Tumor-to-tumor metastasis of colon cancer metastasizing to a pancreatic neuroendocrine tumor associated with von Hippel-Lindau disease: a case report.

Von Hippel-Lindau disease (VHL) is frequently associated with pancreatic neuroendocrine tumors (PNETs). Here, we report a case of tumor-to-tumor metastasis in a VHL patient in whom colon cancer metastasized to the interior of a PNET. A 65-year-old man had undergone bilateral adrenalectomy for pheochromocytomas in both adrenal glands in his 50 s. Genetic screening was performed considering his family history of pheochromocytoma, and he was diagnosed with VHL. PNET was detected, for which the patient was regularly monitored by follow-up imaging. One year ago, the patient underwent right hemicolectomy to remove a tumor in the ascending colon (pT3N0M0, pStage IIA). He was admitted to our department for detailed examination because the pancreatic tumor had grown, and thus, pancreaticoduodenectomy was performed. Diagnostic imaging and histological findings indicated tumor-to-tumor metastasis, in which the patient's previous colon cancer had metastasized to and proliferated within the PNET. Colon cancer metastasizing to a PNET is extraordinarily rare and has never been reported in the literature. Thus, practitioners should be vigilant for tumor-to-tumor metastasis when performing imaging surveillance of PNETs.

[A Case of Ascending Colon Cancer with Essential Thrombocythemia].

Essential thrombocythemia(ET)is a rare myeloproliferative disorder characterized by thrombocytosis and a risk of thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Including our case, only 5 cases of c o l orectal cancer with ET have been reported in Japan. Herein, we report a case of colon cancer in an ET patient who underwent laparoscopic right hemicolectomy. Our perioperative management avoided complications such as thrombosis or bleeding. An 81-year-old woman developed bloody stools. She was previously diagnosed with ET 9 years ago. Aspirin, cilostazol, and hydroxyurea(HU)were prescribed. Colonoscopy revealed a tumor at the ascending colon. Histopathological examination showed a well-differentiated tubular adenocarcinoma. Since the patient had anemia, aspirin and cilostazol were discontinued after diagnosis. HU was discontinued from the day before surgery to 2 days after surgery. Enoxaparin was subcutaneously administered for 1 to 3 days after surgery. Aspirin and cilostazol were resumed on the fourth day post-surgery. The patient could be discharged when her condition stabilizes with no thrombosis and bleeding after 8 days.

The clinical significance of distal spread differs according to the primary tumor location in rectal cancer.

PURPOSE: Treatment strategies of rectal cancer differ between tumors located above (RS/Ra) and below (Rb) the peritoneal reflection. Based on the extent of distal spread (DS), the Japanese Society for Cancer of Colon and Rectum proposed an optimal distal margin in RS/Ra and Rb tumors. In this study, we investigated the clinical significance of DS between RS/Ra and Rb tumors. METHODS: We analyzed 287 stage I-III rectal cancer patients who underwent curative intent resection without preoperative therapy. DS and other pathological factors were evaluated using whole-mount sections. To investigate the clinical significance of DS in RS/Ra and Rb tumors, clinicopathological variables, including DS, were analyzed for the survival outcome according to the tumor group. RESULTS: DS was detected in 20 out of 185 (11%) patients with RS/Ra tumors and 8 out of 102 (8%) patients with Rb tumors. DS was not significantly associated with the overall survival (OS) or relapse-free survival (RFS) in RS/Ra tumors, but was an independent prognostic factor for the OS and RFS in Rb tumors (P = 0.002 and 0.007, respectively). CONCLUSIONS: The clinical significance of DS differs between RS/Ra and Rb tumors. DS is associated with a worse survival in Rb tumors, but not in RS/Ra tumors.

Feasibility of restorative proctocolectomy in patients with ulcerative colitis-associated lower rectal cancer: A retrospective study.

