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 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.

Laparoscopic colectomy after transcatheter aortic valve implantation in an elderly patient with obstructive descending colon cancer and severe aortic stenosis: a case report.

BACKGROUND: The demand for laparoscopic colectomy is increasing due to greater number of elderly colon cancer patients, and it is important to evaluate existing comorbidities to ensure perioperative safety. Aortic stenosis (AS) is one of the most common heart diseases in the elderly, and elderly cancer patients with severe AS may be considered ineligible for optimal cancer treatment if they cannot endure surgical aortic valve replacement (SAVR). Recently, transcatheter aortic valve implantation (TAVI) has become a valid option in patients who are high risk for SAVR. We herein present the first case of an elderly cancer patient with severe AS who underwent laparoscopic colectomy after TAVI. CASE PRESENTATION: An 87-year-old woman with a history of multiple cardiovascular diseases was diagnosed with obstructive descending colon cancer and initially underwent colonic stenting. However, as preoperative echocardiography revealed severe AS, she underwent TAVI prior to the colectomy to reduce perioperative risk. TAVI was chosen instead of SAVR due to high SAVR mortality risk, and laparoscopic colectomy was performed 22 days after TAVI. Her postoperative course was uneventful, and she was discharged 14 days later without any deterioration in general condition. No recurrence was observed at more than 1 year, even without adjuvant therapy. CONCLUSION: TAVI facilitated subsequent laparoscopic colectomy in an elderly cancer patient with severe AS. Our case report shows that TAVI may enable further cancer treatment even in patients with severe AS, who may otherwise be considered not suitable for such treatments.

[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 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.

[Follicular lymphoma with nodular lesions mimicking gallbladder carcinoma].

A 68-year-old female was diagnosed with follicular lymphoma (FL) grade 2, based on the excisional biopsy of her enlarged left cervical lymph node. Positron-emission tomography/computed tomography (PET/CT) revealed the 18F-fluoro-deoxyglucose-avid lesions in the sigmoid colon and at the fundus of the gallbladder, besides those in the left neck. A sigmoid colon polyp, which was endoscopically resected, proved histologically to be a well- to moderately-differentiated tubular adenocarcinoma with deep invasion into the submucosa. In addition, nodular lesions of the gallbladder were enhanced on dynamic CT, markedly suggesting gallbladder carcinoma. Among FL, colorectal cancer, and presumed gallbladder adenocarcinoma, FL was considered having the lowest priority of treatment because of its indolent nature and low tumor burden. We performed laparoscopic-assisted sigmoid colectomy, followed by gallbladder bed resection on the same day. Unpredictably, gallbladder lesions were histologically revealed to be FL. Often, FL involves extranodal sites such as the gastrointestinal tracts. However, the gallbladder involvement is extremely rare, and preoperative distinction from gallbladder adenocarcinoma remains challenging to date; this report discusses its characteristics along with the literature review. Furthermore, our case, in which another malignant neoplasm coexisted, needed histological identification of the gallbladder lesions to ascertain the therapeutic strategy.

[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.

[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.

[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 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.

[A Case of Multiple Pulmonary Metastases of Rectal Cancer Controlled with Pulmonary Resection and Stereotactic Body Radiotherapy for Four Years].

A female in her 40s underwent surgical resection for rectal cancer, and metastases in the liver, ovaries, and peritoneum in 2 stages. Multiple pulmonary metastases appeared after the second operation, and right lung middle lobectomy and left lung S8 wedge resection were performed sequentially. Because another metastatic lesion in the right lung S7 was located deep in the parenchyma, stereotactic body radiotherapy(SBRT), instead of surgery, was selected for this lesion and a right lung S8 nodule. SBRT was also performed for a new metastatic lesion in the right lung S6. Local relapse of resected or irradiated lesions was not recognized for 53 months after the first pulmonary resection, and no new lesions appeared for 20 months after the last SBRT. SBRT for pulmonary metastases of colorectal cancer can achieve good survival and local control comparable to surgery and has the advantage of safety and respiratory reserve over surgery. The combination of surgical resection and SBRT for multiple pulmonary metastases is especially beneficial for relatively young patients with jobs and/or children, because it enables patients to maintain good quality of life by avoiding systemic chemotherapy accompanied with adverse events.

[Resection of a Desmoid Tumor Originating from the Greater Omentum after Surgery for Colon Cancer and Liver Metastasis-A Case Report].

Here, we report the case of a 66-year-old male patient who previously underwent resection of sigmoid colon cancer and its liver metastasis. His follow-up contrast-enhanced CT scan revealed a mass shadow at around the gastrosplenic ligament, which gradually increased in size. Because it could not be pathologically diagnosed by transgastric EUS-FNA, en bloc resection wasperformed surgically for the tumor in the greater omentum. Hematoxylin-eosin staining of the resected specimen showed fibroblast-like cellswith hyperplasia of bold collagen fibersand spindle-shaped nucleus. While the immunostaining findings denied a diagnosis of mesenchymal neoplasm such as GIST, leiomyosarcoma, or schwannoma, it was pathologically diagnosed as a desmoid tumor. He has been followed up without any recurrence for 2-and-a-half years after the surgical resection. Desmoid tumors tend to be locally invasive; thus, there is the potential for local recurrence, although the frequency of distant metastasis is very low. In cases in which the tumor increases in size, en bloc resection with sufficient surgical margin should be performed. Cases of desmoid tumors originating from the greater omentum are reportedly rare; however, en bloc resection may be useful for both diagnosis and treatment of tumors of the greater omentum showing increased size that are also surgically resectable.

[A Case of Advanced Gastric Cancer with Synchronous Liver Metastases Responding to Preoperative Combination Chemotherapy with S-1 plus Oxaliplatin(SOX)].

