[A Case of Lymphoepithelial Cyst of the Pancreas for Which Malignancy Could Not Be Ruled Out Difficult Preoperative Diagnosis].

Lymphoepithelial cyst(LEC)of the pancreas is a relatively rare benign cystic disease of the pancreas. In this report, we describe a case of LEC in which a malignant tumor could not be ruled out by preoperative diagnosis and surgery was performed. The patient was a 72-year-old man. A simple CT scan of the chest and abdomen performed as a follow-up for another disease incidentally revealed a mass in the pancreatic tail. Enhanced CT of the abdomen showed a tumor approximately 3 cm in size at the pancreatic tail with no contrast effect. MRCP showed moderate signal on T2WI, high signal on T1WI, and high signal on T2WI on some cysts inside the pancreas. PET-CT showed slight uptake of FDG. Both tumor markers CEA and CA19-9 were normal. Therefore, malignant disease such as pancreatic IPMC could not be ruled out, and laparoscopic distal pancreatectomy plus splenectomy was performed. The pathology results showed a diagnosis of pancreatic lymphoepithelial cyst with slight differentiation into sebaceous gland.

Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910.

Large-scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted-capture sequencing of 171 potentially colorectal cancer-associated genes was performed, and somatic single-nucleotide variants and insertion-deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra-mutated tumors with POLE mutations. Genes with alterations associated with relapse-free survival were analyzed using multivariable Cox regression models. In all patients (184 right-sided, 350 left-sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty-one tumors were hypermutated (5.8%; 14.1% right-sided, 1.4% left-sided). Modest associations were observed: poorer relapse-free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse-free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse-free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse-free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer.

Clinicopathological features of appendiceal goblet cell adenocarcinoma in Japan: a multicenter retrospective study.

PURPOSE: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. METHODS: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. RESULTS: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4-83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. CONCLUSION: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor.

[A Case of Schwannoma in the Ascending Colon].

A 69-year-old man who was diagnosed with a submucosal tumor in the ascending colon by colonoscopy in X-7 year was presented. The endoscopic biopsy showed normal mucosa, and he had been followed up. During follow-up, computed tomography and colonoscopy performed in X year showed an enlargement of the tumor. Positron emission tomography-computed tomography showed intense FDG uptake. Malignant tumor was suspected, and laparoscopic-assisted right hemicolectomy was performed. The histopathological diagnosis showed spindle-shaped tumor cells proliferating in a fascicular manner. Immunohistochemical staining was positive for S-100 protein and negative for CD34, c-kit, and desmin, and schwannoma was diagnosed. Schwannomas are tumors derived from Schwann cells and therefore rarely develop in the gastrointestinal tract. Careful preoperative diagnosis is important because they do not normally metastasize or undergo malignant transformation.

[A Case of Retroperitoneal Leiomyosarcoma Treated with Repeated Surgical Resection].

A 55-year-old male revealed with a 5 cm-diameter mass in the lower abdomen on ultrasonography incidentally. Computed tomography showed a mass of 7 cm in size on the left side of the bladder. A malignant tumor was suspected, and surgically excised for purpose of diagnosis and treatment. Pathological examination confirmed retroperitoneal leiomyosarcoma, and the resection margins were negative. Follow-up computed tomography scan was performed every 3 months. Repeated resections were performed for twice recurrences within a year after surgery. A year after the first surgery, lung metastasis was detected and chemotherapy was started. Although retroperitoneal leiomyosarcoma is considered to have a poor prognosis, the present case had relatively good prognosis. This may be due to early detection and repeated surgical resection.

[Peritoneal Recurrence of Gastric Cancer Treated with Chemoradiotherapy-A Case Report].

