BRAF V600E-induced distinct DNA damage response defines the therapeutic potential of p53 activation for TP53 wild-type colorectal cancer.

BRAF V600E, one of the most frequent mutations in the MAPK pathway, confers poor prognosis to colorectal cancers (CRCs), partly because of chemotherapeutic resistance. Oncogene-induced DNA damage responses (DDRs) that primarily activate p53 are important mechanistic barriers to the malignant transformation of cells; however, the mechanism underlying this impairment in cancer remains unknown. Here, we evaluated the responses of BRAFV600E-induced DDRs in two CRC cell lines, SW48 and LIM1215, both of which harbor wild-type TP53, KRAS, and BRAF. BRAFV600E transduction exhibited distinct phenotypes in these cells: SW48 cell proliferation markedly decreased, whereas that of LIM1215 increased. BRAFV600E expression induced the activation of oncogene-induced DDR signaling in SW48 cells, but not in LIM1215 cells, whereas chemotherapeutic agents similarly activated DDRs in both cell lines. Knockdown experiments revealed that these responses in SW48 cells were mediated by p53-p21 pathway activation. Comet assay (both alkaline and neutral) revealed that BRAFV600E increased single-strand breaks to the same extent in both cell lines; however, in case of LIM1215 cells, it only facilitated double-strand breaks. Furthermore, the proliferation of LIM1215 cells, wherein no oncogene-induced DDRs occurred, was synergistically inhibited upon MDM2 inhibitor-mediated p53 activation combined with MEK inhibition. Taken together, these distinct DDR signaling responses highlight the novel characteristics of BRAFV600E-mutated CRC cells and define the therapeutic potential of p53 activation combined with MAPK inhibition against TP53 wild-type CRC harboring a BRAFV600E mutation.

Salvage surgery for pouch-related complication after ileal pouch-anal anastomosis: a report of two cases.

BACKGROUND: Pouch-related complications (PRCs), such as pelvic abscesses and perianal complex fistulas, can occur after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). They are often difficult to treat and require salvage surgery. We report two cases of PRC associated with fistulas. CASE PRESENTATION: First case: A 38-year-old man was diagnosed with UC at age 26 years. Four months after the diagnosis of UC, the patient underwent hand-assisted laparoscopic restorative proctocolectomy, IPAA, and ileostomy for acute fulminant UC. Two years after the closure of the ileostomy, the patient developed a perianal abscess and underwent ileostomy reconstruction. He was referred to our department at 35 years of age, because his symptoms did not improve despite repeated seton drainage of a complicated perineal fistula. We diagnosed PRC with a pelvic abscess and complicated pouch fistula and performed salvage surgery. This diagnosis was revised to Crohn's disease. SECOND CASE: A 50-year-old man was diagnosed with UC at age 18 years and was administered high doses of steroids; however, his symptoms did not improve. He underwent restorative proctocolectomy, IPAA, and ileostomy at another hospital. The ileostomy was closed, and his condition stabilized thereafter. At 35 years of age, perianal pain developed, and he was diagnosed with a complicated pouch-perineal fistula. A fistula was observed near the staple line of the ileal end closure on the head side of the pouch. Reconstruction of the ileostomy and seton drainage were performed; however, his symptoms did not improve, and he was referred to our hospital. We diagnosed PRC with a pelvic abscess and a complicated pouch fistula and performed salvage surgery. The resected specimen showed strictures in two locations: at the oral site of the afferent limb (at the pouch) and at the IPAA. Both patients returned to society and are currently outpatients. CONCLUSIONS: We encountered two cases of PRC after IPAA that did not improve with seton drainage or ileostomy. Pouch resection was performed after considering the patient's quality of life and reintegration into society.

Laparoscopic Colectomy for Cecal Cancer and Intestinal Malrotation: A Case Report.