A 67-year-old man was admitted to our hospital because of anemia and weight loss, and diagnosed with a type 3 tumor in the upper gastric body. Pathological examination suggested moderately differentiated adenocarcinoma with immunohistochemically negative staining for HER2. Abdominal CT revealed thickening of the gastric wall and multiple liver metastases. The clinical findings suggested Stage IV disease(T4aN0M1). Chemotherapy was administered with a combination of S-1 plus CDDP(SP). However, the level of CEA(ng/mL)increased from 49.2 to 634.6, and the treatment schedule was changed to a combination of S-1 plus oxaliplatin(SOX). After 3 courses of the SOX regimen, abdominal CT showed a reduction of liver metastases and the level of CEA decreased to 8.4 ng/mL. We performed total gastrectomy with D1 lymph node dissection in September 2016. Post-operative pathological findings were ypStage IV (T3N0M1)and chemotherapeutic effect was grade 2. CT scan revealed regrowth of the tumor in S2 3 months after the operation. The patient underwent transcatheter arterial chemoembolization(TACE)followed by a regimen of paclitaxel plus ramucirumab(PTX/RAM). At present, he is being treated with the PTX/RAM regimen in the outpatient department with no signs of tumor growth. Although the prognosis of gastric cancer with synchronous liver metastases is very poor, it is possible for survival to be prolonged with multimodality therapy.

[A Case of Successful Repeated Metastectomy for Peritoneal Recurrence of over 90 Years Old Colon Cancer Patient].

Treatment for cancer recurrence in elderly people over 90 years old is usually less advantageous in chemotherapy, and surgical resection is considered rather invasive if cure can be expected. We experienced a case of colon cancer in which recurrence of peritoneal dissemination was discovered and resected at the age of 90 years and at 92 years twice. Laparoscopic surgery for colon cancer at the age of 89 years was performed. At 13 months after primary surgery, CT revealed a nodule of 10mm in diameter in the abdominal cavity, and it was also positive in PET-CT. Because there was no other recurrent foci, radical resection was performed. After 14 months(2 years and 4 months after primary surgery), a 17mm large nodule was pointed out and radical resection was done again. Three years later(5 years and 6 months from primary surgery)have passed, she survives without recurrence at 95-years-old and 4 months without any decline in QOL. When recurrence of peritoneal dissemination can obtain radicality in resection, even for elderly persons, surgery should be considered if invasion is minor.

[Curative Resection for Metastatic Lower Rectal Tumor from Ovarian Cancer - Report of a Case].

We here report the case of a 56-year-old female patient who underwent curative resection for right ovarian cancer with intraperitoneal dissemination and liver metastases. She received following adjuvant chemotherapy, and had been visited hospital for regular follow-up since then. One and half a year after surgery, blood examination showed increasing value of CA125. Contrast-enhanced CT scan revealed a tumor whose long diameter was 5 cm at front side of lower rectum. Following MRI and PET-CT examinations indicated the pelvic tumor as recurrence of ovarian cancer, so that laparotomy was carried out. As the tumor was palped through Douglas cavum, we performed low-anterior rectal resection for en bloc tumor extirpation. Tumor cells mainly developed at peri-rectal wall and proper muscle by HE staining of pathological findings, and ER(positive), vimentin(positive), CD56(positive), synaptophysin(negative)and chromogranin A(negative)by immunostaining indicated the tumor as metastasis of ovarian cancer. Though rectal metastasis from ovarian cancer is basically rare, it might be necessary to rule out possibility of metastatic colon tumor from ovarian cancer when treating patient with rectal tumor who had underwent surgery for ovarian cancer before.

[An 85-Year-Old Man with Lymph Node Metastasis of Recurrent Rectal Cancer Treated UsingProton Beam Therapy].

There are few reports that describe the efficacy of proton beam therapy for lymph node metastasis of recurrent rectal cancer, and carbon ion radiotherapy yields higher local tumor control rates. Proton beam therapy needs a longer treatment period but is less toxic to adjacent healthy organs compared to carbon ion radiotherapy. Here we report an 85-year-old man who underwent curative surgery for rectal and sigmoid cancer at the age of 76 years. After 4 years and 2 months, he had liver metastases at S3 and S8, both of which were resected. Eight years and 6 months after primary resection, CT imaging revealed a solitary lymph node metastasis of 28mm in the minor axis, adjacent to the portal vein and IVC. Because of the location and patient's age, proton beam therapy was selected as the treatment strategy, rather than surgery or chemotherapy. A total of 67.5 GyE/25 fx proton beam therapy was applied. CT imaging 4months after irradiation revealed a partial response(PR)and the tumor had shrunk to 8mm. PR continued for 2 years and 1 month. Although the tumor relapsed after 3 years of irradiation and had grown to 16 mm, the patient had no adverse events or symptoms throughout this period. Proton beam therapy may be one of the options for tumors at difficult locations in fragile patients because of its reduced toxicity.

[A Case of Advanced Rectal Cancer Resulting in a Pathologically Complete Response after Neoadjuvant Chemotherapy].

A 61-years-old man was admitted to our hospital because of abdominal pain. Colonoscopy revealed a type 2 tumor in the rectum, which was diagnosed as low differentiated adenocarcinoma. At least 8 abdominal lymph adenopathies were enhanced on contrast-enhanced CT. We diagnosed stage cT3N2H0M0P0, cStage III b. Because of the risk of a poor prognosis, we tried neoadjuvant chemotherapy for the purpose of down staging. A CRT was prevented by Clostridium difficile enteritis, but we completed 80% of the regimen. Laparoscopic abdominoperineal resection was performed after 4 months of chemotherapy. The specimen contained no tumor lesion, and the pathology results were no residue of adenocarcinoma, status postchemoradiation therapy, Grade 3.