Joo Hoon Kim

External validation of nomogram for the prediction of recurrence after curative resection in early gastric cancer

BACKGROUND Nomograms are statistics-based tools that provide the overall probability of a specific outcome. In our previous study, we developed a nomogram that predicts recurrence of early gastric cancer (EGC) after curative resection. We carried out this study to externally validate our EGC nomogram. PATIENTS AND METHODS The EGC nomogram was established from a retrospective EGC database that included 2923 consecutive patients. This nomogram was independently externally validated for a cohort of 1058 consecutive patients. For the EGC nomogram validation, we assessed both discrimination and calibration. RESULTS Within the follow-up period (median 37 months), a total of 11 patients (1.1%) experienced recurrence. The concordance index (c-index) was 0.7 (P = 0.02) and the result of the overall C index was 0.82 [P = 0.006, 95% confidence interval (CI) 0.59-1.00]. The goodness of fit test showed that the EGC nomogram had significantly good fit for 1- and 2-year survival intervals (P = 0.998 and 0.879, respectively). The actual and predicted survival outcomes showed good agreement, suggesting that the survival predictions from the nomogram are well calibrated externally. CONCLUSIONS A preexisting nomogram for predicting disease-free survival (DFS) of EGC after surgery was externally validated. The nomogram is useful for accurate and individual prediction of DFS, patient prognostication, counseling, and follow-up planning.

Effects of microsatellite instability on recurrence patterns and outcomes in colorectal cancers

Background:Among colorectal cancers (CRCs), high-frequency microsatellite instability (MSI-H) is associated with a better prognosis, compared with low-frequency MSI or microsatellite stability (MSI-L/MSS). However, it is unclear whether MSI affects the prognosis of recurrent CRCs.Methods:This study included 2940 patients with stage I–III CRC who underwent complete resection. The associations of MSI status with recurrence patterns, disease-free survival (DFS), overall survival from diagnosis to death (OS1), and overall survival from recurrence to death (OS2) were analysed.Results:A total of 261 patients (8.9%) had MSI-H CRC. Patients with MSI-H CRC had better DFS, compared to patients with MSI-L/MSS CRC (hazard ratio (HR): 0.619, P<0.001). High-frequency microsatellite instability CRC was associated with more frequent local recurrence (30.0% vs 12.0%, P=0.032) or peritoneal metastasis (40.0% vs 12.3%, P=0.003), and less frequent lung (10.0% vs 42.5%, P=0.004) or liver metastases (15.0% vs 44.7%, P=0.01). Recurrent MSI-H CRC was associated with worse OS1 (HR: 1.363, P=0.035) and OS2 (HR: 2.667, P<0.001). An analysis of patients with colon cancer yielded similar results.Conclusions:Recurrence patterns differed between MSI-H CRC and MSI-L/MSS CRC, and recurrent MSI-H CRCs had a worse prognosis.

A case of combined hepatocellular-cholangiocarcinoma with favorable response to systemic chemotherapy.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare form of primary liver cancer composed of cells with histopathologic features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of its low incidence, the information on clinical outcomes of cHCC-CC is very limited and there are no published reports describing non-surgical treatment options for cHCC-CC. We report a case of cHCC-CC exhibiting a favorable response to systemic chemotherapy with doxorubicin and cisplatin. A 62-year-old man who recurred after a right lobectomy for cHCC-CC received sorafenib for palliative systemic therapy, but follow up imaging studies showed disease progression. He received 2nd line chemotherapy with doxorubicin at 60 mg/m2 together with cisplatin at 70 mg/m2. After 2 cycles of chemotherapy, a computed tomography scan of the chest showed markedly decreased size and number of the multiple lung metastases. After completing 8 cycles of 2nd line therapy, we changed the regimen to a fluorouracil (5-FU) mono therapy because of the toxicities associated with doxorubicin and cisplatin. To date, the patient has completed his 15th cycle of 5-FU mono therapy with the disease status remaining stable during 18 months of follow-up.

