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M Mohiuddin

Publications and source records attributed to M Mohiuddin.

At least 73 records · Page 4Linked to original sources
PubMed1996

Different immune effects on cardiac allografts and xenografts induced by neonatal intrathymic inoculation with allogeneic and xenogeneic antigens.

BACKGROUND: In a previous study we demonstrated that intrathymic exposure of neonatal rats to both alloantigens and xenoantigens produced tolerance only to subsequent cardiac allografts and not to xenografts implanted when the animals were 6 weeks old. Interestingly, graft recipients were not sensitized to the xenografts as observed in the adult model. This study was designed to investigate whether earlier grafting would produce tolerance to cardiac xenografts in animals pretreated by neonatal intrathymic inoculation with allogeneic and xenogeneic cells. METHODS: All recipient animals were Lewis rats. Donors were either Lewis Brown Norway rats or Golden Syrian hamsters. Lewis Brown Norway rat and hamster splenocytes (25 x 10(6) cells in a volume of 0.01 ml) were inoculated percutaneously into the thymus of neonatal recipients (n = 22). At age 4 weeks, five pretreated recipients underwent cervical heterotopic heart transplantation with rat hearts, and 2 weeks later abdominal heterotopic transplantation was done with hamster donors. A second group ( n = 6) received hamster hearts as the first graft and then grafts from rat donors. The third group underwent rat followed by hamster heart transplantation at age 6 to 7 weeks. RESULTS: Mean rat allograft survival time for groups 1,2, and 3, respectively was 49.8 days with 4 of 5 surviving indefinitely, 4.3 days with 2 of 3 surviving indefinitely, and 42 days with 7 of 11 surviving indefinitely (p < 0.01 versus untreated control animals, 7.8 days, n = 5). In rats undergoing transplantation at 4 weeks, cardiac xenografts were rejected in 2.5 days 2.3 days, which was significantly shorter than xenograft survival (3.3 days) in rats that underwent transplantation at an older age (p < 0.02), in naive rats (p < 0.05), and in rats treated with hamster cells alone (p < 0.05). Mixed lymphocyte reaction showed a diminished proliferative response to Lewis Brown Norway rat cells in pretreated rats, which retained the ability to respond in culture to hamster cells (p < 0.05). CONCLUSIONS: Earlier grafting in rats pretreated as neonates produces allograft tolerance but may accelerate rejection of xenografts. Preliminary mixed lymphocyte reaction results suggest that only the alloimmune cellular proliferative response is abrogated by this pretreatment.

Animals↗
PubMed1995

Dosimetric properties of megavoltage grid therapy.

PURPOSE: Grid therapy is a technique used to deliver a high dose of radiation (15-20 Gy) in a single fraction to many small volumes within a large treatment field. This treatment modality is used for the palliative treatment of large, deeply seated tumors, which have either been treated to tolerance with conventional radiation, or, due to massive tumor bulk, would most likely not benefit from a conventional course of radiation therapy. As the dose distribution from megavoltage grid therapy differs significantly from that of conventional radiation therapy (i.e., many large dose gradients exist within the tumor volume), we have measured various dosimetric properties inherent in this unique treatment modality. METHODS AND MATERIALS: The grid is a 16 x 16 array of 1-cm diameter holes in a 7-cm thick piece of custom blocking material. The ratio of shielded to open surface area is 1:1. Depth dose, valley-to-peak ratios, and output factors for this square array grid were measured in a water phantom for several field sizes, as well as for a 1-cm diameter narrow beam using 6 MV and 25 MV photon beams. RESULTS: The depth dose curves for the grid fields lie between those for an open portal and a narrow beam. For the 6-MV beam at dmax, the ratios of the doses delivered to the center of the shielded regions to that under the center of the holes, expressed as valley-to-peak ratios, range from 15 to 40%. At 10 cm, the ratios increase to between 25 and 45%. At 25 MV at both dmax and 10 cm, the valley-to-peak ratios are between 40 and 60%. The output factors, 0.89 for 6 MV and 0.77 for 25 MV, do not depend on field size. CONCLUSION: Megavoltage grid therapy is a unique treatment modality where the dose is delivered differentially to a large volume in one fraction. Characterization of the dosimetric properties has allowed clinical implementation of the grid.

