Assessing Residents' Competency at Baseline: How Much Does the Medical School Matter?

BACKGROUND: Although there is some consensus about the competencies needed to enter residency, the actual skills of graduating medical students may not meet expectations. In addition, little is known about the association between undergraduate medical education and clinical performance at entry into and during residency. OBJECTIVE: We explored the association between medical school of origin and clinical performance using a multi-station objective structured clinical examination for incoming residents at the University of Michigan Health System. METHODS: Prior to assuming clinical duties, all first-year residents at the University of Michigan Health System participate in the Postgraduate Orientation Assessment (POA). This assesses competencies needed during the first months of residency. Performance data for 1795 residents were collected between 2002 and 2012. We estimated POA variance by medical school using linear mixed models. RESULTS: Medical school predicted the following amounts of variance in performance-data gathering scores: 1.67% (95% confidence interval [CI] 0.36-2.93); assessment scores: 4.93% (95% CI 1.84-6.00); teamwork scores: 0.80% (95% CI 0.00-1.82); communication scores: 2.37% (95% CI 0.66-3.83); and overall POA scores: 4.19% (95% CI 1.59-5.35). CONCLUSIONS: The results show that residents' medical school of origin is weakly associated with clinical competency, highlighting a potential source of variability in undergraduate medical education. The practical significance of these findings needs further evaluation.

Nuclear forensic analysis of a non-traditional actinide sample.

Nuclear forensic publications, performance tests, and research and development efforts typically target the bulk global inventory of intentionally safeguarded materials, such as plutonium (Pu) and uranium (U). Other materials, such as neptunium (Np), pose a nuclear security risk as well. Trafficking leading to recovery of an interdicted Np sample is a realistic concern especially for materials originating in countries that reprocesses fuel. Using complementary forensic methods, potential signatures for an unknown Np oxide sample were investigated. Measurement results were assessed against published Np processes to present hypotheses as to the original intended use, method of production, and origin for this Np oxide.

Providing Informed Consent: A Standardized Case.

INTRODUCTION: From the first day of residency, residents may be required to consent patients for interventions, procedures, or tests. The ability to perform an informed consent is considered one of the Association of American Medical College's Core Entrustable Professional Activities for entering residency. This case provides learners with the opportunity to obtain informed consent for a lumbar puncture procedure and to receive immediate structured feedback on their performance. This is a formative assessment, which has been used with both senior medical students and first-year residents at our institution. METHODS: The case involves a standardized patient with a history of leukemia who presents to the emergency department with a headache, fever, and lethargy. The learner is charged with the task of compassionately, honestly, and confidently explaining the process of a lumbar puncture in order to appropriately obtain informed consent. RESULTS: This case was well received, with the vast majority of learners rating the instructions as clear and the tasks of the station as appropriate for the level of learner. Comments provided by the learners regarding the standardized patients' feedback indicate that this is a useful exercise to assist with the development of the crucial skill of obtaining informed consent. DISCUSSION: Overall, learners are able to perform this task and find it a meaningful exercise. We are able to measure both content and communication skills. In our cohort, learners are able to perform above the targeted passing score. This provides some evidence of competency in terms of both content and communication skills.

GME Innovations Grant Program at the University of Michigan Health System-Fostering Changes in Education and Clinical Care.

BACKGROUND: Changes in graduate medical education (GME) have resulted in curricula, goals and objectives, and assessment methods becoming more formal, yet there is little financial support for the educational research required to develop better teaching approaches and assessment tools. OBJECTIVE: We sought to encourage the development of new educational tools and assessment methods to improve the overall conduct of GME at the University of Michigan. INTERVENTION: The University of Michigan Health System has recently established a new educational grant that is designed to foster innovative educational research in GME. We describe the experience with a new and robust internal educational grant, including the source of funding, mechanisms for reviewing and assessing the proposals, the types of proposals that have currently been funded, and the effect and results of these studies on GME at the University of Michigan Health System. OUTCOMES: Projects funded by the grant have changed the curriculum in the involved programs, and many have resulted in sustained changes, including new methodologies in the simulation center, the development of an "academy" of faculty physicians with significant teaching expertise, and the creation of web-based teaching and assessment tools for "just in time" learning, and have been disseminated at national meetings and in peer-reviewed journals. CONCLUSIONS: The GME Innovations Grant Program at the University of Michigan Health System has been successful to date, funding 11 proposals during the course of 6 years. Some of these proposals have resulted in permanent changes and additions to residency training programs.

