Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment

Background@#/Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. @*Methods@#A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. @*Results@#The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). @*Conclusions@#Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer

Purpose@#To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution. @*Materials and Methods@#From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50–70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities. @*Results@#The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3–5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity. @*Conclusion@#HFRT with 50–70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.

External Beam Radiotherapy for Hepatocellular Carcinoma: a Review of the Current Guidelines in the East and the West

The incidence of hepatocellular carcinoma (HCC) is geographically heterogeneous depending on the underlying liver disease. Moreover, the decisions and recommendations about standard treatments differ between countries, especially between the East and the West. Because of the complexity of treatment decisions for the management of HCC, a multidisciplinary approach is recommended to maximize the therapeutic efficacy. External beam radiotherapy (RT) has been increasingly used to manage HCC when recommended treatments cannot be applied in real-world clinical practice. However, Western guidelines for the management of HCC do not recommend RT as a treatment option due to the lack of clinical evidence. RT has often been used more in Eastern countries than in Western countries; hence, it is necessary to review both Eastern and Western guidelines for HCC treatment regarding the recommendations about RT. In this study, the comments and potential roles of external beam RT are summarized from several treatment guidelines for the management of HCC.

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer

Purpose@#To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution. @*Materials and Methods@#From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50–70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities. @*Results@#The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3–5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity. @*Conclusion@#HFRT with 50–70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.

External Beam Radiotherapy for Hepatocellular Carcinoma: a Review of the Current Guidelines in the East and the West

The incidence of hepatocellular carcinoma (HCC) is geographically heterogeneous depending on the underlying liver disease. Moreover, the decisions and recommendations about standard treatments differ between countries, especially between the East and the West. Because of the complexity of treatment decisions for the management of HCC, a multidisciplinary approach is recommended to maximize the therapeutic efficacy. External beam radiotherapy (RT) has been increasingly used to manage HCC when recommended treatments cannot be applied in real-world clinical practice. However, Western guidelines for the management of HCC do not recommend RT as a treatment option due to the lack of clinical evidence. RT has often been used more in Eastern countries than in Western countries; hence, it is necessary to review both Eastern and Western guidelines for HCC treatment regarding the recommendations about RT. In this study, the comments and potential roles of external beam RT are summarized from several treatment guidelines for the management of HCC.

Combined Transarterial Chemoembolization and External Beam Radiotherapy in a Patient with Recurrent Huge Hepatocellular Carcinoma after Hepatic Resection

The optimal treatment strategy for unresectable huge hepatocellular carcinoma (HCC) is yet to be established. Non-surgical monotherapy demonstrated insufficient oncologic outcomes in previously reported studies. To improve the clinical outcomes of unresectable huge HCC, combined locoregional treatments can be considered in selected cases. Here, we report a case of 58-year-old male patient who was treated with combined transarterial chemoembolization (TACE) and external beam radiotherapy for recurrent HCC after a previous hepatic resection. After combined TACE and radiotherapy for the intrahepatic lesion, two metastases were diagnosed in the pelvic bones and lung; each lesion was successfully treated with salvage radiotherapy. During the long-term follow-up period (around 8 years 7 months after combined TACE and radiotherapy for the recurrent huge HCC), no definite viable tumors were observed in any of the treated liver, bone, and lung lesions.

Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial

Background/Aims@#Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs. @*Methods@#A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria. @*Results@#Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events. @*Conclusions@#SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.

Radiotherapy for mandibular metastases from hepatocellular carcinoma: a single institutional experience

PURPOSE: A mandibular metastasis is uncommon in patients with hepatocellular carcinoma (HCC). We report the clinical features of this rare lesion and evaluate the effectiveness of radiotherapy in affected patients.MATERIALS AND METHODS: We retrospectively reviewed our institutional medical records for HCC patients who received radiotherapy for bone metastasis, and included cases of mandible metastasis. The clinical features of these cases, and the characteristics and outcomes of the treatments were assessed.RESULTS: A total of 1,498 patients with a bone metastasis from HCC were treated with radiotherapy between July 1998 and April 2012 at our institution. We identified 9 patients (0.6%) in this cohort that received radiotherapy for a mandibular metastasis. The condyle was the most common location of mandibular metastasis. The median radiation dose was 40 Gy (range, 27.5 to 60 Gy), with a daily dose of 2–3 Gy. All of these 9 patients died during a median follow-up of 9 months (range, 1 to 19 months). Symptom relief was achieved in 7 of 8 patients who completed radiotherapy. Tumor size reduction was observed in 2 of 4 patients who underwent radiologic evaluation after radiotherapy.CONCLUSIONS: Metastasis to the mandible from HCC has a poor prognosis. Radiotherapy can be an effective local treatment option for symptomatic relief in these cases.