Background/Aim: Intestinal malrotation (IM) often remains undetected until adulthood, being discovered during testing or surgery for other comorbidities. Preoperative understanding of this anatomical abnormality is crucial. Case Report: An 80-year-old woman presented with cecal cancer. Three-dimensional computed tomography (CT) revealed that the cecum was located at the midline of the abdominal cavity, the duodenum did not cross the midline, and the ileocolic vein ran to the left. Clinically diagnosed with stage IVc cecal cancer complicated by IM, the patient underwent laparoscopic surgery. The ascending colon and cecum were not fixed to the retroperitoneum. The duodenum lacked the second, third, and fourth portions and the small bowel was distributed on the left and right sides of the abdominal cavity. Adhesions had shortened the mesentery, which were released close to their normal positions. Conclusion: Although laparoscopic surgery is superior to open surgery in terms of securing the field of view in a narrow space, providing a magnifying effect, and minimal invasiveness, it has a limited field of view and is inferior in terms of grasping the overall anatomy, which may be disadvantageous in cases of anatomical abnormalities. Colorectal cancer with IM is rare; however, the rate of preoperative diagnosis seems to be increasing thanks to improvements in diagnostic imaging, such as three-dimensional CT scans. In this study, we also reviewed 49 cases of colorectal cancer associated with IM.

Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis.

BACKGROUND: Cell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. METHODS: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. FINDINGS: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. INTERPRETATION: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. FUNDING: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.

Tumor suppressive role of the epigenetic master regulator BRD3 in colorectal cancer.

Bromodomain and extraterminal domain (BET) family proteins are epigenetic master regulators of gene expression via recognition of acetylated histones and recruitment of transcription factors and co-activators to chromatin. Hence, BET family proteins have emerged as promising therapeutic targets in cancer. In this study, we examined the functional role of bromodomain containing 3 (BRD3), a BET family protein, in colorectal cancer (CRC). In vitro and vivo analyses using BRD3-knockdown or BRD3-overexpressing CRC cells showed that BRD3 suppressed tumor growth and cell cycle G1/S transition and induced p21 expression. Clinical analysis of CRC datasets from our hospital or The Cancer Genome Atlas revealed that BET family genes, including BRD3, were overexpressed in tumor tissues. In immunohistochemical analyses, BRD3 was observed mainly in the nucleus of CRC cells. According to single-cell RNA sequencing in untreated CRC tissues, BRD3 was highly expressed in malignant epithelial cells, and cell cycle checkpoint-related pathways were enriched in the epithelial cells with high BRD3 expression. Spatial transcriptomic and single-cell RNA sequencing analyses of CRC tissues showed that BRD3 expression was positively associated with high p21 expression. Furthermore, overexpression of BRD3 combined with knockdown of, a driver gene in the BRD family, showed strong inhibition of CRC cells in vitro. In conclusion, we demonstrated a novel tumor suppressive role of BRD3 that inhibits tumor growth by cell cycle inhibition in part via induction of p21 expression. BRD3 activation might be a novel therapeutic approach for CRC.

Venous Thromboembolism Following Lateral Lymph Node Dissection for Rectal Cancer.

BACKGROUND/AIM: Postoperative venous thromboembolism (VTE) is a well-recognized complication that leads to morbidity and mortality. Lateral lymph node dissection (LLND) for rectal cancer is thought to potentially increase the risk of VTE due to its technical complexity. However, the relationship between LLND and VTE remains inadequately understood. The aim of this study was to elucidate the impact of LLND on the incidence of postoperative VTE. PATIENTS AND METHODS: This is a retrospective analysis of patients who underwent rectal cancer resection between 2010 and 2018 to identify the risk factors associated with postoperative VTE. Patients were divided into two groups: those who underwent surgery with LLND (LLND+ group) and those who underwent surgery without LLND (LLND- group). RESULTS: A total of 543 patients were enrolled in this study, and 113 patients underwent surgery for rectal cancer with LLND. VTE developed in 8 patients (1.47%), with the incidence rates being 4.42% in the LLND+ group and 0.69% in the LLND- group, respectively (p=0.012). Three of 8 patients had developed severe postoperative complications, and the other two patients needed intraoperative repair of the iliac vein during LLND procedure. Multivariate analysis identified the incidence of postoperative complications and LLND as the independent risk factors of VTE. CONCLUSION: Patients undergoing rectal cancer surgery with LLND should be closely monitored for signs of VTE.

Resection of anorectal fistula cancer associated with Crohn's disease after preoperative chemoradiotherapy: a case report.

