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Biomedical subjects

Thomas J Lynch

Publications and source records attributed to Thomas J Lynch.

At least 73 records · Page 4Linked to original sources
PubMed2003

P53 (codon 72) and P21 (codon 31) polymorphisms alter in vivo mRNA expression of p21.

p21 (Waf1/Cip1) is a downstream target of p53. We evaluated the association between p21 polymorphism (codon 31), p53 polymorphism (codon 72) and their corresponding in vivo mRNA expression. In this study, p21 and p53 genetic polymorphisms (using standard PCR-RFLP techniques) and p21 and p53 gene expressions (using a radiolabelled ribonuclease protection assay (RPA) technique) were evaluated in the peripheral leukocytes of 84 individuals (63 with lung cancer). Log-transformed values of mRNA expression by RPA, which approximated a normal distribution, were analyzed. p53 genotypes did not correlate with p53 mRNA log-expression (P>0.05 for all comparisons), but the Pro allele variants of p53 were associated with a significant decrease in mRNA log-expression of its downstream target, p21. The variant Arg allele of p21 was also associated with a significant decrease in p21 mRNA log-expression. When individuals with at least one variant allele of both p53 and p21 (double-variants) were compared with all other genotype groups, these double-variants had significantly lower log-expression of p21 (P<0.005 by both t-tests (crude) and linear regression analyses (adjusted)). This is translated into an approximate 48% reduction in the geometric mean of the mRNA expression of the double-variants, when compared with all other groups. Results were consistent in both patients with lung cancer (n=63) and in normal controls (n=21). In conclusion, the presence of a p53 Pro allele and/or p21 Arg allele is associated with lower downstream target gene expression of p21.

Aged↗
PubMed2003

Smoking and the risk of lung cancer: susceptibility with GSTP1 polymorphisms.

BACKGROUND: GSTP1 is a gene that helps detoxify foreign substances in the body. Functional polymorphisms of GSTP1 have been studied as risk factors for lung cancer. Past studies have compared the effect of the "at risk" polymorphism in two strata of smoking pack-years (usually defined by the median among controls). We examined the interaction between GSTP1 polymorphisms and cumulative exposure to smoking and their association with lung cancer risk. METHODS: Data are from a large hospital-based case-control study of persons treated for primary lung cancer at the Massachusetts General Hospital since 1992. Controls were drawn from friends and nonrelated family members. We genotyped 1,042 cases and 1,161 controls for GSTP1 using polymerase chain reaction-restriction fragment length polymorphism techniques. FINDINGS: The GSTP1 GG genotype approximately doubled the lung cancer risk associated with pack-years. This interaction was stronger among current smokers. At 26 pack-years (median among controls with a smoking history), the adjusted odds ratio for the association between pack-years and lung cancer risk was 13 (95% confidence interval = 6.5-25) among current smokers with the GSTP1 GG genotype compared with 6.1 (95% confidence interval = 4.9-7.5) among those with the GSTP1 AA genotype. CONCLUSIONS: GSTP1 GG increases the lung cancer risk associated with pack-years of smoking.

Adult↗
PubMed2003

Living as a cancer surpriser: a doctor tells his story.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to the caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members. We tell the story of one physician with incurable non-small cell lung cancer (NSCLC) who had an unexpectedly favorable response to an experimental treatment while receiving it as a part of his palliative care. His unique insight provides an opportunity to elucidate some of the issues that arise from living both as a patient-caregiver and as a cancer "surpriser." When caregivers face their own cancer, their reflections as patient-caregivers offer an internal perspective on the illness experience and help us as fellow caregivers to better understand and support all patients who face serious illnesses, both those who are colleagues and those who are not. Just like any patient with cancer, patient-caregivers experience the dramatic changes in health, daily life, and perspective that come with serious illness. Within the context of a life-threatening illness, caregiver-patients and their families search for new meaning as they face an uncertain future and address the issues of life and death. In addition to such processes, patient-caregivers with cancer also find that their own medical knowledge and their colleagues' reactions shape their experiences and to an extent separate them from those of other patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Trust violated: analgesics for addicts.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Addiction among cancer patients on strong analgesics is a rare but difficult management challenge. The case is presented of a 28-year-old woman with breast cancer and painful bone metastases, suffering with dysfunctional social chaos and addicted to Percocet (oxycodone and acetaminophen). Having broken the trust of her health care team, trust was rebuilt by incorporating the substance abuse clinic and enforcing a contractual agreement. With open and honest support, the team was able to both care for and empower the patient. Issues of trust, liability, opioid tolerance, and barriers to optimal analgesia for cancer pain are discussed.