Radiation Protection↗
PubMed1995

Thermal response and hyperthermic radiosensitization of scid mouse bone marrow CFU-C.

PURPOSE: Scid mice are severely immunodeficient as a result of a defective recombinase system. Mice with the scid mutation have been shown to have an increased sensitivity to ionizing radiation, presumably as a result of an inability to repair DNA damage. Little is known of the impact of this mutation on the thermal response and on hyperthermic radiosensitization. This investigation established the thermal response (42-44 degrees C), patterns of thermotolerance development, and the impact of hyperthermia (60 min at 40 degrees C or 42 degrees C) on the radiation response of bone marrow colony forming unit-culture cells (CFU-C) in scid mice. METHODS AND MATERIALS: Anesthetized scid mice (pentobarbital, 90 mg/kg) were killed by cervical dislocation and the nucleated marrow obtained from both tibia and femora by passing 2 ml of cold McCoy's 5A medium supplemented with 15% fetal bovine serum through each bone. Single cell suspensions of nucleated marrow were heated in 12 x 75 mm sterile tissue culture tubes at a concentration of approximately 5 x 10(6) cells/ml. Radiation, when used, was delivered immediately prior to hyperthermia by a 137Cs irradiator (dose rate of 1.20 Gy/min). Colony forming unit-culture were cultured in semisolid agar in the presence of colony stimulating factor (conditioned medium from L929 cells) for 7 days. RESULTS: The slope of the radiation dose-response curve for CFU-C in scid mice was biphasic, the Dos (+/- SE) were 0.29 +/- 0.03 Gy and 1.09 +/- 0.20 Gy, respectively. The Dos of the radiation dose-response curve for wild type marrow from CB-17 and Balb/c mice were 1.28 +/- 0.05 Gy and 1.47 +/- 0.15 Gy, respectively. The Dos of the hyperthermia dose-response curves for scid mice were 75 +/- 5, 10 +/- 1.4, and 4 +/- 0.2 min, respectively, for temperatures of 42 degrees, 43 degrees, and 44 degrees C. Thermotolerance development at 37 degrees C increased to a maximum at approximately 240 min after acute hyperthermia (15 min at 44 degrees C) and thereafter, decreased to control levels within 15 h. Thermotolerance did not develop in scid CFU-C during chronic hyperthermia at temperatures < 42.5 degrees C. Hyperthermia (60 min at 40 degrees or 42 degrees C) immediately after ionizing radiation did not significantly alter the terminal slope of the radiation dose-response curve of scid CFU-C (Do = 1.28 +/- 0.08 Gy). By contrast, hyperthermia following radiation of wild type CFU-C resulted in a decrease in the Do from 1.47 +/- 0.05 Gy (Balb/c, rad only) to 1.31 +/- 0.08 or 1.06 +/- 0.18 Gy for 60 min at 40 degrees or 42 degrees C, respectively. CONCLUSION: These results show that the thermal response and the pattern of thermotolerance development of scid CFU-C were similar to that of wild type Balb/c CFU-C, but that hyperthermia given immediately after ionizing radiation did not alter the radiation response of scid CFU-C. The scid mutation does not increase hyperthermic sensitivity or change the pattern of thermotolerance development of scid mouse CFU-C, implying that the scid mutation is not involved with thermal response, but does render the already radiation-sensitive scid cells incapable of thermal radiosensitization.

Animals↗
PubMed1995

Does pathologic node status affect local control in patients with carcinoma of the head and neck treated with radical surgery and postoperative radiotherapy?