Novel Sunitinib Strategy in Metastatic Renal Cell Carcinoma on Hemodialysis: Intermittent Dose of Sunitinib after Hemodialysis

The proper dose and schedule of sunitinib have yet to be established for patients with metastatic renal cell carcinoma (RCC) on hemodialysis. We reviewed two patients with metastatic RCC on hemodialysis who had been treated with sunitinib in Yonsei Cancer Center, Yonsei University College of Medicine. Fifty milligrams of sunitinib was administered intermittently after each hemodialysis session (3 or 4 times a week). Overall responses were partial response in both cases. Progression-free survivals were 16 and 6 months, respectively, at the time of reporting (April 2010). Both subjects tolerated the treatment.

Wernicke's Encephalopathy in Advanced Gastric Cancer

PURPOSE With their prolonged survival and malnutrition, cancer patients, and especially gastrointestinal (GI) tract cancer patients, can develop Wernickes encephalopathy (WE). The aim of this study is to remind physicians of the importance of WE and prompt management in patients with GI tract cancer. MATERIALS AND METHODS This study is a retrospective review of 2 cases of WE in advanced gastric cancer (AGC) patients, and we review the literature for cases of GI tract cancer related to WE. RESULTS A 48-year-old female with AGC presented dizziness and diplopia for 5 days and a 20 kg weight loss. Neurologic exam showed nystagmus and gaze disturbance. Her symptoms improved after daily parenteral injection of thiamine 100 mg for 17 days. A 58-year-old female with AGC presented with sudden disorientation, confusion and 15 kg weight loss. Neurologic exam showed gaze limitation and mild ataxia. Despite daily parenteral injection of thiamine 100 mg for 4 days, she died 5 days after the onset of neurologic symptoms. Combining the cases noted in the literature review with our 2 cases, the 7 gastric cancer cases and 2 colorectal cancer cases related to WE showed similar clinical characteristics; 1) a history of long-period malnutrition and weight loss, 2) relatively typical neurologic signs and symptoms and 3) specific magnetic resonance image findings. Except for 2 patients who had irreversible neurologic symptoms, the other 7 patients were improved with prompt thiamine treatment. CONCLUSION It is important to consider WE in GI tract cancer patients with acute neurologic symptoms and who are in a state of malnutrition. Thiamine should be given as soon as possible when WE is suspected.

18F-FDG PET/CT in hepatocellular carcinoma: Detection of bone metastasis and prediction of prognosis

ObjectiveThe purpose of this study was to assess the diagnostic accuracy and prognostic value of 18F-fluorodeoxyglucose PET/computed tomography (CT) in bone metastases from hepatocellular carcinoma (HCC). Patients and methodsOf 3912 consecutive HCC patients, 67 patients who had undergone both PET/CT and bone scintigraphy (BS) within a 3-month interval were evaluated. ResultsBone metastases were most frequently found in the pelvis (20%), followed by the lumbar spine (14%) and long bones (13%). PET/CT was significantly more sensitive than BS in region-based analyses, with 273 confirmed bone metastases (96.7 vs. 52.7%, respectively; P<0.001), and in patient-based analyses (99 vs. 85%; P=0.042). The median survival period was 5 (range, 0.4–18) months. On univariate analysis, poor prognostic factors included age (<60 years), multiple bone metastases, lymph node metastasis, high serum &agr;-fetoprotein (≥400 IU/ml), Child–Pugh class B, and high maximum standardized uptake value (SUVmax) of bone metastasis (>5.0). Large metabolic volume (≥200 cm3) of bone metastasis was another poor prognostic factor. On Cox regression analysis, high &agr;-fetoprotein was the only poor prognostic factor with statistical significance. ConclusionPET/CT was more sensitive than BS in bone metastasis from HCC by both patient-based and region-based analyses, and offered additional information on survival. PET/CT can be helpful in early diagnosis and opportune treatment of bone metastasis from HCC.