A 76-year-old male patient underwent a distal gastrectomy for advanced gastric cancer. As the postoperative serum CA19-9 level was elevated, chemotherapy was initiated. Computed tomography(CT)detected a solitary peritoneal recurrence in the left subhepatic space 17 months later. Consequently, chemoradiotherapy(CRT)at a total dose of 60 Gy, combined with S-1 therapy, was administered for local tumor control. After CRT, CT scans revealed a remarkable reduction in the peritoneal recurrence. Presently, 8 months after CRT, the patient remains alive with no indications of regrowth. CRT could prove efficacious as a treatment for gastric cancer patients with localized peritoneal recurrences.

[A Case of Pathologic Complete Response Achieved with Preoperative Pembrolizumab Therapy for Transverse Colon Cancer].

A 77-year-old female patient presented with a medical history of 4 cancerous lesions, each with a surgical history. She was referred to our hospital due to anemia. Upon examination, she was diagnosed with transverse colon cancer. Duodenal invasion was suspected, which made performing R0 surgery difficult; therefore, the NAC approach was chosen. Three courses of CAPOX were administered, resulting in tumor obstruction, leading to the formation of an ileum stoma. MSI testing revealed MSI-H, and pembrolizumab treatment was initiated. CT scans showed tumor shrinkage, and PET scans indicated no accumulation, resulting in a cCR. Colon resection including the lesion suspected of stenosis was performed with a strong desire for stoma closure and the determination of potential curative resection. Additionally, a partial resection of the duodenum was performed. Pathological examination did not reveal any evident tumor cells, leading to the determination for a pCR. The patient has been under postoperative surveillance for 1 year without any recurrence.

Risk factors for postoperative proximal deep vein thrombosis and pulmonary embolism after laparoscopic colorectal cancer surgery: analysis of a multicenter randomized controlled trial.

PURPOSE: Postoperative venous thromboembolism (VTE) is a major and potentially fatal postoperative complication of colorectal cancer surgery. However, there is uncertainty about the necessity for anticoagulant prophylaxis to prevent VTE after laparoscopic colorectal cancer surgery because of its associated relatively lower incidence. Currently, anticoagulant therapy is considered mainly for patients at high risk of the development of VTE. Focusing on proximal deep vein thrombosis (DVT)/ pulmonary embolism (PE), we aimed to identify those cases at high risk of the development of fatal VTE. METHODS: We performed an exploratory retrospective analysis to identify the risk factors for postoperative proximal DVT and PE after laparoscopic colorectal cancer surgery in patients included in our prospective trial. RESULTS: A logistic regression analysis revealed factors that could predict the onset of proximal DVT/PE in patients with colorectal cancer. Blood loss and tumor location were identified as the predictors of proximal DVT/PE. CONCLUSIONS: Patients with rectal cancer and those with excessive blood loss during colon cancer surgery must be monitored carefully for signs of VTE and especially proximal DVT/PE, after laparoscopic surgery.

Randomized phase II study of SOX+B-mab versus SOX+C-mab in patients with previously untreated recurrent advanced colorectal cancer with wild-type KRAS (MCSGO-1107 study).

BACKGROUND: Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. METHODS: This randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled. RESULTS: Overall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively). CONCLUSIONS: The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen. TRIAL REGISTRATION: UMIN Clinical Trials Registry ( UMIN000006706 ). Date of registration: NOV/11/2011. URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920.

Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study.

BACKGROUND: For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. METHODS: We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin-eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. RESULTS: Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). CONCLUSIONS: This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC.

Phase II study of 5-fluorouracil-leucovorin plus bevacizumab for chemotherapy-naïve older or frail patients with metastatic colorectal cancer (OGSG 0802).