CXC receptor-2 knockout genotype increases X-linked inhibitor of apoptosis protein and protects mice from acetaminophen hepatotoxicity.

UNLABELLED: Although acetaminophen is a commonly used analgesic, it can be highly hepatotoxic. This study seeks to further investigate the mechanisms involved in acetaminophen-induced hepatotoxicity and the role of chemokine (C-X-C motif) receptor 2 (CXCR2) receptor/ligand interactions in the liver's response to and recovery from acetaminophen toxicity. The CXC chemokines and their receptor, CXCR2, are important inflammatory mediators and are involved in the control of some types of cellular proliferation. CXCR2 knockout mice exposed to a median lethal dose of acetaminophen had a significantly lower mortality rate than wild-type mice. This difference was at least partially attributable to a significantly decreased rate of apoptosis in CXCR2 knockout mice versus wild-type mice; there were no differences seen in hepatocyte proliferation in wild-type mice versus knockout mice after this injury. CONCLUSION: The decreased rate of apoptosis in the knockout mice correlated with an almost undetectable and significantly decreased level of activated caspase-3 and significantly increased levels of X-linked inhibitor of apoptosis protein, which also correlated with increased levels of nuclear factor kappa B p52 and decreased levels of c-Jun N-terminal kinase; this provides a possible mechanism for the decrease in apoptosis seen in CXCR2 knockout mice.

An assessment tool for aseptic technique in resident physicians: a journey towards validation in the real world of limited supervision.

PURPOSE: The purpose of this study was to describe the validation process for assessing an instrument to assess residents' aseptic technique skills. METHODS: The validation study entailed comparisons of the performance of aseptic technique procedures between postgraduate year-1 (PGY-1) surgical residents and PGY-2/3 surgical residents. We also compared the performance of PGY-1 surgical residents from 2 different academic years for the same procedures. Finally, we compared the performance of novices (medical students) and experts (operating room nurses) in an effort to determine validity. RESULTS: Our initial analysis found no significant difference between the performance of PGY-1 (mean score, 75.8) and PGY-2/3 (mean score, 75.6) surgical residents for aseptic technique (t((55))  =  0.84, P  =  0.404). Further investigation of validity was obtained to determine whether the no difference results reflected a lack of reliability or validity or a true equivalence between the 2 cohorts. The comparison of novices and experts produced the following findings. For reliability, the internal consistency of the checklist for each of the 2 raters was 0.87 and 0.71 (Cronbach α), interrater reliability was 0.74, with P < 0.001 (intraclass correlation coefficient) for the global scale. (Internal consistency was done within instrument, ie, between items not between raters.) For validity, operating room nurses outperformed students on the global scale (t(14)  =  7.47, P < 0.0001 and t((14))  =  10.66, P < 0.0001 for the 2 raters, respectively) and on several checklist items. The effect size values for raters were large (Cohen d  =  3.0 and 4.4), providing validity evidence for the ability of this assessment to detect difference in performance on this task. CONCLUSION: The validation study showed that the instrument exhibited reliability and evidence for validity, making it useful for the assesment of aseptic technique skills in different specialties. Programs may want to consider using a validated instrument to check competence given that appropriate use of sterile technique frequently occurs in the context of unsupervised activities. Further work is needed to enhance resident skills in the area of aspectic technique because of limited improvement despite additional clinical experience.

Evidence for increasing diversity in graduate medical education: the competence of underrepresented minority residents measured by an intern objective structured clinical examination.