BACKGROUND: Anorectal fistula cancer is often diagnosed in an advanced state, and radical resection is difficult when invasion of the pelvic wall is observed. In addition, there is currently no clear evidence for perioperative treatment of locally advanced cases. We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn's disease, which was curatively resected after preoperative chemoradiotherapy. CASE PRESENTATION: A 49-year-old man who had been diagnosed with Crohn's disease (ileocolonic type) at the age of 25 and was found to have an anorectal fistula and perianal abscess at the age of 44 was referred to our department with complaints of abdominal pain and diarrhea. Computed tomography (CT) showed anal stenosis due to a pelvic mass. Pathological analysis of a biopsy taken under general anesthesia indicated mucinous carcinoma. Magnetic resonance imaging (MRI) revealed infiltration into the prostate, seminal vesicles, levator ani muscle, and left internal obturator muscle, and the patient was diagnosed with cT4N0M0 cStage IIIB anorectal fistula cancer (UICC TNM classification 8th edition). After performing a laparoscopic sigmoid colostomy, chemoradiation therapy (capecitabine + oxaliplatin, 50.4 Gy/28fr) was initiated. The patient then underwent laparoscopic total pelvic exenteration, colonic conduit diversion, extensive perineal resection, and reconstruction using bilateral gluteus maximus flaps and a right rectus abdominis musculocutaneous flap. The pathological diagnosis was mucinous adenocarcinoma, pT4, and all margins were negative. No recurrence was evident 6 months after the operation without adjuvant chemotherapy. CONCLUSION: We described a case of curative resection after preoperative chemoradiotherapy for anorectal fistula cancer with extensive invasion that was diagnosed during the course of Crohn's disease.An accumulation of cases is needed to determine the usefulness of preoperative chemoradiation therapy for local control of anorectal fistula cancer associated with Crohn's disease.

High Level Sacral Bone Resection for Locally Recurrent Rectal Cancer.

BACKGROUND/AIM: Locally recurrent rectal cancer (LRRC) involving the upper sacrum is generally considered a contraindication for curative surgery. In the surgical management of LRRC, sacrectomy is frequently performed to secure clear resection margins. Nonetheless, the indications for high sacrectomy remain controversial due to potential postoperative complications, questions about radicality, and the increased complexity of the operation. Furthermore, comprehensive studies addressing this issue are notably absent. This study aimed to assess the feasibility, safety, and surgical prognosis in high sacrectomy for LRRC. PATIENTS AND METHODS: All patients with LRRC who required concomitant sacrectomy, but did not include the inferior margin of the second sacral vertebra, between 2003 and 2014, were reviewed retrospectively. RESULTS: Eight patients with a median age of 59 years were included in this study. The proximal resection line for sacral bone resection was the central part of the S1 vertebra in one patient, lower edge of the S1 vertebra in six patients, and central part of the S2 vertebra in one patient. Negative margin resection was achieved in five out of the eight patients. The median operative time was 922 min, and the median operative blood loss volume was 6,370 ml. Major complications included pelvic abscess (n=5), ileus (n=1), and pulmonary vein embolism (n=1), none of which proved fatal during the postoperative period. Both the 5-year local re-recurrence-free survival rate and the 5-year distant metastasis-free survival rate were 50% (4/8). CONCLUSION: High sacrectomy is safe and feasible to achieve negative margins in patients with LRRC.

Metastases and treatment-resistant lineages in patient-derived cancer cells of colorectal cancer.

Circulating tumor cells (CTCs) play an important role in metastasis and recurrence. However, which cells comprise the complex tumor lineages in recurrence and are key in metastasis are unknown in colorectal cancer (CRC). CRC with high expression of POU5F1 has a poor prognosis with a high incidence of liver metastatic recurrence. We aim to reveal the key cells promoting metastasis and identify treatment-resistant lineages with established EGFP-expressing organoids in two-dimensional culture (2DOs) under the POU5F1 promotor. POU5F1-expressing cells are highly present in relapsed clinical patients' blood as CTCs. Sorted POU5F1-expressing cells from 2DOs have cancer stem cell abilities and abundantly form liver metastases in vivo. Single-cell RNA sequencing of 2DOs identifies heterogeneous populations derived from POU5F1-expressing cells and the Wnt signaling pathway is enriched in POU5F1-expressing cells. Characteristic high expression of CTLA4 is observed in POU5F1-expressing cells and immunocytochemistry confirms the co-expression of POU5F1 and CTLA4. Demethylation in some CpG islands at the transcriptional start sites of POU5F1 and CTLA4 is observed. The Wnt/ß-catenin pathway inhibitor, XAV939, prevents the adhesion and survival of POU5F1-expressing cells in vitro. Early administration of XAV939 also completely inhibits liver metastasis induced by POU5F1-positive cells.

