Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02.

AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

Magnetic resonance tumour regression grade and pathological correlates in patients with rectal cancer.

BACKGROUND: Evidence to support the specific use of magnetic resonance tumour regression grade (mrTRG) is inadequate. The aim of this study was to investigate the pathological characteristics of mrTRG after chemoradiotherapy (CRT) for rectal cancer and the implications for surgery. METHODS: Patients undergoing long-course CRT (45-50 Gy plus a booster dose of 4-6 Gy) for mid or low rectal cancer (cT3-4 or cN+ without metastasis) between 2011 and 2015 who had post-CRT rectal MRI before surgery were included retrospectively. Three board-certified experienced radiologists assessed mrTRG. mrTRG was correlated with pathological tumour regression grade (pTRG), ypT and ypN. In a subgroup of patients with mrTRG1-2 and no tumour spread (such as nodal metastasis) on MRI, the projected rate of completion total mesorectal excision (TME) if they underwent transanal excision (TAE) and had a ypT status of ypT2 or higher was estimated, and recurrence-free survival was calculated according to the operation (TME or TAE) that patients had actually received. RESULTS: Some 439 patients (290 men and 149 women of mean(s.d.) age 62·2(11·4) years) were analysed. The accuracy of mrTRG1 for predicting pTRG1 was 61 per cent (40 of 66), and that for ypT1 or less was 74 per cent (49 of 66). For mrTRG2, these values were 22·3 per cent (25 of 112) and 36·6 per cent (41 of 112) respectively. Patients with mrTRG1 and mrTRG2 without tumour spread were ypN+ in 3 per cent (1 of 29) and 16 per cent (8 of 50) respectively. Assuming mrTRG1 or mrTRG1-2 with no tumour spread on post-CRT MRI as the criteria for TAE, the projected completion TME rate was 26 per cent (11 of 43) and 41·0 per cent (41 of 100) respectively. For the 100 patients with mrTRG1-2 and no tumour spread, recurrence-free survival did not differ significantly between TME (79 patients) and TAE (21) (adjusted hazard ratio 1·86, 95 per cent c.i. 0·42 to 8·18). CONCLUSION: Patients with mrTRG1 without tumour spread may be suitable for TAE.

Survival Benefit of Early Cancer Detection Through Regular Endoscopic Screening for De Novo Gastric and Colorectal Cancers in Korean Liver Transplant Recipients.

BACKGROUND: De novo malignancy is not uncommon after liver transplantation (LT). Gastric cancer is one of the most common malignancies in both the Korean general population and LT recipients, and colorectal cancer prevalence is gradually increasing. METHODS: Among 3690 adult recipients who underwent LT from January 1999 and December 2013, the screening patterns and prognosis of 26 cases of gastric cancer and 22 cases of colorectal cancer were analyzed. RESULTS: For gastric cancer, the mean patient age was 54.6 ± 6.2 years at LT and 59.5 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 60.2 ± 29.8 months. Patients were divided into regular (n = 18) and non-regular (n = 8) screening groups, with early cancer found in 14 and 0 patients; their 2-year survival rates after cancer diagnosis were 93.1% and 33.3% (P = .006), respectively. Endoscopic resection was successfully performed in 8 patients, all in the regular screening group. For colorectal cancer, the mean patient age was 53.3 ± 6.1 years at LT and 58.1 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 54.3 ± 38.0 months. Patients were divided into regular (n = 19) and non-regular (n = 3) screening groups, with early cancer found in 12 and 0 patients; their 2-year survival rates after cancer diagnosis of 92.3% and 33.3% (P = .003), respectively. Endoscopic resection was successfully performed in 6 patients, all in the regular screening group. CONCLUSIONS: LT recipients are strongly advised to undergo regular screening studies for various de novo malignancies, especially cancers common in the general population. Regular endoscopic screening contributes to the timely detection of gastric and colorectal cancers, improving post-treatment survival outcomes.

Late anastomotic leakage after low anterior resection in rectal cancer patients: clinical characteristics and predisposing factors.