Adult↗
PubMed2003

The Kenneth B. Schwartz Center at Massachusetts General Hospital hematology-oncology department: hope for the homeless.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum during which caregivers discuss a specific cancer patient, reflect on the important psychological issues faced by patients, their families, and their caregivers, and gain insight and support from their fellow staff members. A homeless man with head and neck cancer presents to the emergency room: a sad and familiar story. But this story is redeemed by his 35-year friendship with a priest, a man whose unconditional love and support became critical to the patient's care and treatment. The patient had lived for 30 years in homeless shelters, had problems with alcohol abuse, and was notoriously noncompliant with medical caregivers. He could not speak due to his disease, was illiterate with limited intellectual capacity, and had neither a job nor a family. Despite huge and apparently insurmountable problems for the patient, the oncology team was able to carve out a package of care, successfully communicate, and mobilize a support network to allow successful completion of chemoradiation therapy. The team developed a strong commitment to his care and an affectionate bond, which very positively affected all of those involved. We discuss issues of access to cancer care, and the special problems presented by homeless patients.

Aged↗
PubMed2003

Breaking bad news: a patient's perspective.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Clinicians in the field of oncology are unavoidably forced to break bad news. The Schwartz Center Rounds focuses on issues of communication between patients and their caregivers, one of the most difficult aspects of which is breaking bad news. The invited patient, a woman who had been living with a low-grade cancer for many years, spoke about her experiences both as a person living with cancer and as the daughter of a patient diagnosed with cancer. Her father's suicide, precipitated by being told his diagnosis, puts the horror of receiving bad news into stark relief. She provides a fascinating account of how she proactively adjusted to her diagnosis, and fought for optimal quality of life. This article discusses issues of support, abandonment, and how hope is conveyed, and reviews the literature that informs good clinical practice in breaking bad news.

Caregivers↗
PubMed2003

Radiation dose intensification in limited-stage small-cell lung cancer.

Multiple studies have confirmed the value of radiation therapy in limited-stage small-cell lung cancer. The appropriate dose of radiation and the optimal fractionation scheme, however, remain controversial. This article will examine the history of radiation therapy in the management of small-cell lung cancer. It will review the rationale for the various approaches to radiation dose intensification, and review the results of important trials investigating the issue of radiation dose in the management of this disease. Survival outcomes and toxicity of various approaches to radiation dose intensification, including dose escalation and hyperfractionation, will be assessed. The implications of advancements in technology will be examined, and the optimal design of future trials will be discussed.

Journal Article↗
PubMed2003

Duct tape removes warts.

Duct tape (or any durable, occlusive, tacky tape) appears to be at least as effective as traditional cryotherapy for removal of the common wart. It is an unusual and welcome event in health care when a common ailment is proven equally amenable to an inexpensive, tolerable, and safe alternative therapy.

Comment↗
PubMed2003

Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk.

