<Emphasis Type="Italic">KRAS</Emphasis> and <Emphasis Type="Italic">BRAF</Emphasis> Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review

Background

Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing.

Methods

The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay.

Results

The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs.

Conclusions

These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.

     

Perineural Invasion in Extrahepatic Cholangiocarcinoma: Prognostic Impact and Treatment Strategies

Background

The significance of perineural invasion in extrahepatic cholangiocarcinoma has not been fully elucidated. This study aims to determine the prognostic impact of and optimal treatment strategy for perineural invasion in patients with extrahepatic cholangiocarcinoma.

Methods

Medical records of 133 patients with extrahepatic cholangiocarcinoma who underwent curative resection were reviewed retrospectively. Ninety-eight patients had perineural invasion and 35 patients did not. Univariate and multivariate survival analyses were performed to clarify the prognostic impact of and optimal treatment strategy for perineural invasion.

Results

Only tumor differentiation (P?=?0.024) was independently associated with perineural invasion in the multivariate logistic regression model. Multivariate survival analysis revealed that perineural invasion (P?=?0.002), resection margin status (P?=?0.016), and International Union Against Cancer (UICC) pT factor (P?=?0.015) were independent prognostic factors of overall survival. Overall 5-year survival rates for patients with and without perineural invasion were 28 and 74 %, respectively. Among 98 patients with perineural invasion, the use of adjuvant chemotherapy (P?=?0.003), lymph node status (P?=?0.015), resection margin status (P?=?0.008), and UICC pT factor (P?=?0.016) were independently associated with overall survival by multivariate analysis. Overall 5-year survival rates for patients with perineural invasion who did and did not receive adjuvant chemotherapy were 33 and 21 %, respectively (P?=?0.023).

Conclusions

Perineural invasion is a potent prognostic factor in extrahepatic cholangiocarcinoma. Adjuvant chemotherapy may improve the overall survival of patients with perineural invasion.     

Appropriate treatment planning method for field joint dose in total body irradiation using helical tomotherapy

Total body irradiation (TBI) using helical tomotherapy (HT) has advantages over the standard linear accelerator-based approach to the conditioning regimen for hematopoietic cell transplantation. However, the radiation field has to be divided into two independent irradiation plans to deliver a homogeneous dose to the whole body. A clinical target volume near the skin increases the skin surface dose; therefore, high- or low-dose regions arise depending on the set-up position accuracy because the two radiation fields are somewhat overlapped or separated. We aimed to determine an adequate treatment planning method robust to the set-up accuracy for the field joint dose distribution using HT-TBI. We calculated treatment plans reducing target volumes at the interface between the upper and lower body irradiations and evaluated these joint dose distributions via simulation and experimental studies. Target volumes used for the optimization calculation were reduced by 0, 0.5, 1.0, 2.0, 2.5, and 3.0 cm from the boundary surface on the upper and lower sides. Combined dose distributions with set-up error simulated by modifying coordinate positions were investigated to find the optimal planning method. In the ideal set-up position, the target volume without a gap area caused field junctional doses of up to approximately 200%; therefore, target volumes reduced by 2.0–3.0 cm could suppress the maximum dose to within 150%. However, with set-up error, high-dose areas exceeding 150% and low-dose areas below 100% were found with 2.0 and 3.0 cm target volume reduction. Using the dynamic jaw (DJ) system, dose deviations caused by set-up error reached approximately 20%, which is not suitable for HT-TBI. Moreover, these dose distributions can be easily adjusted when combined with the intensity modulation technique for field boundary regions. The results of a simulation and experimental study using a film dosimetry were almost identical, which indicated that reducing the target volume at the field boundary surface by 2.5 cm produces the most appropriate target definition.     

Mortality outcomes and clinical background of children on maintenance dialysis without receiving kidney transplantation

Clinical and Experimental Nephrology - Some pediatric patients on maintenance dialysis may need end-of-life care in the future because of being excluded from the indication of kidney...     

Surgical Apgar Score Predicted Postoperative Morbidity After Esophagectomy for Esophageal Cancer

Background

Recently, a simple and easy complication prediction system, the Surgical Apgar Sore (SAS) calculated by three intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has been proposed for general surgery. This study aimed to determine if the SAS could accurately predict perioperative morbidity in patients undergoing esophagectomy for esophageal cancer.

Methods

We investigated 399 patients who underwent esophagectomy at the Kumamoto University Hospital between April 2007 and March 2015. Clinical data, including intraoperative parameters, were collected retrospectively. Patients had postoperative morbidities classified as Clavien–Dindo grade III or more. Univariate and multivariate analyses were performed to elucidate factors that affected the development of complications.

Results

The mean age of the study population was 65.7 years, 357 patients (89.5 %) were male. The frequency of any morbidity was 32.3 %. Univariate analyses showed that the SAS as well as preoperative chemotherapy, volume of bleeding, and reconstruction of organs were associated with morbidities. Multivariate analysis showed that a SAS < 5 was found to be an independent risk factor for morbidities.

Conclusion

The SAS is considered to be useful for predicting the development of postoperative morbidities after esophagectomy for esophageal cancer.