AIM: The purpose was to examine the clinical characteristics and predisposing factors of late anastomotic leakage following low anterior resection for rectal cancer. METHOD: We retrospectively evaluated the clinicopathological features of patients who experienced anastomotic leakage after low anterior resection for rectal cancer. Patients were divided into two groups according to the time to leakage: early leakage (within 30 days postoperatively) and late leakage (after 30 days postoperatively). Clinicopathological characteristics were compared between the two groups. RESULTS: Anastomotic leakage occurred in 141 patients. Anastomotic leakage was diagnosed at a median of 17 (range 0-886) days postoperatively; 85 (60.3%) and 56 (39.7%) were categorized as the early and late leakage groups, respectively. Radiotherapy (hazard ratio 5.007; 95% CI 2.208-11.354; P < 0.0001) was the only significant independent predisposing factor for late leakage. Diverting stoma did not protect against late leakage. The late leakage group more frequently had the fistula type (46.4% vs. 10.6%; P < 0.001) and less frequently needed laparotomy (55.4% vs. 78.8%; P = 0.001). The rate of long-term stoma over 1 year was greater in the late leakage than the early leakage group (51.8% vs. 29.4%; P = 0.009). CONCLUSION: Late anastomotic leakages that develop after 30 days following low anterior resection are not uncommon and may be associated with the use of radiotherapy. Late leakage should be a different entity from early leakage in terms of the type of leakage, methods of management and subsequent sequelae.

Clinical implications of mucinous components correlated with microsatellite instability in patients with colorectal cancer.

AIM: Colorectal cancer (CRC) with microsatellite instability (MSI) is characterized by frequent poor differentiation or mucinous histology. The purpose of this study was to evaluate the association of MSI with clinicopathological features and the oncological outcome in patients with a mucinous component. METHOD: CRC tissue samples were analysed for histology and MSI. Patients were grouped according to the mucinous content of the tumour, as follows: > 50%, mucinous adenocarcinoma (MA); ≤ 50%, adenocarcinoma with mucinous component (AMC); none, nonmucinous adenocarcinoma (NMA). Clinicopathological parameters and survival were compared between patient groups. RESULTS: Of 2025 patients, 84 (4%) had MA and 124 (6%) had AMC. In addition, 202 (10%) had MSI. Patients with MA and AMC tended to have a younger age of onset, right-colon predilection, large-sized tumour and high frequency of MSI compared with those with NMA (P < 0.001). MA and AMC patients with MSI showed a trend towards right-colon predilection and infrequent lymph-node metastasis compared with those with microsatellite stability (MSS; P = 0.005-0.03). There were no survival differences between the three groups, but patients with MSI-MA demonstrated lower 4-year recurrence and better overall survival rates than those with MSS-MA (P = 0.018 and P = 0.046, respectively). CONCLUSION: Clinicopathological features of AMC and MA were similar and closely associated with MSI status. Although the prognoses of AMC and MA were no different from that of NMA, survival of patients with an MSI-MA tumour was significantly better than for those with MSS-MA tumours.

Development and application of a multiplex PCR assay for rapid detection of 4 major bacterial pathogens in ducks.

Infections with Pasteurella multocida, Salmonella enterica, Riemerella anatipestifer, and Escherichia coli result in high morbidity and mortality, which cause significant economic loss in the poultry industry. It can be difficult to distinguish these pathogens based on clinical signs because these pathogens can cause similar clinical signs and coinfections can occur. Thus, rapid and sensitive detection of these 4 major bacterial pathogens are important in ducks. The aim of this study was to develop a multiplex PCR (mPCR) assay for simultaneously detecting and identifying these 4 pathogenic bacteria in a single tube reaction. The target genes used were KMT1 of P. multocida, the invasion protein gene of S. enterica, 16S rDNA of R. anatipestifer, and the alkaline phosphatase gene of E. coli. The detection limit of the assay for all bacterial DNA was 10 pg. The mPCR did not produce any nonspecific amplification products when tested against other related pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Clostridium perfringens, Mycoplasma gallinarum, Mycoplasma synoviae, and Mycoplasma gallisepticum, which can also infect ducks. We applied mPCR to field samples, and the results were the same as the single PCR results. These results suggest that mPCR for the 4 bacteria is a useful and rapid technique to apply to field samples.