Laparoscopic Colorectal Cancer Surgery for Patients With Severe Chronic Heart Failure.

BACKGROUND/AIM: Laparoscopic surgery with pneumoperitoneum is not usually recommended for patients with heart failure due to the potential risks associated with cardiopulmonary stress. Few studies, however, have directly examined whether a laparoscopic approach can be used safely in patients with severe chronic heart failure. PATIENTS AND METHODS: We retrospectively evaluated the safety and feasibility of laparoscopic colorectal cancer surgery in 13 patients with severe chronic heart failure, defined as left ventricular ejection fraction <40% and/or brain natriuretic peptide >100 pg/ml (NT-proBNP >400 pg/ml). Intraoperative hemodynamics, including systolic blood pressure, diastolic blood pressure, mean blood pressure, and heart rate, were carefully monitored. RESULTS: The median left ventricular ejection fraction value was 35% (18-62%), and the median brain natriuretic peptide value was 171.7 pg/ml (109.5-961.4 pg/ml). The time-series mean ratio of the patients' blood pressure and heart rate during surgery indicated that soon after the induction of general anesthesia, mean blood pressure was significantly decreased (p<0.05) from baseline. In all 13 cases, laparoscopic surgery was performed successfully, with no significant complications. CONCLUSION: The present study showed that laparoscopic surgery for colorectal cancer can be performed safely in patients with severe chronic heart failure.

Treatment response prediction of neoadjuvant chemotherapy for rectal cancer by deep learning of colonoscopy images.

In current clinical practice, several treatment methods, including neoadjuvant therapy, are being developed to improve overall survival or local recurrence rates for locally advanced rectal cancer. The response to neoadjuvant therapy is usually evaluated using imaging data collected before and after preoperative treatment or postsurgical pathological diagnosis. However, there is a need to accurately predict the response to preoperative treatment before treatment is administered. The present study used a deep learning network to examine colonoscopy images and construct a model to predict the response of rectal cancer to neoadjuvant chemotherapy. A total of 53 patients who underwent preoperative chemotherapy followed by radical resection for advanced rectal cancer at the Osaka University Hospital between January 2011 and August 2019 were retrospectively analyzed. A convolutional neural network model was constructed using 403 images from 43 patients as the learning set. The diagnostic accuracy of the deep learning model was evaluated using 84 images from 10 patients as the validation set. The model demonstrated a sensitivity, specificity, accuracy, positive predictive value and area under the curve of 77.6% (38/49), 62.9% (22/33), 71.4% (60/84), 74.5% (38/51) and 0.713, respectively, in predicting a poor response to neoadjuvant therapy. Overall, deep learning of colonoscopy images may contribute to an accurate prediction of the response of rectal cancer to neoadjuvant chemotherapy.

Surgery for Rectal Cancer With Mixed Reality of 3D Model During Operation: A Case Report.

Background/Aim: Recently, robotic surgery for rectal cancer has become a common minimally invasive surgery. In addition, the technology of augmented and mixed reality is applied in various living environments, including medicine. We successfully performed robotic surgery for rectal cancer with three-dimensional (3D) images as mixed reality (MR) using HoloLens2. Case Report: The patient was diagnosed with rectal cancer by colonoscopy and a positron-emission computed-tomography scan, and we performed robot-assisted anterior resection. The operator used HoloLens2 and performed the surgery while visualizing 3D images of pelvic anatomy with the location of the rectal cancer as hologram. The operation was performed completely and safely, and she was discharged 11 days after surgery with no postoperative complications. Conclusion: This case presents the usefulness of a MR system offering organ visualization as hologram during surgery.

The Clinical Potential of FBPA-PET/CT Imaging for Colorectal Cancer and its Liver Metastases Expressing LAT1.