Clinicopathologic Features of Metachronous or Synchronous Gastric Cancer Patients with Three or More Primary Sites

Purpose We investigated the clinicopathologic information of patients with gastric cancer with multiple primary cancers (GC-MPC) of three or more sites. Materials and Methods Between 1995 and 2009, 105,908 patients were diagnosed with malignancy at Severance Hospital, Yonsei University Health System. Of these, 113 (0.1%) patients with MPC of three or more sites were registered, and 41 (36.3%) of these were GC-MPC. We retrospectively reviewed the clinical data and overall survival using the medical records of these 41 GC-MPC patients. We defined synchronous cancers as those occurring within 6 months of the first primary cancer, while metachronous cancers were defined as those occurring more than 6 months later. Results Patients with metachronous GC-MPC were more likely to be female (p=0.003) and young than patients with synchronous GC-MPC (p=0.013). The most common cancer sites for metachronous GC-MPC patients were the colorectum, thyroid, lung, kidney and breast, while those for synchronous GC-MPC were the head and neck, esophagus, lung, and kidney. Metachronous GC-MPC demonstrated significantly better overall survival than synchronous GC-MPC, with median overall survival durations of 4.7 and 14.8 years, respectively, and 10-year overall survival rates of 48.2% and 80.7%, respectively (p<0.001). Conclusion Multiplicity of primary malignancies itself does not seem to indicate a poor prognosis. The early detection of additional primary malignancies will enable proper management with curative intent.

PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer

Background Trastuzumab is an active agent against human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). This study aimed to characterize resistance to trastuzumab-based front-line chemotherapy in HER2+ GC patients and to establish factors predictive of this resistance. Results Among 129 HER2+ GC patients, 25% displayed rapid disease progression within 4 months from initiation of therapy. These patients showed a higher rate of signet ring cell histology, bone metastasis, poor performance status, frequent loss of PTEN expression, and low HER2 amplification index compared with patients who were progression-free for at least 4 months. In contrast, there was no significant difference in the frequency of the PIK3R1 variant. Multivariate analyses confirmed two independent molecular predictors for trastuzumab resistance: loss of PTEN expression and low HER2 amplification index (<5). Patients with one or both molecular predictors at diagnosis exhibited worse progression-free and overall survival compared to those without risk factors (p < 0.001 and p = 0.001, respectively). Conclusion In HER2+ GC patients, loss of PTEN expression and low HER2 AI correlated with resistance to trastuzumab-based therapy and dismal prognosis. Since patients harboring these molecular predictors are unlikely to respond to trastuzumab-based therapy, other novel therapeutic targets needed to be considered. Methods HER2+ GC patients who were treated with trastuzumab in combination with either 5-fluorouracil/cisplatin or capecitabine/cisplatin were enrolled. Clinicopathologic features and molecular alterations of HER2, phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1), and phosphatase and tensin homolog (PTEN) were correlated with treatment outcome. Factors predictive of resistance were also explored.

Effect of belly board with bladder compression device on small bowel displacement from the radiotherapy field for rectal cancer

Background: The aim of this study was to investigate the effect of a belly board (BB) with the addition of a bladder compression device (BCD) for small bowel (SB) displacement from the radiotherapy field for rectal cancer. Patients and Methods: Computed tomography (CT) scans of 38 rectal cancer patients positioned on a BB were analyzed and compared with CT scans from the same patients after the addition of a BCD. The BCD moves the inferior border of the BB from the pubic symphysis to the lumbosacral junction. The treated and irradiated volumes of the SB and bladder were compared. The irradiated volume ratio of SB to abdominopelvic cavity (APC) and that of bladder to APC were analyzed. Results: With the BCD, the treated and irradiated volumes of SB decreased significantly (49.1 ± 48.0 vs. 60.9 ± 50.9 cc, p = 0.006 and 207.5 ± 140.8 vs. 482.8 ± 214.2 cc, p < 0.001, respectively). The irradiated volume ratio of bladder to APC with the BCD increased considerably compared to that without the BCD (25.2 ± 11.5 vs. 18.7 ± 10.5%, p < 0.001), and the ratio of irradiated volume of SB to APC decreased significantly with the BCD (18.8 ± 12.4 vs. 31.8 ± 12.1%, p < 0.001). Conclusion: This study showed that the addition of a BCD to the BB could effectively provide further displacement of SB from the rectal cancer radiotherapy field.

Prognostic implications of PIK3CA amplification in curatively resected liposarcoma

Background We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma. Patients and methods A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH). Results Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival. Conclusions We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.