Effect of proanthocyanidin-rich extract from Pinus radiata bark on immune response of specific-pathogen-free White Leghorn chickens.

Proanthocyanidins are naturally occurring compounds that are widely found in fruits, vegetables, nuts, seeds, flowers, and bark. We evaluated the immunomodulatory effects of proanthocyanidin-rich extract (PAE) from Pinus radiata bark in specific-pathogen-free White Leghorn chickens. Proliferation of peripheral blood mononuclear cells was significantly enhanced in chickens treated for 2 wk with 20 mg/kg of PAE. Proliferation of splenocytes and bursal cells was significantly enhanced in chickens treated for 5 wk with 5, 10, and 20 mg/kg of PAE. Thymocyte proliferation was significantly enhanced in chickens treated for 5 wk with 5 and 10 mg/kg of PAE. These effects were markedly enhanced by the presence of lipopolysaccharide, which acted on B cells responsible for humoral immunity, and concanavalin A, which acted directly on T cells involved in cell-mediated immunity. The PAE significantly promoted the expression of T helper 1 cytokine (interferon-γ) and decreased the expression of T helper 2 cytokine (IL-6). Thus, P. radiata PAE has immunomodulatory effects in specific-pathogen-free White Leghorn chickens.

Relapse and reacquisition of rectal colonization by vancomycin-resistant Enterococcus faecium after decolonization.

To better understand the epidemiology of colonization of vancomycin-resistant enterococci (VRE), we performed an 8-year retrospective study of all hospitalized patients with recurrent VRE colonization after they were documented as being clear of VRE and compared the primary colonization isolates and recolonization isolates by pulsed-field gel electrophoresis and Tn1546 typing. Review of the medical records of all patients showed that of the 15 patients with recurrent colonization, six continued to be hospitalized on the same floor. Five were discharged home and then readmitted. Four were moved to another floor. Patients who remained on the same floor were recolonized with a strain that was indistinguishable from the original colonizing strain. Patients who were moved or were discharged had de novo VRE colonization with strains distinct from the original colonizing strain.

Low-grade fibromyxoid sarcoma of the colon.

Low-grade fibromyxoid sarcoma is a recently recognised soft tissue neoplasm. It is rare and has a tendency to arise from deep soft tissue of the lower extremities. An origin from the colon has not been reported in the medical literature. We report the low-grade fibromyxoid sarcoma originating from the colon in a 43-year-old male patient, treated by right hemicolectomy and nephrectomy.

Efficacy of PET/CT in the accurate evaluation of primary colorectal carcinoma.

AIM: This study was performed to assess in the accurate evaluation of primary colorectal carcinoma using PET/CT. METHODS: One hundred patients with primary colorectal carcinoma were evaluated during 2004. All patients underwent PET/CT when their preoperative serum carcinoembryonic antigen was >or=10 ng/mL or when CT showed equivocal findings. The appropriateness of PET/CT-induced changes was noted by subsequent operative findings and follow-up. RESULTS: PET/CT more detected 15 intra-abdominal metastatic lesions than abdomino-pelvic CT scan. PET/CT showed true negative findings in 13 patients and false positive or negative findings in 10. Due to PET/CT results, management plans were altered in 27 patients; 9 had inter-modality changes, 10 received more extensive surgery, and 8 avoided unnecessary procedures. CONCLUSIONS: PET/CT altered management plan in 24% of patients with primary colorectal carcinoma in correct direction. These findings suggest that PET/CT should be considered a part of standard work up for preoperative evaluation in a subset of patients with colorectal carcinoma.

Laparoscopic colorectal surgery using low-pressure pneumoperitoneum combined with abdominal wall lift by placement of anchoring sutures around the camera port.