Patterns of recurrence after radiation therapy for high-risk neuroblastoma

PURPOSE: To investigate the patterns of recurrence in patients with neuroblastoma treated with radiation therapy to the primary tumor site. MATERIALS AND METHODS: We retrospectively analyzed patients with high-risk neuroblastoma managed with definitive treatment with radiation therapy to the primary tumor site between January 2003 and June 2017. These patients underwent three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. A total of 14–36 Gy was delivered to the planning target volume, which included the primary tumor bed and the selected metastatic site. The disease stage was determined according to the International Neuroblastoma Staging System (INSS). We evaluated the recurrence pattern (i.e., local or systemic), progression-free survival, and overall survival. RESULTS: A total of 40 patients with high-risk neuroblastoma were included in this study. The median patient age was 4 years (range, 1 to 11 years). Thirty patients (75%) had INSS stage 4 neuroblastoma. At the median follow-up of 58 months, there were 6 cases of local recurrence and 10 cases of systemic recurrence. Among the 6 local failure cases, 4 relapsed adjacent to the radiation field. The other 2 relapsed in the radiation field (i.e., para-aortic and retroperitoneal areas). The main sites of distant metastasis were the bone, lymph nodes, and bone marrow. The 5-year progression-free survival was 70.9% and the 5-year overall survival was 74.3%. CONCLUSION: Radiation therapy directed at the primary tumor site provides good local control. It seems to be adequate for disease control in patients with high-risk neuroblastoma after chemotherapy and surgical resection.

Treatment Outcome after Fractionated Conformal Radiotherapy for Hepatocellular Carcinoma in Patients with Child-Pugh Classification B in Korea (KROG 16-05) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B. MATERIALS AND METHODS: We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy₁₀ (α/β = 10 Gy). A total of 184 patients were included in this study. RESULTS: Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy₁₀ (median, 56.0 Gy₁₀). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD. CONCLUSION: Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

With recent remarkable technological advances in radiation therapy, stereotactic body radiation therapy (SBRT) is regarded as an alternative treatment option for hepatocellular carcinoma (HCC) that is not suitable for curative treatment. Several prospective and retrospective studies on the use of SBRT in patients with HCC showed promising results. Furthermore, on-going prospective studies are examining the role of SBRT as a single ablative modality or a combination treatment in patients with HCC. Here, we summarize previous studies and recent updates and discuss the future perspectives of SBRT for HCC.

Refining prognostic stratification of human papillomavirus-related oropharyngeal squamous cell carcinoma: different prognosis between T1 and T2

PURPOSE: To validate the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and investigate whether a modified classification better reflects the prognosis. MATERIALS AND METHODS: Medical records of patients diagnosed with non-metastatic HPV-related OPSCC between 2010 and 2016 at a single institution were retrospectively reviewed. HPV status was determined by immunohistochemical analysis of p16 and/or HPV DNA polymerase chain reaction (PCR). We reclassified TNM stage T0-1 and N0-1 as group A, T2-3 or N2 as B, and T4 or N3 as C. Survival analysis according to 8th AJCC/UICC TNM staging and the modified classification was performed. RESULTS: Of 383 OPSCC patients, 211 were positive for HPV DNA PCR or p16. After exclusion, 184 patients were included in this analysis. Median age was 56 years (range, 31 to 81 years). Most primary tumors were in the palatine tonsil (148 tumors, 80%). The eighth AJCC/UICC TNM classification could not differentiate between stage I and II (p = 0.470) or II and III (p = 0.209). Applying modified grouping, the 3-year overall survival rate of group A was significantly higher than that of group B and C (98% vs. 91%, p = 0.039 and 98% vs. 78%, p < 0.001, respectively). Differentiation between group B and C was marginally significant (p = 0.053). CONCLUSION: The 8th AJCC/UICC TNM staging system did not clearly distinguish the prognosis of stage II from that of other stages. Including the T2N0-1 group in stage II may improve prognostic stratification.

