Computed Tomography Findings Associated with Treatment Failure after Antibiotic Therapy for Acute Appendicitis

Objective@#To identify the CT findings associated with treatment failure after antibiotic therapy for acute appendicitis. @*Materials and Methods@#Altogether, 198 patients who received antibiotic therapy for appendicitis were identified by searching the hospital’s surgery database. Selection criteria for antibiotic therapy were uncomplicated appendicitis with an appendiceal diameter equal to or less than 11 mm. The 86 patients included in the study were divided into a treatment success group and a treatment failure group. Treatment failure was defined as a resistance to antibiotic therapy or recurrent appendicitis during a 1-year follow-up period. Two radiologists independently evaluated the following CT findings: appendix–location, involved extent, maximal diameter, thickness, wall enhancement, focal wall defect, periappendiceal fat infiltration, and so on. For the quantitative analysis, two readers independently measured the CT values at the least attenuated wall of the appendix by drawing a round region of interest on the enhanced CT (HUpost) and non-enhanced CT (HUpre). The degree of appendiceal wall enhancement (HUsub) was calculated as the subtracted value between HUpost and HU pre. A logistic regression analysis was used to identify the CT findings associated with treatment failure. @*Results@#Sixty-four of 86 (74.4%) patients were successfully treated with antibiotic therapy, with treatment failure occurring in the remaining 22 (25.5%). The treatment failure group showed a higher frequency of hypoenhancement of the appendiceal wall than the success group (31.8% vs. 7.8%; p = 0.005). Upon quantitative analysis, both HU post (46.7 ± 21.3 HU vs. 58.9 ± 22.0 HU; p = 0.027) and HUsub (26.9 ± 17.3 HU vs. 35.4 ± 16.6 HU; p = 0.042) values were significantly lower in the treatment failure group than in the success group. @*Conclusion@#Hypoenhancement of the appendiceal wall was significantly associated with treatment failure after antibiotic therapy for acute appendicitis.

Rectal Cancer Patient with Complete Response to Neoadjuvant Chemoradiotherapy

Personalized medicine for rectal cancer patients includes nonoperative management. This strategy is appropriate for select patients who exhibit a clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT). This study presents the case of a 70-year-old female with locally advanced rectal cancer. She received standard nCRT, consisting of 50.4 Gy pelvic radiotherapy and concurrent 5-fluorouracil chemotherapy. The response to nCRT was evaluated at 11 weeks after nCRT completion. Colonoscopy and computed tomography indicated cCR, but a partial residual tumor was suspected based on magnetic resonance imaging. Low anterior resection was performed with the creation of a protective colostomy. The pathological examination of the surgical specimen revealed only a fibrotic mass, no viable tumor cells. The stoma was maintained for 10 months until reversal after adjuvant chemotherapy ended. The patient remains alive with no evidence of disease 4 years later; however, the utility of this radical major surgery was questionable for this patient. Development of a risk-adapted strategy based on the nCRT response would avoid overtreatment, improving functional outcomes and quality of life while also retaining good oncological outcomes.

Circulating Tumor Cells: Liquid Biopsy for Early Detection of Cancer

Cancer is a complex, heterogeneic, and dynamic disease involving multiple gene-environment interactions, and affecting numerous biological pathways. As such, the development of reliable and robust non-invasive platforms constitutes a vital step toward realizing the potential of precision medicine. Distant metastases harbor unique genomic characteristics that are not detectable in the corresponding primary tumor of the same patient, and metastases located at different sites show considerable intra-patient heterogeneity. Thus, the analysis of the resected primary tumor alone or, if possible, re-evaluation of tumor characteristics based on the biopsy of the most accessible metastasis, may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, the analysis of therapeutic targets and drug resistance-conferring gene mutations in or on circulating tumor cells (CTCs). Finally, the analysis of the resected primary tumor alone may provide misleading information with regard to the characteristics of metastases, the key target for systemic anticancer therapy. Liquid biopsies are noninvasive tests using blood or fluids that detect CTCs or the products of tumors, such as fragments of nucleotides or proteins that are shed into biological fluids from the primary or metastatic tumors. Such biopsies are expected to be informative or easily accessible tools to provide comprehensive information regarding cancers beyond conventional biopsies. Thus, this review addresses the use of CTCs in cancer detection, diagnosis and monitoring and discusses the direction of its clinical application in cancer patient care.

Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation

PURPOSE: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. MATERIALS AND METHODS: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. RESULTS: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. CONCLUSION: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.

Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation

PURPOSE: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. MATERIALS AND METHODS: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. RESULTS: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. CONCLUSION: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.

Identification of Hypoxanthine and Phosphoenolpyruvic Acid as Serum Markers of Chemoradiotherapy Response in Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Patients show variable responses to chemoradiotherapy (CRT), which is generally administered before surgery for locally advanced rectal cancer (LARC). The aim of this study was to identify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs) in serum of LARC patients. MATERIALS AND METHODS: LMIs ( 16.0 muM showed significant association with ypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. In contrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared with TRG 2-1 (p=0.012). CONCLUSION: Findings of this study demonstrated that serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC patients before treatment.

