Background The situation of patients developing multiple primary cancers is becoming more frequent and graver. This study investigated the risks of developing second primary cancers that are related to first primary cancers, and the interval times of synchronous and metachronous multiple primary cancers. Patients and methods Retrospective data were retrieved from 109,054 patients aged ≥18 who were diagnosed with a first solid cancer and registered at Siriraj Cancer Center between 1991 and 2015. A two-month period between first- and second- primary cancers was used to differentiate metachronous and synchronous multiple primary cancers. The combinations of subsequent cancers and relative risks (RRs) of having multiple primary cancers versus having single primary cancer for the top-ten first and second primary cancers were examined. The RR was adjusted for age of the first primary cancer. A survival analysis of the time to second-primary-cancer development was performed. Results Multiple primary cancers were found in 1785 (1.63%) patients. Most (70.87%) second primary cancers occurred after 2 months of first breast, skin, colorectal, lung, head and neck, liver, male genital cancer–prostate, thyroid, and female genital cancer–non-uterine cancers, resulting in those cancers being classified as metachronous multiple primary cancer. After adjustment for age at first diagnosis, head and neck cancers had the highest metachronous association with second esophageal cancers (RR, 25.06; 95% CI, 13.41–50.77). Prostate cancer and second colorectal cancer also demonstrated a high metachronous association (RR, 2.00; 95% CI, 1.25–3.05). A strong synchronous association was found between uterine and ovarian cancers (RR, 27.77; 95% CI, 17.97–43.63). The median time from the first uterine cancer to second-cancer development was 55 days. Conclusions The top-ten most frequent multiple primary cancers were the following: breast; liver; head and neck; colorectal; male genital cancer–prostate; skin; female genital cancer–uterine; thyroid; lung; and female genital cancer–non-uterine. Second primary cancers showed specific associations that depended on the first primary cancer. Physicians should be cognizant of the most common combinations and the interval times of metachronous and synchronous multiple primary cancers.

Cholangiocarcinoma (CCA) is a malignant tumor of the biliary epithelium associated with Opisthorchis viverrini, primary sclerosing cholangitis and hepatitis viral infection. In the global population, men have higher incidence rates for CCA than women; thus, a gender disparity in the progression of chronic inflammation of the biliary duct leading to malignancy may involve the effects of estrogen (E2). Genistein (GE), a prominent phytoestrogen found in soy products, is an estrogen receptor β (ERβ) agonist and a tyrosine kinase inhibitor. The present study investigated the effects of GE on the growth of CCA cells by cell viability assay. The effects on signaling proteins were detected by western blot analysis and ELISA. Gene expression was examined by RT-qPCR. Two human intrahepatic CCA cell lines, HuCCA‑1 and RMCCA‑1, were utilized. GE (50‑200 µM) reduced the viability of the two cell lines, and also inhibited the activation of epidermal growth factor receptor (EGFR) and AKT, as evidenced by decreasing protein levels of phosphorylated (p)-EGFR (Tyr1173) and p‑AKT (Ser473), respectively. GE altered the mitogen‑activated protein kinase signaling cascade by mediating decreased protein levels of p‑p38 and increased protein levels of p‑ERK1/2. GE significantly decreased the levels of interleukin 6 (IL6) and induced the expression of inducible nitric oxide synthase (iNOS). GE also downregulated the expression of p‑ERα (Ser118) protein and ERα mRNA levels. Finally, GE induced the downregulation of the protein levels of ERβ. Of note, E2 deprivation potentiated the GE-induced reduction of p‑EGFR (Tyr1173) and total AKT proteins and production of IL6, and mediated the downregulation of GE-induced iNOS protein. In conclusion, GE inhibited the growth of human CCA cell lines by reducing the activation of EGFR and AKT, and by attenuating the production of IL6. E2 and ER were also involved in the growth-inhibitory effect of GE in CCA cells.