XRCC1 (X-ray cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) are two major DNA repair proteins. Polymorphisms of these two genes have been associated with altered DNA repair capacity and cancer risk. We have described statistically significant interactions between the ERCC2 polymorphisms (Asp312Asn and Lys751Gln) and smoking in lung cancer risk. In this case-control study of 1091 Caucasian lung cancer patients and 1240 controls, we explored the gene-environment interactions between the XRCC1 Arg399Gln polymorphism, alone or in combination with the two ERCC2 polymorphisms, and cumulative smoking exposure in the development of lung cancer. The results were analyzed using logistic regression models, adjusting for relevant covariates. Overall, the adjusted odds ratio (OR) of XRCC1 Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was 1.3 [95% confidence interval (CI), 1.0-1.8]. Stratified analyses revealed that the ORs decreased as pack-years increased. For nonsmokers, the adjusted OR was 2.4 (95% CI, 1.2-5.0), whereas for heavy smokers (>/=55 pack-years), the OR decreased to 0.5 (95% CI, 0.3-1.0). When the three polymorphisms were evaluated together, the adjusted ORs of the extreme genotype combinations of variant alleles (individuals with 5 or 6 variant alleles) versus wild genotype (individuals with 0 variant alleles) were 5.2 (95% CI, 1.7-16.6) for nonsmokers and 0.3 (95% CI, 0.1-0.8) for heavy smokers, respectively. Similar gene-smoking interaction associations were found when pack-years of smoking (or smoking duration and smoking intensity) was fitted as a continuous variable. In conclusion, cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk.

Adult↗
PubMed2002

Combinations of the variant genotypes of GSTP1, GSTM1, and p53 are associated with an increased lung cancer risk.

GSTP1 and GSTM1 are genes involved in Phase II metabolism, whereas p53 is a tumor suppressor gene. Individually, functional polymorphisms of these genes have been studied as risk factors for lung cancer. Small sample sizes have hindered the detection of possible increases in risk associated with having two or more "at risk" polymorphisms of these three genes. In a large Caucasian population, we examined the association of combined variant genotypes [or double-variants (DVs)] of these three genes and lung cancer risk, compared with their corresponding "double-wild-type" genotypes. Because these DVs may promote lung carcinogenesis at an earlier age, a subgroup of individuals aged 55 years or younger was examined separately. Using a case-control design, individuals were genotyped for GSTM1, GSTP1, and p53 codon 72 using PCR-RFLP techniques. All of the analyses used multiple logistic regression. Indicator variables were created to evaluate the risk for individuals with the following DVs: GSTP1 GG + GSTM1-null and GSTP1 GG + p53 Arg/Pro or Pro/Pro. A total of 1694 cases and controls were evaluated. In the whole population, those with the double variants have a higher risk of lung cancer when compared with those with the double-wild-type genotypes, supporting our original hypothesis. Individuals with the GSTP1 and GSTM1, DV (P1-M1 DV) had a marginally significant higher risk of lung cancer compared with their double-wild-type counterparts [adjusted odds ratio (AOR), 1.60; 95% confidence interval (CI), 0.95-2.70]. A significantly higher risk was found for the GSTP1, p53 DV (P1-p53 DV; AOR, 1.99; 95% CI, 1.12-3.53). Among individuals aged 55 or younger, these risks were even higher: for the P1-M1 DV the AOR was 4.03 (95% CI, 1.47-11.1); for the P1-p53 DV the AOR was 5.10 (95% CI, 1.42-18.30). Specific DVs of GSTM1, GSTP1, and p53 codon 72 are associated with a higher lung cancer risk. This susceptibility is highest among younger individuals.

Adult↗
PubMed2002

Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer.