OBJECTIVE: Some have commented that the limited number of underrepresented minorities (URMs) in United States' residency programs is due to a lack of qualified candidates. At the University of Michigan, an objective structured clinical examination is administered to incoming residents at the beginning of training to determine baseline competence. In this study we wanted to determine if competence differed for underrepresented minorities when compared to non-URM residents. METHOD: The postgraduate orientation assessment, a 10-station examination, was developed that focused specifically on the knowledge and skills needed in the first 6 to 18 weeks of training. Stations assessed competence in informed consent, aseptic technique, evidence-based medicine, diagnostic images, critical laboratory values, cross-cultural communication, and Joint Commission requirements such as surgical fire safety, pain assessment, and management. We used various assessment measures including standardized patients, computer-based testing, and multiple-choice questions. RESULTS: Our study found no significant differences in overall mean scores between URM residents and all other residents for the 5 years during which we administered the examination, except for 2002. This stands in contrast to the consistently worse performances of URM students on USMLE Step 1 and Step 2 Clinical Knowledge. Also, URM residents did not perform better or worse than their non-URM colleagues on standardized patient stations during the course of 5 years during which the examination was administered. CONCLUSIONS: The postgraduate orientation assessment provides residency program directors with a standard format to measure initial clinical skills. When compared to incoming non-URM residents from a variety of medical schools, URM residents perform as well as other trainees. Our results may aid in the recruitment efforts of URM medical students into academic residency programs such as those at the University of Michigan.

IL-22 is involved in liver regeneration after hepatectomy.

Hepatocyte proliferation following partial hepatectomy is an important component of liver regeneration, and recent in vitro studies have shown that IL-22 is involved in cellular proliferation in a variety of cell types, including hepatocytes. IL-22 functions through IL-10Rbeta and IL-22Ralpha. The goal of this study was to investigate the potential role of IL-22 in liver regeneration after 70% hepatectomy. Following 70% hepatectomy, done under general anesthesia in mice, serum IL-22 and hepatic IL-22Ralpha mRNA were significantly increased. Although administration of exogenous IL-22 prior to hepatectomy did not increase hepatocyte proliferation, administration of anti-IL-22 antibody before hepatectomy did significantly decrease hepatocyte proliferation. Furthermore, IL-22 treatment prior to 70% hepatectomy induced stat-3 activation; no significant changes were seen in ERK1/2 activation, stat-1 activation, or stat-5 activation. IL-22 pretreatment also significantly increased hepatic and serum IL-6 levels. In addition, animals treated with anti-IL-22 antibody also expressed less TGF-alpha. In conclusion, these data suggest that IL-22 is involved in liver regeneration and this may be due to interaction with IL-6 and TGF-alpha cascades.

Gemcitabine-based combination chemotherapy followed by radiation with capecitabine as adjuvant therapy for resected pancreas cancer.

PURPOSE: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. PATIENTS AND METHODS: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m(2) intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m(2) intravenously on Days 1 and 8 or capecitabine 1500 mg/m(2) orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m(2) orally in divided doses) day 1 to treatment completion. RESULTS: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >or=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. CONCLUSIONS: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

Is the accreditation council for graduate medical education a suitable proxy for resident unions?

In 1999, the National Labor Relations Board reversed its own rulings and determined that resident physicians were categorized as employees and not students under the National Labor Relations Act in the private sector. This change opened the door for residents to collectively bargain for employment benefits. Concerns were raised that conflicts in the area of service-versus-educational demands on residents' time were better handled by the Accreditation Council for Graduate Medical Education (ACGME) than by residents' unions. This article explores the extent to which conflicts exist between advocating for working conditions and for educational issues and, more specifically, whether there are any resident interests that are not covered by current ACGME regulations. In other words, has the ACGME evolved into a reasonable proxy for resident unions? The authors describe their experience with the University of Michigan House Officer Association, mutual gains bargaining, the impact that the ACGME 2003 and 2007 institutional requirements have had on employment contracts, and whether these requirements clarify or confuse resident issues. To date, the ACGME continues to revise its requirements, many of which preempt and exceed the power that most local unions have. However, only blunt tools (e.g., removal of accreditation) are available to the ACGME to address violations of requirements. The ACGME, to potentially function as a full resident union, would need to find more precise methods for timely feedback to both resident and hospital parties as well as more powerful tools to deal with violations of its regulations and requirements.