BACKGROUND/OBJECTIVE: Restorative proctocolectomy (RP) may improve quality of life in patients with ulcerative colitis (UC)-associated lower rectal cancer to a greater extent than total proctocolectomy. However, patients with UC-associated cancer often have flat mucosal lesions that make it extremely difficult to endoscopically delineate the tumor margins. Therefore, there is a potential risk of residual tumor and local recurrence after RP in patients with UC-associated lower rectal cancer. The aim of this study was to assess the feasibility of RP in patients with UC-associated cancer of the lower rectum. METHODS: We retrospectively identified nine patients who had undergone RP for UC-associated lower rectal cancer at the Niigata University Medical and Dental Hospital between January 2000 and December 2016. The incidence of flat mucosal cancer, distal margin status, and oncologic outcomes were evaluated in the nine patients. RESULTS: Eight (89%) of the nine patients had flat mucosal cancer in the lower rectum. The median length of the distal margin was 22 mm (range 0-55 mm). No patient developed local or distant recurrence during follow-up. One patient had a positive distal margin. This patient underwent annual pouchoscopy, but had no local recurrence and died of pancreatic cancer 81 months after RP. The remaining eight patients were alive at the final observation. Five-year and 10-year overall survival rates in the nine patients were 100% and 66.7%, respectively. CONCLUSION: Patients with UC-associated lower rectal cancer often have lesions of the flat mucosal type. However, RP is feasible and not necessarily contraindicated in such patients.

Small Bowel Obstruction After Ileal Pouch-Anal Anastomosis With a Loop Ileostomy in Patients With Ulcerative Colitis.

PURPOSE: Small bowel obstruction (SBO) remains a common complication after pelvic or abdominal surgery. However, the risk factors for SBO in ulcerative colitis (UC) surgery are not well known. The aim of the present study was to clarify the risk factors associated with SBO after ileal pouch-anal anastomosis (IPAA) with a loop ileostomy for patients with UC. METHODS: The medical records of 96 patients who underwent IPAA for UC between 1999 and 2011 were reviewed. SBO was confirmed based on the presence of clinical symptoms and radiographic findings. The patients were divided into 2 groups: the SBO group and the non-SBO group. We also analyzed the relationship between SBO and computed tomography (CT) scan image parameters. RESULTS: The study included 49 male and 47 female patients. The median age was 35.5 years (range, 14-72 years). We performed a 2- or 3-stage procedure as a total proctocolectomy and IPAA for patients with UC. SBO in the pretakedown of the loop ileostomy after IPAA occurred in 22 patients (22.9%). Moreover, surgical intervention for SBO was required for 11 patients. In brief, closure of the loop ileostomy was performed earlier than expected. A multivariate logistic regression analysis revealed that the 2-stage procedure (odds ratio, 2.850; 95% confidence interval, 1.009-8.044; P = 0.048) was a significant independent risk factor associated with SBO. CT scan image parameters were not significant risk factors of SBO. CONCLUSION: The present study suggests that a 2-stage procedure is a significant risk factor associated with SBO after IPAA in patients with UC.

Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer.

OBJECTIVES: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing. MATERIALS AND METHODS: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as "all wild-type", while remaining patients were defined as "mutant-type". RESULTS: Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were "all wild-type" compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and "mutant-type" RCRC showed significantly worse PFS compared with "all wild-type" LCRC (P = 0.004). CONCLUSIONS: RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC.

Prophylactic lateral pelvic lymph node dissection in stage IV low rectal cancer.

AIM: To assess the clinical significance of prophylactic lateral pelvic lymph node dissection (LPLND) in stage IV low rectal cancer. METHODS: We selected 71 consecutive stage IV low rectal cancer patients who underwent primary tumor resection, and enrolled 50 of these 71 patients without clinical LPLN metastasis. The patients had distant metastasis such as liver, lung, peritoneum, and paraaortic LN. Clinical LPLN metastasis was defined as LN with a maximum diameter of 10 mm or more on preoperative pelvic computed tomography scan. All patients underwent primary tumor resection, 27 patients underwent total mesorectal excision (TME) with LPLND (LPLND group), and 23 patients underwent only TME (TME group). Bilateral LPLND was performed simultaneously with primary tumor resection in LPLND group. R0 resection of both primary and metastatic sites was achieved in 20 of 50 patients. We evaluated possible prognostic factors for 5-year overall survival (OS), and compared 5-year cumulative local recurrence between the LPLND and TME groups. RESULTS: For OS, univariate analyses revealed no significant benefit in the LPLND compared with the TME group (28.7% vs 17.0%, P = 0.523); multivariate analysis revealed that R0 resection was an independent prognostic factor. Regarding cumulative local recurrence, the LPLND group showed no significant benefit compared with TME group (21.4% vs 14.8%, P = 0.833). CONCLUSION: Prophylactic LPLND shows no oncological benefits in patients with Stage IV low rectal cancer without clinical LPLN metastasis.

Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer.

HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 IHC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P < .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment.

Association between poorly differentiated clusters and efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer.

OBJECTIVE: Although poorly differentiated cluster has been reported to be a useful grading system for predicting prognosis in colorectal cancer, its relationship to chemotherapy efficacy has not been demonstrated. We aimed to investigate the association between poorly differentiated cluster and the efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer. METHODS: This retrospective study enrolled 131 patients with stage III colorectal cancer who underwent curative resection: 72 received 5-fluorouracil-based adjuvant chemotherapy (chemotherapy group) and 59 did not (surgery-alone group). Poorly differentiated cluster was defined as a cancer cluster of ≥5 cancer cells without gland-like structure, and was classified into poorly differentiated cluster G1, G2 and G3 according to the number of clusters. The benefit of 5-fluorouracil-based adjuvant chemotherapy was evaluated based on poorly differentiated cluster grade. RESULTS: Thirty-nine, 40 and 52 patients were classified as poorly differentiated cluster G1, G2 and G3, respectively. Significant differences in the 5-year cumulative recurrence rate and relapse-free survival were observed between poorly differentiated cluster G1/G2 and G3 (26.7% vs. 47.5%, P = 0.010; 66.0% vs. 43.9%, P = 0.004). A comparison of cumulative recurrence rate and relapse-free survival between the chemotherapy and surgery-alone groups showed a significant benefit of adjuvant chemotherapy in poorly differentiated cluster G1/G2 patients (cumulative recurrence rate: 17.4% vs. 37.3%, P = 0.035; relapse-free survival: 79.5% vs. 51.9%, P = 0.002), but not in poorly differentiated cluster G3 patients (cumulative recurrence rate: 48.6% vs. 44.8%, P = 0.885; relapse-free survival: 51.4% vs. 32.7%, P = 0.068). CONCLUSIONS: In stage III colorectal cancer, poorly differentiated cluster G1/G2 predicts a significant benefit from 5-fluorouracil-based adjuvant chemotherapy, whereas poorly differentiated cluster G3 predicts a poor response to it.

[Quality of Life of Patients after Colorectal Cancer Surgery as Assessed Using EQ-5D-5L Scores].

This study aimed to evaluate the health-related quality of life(QOL)using EQ-5D-5L scores for patients who underwent surgery for colorectal cancer. A total of 30 consecutive patients(14 men and 16 women; median age: 67.5 years)from the outpatient clinic of our institute in January 2017 were eligible for this study. The primary tumor was located in the colon(n= 18)or rectum/anu(s n=12). Twelve patient(s 40.0%)had cancer recurrence, and 3 patient(s 10.0%)had a stoma. In addition, 11 patients(36.7%)underwent chemotherapy. The median EQ-5D-5L score for all the patients was 0.867(range, 0.324- 1.000). The EQ-5D-5L score of patients with recurrence was significantly lower(0.820)than that of patients without recurrence( 0.948)(p=0.002). Furthermore, the EQ-5D-5L score of women(0.834)was significantly lower than that of men (0.942)(p=0.015). No significant difference was noted between the EQ-5D-5L score and other factors, such as age, cancer stage, location of primary tumor, absence/presence of chemotherapy, and absence/presence of stoma. In conclusion, using EQ-5D-5L scores, female gender and cancer recurrence were found to be associated with low QOL of patients after surgery for colorectal cancer.

[A Case of Ascending Colon Cancer with Synchronous Liver Metastases and Peritoneal Dissemination].