PURPOSE: To evaluate the effect of pathologic lymph node status and nodal stage on local control at the primary site in patients with advanced squamous cell carcinomas of the head and neck, treated with radical surgery and postoperative irradiation. METHODS AND MATERIALS: Fifty-seven patients with advanced squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx, larynx, and supraglottic larynx were analyzed. All patients underwent resection of the primary lesion, neck dissection, and postoperative radiotherapy. Minimum follow-up was 2 years. The median dose to the primary tumor bed was 60.4 Gray (range 39.7-72.0). Besides pathologic nodal status (pN0 vs. pN+) and nodal stage, the following factors were analyzed for their impact on local control: age, gender, T stage, tumor grade, resection margins, interval from surgery to irradiation, dose to the primary site, and overall treatment time. RESULTS: The 3-year actuarial local control rate was 78%. When all patients were analyzed, nodal status (pN0 vs. pN+) did not affect control at the primary site (71% vs. 82%, p = 0.42). Nodal stage (pN0-N2a va. pN2b-N2c) was also not a significant factor for local control (74% vs. 82%, p = 0.57). When only patients with negative margins were analyzed, nodal status again did not impact on local control (79% vs. 90% for pN0 vs. pN+, p = 0.39). On univariate analysis, only tumor grade, margin status, and elapsed days were significant factors for local control. Local control was 85% for patients with negative margins vs. 60% for those with positive margins (p = 0.016). For patients with moderately and poorly differentiated tumors, local control was 86% as compared to 50% for patients with well-differentiated tumors (p = 0.007). When radiotherapy was completed within 50 days, local control was 93% as opposed to 63% for > 50 days (p = 0.016). On multivariate analysis, only margin status (p = 0.002) and tumor grade (p = 0.007) remained significant. CONCLUSION: We conclude that neither the presence of pathologically positive nodes nor nodal stage is a prognostically significant factor for local control in patients who have undergone radical surgery and postoperative radiotherapy for advanced squamous cell carcinomas of the head and neck. We do not recommend a change in treatment philosophy, such as an increase in dose to the primary site, based on the pathologic status of the neck.

Carcinoma, Squamous Cell↗
PubMed1995

Radical and local excisional methods of sphincter-sparing surgery after high-dose radiation for cancer of the distal 3 cm of the rectum.

BACKGROUND: Despite conventional attitudes that interdict sphincter-preservation surgery (SPS) for cancers arising in the terminal 3 cm of rectum, we have selectively employed high-dose preoperative external radiation (HDPER) and either radical or local excisional SPS techniques for rectal cancer arising between the 0.5 and 3 cm levels above the anorectal ring. We have reported a preliminary experience with HDPER and full-thickness local excision (FTLE) and three different methods of radical SPS. We now describe our experience with a single method of radical excision, transanal abdominal transanal proctosigmoidectomy with coloanal anastomosis (TATA) and FTLE in conjunction with HDPER for cancers of the distal 3 cm of rectum based on specific guidelines. METHODS: Since 1984, 109 patients with cancers at or below the 3 cm level have been treated with HDPER in doses of 4,500-7,000 cGy and a sphincter-preserving radical or local excision method in a prospective rectal cancer management program. Sixty-five patients (group A) underwent transanal abdominal transanal radical proctosigmoidectomy with colonal anastomosis (TATA) and 44 patients (group B) underwent FTLE. RESULTS: There was one death (1%). Mean follow-up was 40 months. Local recurrence rates for groups A and B were 9 and 14%, respectively. Kaplan-Meier 5-year actuarial survival was 85 and 90% for groups A and B, respectively, and 87% collectively. CONCLUSION: Experience with 109 patients with cancers of the distal 3 cm of rectum indicates that SPS can be accomplished by either radical or local excisional methods with acceptable local control and survival if HDPER and strict selection guidelines are employed.

Adult↗
PubMed1995

Suppressor cells and intrathymic inoculation of donor alloantigens in cardiac transplantation.