Stem cell factor and its receptor, c-kit, are important for hepatocyte proliferation in wild-type and tumor necrosis factor receptor-1 knockout mice after 70% hepatectomy.

BACKGROUND: Stem cell factor (SCF) has well-known proliferative effects on hematopoietic cells. SCF also has effects on differentiation and proliferation in other cell types. Interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha have proliferative effects in the liver. Recent studies in our laboratory have linked SCF's hepatoproliferative actions to those of IL-6, demonstrating that IL-6-induced hepatocyte proliferation depends, at least in part, on SCF. We now hypothesize that TNF-alpha's hepatoproliferative effects are also dependent on SCF. METHODS AND RESULTS: In vitro studies using primary mouse hepatocytes show that SCF is induced by TNF-alpha; anti-SCF antibody treatment in this system inhibits TNF-alpha-induced hepatocyte proliferation, suggesting that TNF-alpha-induced hepatocyte proliferation is also SCF dependent. Additional in vivo experiments were performed in which wild type and/or TNF-alpha receptor-1 knockout mice (TNFR1(-/-)) were subjected to 70% hepatectomy or sham laparotomy. TNFR1(-/-) mice are known to have delayed hepatic regeneration after partial hepatectomy. Initial experiments demonstrated that the SCF receptor, c-kit, is upregulated after partial hepatectomy in wild-type mice, further emphasizing the importance of this system in the restoration of hepatic mass. SCF administration to TNFR1(-/-) mice in the context of partial hepatectomy restores hepatocyte proliferation to normal. Further, SCF administration to TNFR1(-/-) mice before hepatectomy increases phosphotyrosine signal transducer and activator (p-stat-3) levels, suggesting that SCF-induced increases in hepatocyte proliferation may also be stat-3 mediated. CONCLUSIONS: These data suggest that TNF-alpha-induced hepatocyte proliferation depends, at least in part, on SCF and that SCF and its receptor, c-kit, are important for the liver's regenerative processes.

Stem cell factor and c-kit are involved in hepatic recovery after acetaminophen-induced liver injury in mice.

Stem cell factor (SCF) and its receptor c-kit are important in hematopoiesis and cellular proliferation. c-kit has also been identified as a cell surface marker for progenitor cells. We have previously shown that there is a large reservoir of hepatic SCF, and this molecule plays a significant role in liver regeneration after 70% hepatectomy. In the current study, we further examined the expression of SCF and c-kit in acetaminophen (APAP)-induced liver injury in C57BL/6J mice or SCF-deficient sl-sld mice and their appropriate wild-type controls. Following APAP-induced liver injury, c-kit mRNA expression increased, with peak levels detected 48 h postinjury. Hepatic SCF mRNA levels after APAP injury were also increased, with peak levels seen 16 h post-APAP. The mortality rate in SCF-deficient mice treated with APAP was significantly higher than that of wild-type mice; furthermore, administration of exogenous SCF significantly reduced the mortality of APAP-treated wild-type mice. Bromodeoxyuridine incorporation experiments showed that SCF significantly increased hepatocyte proliferation at 48 and 72 h in APAP-treated mice. SCF inhibited APAP-induced hepatocyte apoptosis and increased Bcl-2 and Bcl-xL expression, suggesting that this decrease in hepatocyte apoptosis is mediated through Bcl-2 and Bcl-xL. In summary, SCF and c-kit expression was increased after APAP-induced liver injury. Administration of exogenous SCF reduces mortality in APAP-treated mice, increases hepatocyte proliferation, and prevents hepatocyte apoptosis induced by APAP, suggesting that these molecules are important in the liver's recovery from these injuries.

VIP inhibits human HepG2 cell proliferation in vitro.