Excision repair cross-complementing group 2 (ERCC2), a major DNA repair protein, is involved in nucleotide excision repair and basal transcription. The ERCC2 polymorphisms have been associated with altered DNA repair capacity. We investigated two ERCC2 polymorphisms, Asp312Asn and Lys751Gln, in 1092 Caucasian lung cancer patients and 1240 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. The overall adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.47 (95% CI, 1.1-2.0) for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp) and 1.06 (95% CI, 0.8-1.4) for the Lys751Gln polymorphism (Gln/Gln versus Lys/Lys). Gene-smoking interaction analyses revealed that the adjusted ORs for each of the two polymorphisms decreased significantly as pack-years increased. When comparing individuals with Asn/Asn + Gln/Gln versus individuals with Asp/Asp + Lys/Lys, the fitted ORs (95% CIs) were 2.56 (95% CI, 1.3-5.0) in nonsmokers and 0.69 (95% CI, 0.4-1.2) in heavy smokers (80 pack-years; P < 0.01 for the interaction term). Consistent and robust results were found when models incorporated different definitions of cumulative cigarette smoking. A stronger gene-smoking interaction was observed for the Asp312Asn polymorphism than for the Lys751Gln polymorphism. In conclusion, cumulative cigarette smoking modifies the associations between ERCC2 polymorphisms and lung cancer risk.

Adult↗
PubMed2002

Induction chemoradiation compared with induction radiation for lung cancer involving the superior sulcus.

BACKGROUND: The usual approach of induction radiation therapy (RT) followed by resection of superior sulcus tumors results in many incomplete resections, a high local recurrence rate, and suboptimal survival. Induction chemoradiotherapy (CT/RT) has been shown to reduce local and distant recurrences and improve survival in stage III lung cancer. We investigated the role of induction CT/RT in superior sulcus patients. METHODS: This was a single-institution, retrospective study. RESULTS: From 1985 to 2000, 35 consecutive patients underwent induction treatment followed by resection of a superior sulcus tumor. All patients had mediastinoscopy first to exclude N2 disease, and all were N0 at final pathologic examination. Twenty patients had induction RT (mean, 39 Gy), and 15 had induction CT/RT (mean, 51 Gy) with concurrent cisplatin-based chemotherapy. There was no treatment mortality. Complete resection was performed in 16 of 20 (80%) of the RT patients and in 14 of 15 (93%) of the CT/RT patients (p = 0.15). The pathologic response from the induction treatment was complete or near complete in 7 of 20 (35%) of the RT patients and in 13 of 15 (87%) of the CT/RT patients (p = 0.001). The median follow-up was 167 months in the RT patients and 51 months in the CT/RT patients. Two-year and 4-year survival was 49% and 49% (95% confidence interval, 26% to 71%) in the RT patients and 93% and 84% (95% confidence interval, 63% to 100%) in the CT/RT patients, respectively (p = 0.01). The local recurrence rate was 6 of 20 (30%) in the RT patients and 0 in the CT/RT patients (p = 0.02). CONCLUSIONS: Induction CT/RT for superior sulcus tumors appears to offer improved survival compared with induction RT alone.

Adult↗
PubMed2002

FDG-PET in staging and restaging non-small cell lung cancer after neoadjuvant chemoradiotherapy: correlation with histopathology.