The patient was a 73-year-old man with ascending colon cancer and synchronous liver metastases. A right hemicolectomy with a lymph node dissection was performed for the primary lesion. The resected specimen revealed a KRAS codon 12 mutation. After 6 courses of chemotherapy with capecitabine, oxaliplatin, and bevacizumab(Bv), we performed a partial hepatectomy and resection of the peritoneal dissemination. A computed tomography(CT)scan 5 months later revealed the recurrence of the liver metastases. After 8 courses of chemotherapy with 5-fluorouracil, Leucovorin, irinotecan, and Bv, we performed a partial hepatectomy. CT scan after 13 months revealed a recurrence in the peritoneal dissemination in the Douglas pouch and the right subphrenic space; therefore, we performed a low anterior resection and resection of the peritoneal dissemination with curative intent. CT scan after 19 months revealed a recurrence in the right subphrenic dissemination, a lung metastasis, and pleural dissemination. Chemotherapy with 5-fluorouracil, Leucovorin, and Bv was administered for 2 years and 5 months. After 5 years and 9 months of the primary operation, the patient is alive. Recently, we have focused on the mechanism of multidrug resistance through NAD(P)H: quinone oxidoreductase-1(NQO1)overexpression, which can be used to determine the role of an enzyme in sensitivity to toxicity and carcinogenesis. In this case, the pathological examination of the resected specimen revealed NQO1 negative expression. In conclusion, NQO1 may play a significant role in chemotherapy resistance in colorectal cancer patients.

[Two Cases of Colorectal Cancer with SRC Amplification].

Carcinoma with elevated SRC expression is associated with distant metastasis and drug resistance. We report 2 cases of SRC amplification observed after retrospective comprehensive genomic sequencing. Case 1 was a 62-year-old man who had RAS wild-type stage IV carcinoma of the sigmoid colon with multiple liver metastases in both lobes. He underwent low anterior resection and systemic chemotherapy was initiated to treat the unresectable multiple liver metastases. Case 2 was a 73-yearold man who had RAS wild-type stage IV carcinoma of the descending colon with metastasis in the lateral segment of the liver. He underwent left hemicolectomy and lateral segmentectomy. He subsequently underwent open radiofrequency ablation and systemic chemotherapy to treat a hepatic recurrence. Several previous studies have found that molecular targeted therapy with tyrosine kinase inhibitors is effective against colorectal cancer with elevated SRC expression. This suggests that the results of comprehensive genomic sequencing may support the implementation of new treatments.

Genomic landscape of colorectal cancer in Japan: clinical implications of comprehensive genomic sequencing for precision medicine.

BACKGROUND: Comprehensive genomic sequencing (CGS) has the potential to revolutionize precision medicine for cancer patients across the globe. However, to date large-scale genomic sequencing of cancer patients has been limited to Western populations. In order to understand possible ethnic and geographic differences and to explore the broader application of CGS to other populations, we sequenced a panel of 415 important cancer genes to characterize clinically actionable genomic driver events in 201 Japanese patients with colorectal cancer (CRC). METHODS: Using next-generation sequencing methods, we examined all exons of 415 known cancer genes in Japanese CRC patients (n = 201) and evaluated for concordance among independent data obtained from US patients with CRC (n = 108) and from The Cancer Genome Atlas-CRC whole exome sequencing (WES) database (n = 224). Mutation data from non-hypermutated Japanese CRC patients were extracted and clustered by gene mutation patterns. Two different sets of genes from the 415-gene panel were used for clustering: 61 genes with frequent alteration in CRC and 26 genes that are clinically actionable in CRC. RESULTS: The 415-gene panel is able to identify all of the critical mutations in tumor samples as well as WES, including identifying hypermutated tumors. Although the overall mutation spectrum of the Japanese patients is similar to that of the Western population, we found significant differences in the frequencies of mutations in ERBB2 and BRAF. We show that the 415-gene panel identifies a number of clinically actionable mutations in KRAS, NRAS, and BRAF that are not detected by hot-spot testing. We also discovered that 26% of cases have mutations in genes involved in DNA double-strand break repair pathway. Unsupervised clustering revealed that a panel of 26 genes can be used to classify the patients into eight different categories, each of which can optimally be treated with a particular combination therapy. CONCLUSIONS: Use of a panel of 415 genes can reliably identify all of the critical mutations in CRC patients and this information of CGS can be used to determine the most optimal treatment for patients of all ethnicities.