BACKGROUND: Older or frail patients are often underrepresented in clinical trials for metastatic colorectal cancer (mCRC). We here assessed the efficacy and safety of 5-fluorouracil (5-FU)-leucovorin plus bevacizumab in such patients. METHODS: The study (OGSG 0802) was designed as a single-arm, open-label, multicenter phase II trial. Eligible patients had mCRC and at least one of the following: an age of ≥ 65 years, an Eastern Cooperative Oncology Group performance status of 1 or 2, a serum albumin level of ≤ 3.5 g/dL, incompatibility with oxaliplatin or irinotecan, and a history of abdominal or pelvic radiotherapy. Patients received 5-FU (600 mg/m2) and l-leucovorin (200 mg/m2) on days 1, 8, and 15 together with bevacizumab (5 mg/kg) on days 1 and 15 every 4 weeks. The primary end point was objective response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty-one patients were enrolled and eligible. Median age was 76 years (range 56-90 years), and 51% of patients had a performance status of 0. The ORR was 36.6% [95% confidence interval (CI) 22.1-53.1%], median PFS was 9.4 months (95% CI 7.4-17.7 months), and median OS was 24.0 months (95% CI 19.9 months-not reached). The most common treatment-related adverse events of grade ≥ 3 were neutropenia (24%), anorexia (10%), leukopenia (7%), and mucositis/stomatitis (7%). There were no treatment-related deaths. CONCLUSION: Weekly 5-FU-leucovorin with biweekly bevacizumab may be a tolerable and effective treatment option for older or frail patients with mCRC.

[A Case of Medullary Carcinoma of the Colon with Poor Prognosis].

An 87-year-oldwoman was referredowing to lightheadedness. Severe anemia(Hb 3.9 g/dL)was detected, and colonoscopy revealeda circumferential elevatedlesion at the transverse colon(Group 5, por). The patient was diagnosed with colon cancer(cT4a, N0, M0, Stage Ⅱ), andright hemicolectomy was performed. Immunochemical analysis showedthat the lesion was MLH1- andPMS2- and confirmed a diagnosis of medullary carcinoma. Although the patient was discharged 48 days after surgery without any incident, she was readmitted because of lower leg edema. Liver metastasis and peritoneal dissemination were suspectedon performing computedtomography, andthe patient died3 5 days after readmission. Medullary carcinoma has molecular pathological features such as methylation of the promoter region andassociatedattenuation of MLH1 protein expression, as well as microsatellite instability. The prognosis for medullary carcinoma is relatively good comparedto that for poorly differentiatedad enocarcinoma, though the present case hada poor prognosis. Herein, we report a literature review.

[A Case of Hepatocellular Carcinoma Complicated with Idiopathic Thrombocytopenic Purpura].

The patient was a 72-year-oldwoman. She had been diagnosed with idiopathic thrombocytopenic purpura(ITP), hepatitis B, and diabetes mellitus. She was admitted to our hospital because of anemia andvomiting of blood vomiting and was diagnosed with hepatocellular carcinoma at S6. A splenectomy was performed, with a temporary improvement of her platelet count. We tried to control the platelet count with medication and performed transcatheter arterial embolization(TACE)3 times. However, the tumor size decreased only slightly anda new tumor was observed on S2. Therefore, we increased the patient's platelet count to 109×10 4/mL and performed a partial hepatectomy of 4 lesions. The postoperative complications included intraabdominal abscess, but there was no bleeding and the patient was discharged on POD 114. Platelet count is often difficult to maintain in patients diagnosed with ITP. We report our experiences and also provide a discussion of a case of operated hepatocellular carcinoma complicated with refractory ITP.

[A Case of a Duodenal GIST Observed as a Non-Functional Pancreatic Neuroendocrine Tumor].

A 67-year-oldman was referredto our hospital because his CEA level was increasing. In March 2007, abdominal computed tomography(CT)showedthe presence of a tumor(30mm in diameter)in the pancreatic head. Upon close inspection, the patient was diagnosed with a non-functional pancreatic neuroendocrine tumor and was observed. In September 2016, the patient showedhyperglycemia, liver dysfunction, andelevation of tumor markers. CT revealeda tumor(42mm in diameter) in the pancreatic head. It hadincreasedmore than before. We diagnosedhim with a gastrointestinal stromal tumor(GIST)of the duodenum based on endoscopic ultrasound-guided fine-needle aspiration biopsy and performed pancreaticoduodenectomy. Immunohistochemical staining showedpositive c-kit, andmore than 10%positive MIB-1. Currently, the patient is alive after the surgery.

