Analysis of Clinical Predictive Factors Affecting the Outcome of Second-Line Chemotherapy for Gemcitabine-Refractory Advanced Pancreatic Cancer

Background/Aims@#The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. @*Methods@#The records of patients who received gemcitabine-based FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. @*Results@#SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19-9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell’s C-index of the final prognosis prediction model was 0.62. @*Conclusions@#SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabine-based FL.

Morphologic Restoration After Peroral Endoscopic Myotomy in Sigmoid-type Achalasia

Background/Aims@#Achalasia is a chronic, progressive motility disorder of the esophagus. The sigmoid-type achalasia is an advanced stage of achalasia characterized by severe dilatation and tortuous angulation of the esophageal body. Peroral endoscopic myotomy (POEM) has been reported to provide excellent clinical outcomes for achalasia, including the sigmoid type, but the restoration of esophageal morphology and function remain poorly described. The aim of our study is to investigate esophageal restoration after POEM for sigmoid-type achalasia. @*Methods@#From 98 patients with achalasia who underwent POEM in the Yonsei University Health System from 2013 to 2018, we recruited 13 patients with sigmoid-type achalasia (7 male; mean age 53.3 years) and assessed morphological and manometric changes in the esophagus. @*Results@#Clinical success (Eckardt score < 3) was achieved in all cases. After POEM, the average angle of esophageal tortuosity became more obtuse (91.5° vs 114.6°, P = 0.046), esophageal body diameter decreased (67.6 vs 49.8 mm, P = 0.002), and esophagogastric junction opening widened (6.4 vs 9.5 mm, P = 0.048). Patients whose esophageal tortuosity did not improve had longer durations of symptoms than patients with improvement (80.2 vs 636 months, P < 0.001). An absence of peristalsis was observed in all patients pre- and post-POEM. @*Conclusions@#POEM resulted in excellent clinical outcomes and morphologic improvement in sigmoid-type achalasia. These results suggest that the improvement of esophageal tortuosity through POEM reflects a reduced esophageal burden.

Atrial Septal Defect with Normal Pulmonary Arterial Pressure in Adult Cyanotic Patient

A 22-year-old male presented with recurrent stroke, central cyanosis, and dyspnea. Transesophageal echocardiography and cardiac catheterization revealed bidirectional shunt flow through atrial septal defect (ASD) without pulmonary arterial hypertension. The orifice of inferior vena cava facing towards ASD opening led partially right to left shunt resulting in cyanosis with normal pulmonary arterial pressure.

Risk factors of gastrointestinal bleeding for end-stage renal disease patients / 대한내과학회지

BACKGROUDN: Gastrointestinal bleeding (GIB) is not a rare complication in end-stage renal disease (ESRD) patients on dialysis and the occurrence of GIB has also been associated with higher morbidity and mortality rates. However, reasons for the high incidence of GIB are not clear. This retrospective study was undertaken not only to analyze the clinical features of GIB but also to elucidate the independent risk factors for GIB in Korean ESRD patients. METHODS: One hundred thirty ESRD patients on dialysis at the Severance Hospital of Yonsei University College of Medicine from January 2000 to December 2005 were included in the study. The patients were divided into two groups: 65 patients with GIB (the GIB group) and 65 age-, sex-, and dialysis modality-matched patients without GIB (the C group). Clinical characteristics, medications, and laboratory findings were compared between the two groups. RESULTS: Compared to the C group, congestive heart failure (40.0% vs. 21.5%, p<0.05), coronary arterial occlusive disease (CAOD) (32.3% vs. 4.6%, p<0.005), and nonsteroidal anti-inflammatory drug (NSAID) use (18.4% vs. 1.5%, p<0.01) were significantly more common in the GIB group. The baseline serum albumin levels were significantly lower in the GIB group than in the C group (2.53+/-0.67 g/dL vs. 3.56+/-0.63 g/dL, p<0.005). Using logistic regression analysis, CAOD (OR=23.0), NSAID use (OR=12.5), and lower serum albumin levels (OR=2.9) were identified as independent risk factors for GIB (p<0.05). CONCLUSIONS: Careful attention must be paid to ESRD patients with CAOD, taking NSAIDs, or with low serum albumin levels in view of GIB.

