F(ab')2 BFA, induced some activation of T cells in vitro even in the absence of p97+ target cells. In nontumor-bearing mice, administration of F(ab')2 BFA, in contrast to intact BFA, did not increase cytotoxic activity of lymph node (LN) cells and splenocytes. However, when F(ab')2 BFA was administrated into CL-62-bearing mice, an increase of BFA-mediated cytotoxicity of tumor-infiltrating lymphocytes, but not splenocytes nor LN cells, was observed. Moreover, in D-galactosamine-sensitized mice, injection of intact BFA (1 microgram/mice) induced 100% lethality, whereas the same dose of F(ab')2 BFA was not toxic. These results demonstrate that F(ab')2 BFA can induce activation of cytotoxic lymphocytes only in the presence of relevant tumor cells, both in vitro and in vivo. That these activated lymphocytes can be redirected to lyse relevant tumor cells by the same BFA has important implications for the clinical application of BFA anti-tumor therapies.
Animals↗
Cloning and expression of a yeast gene encoding a protein with ATPase activity and high identity to the subunit 4 of the human 26 S protease.
The cloning, expression, and biochemical characterization of an essential gene of Saccharomyces cerevisiae that encodes for a new member of the TBP1-like subfamily of putative ATPases are described. The protein is 72% identical at the amino acid level to subunit four (S4) of the human 26 S protease and 73% identical to Schizosaccharomyces pombe MTS2 gene product. The purified, recombinant protein, designated Yhs4p, has an estimated molecular mass of 49 kDa and exhibits a Mg(2+)-dependent ATPase activity with nucleotide specificity and Km for ATP similar to those exhibited by the human 26 S protease. The observed ATPase activity was reduced by 73% upon the introduction of point mutation K229Q in the "P-loop" domain of the ATP-binding site relative to the nonmutated form of the protein. This is the first direct biochemical evidence supporting the putative ATPase activity of a member of the TBP1-like subfamily. Furthermore, the experimental results demonstrate a regulatory function for the amino-terminal region of the molecule. The amino-terminal truncated form of Yhs4p lacking two clusters of positively charged amino acids exhibits a greater ATPase activity. The ATPase activity of both the truncated and complete forms of Yhs4p is stimulated by polyanions. Polylysine partially inhibits the ATPase activity of the amino-terminal truncated form having no observable effect on the complete protein. N-Ethylmaleimide inhibits the ATPase activity of both forms of Yhs4p. We propose that Yhs4p ATPase may play an essential role in the regulatory function of the proteolytic activity of the yeast 26 S protease.
Adenosine Triphosphatases↗
A bovine cDNA and a yeast gene (VMA8) encoding the subunit D of the vacuolar H(+)-ATPase.
Subunit D of vacuolar H(+)-ATPase (V-ATPase) from bovine chromaffin granules was subjected to partial proteolysis and amino acid sequencing. A cDNA encoding this subunit was isolated and sequenced. The predicted open reading frame encodes a protein of 247 amino acids with a calculated molecular weight of 28,336. Northern blot analysis revealed an mRNA distribution with higher transcript amounts in tissues that are active in secretion. A homologous gene was identified as open reading frame 11 in chromosome V of Saccharomyces cerevisiae. The two proteins exhibit 55% identity with several conservative replacements. Interruption of the yeast gene, denoted as VMA8, resulted in the null mutant delta vma8::URA3 that, like all the other V-ATPase null mutants, did not grow on medium buffered at pH 7.5 and showed no accumulation of quinacrine into their vacuoles. Transformation of the null mutant with a plasmid containing the VMA8 gene restored the wild-type phenotype. This supports the conclusion that subunit D is an integral subunit of the catalytic sector of V-ATPase and its structural analysis suggests analogy to the gamma subunit of F-ATPases.
Adrenal Medulla↗
Management of sacral and perineal defects following abdominoperineal resection and radiation with transpelvic muscle flaps.
PURPOSES: In this study we present our experience with treating persistent sacral and perineal defects secondary to radiation and abdominoperineal resection with or without sacrectomy. METHODS: Fifteen consecutive patients were treated with an inferiorly based transpelvic rectus abdominis muscle or musculocutaneous flap. RESULTS: Fourteen of the 15 patients achieved healing, and 7 patients had no complications. The remaining eight patients required one or more operative debridements and/or prolonged wound care to accomplish a healed wound. Our technique for the dissection and insetting of the transpelvic muscle flap is presented. CONCLUSION: The difficult postirradiated perineal and sacral wounds can be healed with persistent surgical attention to adequate debridement, control of infections, and a well-vascularized muscle flap. The most satisfying aspects for patients are the discontinuance of foul-smelling discharge, discontinuation of multiple, daily dressing changes, and reduction in the degree of chronic pain.
Adult↗
Ileal pouch-anal anastomosis function following childbirth. An extended evaluation.