Role of fractionated radiotherapy in patients with hemangioma of the cavernous sinus

PURPOSE: We performed this retrospective study to investigate the outcomes of patients with hemangioma of the cavernous sinus after fractionated radiotherapy. MATERIALS AND METHODS: We analyzed 10 patients with hemangioma of the cavernous sinus who were treated with conventional radiotherapy between January 2000 and December 2016. The median patient age was 54 years (range, 31–65 years), and 8 patients (80.0%) were female. The mean hemangioma volume was 34.1 cm3 (range, 6.8–83.2 cm3), and fractionated radiation was administered to a total dose of 50–54 Gy with a daily dose of 2 Gy. RESULTS: The median follow-up period was 6.8 years (range, 2.2–8.8 years). At last follow-up, the volume of the tumor had decreased in all patients. The average tumor volume reduction rate from the initial volume was 72.9% (range, 18.9–95.3%). All 10 of the cranial neuropathies observed before radiation therapy had improved, with complete symptomatic remission in 9 cases (90%) and partial remission in 1 case (10%). No new acute neurologic impairments were reported after radiotherapy. One probable compressive optic neuropathy was observed at 1 year after radiotherapy. CONCLUSION: Fractionated radiotherapy achieves both symptomatic and radiologic improvements. It is a well-tolerated treatment modality for hemangiomas of the cavernous sinus.

Refining prognostic stratification of human papillomavirus-related oropharyngeal squamous cell carcinoma: different prognosis between T1 and T2

PURPOSE: To validate the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and investigate whether a modified classification better reflects the prognosis. MATERIALS AND METHODS: Medical records of patients diagnosed with non-metastatic HPV-related OPSCC between 2010 and 2016 at a single institution were retrospectively reviewed. HPV status was determined by immunohistochemical analysis of p16 and/or HPV DNA polymerase chain reaction (PCR). We reclassified TNM stage T0-1 and N0-1 as group A, T2-3 or N2 as B, and T4 or N3 as C. Survival analysis according to 8th AJCC/UICC TNM staging and the modified classification was performed. RESULTS: Of 383 OPSCC patients, 211 were positive for HPV DNA PCR or p16. After exclusion, 184 patients were included in this analysis. Median age was 56 years (range, 31 to 81 years). Most primary tumors were in the palatine tonsil (148 tumors, 80%). The eighth AJCC/UICC TNM classification could not differentiate between stage I and II (p = 0.470) or II and III (p = 0.209). Applying modified grouping, the 3-year overall survival rate of group A was significantly higher than that of group B and C (98% vs. 91%, p = 0.039 and 98% vs. 78%, p < 0.001, respectively). Differentiation between group B and C was marginally significant (p = 0.053). CONCLUSION: The 8th AJCC/UICC TNM staging system did not clearly distinguish the prognosis of stage II from that of other stages. Including the T2N0-1 group in stage II may improve prognostic stratification.

Role of fractionated radiotherapy in patients with hemangioma of the cavernous sinus

PURPOSE: We performed this retrospective study to investigate the outcomes of patients with hemangioma of the cavernous sinus after fractionated radiotherapy. MATERIALS AND METHODS: We analyzed 10 patients with hemangioma of the cavernous sinus who were treated with conventional radiotherapy between January 2000 and December 2016. The median patient age was 54 years (range, 31–65 years), and 8 patients (80.0%) were female. The mean hemangioma volume was 34.1 cm3 (range, 6.8–83.2 cm3), and fractionated radiation was administered to a total dose of 50–54 Gy with a daily dose of 2 Gy. RESULTS: The median follow-up period was 6.8 years (range, 2.2–8.8 years). At last follow-up, the volume of the tumor had decreased in all patients. The average tumor volume reduction rate from the initial volume was 72.9% (range, 18.9–95.3%). All 10 of the cranial neuropathies observed before radiation therapy had improved, with complete symptomatic remission in 9 cases (90%) and partial remission in 1 case (10%). No new acute neurologic impairments were reported after radiotherapy. One probable compressive optic neuropathy was observed at 1 year after radiotherapy. CONCLUSION: Fractionated radiotherapy achieves both symptomatic and radiologic improvements. It is a well-tolerated treatment modality for hemangiomas of the cavernous sinus.