Serial Changes of QT Dispersion in Continuous Ambulatory Peritoneal Dialysis Patients / 대한신장학회잡지

PURPOSE:To evaluate the changes of QT dispersion (QTd) in CAPD patients serially from the period before the initiation of CAPD until several years after CAPD, and to find any associated factors. METHODS:We performed a retrospective cohort study with a total of 101 patients who initiated CAPD between 1990 and 1996. All data were recruited from the patients' medical records before CAPD initiation, within one year after CAPD, and between one and three years after CAPD. RESULTS:QTd and Corrected QTd (QTdc) values after CAPD did not show differences in the paired t-test of those before CAPD and within one year after CAPD. There was a definite correlation between the QTds before CAPD and that within one year after CAPD (r=0.530, p<0.001). In addition, the QTds from within one year after CAPD showed a correlation with those taken from one to three years after CAPD (r=0.487, p=0.019). Upon analysis of all-cause mortality, the change rate of QTd after CAPD initiation was revealed as a predicting factor along with the QTd, QTc max, and QTdc within one year after CAPD (RR=1.055, p=0.005). The change rate also remained a predictor of cardiovascular mortality (RR= 1.088, p=0.007). In a multivariate Cox regression, cardiomegaly and previous cardiovascular disease were revealed to be independent factors for the change rate of QTd. CONCLUSION:QTd in CAPD patients did not change after initiation of CAPD, and the change rate of QTd after CAPD initiation was revealed as a risk factor for both all-cause mortality and cardiovascular mortality.

Usefulness of Peritoneal Dialysis (PD) in Patients with Refractory Heart Failure (RHF) / 대한신장학회잡지

BACKGROUND:Though PD has served as a treatment method for metabolic derangement in acute or chronic renal failure, it has also been used as a palliative therapy or as a bridge to definite surgery or transplantation in patients with RHF. Some studies have demonstrated that PD reduced hospitalization rates and improved functional capacity in these patients, but changes in echocardiographic findings after PD have not been thoroughly explored. In this study, the effects of PD on hospitalization rates and days, functional status, and echocardiographic parameters were evaluated. METHODS:Thirteen patients, in whom PD was performed to treat heart failure, were enrolled. Patients with serum creatinine levels more than 3.0 mg/dL and with acute cardiac event within 1 month before the start of PD were excluded. The clinical, laboratory, and echocardiographic findings before and after the start of PD were compared by carrying out a paired t-test or Wilcoxon signed rank test. RESULTS:Among 13 patients, 11 patients experienced improvement in functional status after the initiation of PD, and the mean NYHA class improved from 3.5+/-0.5 to 2.3+/-0.9 after PD treatment (p<0.005). Significant reductions in hospitalization rates (from 1.7+/-0.4 to 0.2+/-0.4 episodes/patient-year, p<0.001) and in hospitalization days (from 62.1+/-26.5 to 3.8+/-8.9 days/patient-year, p<0.001) were also observed since the start of PD. Echocardiographic findings revealed that right ventricular pressure was significantly reduced in both right-sided and left-sided heart failure patients (p<0.05), whereas there were no significant changes in left ventricular end-diastolic diameter and left ventricular ejection fraction after PD therapy. CONCLUSION:PD treatment improved quality of life, shortened hospitalization period, and reduced right ventricular pressure in patients with RHF. These findings suggest that PD should be considered as an alternative therapeutic modality for RHF.

Usefulness of autofluorescence bronchoscopy for detecting bronchial premalignant lesions / 대한내과학회지