Colorectal cancers (CRC) with KRAS mutations (KRASmut) are frequently included in consensus molecular subtype 3 (CMS3) with profound metabolic deregulation. We explored the transcriptomic impact of KRASmut, focusing on the tumor microenvironment (TME) and pathways beyond metabolic deregulation. The status of KRASmut in patients with CRC was investigated and overall survival (OS) was compared with wild-type KRAS (KRASwt). Next, we identified CMS, and further investigated differentially expressed genes (DEG) of KRASmut and distinctive pathways. Lastly, we used spatially resolved gene expression profiling to define the effect of KRASmut in the TME regions of CMS3-classified CRC tissues. CRC patients with KRASmut were mainly enriched in CMS3. Their specific enrichments of immune gene signatures in immunosuppressive TME were associated with worse OS. Activation of TGFβ signaling by KRASmut was related to reduced pro-inflammatory and cytokine gene signatures, leading to suppression of immune infiltration. Digital spatial profiling in TME regions of KRASmut CMS3-classified tissues suggested up-regulated genes, CD40, CTLA4, ARG1, STAT3, IDO, and CD274, that could be characteristic of immune suppression in TME. This study may help to depict the complex transcriptomic profile of KRASmut in immunosuppressive TME. Future studies and clinical trials in CRC patients with KRASmut should consider these transcriptional landscapes.

Samples from patients with colorectal cancer (CRC) are valuable tools for understanding the development, progression, and treatment of the disease. However, to date, the integrity of long-term preserved human specimens in biobanks has not been well understood. In this study, we investigated the RNA quality of 12-year-stored specimens, including frozen and formalin-fixed, paraffin-embedded (FFPE) tumor tissues from CRC patients at the Siriraj Biobank. We assessed the RNA quality of 12-year and 2-year storage samples using three technologies: next-generation sequencing (NGS), Nanostring nCounter® platform, and GeoMx® digital spatial profiling (DSP). We found that the RNA quality of 12-year storage frozen tissues was consistent with the criteria for RNA sequencing. Although RNA in long-term storage FFPE tissues was degraded, the normalized counts of RNA from the 12-year-stored FFPE samples were comparable to those from the 2-year-stored FFPE samples in the Nanostring nCounter® gene expression assay. For histological staining, clear tissue microanatomy was observed in the FFPE blocks stored for 12 years. In GeoMx® DSP, there was no statistically significant difference in the normalized counts of RNA from the 12- and 2-year stored FFPE samples. Our results suggest the potential utilization of long-term storage biobank specimens from patients with CRC for NGS, Nanostring nCounter® gene expression analysis, and GeoMx® DSP.

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Objective: The aim of this study was to evaluate the efficacy and cost-effectiveness of a ready-to-use applicatorcontaining iodine povacrylex and isopropyl alcohol (IPIA) for the prevention of surgical site infection (SSI) followingintra-abdominal surgery.Materials and Methods: The IPIA was randomly used in patients who underwent colorectal surgical procedures.The control group for comparison was a group of patients who underwent colorectal surgical procedures usingconventional skin scrubbing and painting with antiseptic solutions without IPIA. In total, 100 patients were includedin the study, randomized into 2 groups: one was applied IPIA and another group a conventional skin preparation.The outcome measurements included ease-of-use as assessed by a questionnaire, preparation time comparison,estimated skin preparation expense, adverse reactions, and rate of SSI. All the patients were visited daily up to 7 dayspostoperation or until discharge, and then 14 and 30 days postoperatively for monitoring the occurrence of SSI.Results: Of the 100 patients undergoing elective intra-abdominal surgery enrolled in the study, 51 were males and49 females, with the mean age of 63.5 ± 11.3 years. The majority of the patients had undergone colorectal cancercolectomies or rectal resections. There was no mortality. Seven patients (7%) had postoperative SSI (4 patients inthe control group and 3 patients in the IPIA group, 4% vs. 3%, p = 0.45). The bacterial cultures revealed Gramnegative-bacilli in all of the patients with SSI. The preparation time for the skin preparation was 5.48 ± 2.49 min inthe control group and 2.65 ± 1.55 min in the IPIA group (p = 0.002), without statistical significance of expenses.Conclusion: IPIA was demonstrated to be as safe and effective as conventional antiseptic solutions as a skinpreparation to prevent SSI following colorectal surgery. With good ease of use, IPIA proved more convenient thana scrubbing preparation as well as offered better cost effectiveness by significantly reducing the time and cost ofthe skin preparation.