BACKGROUND: This study aimed to evaluate the feasibility of low-pressure pneumoperitoneum in laparoscopic colorectal surgery. METHODS: The authors designed low-pressure (8 mmHg) laparoscopy combined with abdominal wall lift simply by placement of anchoring sutures around the camera port. RESULTS: The operative indications were 176 colon cancers, 297 rectal cancers, and 45 benign diseases. The average blood loss was 92 ml (range, 20-1200 ml), and the mean operating time was 204 min (range, 23-525 min). Conversion to an open procedure was required in eight cases (1.5%). Two patients experienced intraoperative complications. The mean number of removed lymph nodes was 28.9 in the colon cancer cases and 23.1 in the rectal cancer cases. The mean length of resected specimen was 27.3 cm (range, 8.5-136 cm). Postoperatively, cardiopulmonary complications developed in five patients (0.9%). CONCLUSIONS: Abdominal wall lifting by anchoring sutures around the camera port in addition to low-pressure pneumoperitoneum is a simple, safe, and effective method for laparoscopic colorectal procedure.

Metachronous colorectal cancer.

OBJECTIVE: Although the diagnosis of metachronous colorectal cancer have increased, due primarily to improvements in diagnostic modalities, the potential risk factors for these tumours are not well known. We compared the characteristics of patients with metachronous and sporadic primary colorectal cancer to determine risk factors for its occurrence. PATIENTS AND METHODS: We reviewed the records of 5447 patients with colorectal cancer, who had been treated at Asan Medical Centre between July 1989 and January 2004. A metachronous cancer was defined as a secondary colorectal cancer occurring more than 6 months after the index cancer. RESULTS: Metachronous colorectal cancer occurred in 39 (0.7%) patients. Their average age was 53 years, somewhat younger than the average age of sporadic colorectal cancer patients (58 years). In patients with metachronous cancer, the cancer was more likely to be located in the right colon (P < 0.03), and the incidence of synchronous polyps or cancer was significantly higher (P < 0.001). The relative distributions of histological grades and clinicopathological characteristics were similar in index and metachronous cancers. Metachronous cancers were diagnosed more frequently at an early stage. The time interval between index and metachronous cancer ranged from 6 to 215 months (mean 39 months), with 13 (33.3%) patients diagnosed with metachronous cancer after 5 years. CONCLUSION: We found that in patients aged < 50 years, existence of synchronous polyps or cancer influence on the development of metachronous colorectal cancer. Regular follow-up is necessary for early detection, even after 5 years, for these patients.

Development of a pMOSFET sensor with a Gd converter for low energy neutron dosimetry.

A pMOSFET having a 10 microm thick Gadolinium (Gd) layer has been invented as a slow neutron sensor. When slow neutrons are incident to the Gd layer, conversion electrons, which generate electron-hole pairs in the SiO2 layer of the pMOSFET, are generated by a neutron capture process. The holes are easily trapped in the oxide and act as positive-charge centres in the oxide. Due to the induced charges, the threshold turn-on voltage of the pMOSFET is changed. The developed sensors were tested at a neutron beam port of the HANARO research reactor and a 60Co irradiation facility to investigate slow neutron response and gamma ray contamination, respectively. The resultant voltage change was proportional to the accumulated neutron dose and it was very sensitive to slow neutrons. Moreover, ionising radiation contamination was negligible. It can also be used in a mixed radiation field by subtracting the voltage change of a pMOSFET without Gd from that of the Gd-pMOSFET.

Biological monitoring of occupational exposure to N,N-dimethylformamide--the effects of co-exposure to toluene or dermal exposure.

OBJECTIVES: The objective of this study is to assess the exposure and intake dose of N,N-dimethylformamide (DMF) and the correlation between them, according to the type of exposure for the workers in the DMF industry. METHODS: We monitored 345 workers occupationally exposed to DMF, from 15 workshops in the synthetic fiber, fiber coating, synthetic leather and paint manufacturing industries. Ambient monitoring was carried out with personal samplers to monitor the external exposure. Biological monitoring was done to determine the internal dose by analyzing N-methylformamide (NMF) in end-shift urine. Work procedure and exposure type of each DMF workshop was carefully surveyed, to classify workers by exposure type according to work details. Workers were classified into three groups (Group A: continuous and direct exposure through inhalation and skin; Group B: intermittent and short-term exposure through inhalation and skin; Group C: continuous and indirect exposure mostly through inhalation). RESULTS: Geometric mean of DMF concentration in air was 2.62 (GSD 5.30) ppm and that of NMF in urine was 14.50 (GSD 3.89) mg/l. In the case of continuous absorption through inhalation and dermal exposure (Group A), the value of NMF in urine corresponding to 10 ppm of DMF was 45.3 mg/l (r = 0.524, n = 178), 39.1 mg/g creatinine (r = 0.424), while it was 37.7 mg/l (r = 0.788, n = 37), 24.2 mg/g creatinine (r = 0.743) in the case of absorption mostly through inhalation (Group C). Creatinine correction reduced the correlation between two parameters. CONCLUSION: The NMF in urine corresponding to 10 ppm DMF, of the dermal and inhalation exposure group was 39.1 mg/g creatinine (r = 0.424, n = 178), while that of the inhalation exposure-only group was 24.2 mg/g creatinine (r = 0.743, n = 37). Co-exposure with toluene reduced the NMF excretion in urine.