BACKGROUND: Donor-specific tolerance to a rat heterotopic cardiac allograft has been achieved by the pretransplantation intrathymic injection of donor splenocytes and a single intraperitoneal injection of antilymphocyte serum (ALS). Permanent tolerance is achieved without subsequent immunosuppression therapy. This study investigated the mechanisms responsible for maintenance of the tolerant state. METHODS: Tolerance was produced in Lewis rats by the administration of 1 mL of ALS intraperitoneally and 5 x 10(7) Lewis Brown Norway (LBN) splenocytes intrathymically 21 days before heterotopic transplantation using an LBN donor. RESULTS: In tolerant Lewis rats bearing LBN allografts for more than 100 days, rejection could not be produced by the intravenous injection of naive Lewis spleen cells (5 x 10(7) cells x 1 day, n = 5; 5 x 10(7) cells x 3 days, n = 5) or cells from Lewis rats sensitized to LBN tissues (5 x 10(7) cells x 3 days, n = 5). Naive Lewis recipients were pretreated with ALS and 6 days later with intravenous spleen cells (25 x 10(7), n = 5) or lymphoid cells (10 to 15 x 10(7), n = 5) from a tolerant animal bearing a viable LBN graft. When transplantation with an LBN donor was done the next day, significant prolongation of LBN allograft survival (mean survival time 32.8 days, p < 0.01; and 22.2 days, p < 0.01; respectively) was seen. Wistar-Furth allograft survival was not prolonged by treatment with ALS and intravenous spleen (n = 5) or lymph node (n = 5) cells from rats tolerant to LBN tissues (mean survival time 8.6 and 9.2 days, control 9 days; p = not significant). The administration of ALS alone (n = 5) did not prolong LBN graft survival (mean survival time 11.8 days). CONCLUSION: These data suggest that transferable suppressor cells specific for the donor strain are at least in part responsible for the maintenance of long-term allograft survival after intrathymic pretreatment with allogeneic cells.

Animals↗
PubMed1995

Non-uniform dose/time fractionated radiation therapy and chemotherapy for non-small cell lung cancer.

PURPOSE: A Non-uniform Fractionation schedule of large priming doses combined with concurrent chemotherapy and protracted RT was undertaken for the treatment of NSCLC. With several 5-year survivors, this study is reviewed with regard to local control, toxicity, and survival of patients. METHODS AND MATERIALS: Forty-two patients with unresectable NSCLC were treated prospectively with initial priming doses followed by large field irradiation to the tumor and regional nodes to 3500 cGy. Patients were given a 1-week break and the treatment was repeated. A total dose of 7000 cGy was delivered over 9 weeks. Thirteen patients (Group A) were treated with RT alone. Twenty-nine patients (Group B) received concurrent chemotherapy; Cisplatin, 100 mg/m2, and 5-FU, 1 g/m2 for 24 h times 5 days. Sixteen patients also received Vinblastine, 3 mg/m2 on a weekly schedule. All patients have been followed more than 5 years. RESULTS: Overall complete response rate was 36% and partial response rate was 57%. Absolute survival at 2 years was 26% and at 5 years was 14%. Local failure occurred in 28/42 (67%) patients. Late complications included pulmonary fibrosis (3), and osteochondritis (2). CONCLUSION: This approach of high-dose Non-uniform fractionated radiation therapy has yielded an absolute 5-year survival of 14%, which appears better than the long-term results often seen in treatment of NSCL cancer.

Adult↗
PubMed1995

Potential underdosing with the use of electron beam therapy in patients with cervical adenopathy and advanced head and neck cancer.

To define the adequacy of electron beam therapy in the treatment of N1-N3 head and neck cancer, 24 patients with primary head and neck cancers and N1-N3 cervical adenopathy received primary radiation therapy with or without chemotherapy for definitive control of their disease. All patients underwent computerized tomography (CT) to assist in the design of treatment to the posterior neck with electron beams after photon therapy to the level of spinal cord tolerance. Treatment with electrons to the posterior neck in patients with N1 disease was adequate in 92% (11/12) of patients. However, in patients with N2 and N3 disease, electron beam treatment failed, because of spinal cord tolerance problems, to cover the disease adequately in 92% (11/12). It is concluded that CT should be employed routinely in patients with N1-N3 neck disease to determine the proper electron energy prescription. For some patients, electron beam may not be appropriate, making it necessary to use individual planning to treat adequately the neck disease and avoid the spinal cord.