BACKGROUND/AIM: 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) has become indispensable for staging colorectal cancer but has limitations. Thus, PET with a focus on metabolism other than glucose, mainly amino acid metabolism, has been developed. L-type amino acid transporter 1 (LAT1) is known to be a cancer-specific amino acid transporter and, although 4-Borono-2-(18)F-fluoro-phenylalanine (FBPA) has been reported to be useful as a probe for LAT1, the significance of LAT1 expression in colorectal cancer is ambiguous and implementation of 18F-FBPA-PET in colorectal cancer has not yet been reported. MATERIALS AND METHODS: The aims of this study were to investigate the expression of LAT1 in primary lesions and metastatic lesions of colorectal cancer by immunohistochemical analysis and report the initial experience of performing 18F-FBPA-PET on colorectal cancer patients in clinical practice. RESULTS: There was a significant correlation between LAT1 protein expression in primary tumors and liver metastases. Furthermore LAT-1 expression was positively correlated with recurrence (p=0.033). We performed 18F-FBPA-PET on three rectal cancer patients and detected cancer. CONCLUSION: LAT1 protein is expressed not only in the primary colorectal tumor, but also in liver metastases. 18F-FBPA-PET can be safely performed in patients with colorectal cancer.

A case of fulminant amoebic colitis during systemic chemotherapy for gastric cancer.

Amoebiasis is a parasitic infection caused by the protozoan, Entamoeba histolytica. At times, amoebiasis is activated under immunosuppressive conditions such as chemotherapy. We report a case of fulminant amoebic colitis resulting from an asymptomatic Entamoeba histolytica infection, which was activated by chemotherapy for gastric cancer. The patient developed diarrhea and fever after three courses of chemotherapy for gastric cancer and was diagnosed with acute enteritis. A colonoscopy and biopsy were performed because of the bloody stool. Histopathological findings revealed amoebic invasion of the rectum. Therefore, the patient was diagnosed with amoebic colitis and was treated with metronidazole. Emergency surgery was performed because intestinal perforation was suspected after which his general condition improved and was discharged. Subsequently, gastric cancer surgery was performed and the patient was discharged without postoperative complications. Hence, amoebic colitis should be listed as a differential diagnosis, and a colonoscopic biopsy should be performed when colitis occurs during chemotherapy for cancer.

Establishment of induced pluripotent stem cells derived from patients and healthy siblings of a nevoid basal cell carcinoma syndrome family.

It is known that a nevoid basal cell carcinoma syndrome (NBCCS) is characterized by a combination of developmental abnormalities and a predisposition to form various tumors. Although it is possible to create disease models via gene editing, there are significant potential problems with this approach such as off-target mutations and differences in SNPs. On the other hand, since disease families share common SNPs, research using iPSCs derived from both patients and healthy siblings of the same disease family is very important. Thus, establishment of induced pluripotent stem cells derived from patients and healthy siblings of the same NBCCS family will be of great importance to study the etiology of this disease and to develop therapeutics. In this study, we generated hiPSCs using peripheral blood mononuclear cells derived from the patients and healthy siblings of familial NBCCS with the novel mutation in PTCH1_c.3298_3299insAAG in the feeder- and serum-free culture conditions using SeVdp. In addition, disease-specific hiPSCs such as those expressing the PTCH1_c.3298_3299insAAG mutation could be powerful tools for revealing the genotype-phenotype relationship and pathogenicity of NBCCS.

A Case of Rectal Cancer with Vaginal Invasion Using Indocyanine Green to Determine the Extent of Resection.

Here we report a case of locally advanced rectal cancer with vaginal invasion, which was successfully resected via laparoscopic surgery using intraoperative indocyanine green (ICG) navigation to determine the vaginal cut line. Based on preoperative examinations, an 81-year-old female was diagnosed with locally advanced rectal cancer with vaginal invasion. After preoperative chemoradiotherapy, the lesion was judged to be resectable. During surgery, the gynecologist transvaginally injected ICG into the vaginal submucosa to determine the caudal margin of the vaginal invasion, and laparoscopically dissected under the near-infrared image of the stained area. Pathological analysis of the resection specimen revealed negative resection margins. One year after surgery, there has been no recurrence.

Cancer Stem Cells Persist Despite Cellular Damage, Emergence of the Refractory Cell Population.