This study was performed to investigate the utility of FDG-PET for: (1) initial staging, and (2) restaging of the primary and mediastinal nodal lesions 2 weeks after the completion of preoperative chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). Twenty-six patients with histologically confirmed stage III NSCLC were accrued to this study from April 1993 to July 1998. They included 21 with stage IIIA (N2) NSCLC who were enrolled into an institutional phase II study, and 5 patients with a highly selected subset of stage IIIB disease characterized by the presence of microscopic metastatic disease in contralateral mediastinal lymph nodes who were also treated with preoperative chemoradiotherapy; N3 lesions (n=3) and minimal T4 lesions. Demographic characteristics included median age 62 years (a range from 47 to 73) and gender ratio of male 15 to female 11. Histologic types of tumor consisted of squamous cell carcinoma 6, adenocarcinoma 11, large cell carcinoma 5, and non-small cell carcinoma 4. All patients had FDG-PET imaging of the chest before the initiation and 2 weeks after completion of preoperative therapy. The FDG-PET images were evaluated qualitatively for uptake at the primary tumor sites and mediastinal lymph nodes. Standard uptake values (SUVs) were also calculated for the primary tumors and all PET findings were correlated with surgical histopathologic data. Preoperative chemoradiotherapy resulted in complete pathologic response in 8 of 26 primary lesions. By qualitative analysis, 96% of these tumors showed level 3 or 4 uptake before preoperative chemoradiotherapy. After chemoradiotherapy, 57% (15/26) of patients showed at least a one level decrease in uptake, and the sensitivity and specificity of FDG-PET for differentiating residual tumor from pathologic complete response were 67% (12/18) and 63% (5/8). Mean SUV was 14.87+/-7.11 at baseline and decreased to 5.72+/-3.35 after chemoradiotherapy (n=21, P<0.00001). When a value of 3.0 was used as the SUV cut-off, sensitivity and specificity were 88 and 67%, respectively. The mean values of visual intensity were 3.87+/-0.35 and 3.8+/-0.51 for patients who achieved pathologic complete response (n=8) and for those who showed residual cancer after the preoperative therapy (n=18), respectively. The mean SUVs were 16.97+/-8.52 and 14.03+/-6.61 for patients who achieved pathologic complete response (n=6) and for those who showed residual cancer (n=15) after the preoperative therapy, respectively. Therefore, the degree of FDG uptake before preoperative chemoradiotherapy did not provide predictive value for subsequent tumor response. For mediastinal initial staging, the sensitivity and specificity of FDG-PET were 75 and 90.5%. The sensitivity and specificity of FDG-PET for mediastinal restaging were 58.0 and 93.0%. These results indicate that FDG-PET is useful for monitoring the therapeutic effect of neoadjuvant chemoradiotherapy in patients with stage III NSCLC. For the primary lesions, SUV based analysis has high sensitivity but limited specificity for detecting residual tumor. In contrast, for restaging of mediastinal lymph nodes, FDG-PET is highly specific, but has limited sensitivity.

Aged↗
PubMed2002

Building a better therapy for stage IIIA non-small cell lung cancer.

What do clinicians know about stage IIIA lung cancer? They know accurate staging is critical and requires wide application of mediastinoscopy. They know that surgery and radiation alone each can cure a small subset of patients, and complete resection is of the utmost importance in surgically treated patients. They know that chemotherapy can increase the number of patients cured when combined with definitive radiation, and concurrent chemoradiotherapy seems superior to sequential. Neoadjuvant chemotherapy also seems to cure more patients than surgery alone, but more data are necessary. Trimodality therapy remains a promising but unproved approach in patients with stage IIIA disease. With the exciting new molecularly targeted agents, trials examining quad-modality therapy are just around the corner.

Clinical Trials as Topic↗
PubMed2002

Between parent and child: negotiating cancer treatment in adolescents.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Cancer in adolescents presents an extra dynamic of psychosocial complexity. The case of a 19-year-old woman with acute myelocytic leukemia is discussed. Her disease was refractory to allogeneic transplantation, and she died with severe graft-versus-host disease. Ms. P and her mother established very different relationships with the team which supported them through the transitions in her care, and Ms. P was able to die at home, with hospice care. The personal connection with the team enabled a degree of positive adjustment through the nightmare of loss. The epidemiology of cancer in adolescents and paradigms of care are reviewed. Psychosocial aspects of adolescence, opportunities for personal growth and support, and the challenge of end-of-life care are discussed.

Acute Disease↗
PubMed2002

Faith, identity, and leukemia: when blood products are not an option.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members. When a competent adult patient refuses lifesaving treatment for religious or personal reasons, caregivers have a legal obligation to respect this decision. A patient's refusal of treatment adds particular challenges to the delivery of compassionate care. The case of a 50-year-old Jehovah's Witness with acute myelocytic leukemia who declined blood product support is presented. Respecting her religious beliefs during chemotherapy required balancing risk and benefit, watching her suffer while unable to intervene with what the staff saw as simple treatment, and eventually undertaking a complicated grief process. Jehovah's Witness beliefs regarding blood products are reviewed. Caregiver roles and responsibilities are discussed in the context of psychosocial, legal, familial, and ethical issues.

Blood Transfusion↗