Background Multiple primary cancer refers to the synchronous or metachronous appearances in the same individual. The accurate approach, which distinguishes between multiple primary cancer and metastasis, is important to make an appropriate management. This study aims to systematically classify the synchronous and metachronous multiple primary cancers, and to identify multiple primary cancer from cancer metastasis. Methods Cancer registry was compiled at the Faculty of Medicine Siriraj Hospital, Mahidol University based on guidelines from the Surveillance Epidemiology and End Results (SEER) project. Data was validated through clinical records, coded, and verified for multiple primary cancer according to International Classification of Diseases for Oncology 3rdEdition (ICD-O-3). The cancer registry for the year 1991-2015 was queried for numbers of the multiple primary cancer. Results A total of 1,913 patients presented multiple primary cancer, accounting for 1.48% of all patients (129,216). Median age at diagnosis of the first cancer was 60. The most multiple primary cancer in female is synchronous breast cancers, diagnosed two or more histologically distinct cancer within two months. In male, the most combination is prostate, urinary tract, and gastrointestinal cancer. In addition to understanding of the connections between primary and subsequent cancer, we plan to perform panel sequencing in each primary site of multiple gastrointestinal primary cancer to access for the causal driver mutation. Conclusion Cancer registry is a valuable approach to punctually identify and record multiple primary cancer. Further study in genetic profiles of each primary cancer may improve our understanding of multiple primary cancer for enhancing cancer management. Citation Format: Pariyada Tanjak, Benjarat Thiengtrong, Kanokporn Thamapala, Tippawan Gerdsuriwong, Cholticha Songjang, Aem-on Rattanakumnerd, Onchira Acharayothin, Supatee Karakate, Nongnard Thamnongdee, Suwanit Therasakvichya, Somsri Laiteerapong, Vitoon Chinswangwatanakul. Multiple primary cancer from a retrospective population-based cancer registry, 1991 through 2015 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5767.

Objective: The aim of this study was to evaluate the efficacy and cost-effectiveness of a ready-to-use applicatorcontaining iodine povacrylex and isopropyl alcohol (IPIA) for the prevention of surgical site infection (SSI) followingintra-abdominal surgery.Materials and Methods: The IPIA was randomly used in patients who underwent colorectal surgical procedures.The control group for comparison was a group of patients who underwent colorectal surgical procedures usingconventional skin scrubbing and painting with antiseptic solutions without IPIA. In total, 100 patients were includedin the study, randomized into 2 groups: one was applied IPIA and another group a conventional skin preparation.The outcome measurements included ease-of-use as assessed by a questionnaire, preparation time comparison,estimated skin preparation expense, adverse reactions, and rate of SSI. All the patients were visited daily up to 7 dayspostoperation or until discharge, and then 14 and 30 days postoperatively for monitoring the occurrence of SSI.Results: Of the 100 patients undergoing elective intra-abdominal surgery enrolled in the study, 51 were males and49 females, with the mean age of 63.5 ± 11.3 years. The majority of the patients had undergone colorectal cancercolectomies or rectal resections. There was no mortality. Seven patients (7%) had postoperative SSI (4 patients inthe control group and 3 patients in the IPIA group, 4% vs. 3%, p = 0.45). The bacterial cultures revealed Gramnegative-bacilli in all of the patients with SSI. The preparation time for the skin preparation was 5.48 ± 2.49 min inthe control group and 2.65 ± 1.55 min in the IPIA group (p = 0.002), without statistical significance of expenses.Conclusion: IPIA was demonstrated to be as safe and effective as conventional antiseptic solutions as a skinpreparation to prevent SSI following colorectal surgery. With good ease of use, IPIA proved more convenient thana scrubbing preparation as well as offered better cost effectiveness by significantly reducing the time and cost ofthe skin preparation.