Electrons↗
PubMed1995

Cholangiocarcinoma: clinical significance of tumor location along the extrahepatic bile duct.

PURPOSE: To define the criteria for resection and/or radiation therapy (RT) of extrahepatic bile duct cancer. MATERIALS AND METHODS: Of 81 patients with extrahepatic bile duct cancer treated from 1983 to 1992, those with proximal duct lesions (n = 56) underwent RT and/or resection or palliative care, and those with distal lesions (n = 25) underwent resection with or without RT. Follow-up was available 3-114 months (median, 28 months). RESULTS: Patients with distal bile duct cancer lived longer than patients with proximal bile duct cancer (survival with Kaplan-Meier analysis, 53% vs 13% at 5 years, respectively, P < .01). Median survival in patients with proximal cancer after RT was more than double that without RT (17 months vs 6 months, respectively, regardless of stage [P = .01]); survival was not significantly different after resection. In patients with distal cancer, RT after resection made no significant difference in median survival (68 months). CONCLUSION: Patients with proximal cancer should undergo primary RT, and expectations should be limited. Patients with distal cancer should undergo resection, and RT may not be needed.

Aged↗
PubMed1995

Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas.

PURPOSE: To evaluate the effectiveness of combined intraoperative radiation therapy (IORT) and perioperative chemotherapy in the management of unresectable pancreatic cancer. MATERIALS AND METHODS: Forty-nine patients with localized unresectable adenocarcinoma of the pancreas were treated in a multimodality program of initial IORT and perioperative chemotherapy (fluorouracil [5-FU]/leucovorin) followed by combined external-beam radiation (40 to 55 Gy) and continued chemotherapy. Patients were evaluated for toxicity, pattern of failure, and survival. The follow-up times of these patients range from a minimum of 12 months to a maximum of 62 months, with a median of 28 months. RESULTS: The incidence of perioperative mortality was 0%. Early postsurgical morbidity (grade 3/4) was observed in seven of 49 patients (14%) and late treatment-related morbidity (grade 3/4) in eight of 43 patients (19%) alive beyond 6 months. Morbidity was primarily gastrointestinal (GI), with no hematologic toxicities observed. The median survival time in the total group of patients is 16 months, with a 2-year survival rate of 22% and a 4-year survival rate of 7%. Freedom from local progression of disease was achieved in 71% of patients. CONCLUSION: The patients who undergo IORT with electrons and treated with perioperative chemotherapy (5-FU leucovorin) followed by additional external-beam radiation and chemotherapy appear to have improved survival, with few early or late complications. Dose escalation of external-beam radiation and chemotherapy may further improve local control of disease and survival of patients.

Actuarial Analysis↗
PubMed1994

High-dose preoperative radiation and full thickness local excision: a new option for selected T3 distal rectal cancers.