Hepatocellular carcinoma (HCC) is an aggressive and often fatal neoplasm. HepG2 cells are a cell line derived from HCC. This investigation shows that vasoactive intestinal peptide (VIP) inhibits HepG2 cell proliferation in vitro. In addition, VIP decreases the expression of signal transducers and activators of transcription-3 (STAT-3) and phosphorylated STAT-3 (pSTAT-3). Transfection of HepG2 cells with STAT-3 siRNA also dose-dependently inhibits proliferation. These findings suggest that VIP-mediated inhibition of HepG2 proliferation may be mediated by STAT-3. Further studies demonstrate that VIP increases HepG2 cAMP levels and 8-cl-cAMP inhibits HepG2 proliferation as well as pSTAT-3 and STAT-3 levels, suggesting that cAMP is also involved in the inhibition of HepG2 proliferation. VIP also attenuates the proliferative effects of hepatocyte growth factor (HGF) and interleukin-6 (IL-6) on HepG2 cells. These preliminary studies suggest that the antiproliferative actions of VIP may offer a new and promising means of suppressing HCC.

Phase I study of oxaliplatin, full-dose gemcitabine, and concurrent radiation therapy in pancreatic cancer.

PURPOSE: To determine a biweekly dose of oxaliplatin for combination with full-dose gemcitabine and concurrent radiation therapy (RT) in pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated pancreatic cancer received gemcitabine days 1, 8, and 15, and oxaliplatin days 1 and 15, repeated at 28-day intervals. RT (27 Gy in 1.8-Gy fractions) was administered during cycle 1. Dose escalation was guided using the time-to-event continuous reassessment method. Dose levels 1 to 4 included gemcitabine 1 g/m2 intravenously (IV) during 30 minutes and oxaliplatin 40, 55, 70, or 85 mg/m2 IV during 90 minutes, respectively; for dose levels 5 and 6, oxaliplatin dose remained 85 mg/m2 but infusion time for gemcitabine 1 g/m2 was increased to 65 or 100 minutes, respectively. The trial objective was to determine the dose level associated with dose-limiting toxicity (DLT) through cycle 2 in < or = 20% of patients. RESULTS: Forty-four patients were enrolled (median age, 64 years; 27 men, 17 women) with resectable (n = 12), unresectable (n = 29), and metastatic (n = 3) pancreatic cancer. Ten DLTs occurred in nine patients, including grade 4 platelets (n = 4), decline in performance status (n = 2), GI bleeding (n = 2), and GI toxicity (n = 2). The estimated probability of DLT for dose level 3 was .21 (90% posterior probability interval [PI], .12 to .33); for dose level 4, the estimated probability was .24 (90% PI, .14 to .36). CONCLUSION: The addition of oxaliplatin 85 mg/m2 days 1 and 15 to full-dose gemcitabine and radiation therapy was well tolerated. On the basis of these results, a multi-institutional neoadjuvant phase II study in resectable pancreatic cancer is planned.

Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice.

Partial hepatectomy triggers hepatocyte proliferation, hepatic matrix remodeling, and hepatocyte apoptosis, all of which are important processes in the regenerating liver. Previous studies have shown an increase in the levels of matrix metalloproteinases gelatinase A (MMP-2) and gelatinase B (MMP-9) after partial hepatectomy. The goal of this study was to investigate the role of MMP-9 in liver regeneration after partial hepatectomy. A 70% hepatectomy or sham laparotomy was performed in wild-type or MMP-9-deficient (MMP-9-/-) mice. Hepatic regeneration was determined by liver weight/total body weight ratios and BrdU staining, which was used to a calculate mitotic index at several times postoperatively. Cytokine and growth factor expression was evaluated by Luminex bead-based ELISA and Western blots. Finally, the effect of MMP-9 on apoptosis was measured using TUNEL and caspase expression. The MMP-9-/- animals had a delayed hepatic regenerative response when compared with wild-type controls. The MMP-9-deficient animals expressed significantly less VEGF, HGF, and TNF-alpha between days 2 and 3 post-hepatectomy. Apoptosis, as measured by TUNEL staining and caspase expression, was decreased in the MMP-9-/-. In conclusion, MMP-9 plays an important role in liver regeneration after partial hepatectomy by affecting matrix remodeling, as well as cytokine, growth factor, and caspase expression.

A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma.