Clinical Practice Patterns of Radiotherapy in Patients with Hepatocellular Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-07) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC). MATERIALS AND METHODS: We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions. RESULTS: The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy10 vs. 56.3 Gy10). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT. CONCLUSION: Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival.

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

The General Rules for the Study of Primary Liver Cancer

The General Rules for the Study of Primary Liver Cancer was published in June 2001 as the first edition. Since then, the 5th edition of the General Rules for the Study of Primary Liver Cancer was published by the 17th Committee of the Korean Liver Cancer Association based on the most recent data. The 5th edition of the General Rules for the Study of Primary Liver Cancer ranged over numerous topics such as anatomy, medical assessment of the patients, staging of hepatocellular carcinoma, description of the image findings, summary of hepatic resection, description of the surgical specimens, liver transplantation, reporting the pathological findings, pathological examinations of liver specimen, non-surgical treatment, radiotherapy, and assessment of tumor response after non-surgical treatment of hepatocellular carcinoma. The 5th General Rules for the Study of Primary Liver Cancer will not only become the basis of academic development for liver cancer studies in Korea, but also serve as the primary form of national liver cancer data accumulation based on standardized rules.

Near-Normalized Gene Expression Profiles in Bladder With Detrusor Overactivity in Rats With Bladder Outlet Obstruction After Deobstruction / 대한배뇨장애요실금학회지

PURPOSE: The pathophysiological role of detrusor overactivity (DO) in the bladder, which is commonly observed in various bladder diseases, is not well understood. DO appears in bladder outlet obstruction (BOO), and may continue even after subsequent deobstruction. DO therefore provides an excellent opportunity to observe molecular biological changes. METHODS: In this study, to understand the molecular effects of persistent DO after BOO induction and deobstruction, we performed awake cystometry on female Sprague-Dawley rats divided into 4 groups: a sham group, a BOO group, a deobstructed group with DO after BOO (DDO), and a deobstructed group without DO after BOO (non-DDO). Total RNA was extracted from the bladder samples, and gene expression profiles were compared between the sham and model groups. RESULTS: DO was observed in 5 of the 6 rats (83%) in the BOO group, and in 6 of the 13 rats (46%) in the deobstructed group. The non-DDO group showed a significantly greater residual volume than the DDO group. Through a clustering analysis of gene expression profiles, we identified 7,532 common upregulated and downregulated genes, the expression of which changed by more than 2 fold. In the BOO group, 898 upregulated and 2,911 downregulated genes were identified. The non-DDO group showed 3,472 upregulated and 4,025 downregulated genes, whereas in the DDO group, only 145 and 72 genes were upregulated and downregulated, respectively. CONCLUSIONS: Abnormal function and gene expression profiles in bladders after BOO were normalized in the BOO rats with DO after deobstruction, whereas in those without DO, abnormal function persisted and the gene expression profile became more abnormal. DO may play a protective role against the stress to the bladder induced by BOO and deobstruction as a form of adaptive neuroplasticity.

A Case of Post-radiotherapy Urethral Stricture with Spontaneous Bladder Rupture, Mimicking Obstructive Uropathy due to Cancer Metastasis

Non-traumatic, spontaneous urinary bladder rupture is a rare complication of urethral stricture. Furthermore, its symptoms are often nonspecific, and misdiagnosis is common. The authors experienced a case of urethral stricture with spontaneous bladder rupture and bilateral hydronephrosis, mimicking obstructive uropathy attributed to cancer metastasis. A 55-year-old woman was admitted with abdominal pain and distension, oliguria, and an elevated serum creatinine level. She had undergone radical hysterectomy for uterine cervical cancer and received post-operative concurrent chemoradiation therapy 13 years previously. Non-contrast enhanced computed tomography showed massive ascites and bilateral hydronephrosis. The initial diagnosis was acute kidney injury due to obstructive uropathy caused by malignant disease. After improvement of her renal function by bilateral percutaneous nephrostomy catheterization, contrast-enhanced computed tomography and a cytologic examination of ascites showed no evidence of malignancy. However, during retrograde pyelography, a severe urethral stricture was found, and subsequent cystography showed leakage of contrast into the peritoneal cavity and cystoscopy revealed a defect of the posterior bladder wall. After urethral dilatation and primary closure of the bladder wall, acute kidney injury and ascites were resolved.