PURPOSE: To assess the efficacy of high-dose preoperative radiation and full thickness local excision as an option for the management of selected distal rectal cancers. METHODS AND MATERIALS: Forty-eight patients with invasive distal rectal cancer have been treated with high-dose preoperative radiation (45-55 GY at 180 cGy/fx) followed 6 to 8 weeks later by full thickness local excision. Three groups of patients are included in this study. Group 1 (N = 15) Medically Compromised: patients with rectal cancers Stages T3 or > 3 cm in size and significant cardiorespiratory disease that precluded radical surgery. Group 2 (N = 18) Elective: patients suitable for local treatment by standard criteria (Stages < T2 and < 3 cm in size), and group 3 (N = 15) Staged: patients with Stages T3 or > 3 cm in size that postradiation were downstaged and met the criteria as in group 2. One patient in group 3 was found to be pathologically T3 following full thickness local excision and was converted to an abdominoperineal resection. Follow-up ranges from 6-96 months with a median of 40 months. RESULTS: The overall 5-year actuarial survival for the whole group is 83.5% and local recurrence is 10%. The 5-year survival is 74%, 92%, and 88% for Groups 1, 2, and 3 and 90%, 89%, and 50% for postradiation pathologic stages T0/T1, T2, and T3, respectively. Local recurrence rate by treatment groups are 20%, 11%, and 0% for groups 1, 2, and 3 and 11%, 0%, and 67% for postradiation Stages T0/T1, T2, and T3, respectively. Surgical complications, primarily wound healing, were observed in five patients (10%). Four patients required a subsequent colostomy (three for recurrence and one for a rectovaginal fistula). Sphincter function as measured by Parks criteria was good/excellent in 88% of patients. CONCLUSION: High-dose preoperative radiation and full thickness local excision appear to be a promising new option for the management of selected patients with invasive distal rectal cancers. Selected patients with Stage T3 cancers that as a result of preoperative radiation are downstaged and met the criteria for primary local therapy (T2 or less) appear to have an excellent survival with retained normal sphincter function following full thickness local excision.

Adenocarcinoma↗
PubMed1994

Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation.

PURPOSE: To assess the potential downstaging of advanced rectal cancer with combined preoperative chemoradiation. METHODS AND MATERIALS: Thirty-one patients with fixed rectal cancers (stage > or = cT3) were treated with concomitant preoperative chemotherapy and high-dose radiation in an effort to improve resectability. Three (10%) patients had partially fixed low rectal cancers, 24 (77%) patients had fixed tumors, and 4 (13%) had advanced fixation with pelvic sidewall invasion. Radiation was delivered to the whole pelvis using shaped anterior and posterior and lateral fields to 45 Gy followed by a boost to the tumor. Median total radiation dose was 55.8 Gy. Chemotherapy consisted of low dose continuous infusion of 5-FU (200-300 mg/m2/day) for the duration of radiation treatment. All 31 patients underwent surgical resection of tumor 6-8 weeks following treatment. Median follow up is 24 months (range 9-60). RESULTS: Twenty-three (74%) of the tumors were clinically downstaged following preoperative treatment. Of 24 fixed cancers, 11 (46%) became mobile, 6 (25%) became partially fixed, and 7 remained fixed. Of the four tumors with advanced fixation, two (50%) became mobile and two (50%) no longer had tumor extension to the pelvic sidewall. Two of the three initially partially fixed cancers became mobile and one remained partially fixed. Following surgery, the pathologic postradiation T-stages were as follows: T0: 10%, T1: 0%, T2: 32%, T3: 42%, and T4:16%. Seven patients (23%) were also node-positive (T0-2: 2, T3: 4, T4: 1), and two patients (6%) had liver metastases at surgery. Preoperative chemoradiation was well tolerated. There was no significant hematological toxicity. Acute grade 3 gastrointestinal toxicity was seen in six patients requiring a short hospitalization for dehydration and/or abdominal discomfort. No patient developed grade 4 toxicity. Five patients (16%) developed local recurrence of disease (T0-2: 0/13, T3: 1/13, and T4: 4/5). The actuarial 3-year survival is 68%. CONCLUSIONS: Concomitant preoperative chemoradiation using low dose continuous infusional 5-FU for advanced rectal cancer is relatively safe with acceptable morbidity. This approach is associated with considerable clinical and pathologic downstaging of cancer. Tumor resectability is improved with potential for improved local control of disease and survival.

Adult↗
PubMed1994

The importance of patient selection for adjunctive postoperative radiation therapy for cancer of the rectum. Patient selection in adjunctive therapy.