CD56 expression in a case of primary cutaneous CD30+ anaplastic large cell lymphoma.

We describe clinicopathological features of an unusual case of CD30+/CD56+ T-cell lymphoma in a 58-year-old Korean man who presented with disseminated nodules, papules and hyperpigmented patches. Coexpression of CD30 and CD56 in T-cell lymphoma is very rare. Our patient did not respond to an intensive chemotherapy regimen, in contrast to the previously reported cases of primary cutaneous CD30+ anaplastic large cell lymphoma. Coexpression of CD56 might therefore identify a subset of CD30+ lymphomas with more aggressive features.

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers.

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.

Two cases of linear focal elastosis (elastotic striae).

Linear focal elastosis (LFE) or elastotic striae was first described by Burket in 1989 in three elderly men. They presented with striae-like yellow palpable bands on their backs. Burket described many fine wavy bundles of elastic fibers separating the collagen in the middle to reticular dermis under microscopic examination. Until recently, there have been about 14 reported cases of LFE; elderly males are predominant. We encountered two Korean teen-aged males with linear, reddish, palpable bands and some atrophic bands across their backs. Histopathological examination revealed that elastosis was not as prominent as in previously reported cases. Our cases might represent early-evolving LFE.

Korean analytical quality assurance (KAQUA) program for biological monitoring.

The Korean analytical quality assurance (KAQUA) program on biological monitoring was performed by the Industrial Health Research Institute in Korea in spring, 1995. The object of the KAQUA program is to improve the analysis capability for the biological monitoring of hazardous chemicals and to confirm the reliability of data from each laboratory. The items chosen for the first round were analyses of lead in blood (PbB) and of hippuric acid in urine (HAU). Eighty-eight laboratories in Korea participated in this program. Two levels of samples, randomly chosen among six levels for each item, were sent to the participants. The consensus value from participants and reference laboratories was determined by statistical analysis and used as a reference value. The tolerance range was +/-15% (+/-6 micrograms/dl for PbB below 40 micrograms/dl) of the reference value. The mean proficiency rate of analytical data increased dramatically in the first round compared with a pre-round that was provided as part of a training course for participants before performing the first round. The mean proficiency rate of PbB was 69% at pre-round and increased at 91% at the first round; for HAU the increase was from 58% to 88%. Not only the analytical results but also raw data were reviewed to find problems which might have arisen during the analytical process. Re-education courses provided after final evaluation of each participant by means of telephone discussion, correspondence course, and experimental practice, were helpful in achieving the purpose of the analytical quality assurance program.

Lead concentrations in blood among the general population of Korea.

The purpose of this survey was to obtain information on the overall blood lead concentrations of the Korean population due to environmental exposure. Five hundred and twenty-five Korean adults from four provinces who had no previous occupational exposure to lead were chosen by random sampling to represent the general (normal) population. Blood lead determinations were performed by atomic absorption spectrometry with a graphite furnace. Interlaboratory quality control for analysis of blood lead was carried out in seven laboratories in Korea and Europe. The geometric mean were 6.36 micrograms/dl for males and 5.09 micrograms/dl for females. There was no correlation between blood lead concentration and age. The mean concentration of blood lead in smokers was higher than that in nonsmokers (P < 0.0005). The mean blood lead concentration in male nonsmokers was higher than that in female nonsmokers (P < 0.0005). Differences in mean blood lead values according to residential area were observed, and this result showed good agreement with the results of ambient monitoring.