Long-term survival in pseudo-Meigs' syndrome caused by ovarian metastases from colon cancer.

BACKGROUND: Meigs' syndrome is defined as the co-existence of benign ovarian fibroma or fibroma-like tumor, ascites, and pleural effusion. In contrast, pseudo-Meigs' syndrome is defined as the co-existence of other ovarian or pelvic tumors, ascites, and pleural effusion. In Meigs' and pseudo-Meigs' syndromes, ascites and pleural effusion resolve promptly after the complete resection of the ovarian or pelvic tumor(s). Secondary ovarian tumors from colorectal gastrointestinal metastases rarely cause pseudo-Meigs' syndrome; only 11 cases of pseudo-Meigs' syndrome secondary to colorectal cancers have been reported in the literature. Therefore, the prognosis and etiology of pseudo-Meigs' syndrome caused by ovarian metastasis from colorectal cancers remain unclear. CASE PRESENTATION: We report here a rare case of pseudo-Meigs' syndrome caused by ovarian metastases from sigmoid colon cancer with long-term survival. A 47-year-old woman presented with abdominal distention of 1-month duration. She developed acute dyspnea 2 weeks after the initial presentation. Colonoscopy and computed tomography revealed sigmoid colon cancer with an ovarian metastasis, along with massive ascites and bilateral pleural effusion. Emergency operation, including bilateral oophorectomy and sigmoidectomy, was performed. Subsequently, ascites and bilateral pleural effusion resolved rapidly. Curative hepatic resection was performed for liver metastases 29 months after the first operation, and as of this writing, the patient is alive with no evidence of a disease 78 months after the first operation. In general, colorectal cancer with ovarian metastasis is hard to cure, and long-term survival in patients with colorectal cancer with pseudo-Meigs' syndrome is rare. Our experience suggests that curative resection for pseudo-Meigs' syndrome caused by ovarian metastasis from colorectal cancer may offer long-term survival. CONCLUSIONS: Our experience suggests that pseudo-Meigs' syndrome can occur in a patient with colorectal cancer after metastasis to the ovaries, causing massive ascites and pleural effusion. Aggressive treatment, including R0 resection, for this disease if allowed by the patient's general condition may offer long-term survival.

Clinical Significance of Extramural Tumor Deposits in the Lateral Pelvic Lymph Node Area in Low Rectal Cancer: A Retrospective Study at Two Institutions.

BACKGROUND: The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer. METHODS: This retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses. RESULTS: Classification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P < 0.001). The corresponding 5-year RFS rates were 62.2, 33.8, and 14.3 %, respectively (P < 0.001). A multivariate Cox proportional hazards regression analysis showed that the presence of LP-EX was an independent prognostic factor for OS (P = 0.006) and RFS (P = 0.001). CONCLUSIONS: The LP-EX classification is a useful pathologic parameter that can be used to stratify patients with metastasis in the LPLN area.

[A Systematic Analysis of Oncogene and Tumor Suppressor Genes for Panitumumab-Resistant Rectal Cancer with Wild RAS Gene - A Case Report].

A 58-year-old man was admitted with the complaint of bloody stools. Colonoscopy and computed tomography revealed a rectal cancer with a liver metastasis and multiple lung metastases. After administering a regimen comprising 3 courses of XELOX plus bevacizumab chemotherapy, the sizes of the primary and metastatic lesions decreased remarkably. Abdominoperineal resection was performed for local control of the cancer; the specimen from the initial tumor was found to be KRAS wild type. After 14 courses of XELOX chemotherapy, brain metastases were detected. Although 3 courses of IRIS plus panitumumab were administered, the liver, lung, and brain metastases spread rapidly. A comprehensive genomic analysis focused on cancer-related genes with CancerPlex®found a mutation of the BRAF gene(I326V). BRAF is a downstream molecule of KRAS in the RAS-RAF-MAPK pathway. Therefore, this mutation of the BRAF gene has the possibility of causing resistance against panitumumab that was found in this case. Furthermore, we expect that the systematic analysis of oncogene and suppressor oncogenes will enable us to choose the optimal regimen of chemotherapy or molecular targeting therapy for each patient with colorectal cancer.