Efficient approach for determining four-dimensional computed tomography-based internal target volume in stereotactic radiotherapy of lung cancer

PURPOSE: This study aimed to investigate efficient approaches for determining internal target volume (ITV) from four-dimensional computed tomography (4D CT) images used in stereotactic body radiotherapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: 4D CT images were analyzed for 15 patients who received SBRT for stage I NSCLC. Three different ITVs were determined as follows: combining clinical target volume (CTV) from all 10 respiratory phases (ITV10Phases); combining CTV from four respiratory phases, including two extreme phases (0% and 50%) plus two intermediate phases (20% and 70%) (ITV4Phases); and combining CTV from two extreme phases (ITV2Phases). The matching index (MI) of ITV4Phases and ITV2Phases was defined as the ratio of ITV4Phases and ITV2Phases, respectively, to the ITV10Phases. The tumor motion index (TMI) was defined as the ratio of ITV10Phases to CTVmean, which was the mean of 10 CTVs delineated on 10 respiratory phases. RESULTS: The ITVs were significantly different in the order of ITV10Phases, ITV4Phases, and ITV2Phases (all p < 0.05). The MI of ITV4Phases was significantly higher than that of ITV2Phases (p < 0.001). The MI of ITV4Phases was inversely related to TMI (r = -0.569, p = 0.034). In a subgroup with low TMI (n = 7), ITV4Phases was not statistically different from ITV10Phases (p = 0.192) and its MI was significantly higher than that of ITV2Phases (p = 0.016). CONCLUSION: The ITV4Phases may be an efficient approach alternative to optimal ITV10Phases in SBRT for early-stage NSCLC with less tumor motion.

An Update on Preoperative Radiotherapy for Locally Advanced Rectal Cancer

Even in patients undergoing an optimal surgical technique (e.g., total mesorectal excision), radiotherapy provides a significant benefit in the local control of rectal cancer. Compared with postoperative treatment, chemoradiotherapy given preoperatively has been shown to decrease local recurrence rates and toxicity. Additionally, preoperative chemoradiotherapy permits the early identification of tumor responses to this cytotoxic treatment by surgical pathology. Pathological parameters reflecting the tumor response to chemoradiotherapy have been shown to be surrogate markers for long-term clinical outcomes. Post-chemoradiotherapy downstaging from cStage II-III to ypStage 0-I indicates a favorable prognosis, with no difference between ypStage 0 and ypStage I. Research is ongoing to develop useful tools (clinical, molecular, and radiological) for clinical determination of the pathologic chemoradiotherapeutic response before surgery, and possibly even before preoperative treatment. In the future, risk-adapted strategies, including intensification of preoperative therapy, conservative surgery, or the selective administration of postoperative chemotherapy, will be realized for locally-advanced rectal cancer patients based on their response to preoperative chemoradiotherapy.

Twice Daily Radiation Therapy Plus Concurrent Chemotherapy for Limited-Stage Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. MATERIALS AND METHODS: Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32~75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45~51 Gy). Concurrent chemotherapy consisted of CAV (cytoxan 1000 mg/m2, adriamycin 40 mg/m2, vincristine 1 mg/m2) alternating with PE (cisplatin 60 mg/m2, etoposide 100 mg/m2) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1~9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/ 10 fractions. Median follow up was 18 months (range, 1~136 months). RESULTS: Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival (p<0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. CONCLUSION: Twice daily radiation therapy plus concurrent chemotherapy produced favorable response and survival for LS-SCLC patients with tolerable toxicities. To improve the treatment response, which proved as a significant prognostic factor for survival, there should be further investigations about fractionation scheme, chemotherapy regimens and compatible chemoradiotherapy schedule.

Treatment Outcomes of Three-Dimensional Conformal Radiotherapy for Stage III Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the treatment outcomes of the three-dimensional conformal radiotherapy (3D-CRT), in conjunction with induction chemotherapy, for the treatment of stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between November 1998 and March 2003, 22 patients with histologically proven, clinical stage III NSCLC, treated with induction chemotherapy, followed by 3D-CRT, were retrospectively analyzed. There were 21 males (96%) and 1 female (4%), with a median age of 68.5 (range, 42~79). The clinical cancer stages were IIIA and IIIB in 41 and 59%, respectively. The histologies were squamous cell carcinoma, adenocarcinoma and others in 73, 18 and 9%, respectively. Twenty patients (91%) received induction chemotherapy before radiation therapy. The majority of the chemotherapy regimen consisted of cisplatin and gemcitabine. Radiation was delivered with conventional anteroposterior/ posteroanterior fields for 36 Gy, and then 3D-CRT was performed. The total radiation dose was 70.2 Gy. The median follow-up period was 17 months (range, 4~59 months). RESULTS: The median overall survival was 19 months. The two and four-year overall survival rates were 37.9 and 30.3%, respectively. The median progression-free survival was 21 months. The two and four-year progression-free survival rates were 42.1 and 21%, respectively. The prognostic factors for overall survival by a univariate analysis were age, histology and T stage (p<0.05). Acute radiation toxicities, as evaluated by the RTOG toxicity criteria, included two cases of grade 3 lung toxicity and one case of grade 2 esophagus toxicity. CONCLUSIONS: The radiation dose could be increased without a significant increment in the acute toxicities when using 3D-CRT. It also seems to be a safe, well- tolerated and effective treatment modality for stage III NSCLC.