[Curative Resection for Liver Metastasis Ten Years after Surgery for Rectosigmoid Cancer-A Case Report].

Here, we report the case of a 73-year-oldfemale patient, who previously underwent high anterior resection for rectosigmoidcancer at the age of 63. Her scheduled5 years of follow-up after colorectal surgery hadbeen finished, but she kept undergoing endoscopic mucosal resection for colorectal polyps every 1 or 2 years since then. Blood examination 10 years 6 months after surgery for rectosigmoidcancer revealedthat the value of her serum CEA was 5.5 ng/mL, which was slightly higher than the normal range. Contrast-enhancedCT showedan irregular-shapedtumor with a diameter of 3 cm in which the contrast of the peripheral area was mainly emphasized. When combining the results of MRI and PET-CT examinations, the liver tumor was clinically diagnosed as either intrahepatic cholangiocarcinoma or metastatic liver cancer. Since the first choice of therapy was tumor resection for both diagnoses, S8 subsegmental hepatectomy was performed 10 years 8 months after surgery for rectosigmoidcancer. HE staining of the resectedspecimen showedwell or moderately differentiatedad enocarcinoma, andits immunostaining findings were as follows: CDX-2: positive, CK20: positive, CK7: negative. It was pathologically diagnosed as liver metastasis from rectal cancer. It is rare for colorectal cancer to have metachronous liver metastasis more than 10 years after surgery. However, in any case where a tumor marker for colorectal cancer increases, it is necessary to examine carefully with the possibility of any metastasis in mind.

[Pregnancy-Associated Stage â £ Gastric Cancer with No Recurrence for a Long Time-A Case Report].

A 28-year-oldwoman visiteda clinic with a complaint of epigastralgia 3 months after delivery. She was diagnosedwith gastritis andtreatedwith medication. Two months later, in January 2006, she was admittedto our hospital with a complaint of dysphagia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer in the lesser curvature of the cardia, and abdominal CT scan showed wall thickening of the upper gastric body. No apparent distant metastases were found. The patient underwent total gastrectomy with D2 lymph node dissection in February 2006. Although there was no peritoneal dissemination, the patient testedpositive in peritoneal lavage cytology. The postoperative pathological diagnosis was gastric cancer pT4aN2M1(P0CY1H0), Stage Ⅳ. She was discharged on postoperative day 22. S-1 monotherapy(100mg/day, day 1- 28q6wks)was performedfor 1 year on an outpatient basis. For 13 years and1 0 months after the surgery, no apparent recurrences of gastric cancer have been observed. In gastric cancers associated with pregnancy, it is difficult to distinguish between perinatal symptoms andsymptoms of gastric disease. Therefore, endoscopic examination shouldbe performedfor perinatal patients presenting with persistent gastrointestinal symptoms.

[A Case of Extramedullary Plasmacytoma of the Stomach Detected Due to Severe Anemia].

A 78-year-oldwoman was referredfor exertional dyspnea. Severe anemia(Hb 4.2 g/dL)was detected, and upper endoscopy revealeda giant ulcer at the posterior wall of the gastric body. Computedtomography showeda mass protruding from the gastric wall, suggestive of a submucosal tumor. Although biopsy did not confirm a diagnosis, we performed distal gastrectomy to control the bleeding. The pathological findings and systemic examination confirmed a diagnosis of extramedullary plasmacytoma of the stomach. Plasmacytoma is a tumor of the bone marrow derived from plasma cells that mature from B cells. The frequency of extramedullary plasmacytoma for all plasmacytoma is about 5% and plasmacytoma derived from the stomach occurs in approximately 2%of these cases. Complete resection with lymph node dissection according to the surgical treatment of gastric cancer is recommended. Large tumors, such as that in the present case, may have a poor prognosis; thus, careful follow-up is required for the early detection of recurrence. We report a case of extramedullary plasmacytoma of the stomach with a literature review.