[A Case of Metastatic Colorectal Cancer with HER2 Overexpression/Amplification].

We report a case of panitumumab-resistant rectal cancer with HER2 gene amplification detected by CancerPlex®. A 51- year-old man was diagnosed with an obstructive rectal cancer having lung and adrenal metastases. He underwent the Hartmann 's operation, and KRAS mutations were not detected. After the surgery, 3 courses of CapeOx plus bevacizumab were administered as first-line chemotherapy; however, the lung and adrenal metastases progressed. Subsequently, 24 courses of IRIS/panitumumab was administered as second-line chemotherapy, and the metastases slowly progressed. Six courses of regorafenib were administered as third-line chemotherapy followed by a course of TAS-102 as fourth-line chemotherapy. Subsequently, a left femoral head metastasis and cerebellar metastases were detected. The patient received best supportive care including palliative femoral head replacement and stereotactic irradiation for the cerebellar metastases, and he died of cancer 3 years 5 months after the primary surgery. The comprehensive genomic analysis focusing on 413 cancer-related genes with CancerPlex®revealed that EGFR, BRAF, KRAS, NRAS, and HRAS had no mutations; however, ERBB2 amplification was detected. Furthermore, immunohistochemical staining revealed overexpression of HER2 protein in both the primary and bone metastatictumor. HER2 and EGFR independently promote the RAS-RAF-MAPK pathway. In the present case, the efficacy of anti-EGFR therapy may be attenuated because of ERBB2 amplification in the metastatic tumor.

[A Case of Metastatic Colon Cancer Dramatically Affected by Anti-EGFR Antibody Therapy].

RAS mutation is an established predictive biomarker of resistance to anti-epidermal growth factor receptor(EGFR)therapy in metastatic colorectal cancer. In addition, previous studies identified mutations in ERBB2, FGFR1, PDGFRA, BRAF, MAP2K1, PTEN, and PIK3CA as potential mechanisms of resistance to anti-EGFR therapy. Testing for these mutations might be necessary to determine eligibility for anti-EGFR therapy in patients with metastatic colorectal cancer. CancerPlex®is a nextgeneration sequencer for 413 cancer genes. An analysis panel includes genes that may be associated with resistance to anti- EGFR therapy. A 65-year-old man with unresectable rectal cancer, multiple lung metastases, and a bulky liver metastasis was evaluated for expression of genes associated with resistance to anti-EGFR. The analysis found that all genes indicating resistance were wild-type genes. Cetuximab monotherapy was administered after rectal resection, with dramatic shrinkage of the metastatic tumors. A more accurate selection of patients according to tumor genetic status using CancerPlex®might improve the risk-benefit profile of anti-EGFR therapy.

[A Case of Long-Term Survival after Repeated Peritoneal Recurrences of Perforated Sigmoid Colon Cancer Treated with Systemic Chemotherapy and R0 Resection of Peritoneal Tumors].

We report here a case of long-term survival with repeated peritoneal recurrences after resection of perforated sigmoid colon cancer. A 65-year-old man presented with diarrhea and abdominal pain. Computed tomography(CT)revealed diffuse peritonitis caused by perforated sigmoid colon cancer. We performed sigmoidectomy with D2 lymphadenectomy and descending colostomy. Postoperatively, S-1 was administered for 12 months as adjuvant chemotherapy. CT showed peritoneal nodules 56 months after the surgery. After 10 courses of mFOLFOX6 plus bevacizumab, the tumors decreased in size (reduction rate of 34.4%; a partial response). Subsequently, 3 peritoneal nodules were resected with curative intent. Another peritoneal nodule was detected 57 months after the second surgery. After 3 courses of XELOX plus bevacizumab, the nodule decreased in size(reduction rate of 69.0%; a partial response). The nodule was resected with a curative intent. At the last follow-up 135 months after the first surgery, the patient remains alive with no evidence of disease.