PURPOSE: Women undergoing ileal pouch-anal anastomosis (IPAA) are frequently within reproductive years and eager to bear children. Management issues have been raised regarding the effects of pregnancy and delivery on the pouch, particularly with respect to obstetric care. Our experience is updated to search for delayed sequelae of pregnancy and delivery and to establish whether other factors have an adverse effect on pouch function. These results are also compared with the outcome of pregnancy and delivery in patients with ileostomy or Kock pouch. METHODS: Records of 43 women who had a successful pregnancy and delivery following IPAA were reviewed, including 8 women who had more than 1 pregnancy. RESULTS: Pregnancy was generally well tolerated, with complications being managed nonoperatively. Stool frequency (P < 0.01), incontinence (P < 0.01), and pad usage (P < 0.05; sign rank test) were significantly increased during pregnancy, but prepregnancy function was restored following delivery. Vaginal delivery, multiple births, length of labor, and birth weight had no adverse permanent effect on subsequent pouch function. Longer follow-up after vaginal delivery (mean, 2.4 years) demonstrated no compromise of pouch function. CONCLUSIONS: Incidence of pouch-related complications in patients with IPAA compares favorably with incidence in patients with ileostomy or Kock pouch. Operative rate for complications was 0 percent in IPAA patients compared with 9 percent in patients with ileostomy and 19 percent in patients with Kock pouch. The cesarean section rate was higher in patients with IPAA than in those with ileostomy or Kock pouch, and this may be caused by uncertainty about how to manage delivery in patients with IPAA. Pregnancy and childbirth are well tolerated in women with IPAA, with a lower complication rate and a higher cesarean section rate than women with ileostomy or Kock pouch. Type of delivery should be influenced by obstetric considerations, with vaginal delivery avoided in patients with a noncompliant, rigid perineum.
Adult↗
Bifunctional antibody retargeting in vivo-activated T lymphocytes: simplifying clinical application.
For antitumor x anti-CD3 bifunctional antibody (BFA) therapy to be clinically relevant in solid tumors, activated lymphocytes must be present within tumors. Toward that end, three uniquely different in vivo activation approaches were investigated in a p97 human antigen expressing syngeneic murine melanoma model. beta-Glucan (200 micrograms), staphylococcal enterotoxin B (SEB) (50 micrograms), and F(ab')2 BFA (10 micrograms) were tested for their ability to activate lymphocytes, neutralize pulmonary metastases, and treat established tumors. Systemic activation, measured as the ability of splenocytes to lyse tumor cells in vitro in the presence of BFA, was enhanced by the in vivo administration of SEB but not by beta-glucan or F(ab')2 BFA. Despite lacking a systemic effect, F(ab')2 BFA increased both direct and BFA-mediated cytotoxicity in fresh tumor infiltrating lymphocytes. beta-Glucan did not increase systemic or intratumor T cell activation. However, it significantly enhanced the ability of splenocytes to lyse NK-sensitive YAC-1 cells. When tested in a pulmonary metastases model, all three forms of immune modulation combined with F(ab')2 BFA significantly reduced the number of metastases. BFA were more effective at tumor neutralization when combined with SEB compared with adoptively transferred, in vitro-activated splenocytes. These studies demonstrate that immune modulators when combined with F(ab')2 BFA can provide effective antitumor therapy. Several clinical obstacles may be overcome by the application of these reagents.
Animals↗
Perioperative blood transfusions do not affect disease recurrence of patients undergoing curative resection of colorectal carcinoma: a Mayo/North Central Cancer Treatment Group study.
PURPOSE: To evaluate the effect of perioperative blood transfusions on colorectal cancer recurrence and patient survival. PATIENTS AND METHODS: A total of 1,051 patients treated with curative surgery for stage II or III colorectal adenocarcinoma were retrospectively studied for the effect of perioperative blood transfusions on disease recurrence and patient survival. Forty-two percent of patients received perioperative blood components. RESULTS: Perioperative transfusions had no effect on disease progression in univariate or multivariate analysis. Tumor stage (P = .0001), locally advanced tumor characteristics (adherence, involvement of adjacent structure, or perforation; P = .0001), location (rectal v colon; P = .0002), grade (P < .001), and cell kinetic profile (nondiploid or high percent synthetic phase [%S]+ percent gap 2 mitosis phase [%G2M]; P = .0003) were the most powerful independent predictors of tumor recurrence. Use of transfusions was associated with an adverse effect on overall survival (P < .004) using multivariate analysis, as well as tumor stage (P = .0001), location (P = .004), grade (P = .001), patient age (P = .0001), sex (P < .04), and cell kinetic profile (P = .0001). In further evaluation of the prognostic effects of transfusions, there was no increased risk of disease recurrence after whole-blood transfusion (P = .14) as compared with packed RBC or no transfusions, although the disease-specific survival for patients who received whole blood was lower than for nontransfused patients (P < .0005) patients who received other blood components (P < .03). CONCLUSION: With transfusion practices that use blood components, most commonly RBCs, medically indicated transfusions to patients with colorectal carcinoma seem to have no impact on disease recurrence. The adverse impact of transfusions on cancer patient survival is more likely due to other unevaluated tumor variables or underlying illness rather than tumor recurrence enhancement by immunosuppression induced by transfusion of blood components.
Adenocarcinoma↗