BACKGROUND: Clinical stage of disease is an important selection criterion for choice of primary treatment and strategies for adjunctive therapy for most cancers. For adenocarcinoma of the rectum, strategies for adjuvant treatment are based primarily on pathologic stage alone, without consideration of presenting clinical factors. This analysis was undertaken to assess the effect of patient selection on results of adjunctive therapy. METHODS: Three groups of patients with Astler-Coller Stage B2 and C rectal cancer were compared to assess the effect of patient selection factors on outcome of treatment after adjuvant postoperative radiation. Thirty-two patients in Group 1 received only 5 Gy preoperatively; 54 patients in Group 2 received low-dose (5 Gy) preoperative and high-dose (45 Gy) postoperative radiation; and 53 patients in Group 3 received high-dose (45 Gy) postoperative radiation. All patients have a minimum follow-up of 5 years. Whereas Group 1 and Group 2 patients were similar in distribution by clinical tumor characteristics, Group 3 had more patients with poor clinical features: higher median age, more men, and a higher proportion of tumors in the distal rectum. Group 3 also had a slightly higher percentage of C2 tumors compared with the other two groups. RESULTS: Treatment was well tolerated with minimal side effects. Patients in Group 1 had no long-term complications. Four percent of patients (2 of 54) in Group 2 and 6% of patients (3 of 53) in Group 3 experienced major small bowel complications. The incidence of local recurrence was 34% (11 of 32) in Group 1, 9% (5 of 54) in Group 2, and 21% (11 of 53) in Group 3. The incidence of distant metastasis was 28% (9 of 32), 22% (12 of 54), and 38% (20 of 53), respectively. Absolute 5-year survival rates were 54%, 72%, and 41% in these three groups, respectively. CONCLUSIONS: Low-dose preoperative adjunctive radiation alone (Group 1) resulted in a high incidence of local recurrence and poor survival compared with patients treated more appropriately with low-dose preoperative plus adjunctive postoperative irradiation (Group 2). In spite of postoperative radiation, patients with clinically unfavorable rectal cancer (Group 3) did worse than carefully selected patients, although both were nominally Stage B2 and C. Careful patient selection before surgery, histopathologic stage of disease postsurgery, and adequate adjunctive therapy are all important factors in obtaining the best results from adjunctive therapy.

Adenocarcinoma↗
PubMed1994

The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer.

PURPOSE: To examine the impact of radiation dose on both survival and morbidity in combined modality treatment of bile duct cancer. METHODS AND MATERIALS: Forty-eight patients with cancer of the extrahepatic bile ducts were treated at Thomas Jefferson University Hospital from 1984-1990. Twenty-four patients received radiation as part of a combined modality approach using external beam radiation, brachytherapy implant and chemotherapy. Twenty-four patients received no radiation in the course of their treatment. Radiation was delivered via high energy photons at standard fractionation, 5 days/week, for an average of 46 Gy. The implant used Ir-192 ribbon sources (average activity was 29 mCi, active length was 6 cm) for a mean dose of 25 Gy at 1 cm. Chemotherapy consisted of 5-FU alone or combined with adriamycin or mitomycin-C. RESULTS: Two-year survival for all 48 patients was 18% (median 9 months). Patients treated with radiation had a 2-year survival of 30% (median 12 months) vs. the no-radiation group, 17% (5.5 months, median), p = 0.01. Those treated to > 55 Gy experienced an extended 2-year survival of 48% (24 months, median), vs. those receiving < 55 Gy, 0% (6 months, median), p = 0.0003. This benefit was also seen when patients were stratified by T-stage. A dose response is further suggested by a lengthening of the median survival with increasing radiation dose (4.5 months, 9 months, 18 months and 25 months for < 45 Gy, 45-55, 55-65, 66-70 Gy, respectively). Neither surgical resection nor chemotherapy produced statistically significant benefits as independent variables. Complications due to radiation occurred in only one patient. CONCLUSION: A dose response is shown with more than double the 2-year and median survival for doses > 55 Gy. A brachytherapy dose of 25 Gy, plus 44-46 Gy external beam is well tolerated. High dose combined brachytherapy and external beam radiation (60-75 Gy) appears to be the most effective modality for extrahepatic bile duct cancer.