BACKGROUND: Autofluorescence bronchoscopy (AFB), when used as an adjunct to conventional white light bronchoscopy (WLB) improves the bronchoscopist's ability to localized small intraepithelial lesions. Current study was undertaken to evaluate prevalence of preinvasive intraepithelial lesions (dysplasia II-III and CIS) and efficacy of additional AFB system to WLB in comparison with WLB alone. METHODS: In patients with suspicion of lung cancer or follow-up ones with known lung cancer, WLB (Pentax; BP 3500, Japan) and AFB (Richard Wolf, Germany) were done and all subjects with endoscopic abnormalities underwent biopsies from January 2005 to December 2005. RESULTS: 169 patients (134 suspected to have lung cancer radiologically, 18 with known lung cancer, and 17 with initial abnormal WLB visual findings) were enrolled. Overall preinvasive intraepithelial lesions were detected in 6.5% (11 persons). Biopsy based sensitivity of WLB+AFB and WLB alone for detecting preinvasive intraepithelial lesions was 77.8% compared with 22.2% (relative ratio 3.5, 95% CI 0.93-13.24). Corresponding specificity was 56.9% compared with 89.2% (relative ratio 0.64, 95% CI 0.54-0.75). The positive predicitve value was 6% and 3%, and the negative predictive value was 94% and 87%, respectively, for WLB+AFB and WLB alone. CONCLUSIONS: WLB+AFB was superior to WLB alone in detecting preinvasive intraepithelial lesions, but general use of AFB as a screening tool seems to be limited in suspected or known lung cancer group because of low prevalence. It is necessary of further study for precise indication for AFB among the lung cancer risk groups.

Small Bowel Sparing Effect of Small Bowel Displacement System in 3D-CRT and IMRT for Cervix Cancer / 대한방사선종양학회지

PURPOSE: In radiotherapy for cervix cancer, both 3-dimensioal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) could reduce the dose to the small bowel (SB), while the small bowel displacement system (SBDS) could reduce the SB volume in the pelvic cavity. To evaluate the effect of the SBDS on the dose to the SB in 3D-CRT and IMRT plans, 3D-CRT and IMRT plans, with or without SBDS, were compared. MATERIALS AND MEHTODS: Ten consecutive uterine cervix cancer patients, receiving curative radiotherapy, were accrued. Ten pairs of computerized tomography (CT) scans were obtained in the prone position, with or without SBDS, which consisted of a Styrofoam compression device and an individualized custom-made abdominal immobilization device. Both 3D-CRT, using the 4-field box technique, and IMRT plans, with 7 portals of 15 MV X-ray, were generated for each CT image, and prescribed 50 Gy (25 fractions) to the isocenter. For the SB, the volume change due to the SBDS and the DVHs of the four different plans were analyzed using paired t-tests. RESULTS: The SBDS significantly reduced the mean SB volume from 522 to 262 cm3 (49.8% reduction). The SB volumes that received a dose of 10~50 Gy were significantly reduced in 3D-CRT (65~80% reduction) and IMRT plans (54~67% reduction) using the SBDS. When the SB volumes that received 20~50 Gy were compared between the 3D-CRT and IMRT plans, those of the IMRT without the SBDS were significantly less, by 6~7%, than those for the 3D-CRT without the SBDS, but the volume difference was less than 1% when using the SBDS. CONCLUSION: The SBDS reduced the radiation dose to the SB in both the 3D-CRT and IMRT plans, so could reduce the radiation injury of the SB.

Radical Radiotherapy for Locally Advanced Cancer of Uterine Cervix / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was performed to evaluate the treatment results, prognostic factors and complication rates in patients with locally advanced cancer of uterine cervix after radiotherapy with high-dose rate (HDR) brachytherapy. MATERIALS AND METHODS: One hundred and twenty patients with a locally advanced (stages IIB~IVA according to FIGO classification) carcinoma of the uterine cervix were treated with radiotherapy at the Department of Radiation Oncology, Samsung Medical Center between September 1994 and December 2001. The median age of the patients was 61 years (range 29 to 81). Sixty-one, 56 and 3 patients had FIGO stage IIB, III, and IV diseases, respectively. All patients were given external beam radiotherapy over the whole pelvis (median 50.4 Gy) and HDR intracavitary brachytherapy, with a median of 4 Gy per fraction, to point A. Twenty-one patients received chemotherapy, of which 13 and 21 received neoadjuvant chemotherapy and concurrent chemotherapy, respectively, during the first and fourth weeks of external beam radiotherapy. The chemotherapy was not randomly assigned and the median follow-up time was 28.5 months (range: 6~100 months). RESULTS: The three- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 64.4 and 57.0%, and 63.7 and 60.2%, respectively. The 5-year OS and DFS rates of the patients at stages IIB, III and IV were 602, 57.9 and 33.3%, and 57.4, 65.4 and 33.3%, respectively. Univariate analysis indicated that the FIGO stage, overall treatment time (OTT) and treatment response were significant variables for the OS (p=0.035, p=0.0649 and p=0.0009) and of the DFS (p=0.0009, p=0.0359 and p=0.0363). Multivariate analysis showed that the treatment response was the only significant variable for the OS (p=0.0018) and OTT for the DFS (p=0.0360). The overall incidence of late complications in the rectum and bladder were 11.7 and 6.7%, respectively. In addition, insufficiency fractures were observed in 7 patients (5.8%). CONCLUSION: The results of this study suggest that radical radiotherapy with HDR brachytherapy was appropriate for the treatment of locally advanced uterine cervix cancer. Also, the response after treatment and OTT are significant prognostic factors.