[A Case of Long-Term Control of Stage â £ Gastric Cancer by Multimodal Therapy].

An 82-year-oldwoman was admittedto our hospital because of appetite loss andwas diagnosedwith a Type 3 tumor in the lower gastric body. Pathological examination suggested moderately differentiated adenocarcinoma with negative staining for HER2 by immunohistochemistry. An abdominal CT revealedthickening of the gastric wall andparaaortic lymph node metastases. The clinical findings suggested Stage Ⅳ disease(T4aN3M1). Chemotherapy was administered with a combination of S-1 plus oxaliplatin(SOX). After 2 courses of the SOX regimen, an abdominal CT showed a reduction of the paraaor- tic lymph node metastases, and the CEA level hadd ecreasedto 6.2 ng/mL. After 7 courses of the SOX regimen, the CEA level hadincreasedto 10.1 ng/mL, and the treatment schedule was changed to a regimen of paclitaxel plus ramucirumab(PTX/ RAM). However, grade 4 neutropenia was observed after the first treatment. Distal gastrectomy with D1+lymph node dissection was performedfor local control in September 2016. The post-operative pathological findings were ypT1b2ypN2M1, ypStage Ⅳ and the chemotherapeutic effect was grade 1a. A CT scan revealedregrowth of the paraaortic lymph node 3 months after the operation. Chemotherapy was administered with a combination of capecitabine plus oxaliplatin(CapeOX). At present, the patient is being treatedwith capecitabine monotherapy in the outpatient department with no signs of tumor regrowth.

[Role of Palliative Chemotherapy for Peritonitis Carcinomatosa of Inoperable Advanced Gastric Cancer].

We report a case of peritoneal dissemination of gastric cancer in which the QOL was maintained with a less-than-optimum dose of anticancer agent. A 64-year-old man underwent total gastrectomy for corpus gastric cancer without distant metastasis performedas an open-laparotomy. Peritoneum disseminations were observed in the left sub-diaphragmatic space and back side of the mesocolon, andthe tumor passedd irectly to the superior mesenteric vein of transverse mesocolon. As a first- line chemotherapy, G-SOX therapy(S-1 80mg/day/body and oxaliplatin 100mg/m2)was administered for 15 courses. After these courses, the disease was categorized as PD. Next, RAM/PTX(ramucirumab 8mg/kg andpaclitaxel 80mg/m2) were administered as second-line chemotherapy. However, the PTX, especially causedprolongedad verse effects such as G4- leveledbloodtoxicity andsevere general fatigue. Therefore, we administereda lower dose of PTX than the original optimal minimum dose. This lower dose chemotherapy resulted in effective changes such as decreased pain and general fatigue and resolution of the bloodtoxicity. As a result, the patient's QOL improved, and his condition has been maintained as SD for 2 years after the operation. For these reasons, this ordinary chemotherapy may be used as a palliative chemotherapy.

[A Case of Locally Advanced and Metastatic Breast Cancer Treated with Preoperative Bevacizumab Combination Chemotherapy That Attained Local Control].

We report a case of a 74-year-old woman with a left breast tumor with skin infiltration. Luminal type breast cancer with lung, bone, and parasternal lymph node metastases was diagnosed. She received paclitaxel and bevacizumab treatment. After chemotherapy, the lung metastasis and parasternal lymph node metastasis had disappeared, and the breast tumor had shrunk. Mastectomy and axillary lymph node dissection were performed. She has been receiving post-operative endocrine therapy. Paclitaxel and bevacizumab combination therapy is one of the useful treatments for metastatic breast cancer with skin infiltration.