PURPOSE: Cancer stem cells (CSCs) are responsible for chemotherapy resistance and have unique properties that protect them from chemotherapy. Investigating CSCs may help to identify the population that is more resistant to treatments, leading to recurrence. We evaluated persisting CSCs, emerging after chemotherapy that cause tumor recurrence. METHODS: Using human colorectal cancer organoids prepared from surgical specimens, we looked at changes in CSCs, the emergence and changes in the original population, which single-cell analysis identified. RESULTS: With regards to changes in cancer stem cell markers, CD44 showed low levels after 5-fluorouracil administration. Once the CD44-ve population was sorted and cultured, the CD44+ve population gradually emerged, and the CD44-ve population decreased. Compared with the CD44-ve population of an organoid parent, the CD44-ve population proliferated after chemotherapeutic agent stimulation. The CD44-ve population was derived from the CD44+ve population before chemotherapeutic agents. In addition, when the CD44 variants were evaluated, the CD44v9 population remained. In single-cell analysis, we found that POU5F1 was highly expressed in the CD44low population. Velocity analysis showed that the CD44-ve population was induced after chemotherapy and expressed POU5F1. POU5F1-EGFP-Casp9 transfected organoids resulted in the appearance of a CD44-ve population after administration of a chemotherapeutic reagent. Both in vivo and in vitro, the dimerizer administration inhibited tumor growth significantly. CONCLUSIONS: POU5F1 is involved in chemotherapy resistance in relation to stemness. For the treatment against refractory tumors, such as the recurrence after chemotherapy, the treatment should target the emerging specific population such as CD44 (or CD44v9) and proliferative cancer cells.

Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.

Integrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East Asians (Biobank Japan) and 377,441 Europeans (UK Biobank). We identify ten cancer risk variants including five pleiotropic associations (e.g., rs2076295 at DSP on 6p24 associated with lung cancer and rs2525548 at TRIM4 on 7q22 nominally associated with six cancers). Quantifying shared heritability among the cancers detects positive genetic correlations between breast and prostate cancer across populations. Common genetic components increase the statistical power, and the large-scale meta-analysis of 277,896 breast/prostate cancer cases and 901,858 controls identifies 91 newly genome-wide significant loci. Enrichment analysis of pathways and cell types reveals shared genetic backgrounds across said cancers. Focusing on genetically correlated cancers can contribute to enhancing our insights into carcinogenesis.

Testicular metastasis 9 years after resection of primary descending colon cancer with simultaneous pulmonary metastasis: a case report.

BACKGROUND: Metastatic testicular cancer is rare. In particular, primary colorectal cancer rarely metastasizes to the testes. This study reports a case of testicular metastasis recurrence 9 years after the resection of a primary colorectal cancer and a simultaneous metastatic lung tumour. CASE PRESENTATION: A 69-year-old man underwent a laparoscopic left hemicolectomy for descending colon cancer. Preoperative computed tomography revealed a solitary left lung mass. Postoperative chemotherapy reduced the size of the lung mass, and 6 months after the primary resection, the patient underwent a left upper segmentectomy. Based on the pathological examination, he was diagnosed with pulmonary metastasis from colorectal cancer. After four courses of adjuvant chemotherapy, the patient was recurrence-free. However, 9 years and 6 months after the primary resection, he complained of discomfort in his left testicle. Physical examination revealed a left testicular mass. Since a malignancy was not excluded via imaging, left testicular resection was performed to confirm the diagnosis. The pathological diagnosis was testicular metastasis from colorectal cancer. The patient was followed up without medication, and remained healthy, without recurrence, 11 months postoperatively. CONCLUSIONS: It is important to follow up with testicular metastasis in mind, although it is rare.

[A Case of Squamous Cell Carcinoma of the Lower Rectum].

A 61-year-old man presented with dyschezia, and further examination revealed squamous cell carcinoma of the lower rectum invading the bladder and seminal vesicles. The clinical diagnosis was squamous cell carcinoma of the lower rectum, cT4b(bladder and seminal vesicle)N0M0, cStage Ⅱc. Neoadjuvant chemoradiotherapy was administered with external irradiation of the entire pelvis(50.4 Gy/28 Fr)and chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin(FOLFOX). Once tumor shrinkage was observed 3 months after chemoradiotherapy, laparoscopic total pelvic exenteration with TaTME approach was performed. The patient was discharged on the 26th postoperative day without any postoperative complications. Histopathological examination showed only squamous cell carcinoma component with Grade 1a histological treatment effect. The pathological diagnosis was ypT4b(bladder, seminal vesicle)ypN0cM0, ypStage Ⅱc. The patient was alive without any recurrence 6 months after surgery.