Prediction of Late Rectal Complication Following High-dose-rate Intracavitary Brachytherapy in Cancer of the Uterine Cervix / 대한방사선종양학회지

PURPOSE: Although high-dose-rate intracavitary radiotherapy (HDR ICR) has been used in the treatment of cervical cancer, the potential for increased risk of late complication, most commonly in the rectum, is a major concern. We have previously reported on 136 patients treated with HDR brachytherapy between 1995 and 1999. The purpose of this study is to upgrade the previous data and confirm the correlation between late rectal complication and rectal dose in cervix cancer patients treated with HDR ICR. MATERIALS AND METHODS: A retrospective analysis was performed for 222 patients with cervix cancer who were treated for curative intent with external beam radiotherapy (EBRT) and HDR ICR from July 1995 to December 2001. The median dose of EBRT was 50.4 (30.6~56.4) Gy with a daily fraction size 1.8 Gy. A total of six fractions of HDR ICR were given twice weekly with fraction size of 4 (3~5.5) Gy to A point by Iridium-192 source. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. in vivo measurement of the rectal dose was performed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 39 months, ranging from 6 to 90 months. RESULTS: Twenty-one patients (9.5%) experienced late rectal bleeding, from 3 to 44 months (median, 13 months) after the completion of RT. The calculated rectal doses were not different between the patients with rectal bleeding and those without, but the measured rectal doses were higher in the complicated patients. The differences of the measured ICR rectal fractional dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose was beyond 16 Gy, when the ratio of the measured rectal dose to A point dose was beyond 70%, or when the measured rectal BED was over 110 Gy3, a high possibility of late rectal complication was found. CONCLUSION: Late rectal complication was closely correlated with measured rectal dose by in vivo dosimetry using TLD during HDR ICR. If data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.

Positional Change of the Uterus during Definitive Radiotherapy for Cervix Cancer / 대한방사선종양학회지

PURPOSE: The purpose of this study was to investigate the positional change of the uterus during radiotherapy MATERIALS AND METHODS: Between 1997 and 2001, 47 patients received definitive radiotherapy for cervical cancer at the Samsung Medical Center. For each patient, two MRI scans were taken; one before and the other 3~4 weeks after the radiotherapy treatment. In T2 weighted MRI images, the positional change of the uterine was quantified by measuring six quantities; the distance from the cervix os to the isthmus of the uterus (Dcx), the maximum length from the isthmus of the uterus to the uterine fundus (Dco), the maximum vertical distance of the uterine body (Dco-per), the angle between the vertical line and the cervical canal in the sagittal images (Acx), the angle of the uterine corpus from the vertical line in the sagittal plan (Aco-ap), and the relative angle of the uterine corpus from a fixed anatomical landmark in the axial images (Aco-axi). RESULTS: The mean Dcx values, before and during the treatment, were 36.7 and 27.8 mm, respectively. The Dco deviated by more than 10 mm in 14 cases (29.8%). The change in the Acx ranged from 0.1 to 67.8degrees (mean 13.2degrees). The Aco-ap changed by a maximum of 84.8degrees (mean 16.9degrees). The differences in the Dcx plus the Dco in the smaller (or= 4 cm) tumors were 5.3 and 19.4 mm, respectively. With patients less than 60 years old, or with a tumor size larger than 4 cm, the difference in the Acx was statistically significant. CONCLUSION: The positional changes of the uterus, during radiation treatment, should be considered in the 3DCRT or IMRT treatment planning, particularly in patients under 60 years of age or in those with a tumor size greater than 4 cm in maximum diameter.