BACKGROUND: We report the results of a multi-institutional phase II trial that used preoperative full-dose gemcitabine and radiotherapy for patients with potentially resectable pancreatic carcinoma. METHODS: Patients were treated before surgery with three cycles of full-dose gemcitabine (1000 mg/m2 intravenously), with radiation during the second cycle (36 Gy in daily 2.4-Gy fractions). Patients underwent surgery 4 to 6 weeks after the last gemcitabine infusion. RESULTS: There were 10 men and 10 women, with a median age of 58 years (range, 50-80 years). Nineteen patients (95%) completed therapy without interruption, and one experienced grade 3 gastrointestinal toxicity. The mean weight loss after therapy was 4.0%. Of 20 patients taken to surgery, 17 (85%) underwent resections (16 pancreaticoduodenectomies and 1 distal pancreatectomy). The complication rate was 24%, with an average length of stay of 13.5 days. There were no operative deaths. Pathologic analysis revealed clear margins in 16 (94%) of 17 and uninvolved lymph nodes in 11 (65%) of 17 specimens. One specimen contained no residual tumor, and three specimens revealed only microscopic foci of residual disease. With a median follow-up of 18 months, 7 (41%) of the 17 patients with resected disease are alive with no recurrence, 3 (18%) are alive with distant metastases, and 7 (41%) have died. CONCLUSIONS: Preoperative gemcitabine/radiotherapy is well tolerated and safe when delivered in a multi-institutional setting. This protocol had a high rate of subsequent resection, with acceptable morbidity. The high rate of negative margins and uninvolved nodes suggests a significant tumor response. Preliminary survival data are encouraging. This regimen should be considered in future neoadjuvant trials for pancreatic cancer.

Preventing surgical fires: who needs to be educated?

UNLABELLED: BACKGROUND AND CASE STUDY: Surgical fires are rare but preventable. During facial surgery for a 68-year-old man, a fire broke out, resulting in first- and second-degree burns after a nasal cannula ignited in an oxygen-rich environment because of improper draping and tenting. DISCUSSION: Operating room (OR) fires can be prevented if any component of the "fire triangle"-fuels, ignition sources, and oxidizers-is reduced or eliminated. The use of supplemental oxygen in the OR via nasal cannulae, nebulizers, and oxygen cylinders must always considered a potential source of fire. Deficits in knowledge among the surgical team with respect to the prevention and management of surgical fires were apparent. A plan was put into place to improve fire safety education, entailing an educational program that is included in intern and resident orientation. Surgical fire safety training was also put into place for anesthesia and surgical faculty. The anesthesia preoperative evaluation was modified to include an assessment of the patients' ability to tolerate short periods without oxygen. Posters and signs are now displayed in each OR suite. A complete policy review and update ensures that at least two fire drills are performed annually. CONCLUSION: Surgical fires can usually be prevented by educating staff about risk and prevention strategies. Such education should be part of all undergraduate medical, nursing, and other allied health profession education.

Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer.

PURPOSE: The primary objective of this study was to evaluate the tolerance and toxicity of radiation therapy (RT) and capecitabine in patients with advanced, unresectable pancreatic carcinoma. To control micrometastatic disease, combination chemotherapy (gemcitabine and cisplatin) before and after combined modality therapy (CMT) was planned. METHODS AND MATERIALS: Patients with unresectable or metastatic pancreatic cancer were eligible. Gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 were administered on Days 1 and 8 of a 21-day cycle for two cycles. RT was then given to a dose of 50.4 Gy in 1.8 Gy fractions. Patients were treated with capecitabine 1330 mg/m2 daily during RT. After CMT, two additional cycles of gemcitabine and cisplatin completed the treatment. RESULTS: Twenty-three patients were treated. Eighteen patients completed CMT. One patient was removed from study during CMT for toxicity issues. Treatment delays and dose reductions were common during the final two cycles of gemcitabine and cisplatin as a result of myelosuppression. Median survival was 10.1 months (95% confidence interval [CI] = 7.6, 13.7) for all 23 patients and 12.8 months (95% CI = 8.2, 18.9) for 18 patients without metastasis. CONCLUSION: Combined modality therapy with RT and capecitabine was well tolerated. Chemotherapy after CMT was difficult to complete owing to cumulative myelosuppression. Survival, response, and toxicity were comparable to infusional 5-fluorouracil and RT.