Adult↗
PubMed1994

Development of tolerance to experimental cardiac allografts in utero.

"Actively acquired tolerance" to foreign cells was described in 1953 by Medawar and colleagues and formed the basis for subsequent efforts in organ transplantation. We have applied these historic principles of intrauterine immune manipulation in a vascularized cardiac allograft model. Allogeneic Lewis-Brown Norway (LBN) splenocytes (0 to 5 x 10(7) cells) were injected intraperitoneally into each fetus of a pregnant Lewis rat at day 14 to 16 of gestation, when T cells are "educated" to distinguish self from foreign. This manipulation causes fetal attrition inversely proportional to the number of cells injected. Heterotopic transplantation using an LBN heart was carried out in each surviving fetus at 6 to 8 weeks of age. Untreated Lewis rats rejected LBN hearts within 7.6 days. Rats receiving LBN splenocytes in utero demonstrated prolongation of graft survival proportional to the number of cells given. Surviving animals exposed to 5 x 10(7) allogeneic cells in utero (n = 4) had graft survivals of 24 to more than 150 days (mean, 88.0 days), significantly longer than control animals (6 to 10 days; mean, 7.6 days; p < 0.02). Significant prolongation of cardiac allograft survival and in some cases complete tolerance can be achieved by intrauterine exposure to allogeneic cells at a critical period of immunologic development. Because many serious cardiac defects amenable to treatment by cardiac transplantation can be detected by ultrasound early in gestation, treatment based on this strategy may become useful in pediatric heart transplantation.

Animals↗
PubMed1994

Tolerance to experimental cardiac allografts produced by neonatal intrathymic injection of donor cells.

Intrathymic inoculation of allogeneic cells after systemic administration of antilymphocyte serum in adult experimental animals has produced donor-specific tolerance to cardiac allografts. We investigated whether thymic injection of allogeneic cells without antilymphocyte serum in neonatal Lewis rats (day 1 of life) with immature immune systems also produced tolerance to cardiac grafts. Intrathymic or intraperitoneal injection of 5 x 10(7) Lewis (control) or Lewis-Brown Norway (allogeneic) spleen cells in Lewis neonates was followed by heterotopic cardiac transplantation using Lewis, Lewis-Brown Norway, or Wistar Furth (third-party allograft) hearts at 6 to 8 weeks of age. Graft survival was prolonged with both intraperitoneal and intrathymic allogeneic cells. Recipients of cells by the intrathymic route had longer graft survival, and 2 of 5 animals achieved permanent graft acceptance (longer than 100 days). As expected, Lewis isografts survived indefinitely, whereas third-party Wistar Furth allografts were rejected in the usual time frame. Intrathymic introduction of allogeneic cells in a neonatal recipient with an immature immune system can produce donor-specific tolerance to a subsequent graft without the need for a systemic immunosuppression regimen, even transiently.

Animals↗
PubMed1994

Potential underdosing with the use of electron-beam therapy in patients with cervical adenopathy and advanced head and neck cancer.

To define the adequacy of electron-beam therapy in the treatment of N1-N3 head and neck cancer, 24 patients with primary head and neck cancers and N1-N3 cervical adenopathy received primary radiation therapy with or without chemotherapy for definitive control of their disease. All patients underwent computerized tomography (CT) to assist in the design of treatment to the posterior neck with electron beams after photon therapy to the level of spinal cord tolerance. Treatment with electrons to the posterior neck in patients with N1 disease was adequate in 92% (11/12) of patients. However, in patients with N2/N3 disease, electron beam failed, because of spinal-cord tolerance problems, to adequately cover disease in 92% (11/12). It is concluded that CT should be routinely employed in patients with N1-N3 neck disease to determine the proper electron-energy prescription. For some patients, electron beam may not be appropriate, making it necessary to use individual planning to treat adequately the neck disease and avoid the spinal cord.

Electrons↗