[Cases of Advanced Colorectal Cancer with Nephrotic Syndrome after FOLFIRI plus Ramucirumab Administration].

We report 2: Cases of advanced colorectal cancer that developed nephrotic syndrome after ramucirumab(RAM)administration. Case 1: A 54-year-old woman with rectal cancer, liver and lung metastases, and peritoneal dissemination underwent sigmoid colon double-barrel colostomy for perforation management. The patient received 15 postoperative CAPOX plus bevacizumab(Bev)courses. FOLFIRI plus RAM was introduced as the second-line treatment. After 2 courses, the patient showed marked proteinuria and hypoalbuminemia and was diagnosed with nephrotic syndrome. The patient's condition improved promptly with administrating diuretics and antihypertensive drugs. Case 2: A 72-year-old man underwent sigmoid colon cancer resection with duodenal infiltration. Despite the treatment, a tumor was identified at the radial margin(RM1), with a positive cytological test(CY1)result. Therefore, postoperative mFOLFOX6 plus Bev was administered for 17 courses. FOLFIRI plus RAM was introduced as the second-line treatment due to residual tumor growth. After 2 courses, the patient showed accentuated proteinuria and was diagnosed with nephrotic syndrome and heart failure. The patient's condition improved after administrating diuretics, antihypertensive drugs, and V2-receptor antagonists. In both cases, marked proteinuria was observed after shifting to second-line treatment with two RAM administrations. Therefore, monitoring nephrotic syndrome development during the early RAM introduction stage is essential.

[A Case of Type 4 Ascending Colon Cancer Showing Early Postoperative Lymphangitis Carcinomatosa].

A 56-year-old man was admitted to our hospital because abdominal CT showed wall thickening of the ascending colon. Colonoscopyshowed type 4 colon cancer, diagnosed as poorlydifferentiated adenocarcinoma bybiopsy , with circumferential stenosis. Enhanced CT after admission also showed obstructive ileus and lymphadenopathy leading to a paraaortic lesion, but no other distant metastases were seen. Right hemicolectomywas performed. Histological examination showed poorlydifferentiated adenocarcinoma extending from the hepatic flexure to the terminal ileum, with marked invaded vessels and stromal fibrosis, which was diagnosed as type 4 colon cancer of scirrhous and lymphangiosis types. On the 10th postoperative day, he developed lymphangitis carcinomatosa. Intensive treatment including steroid therapy was not effective, and he died of respiratory failure on the 26th day. Type 4 colon cancer is rare and has very poor prognosis. We report a case and literature review.

[A Case of Type 4 Gastric Cancer with Esophageal Invasion That Responded to Neoadjuvant Chemotherapy Containing S-1 and Oxaliplatin followed by Surgery].

We encountered a case of type 4 gastric cancer with esophageal invasion that responded to neoadjuvant chemotherapy containing S-1 and oxaliplatin(SOX)followed by surgery, which could be curative resection. A 46-year-old man was referred to our hospital because of abnormal upper gastrointestinal series findings. He was diagnosed with type 4 advanced gastric cancer with esophageal invasion, cT4b(diaphragm)N2M0, Stage ⅢC, and 3 courses of neoadjuvant SOX therapy were administered. Adverse events were minor. After NAC, the primary lesion and lymph nodes showed marked reductions on CT; total gastrectomy and subtotal thoracic esophagectomy were performed. The pathological response to NAC was evaluated as Grade 2 in the primary tumor and Grade 3 in the lymph node; overall, NAC showed considerable antitumor effects. The final diagnosis was ypT3N0M0P0CY0H0, StageⅡA, and was judged as curatively resected. Currently, we are continuing to administer adjuvant chemotherapy containing S-1.

[A Study of Patients with Regional Lymph Node Recurrence after Breast Surgery].

Regional lymph node recurrence without distant metastasis after the initial treatment of breast cancer is a relatively rare event. The optimal management for regional lymph node recurrence is poorly understood. We retrospectively evaluated 21 patients who developed regional lymph node recurrence between January 1, 2003 and December 31, 2014. The median interval between regional lymph node recurrence and distant metastasis was 1.0 years(range, 0.4 to 2.5 years). On followup, 15 cases(71.4%)were found to eventually develop distant metastases. Median follow-up time after lymph node recurrence was 1.8 years(range, 0.4 to 20.3 years). The 2-year survival rate after regional lymph node recurrence was 65.5%. The mean distant-disease-free interval was 2.2 years in patients with estrogen receptor(ER)-positive tumor(n=10)and 0.7 years in patients with ER-negative tumor(n=11). The distant-disease-free interval after regional lymph node recurrence was significantly shorter in patients with ER-negative tumor than in patients with ER-positive tumor(p=0.008). The 2-year survival rate after regional lymph node recurrence was significantly lower in patients with ER-negative tumor(33.3%)than in patients with ER-positive tumor(100%, p=0.016). This study revealed that regional lymph node recurrence after initial treatment is associated with an increased risk of distant metastasis and death and ER-negative tumors are indicative of a poor prognosis.

[A Case of Gastrointestinal Stromal Tumor(GIST)Originating in the Anal Canal].

We report a case of a gastrointestinal stromal tumor(GIST)that originated in the anal canal. A 70's woman with a subcutaneous tumor reaching from the anal canal was referred to our hospital. After a thorough examination, the tumor was resected percutaneously in the jackknife position. Histopathological examination showed proliferation of spindle-shaped tumor cells arranged in irregular bundles. Immunohistochemical staining showed that the tumor was positive for c-kit and CD34, and negative for a-SMA and S-100, so the tumor was diagnosed as GIST. As a-SMA-positive smooth muscle cells were seen around the tumor, we suspected that this tumor originated from the internal sphincter muscle.

Massive pneumoretroperitoneum arising from emphysematous cholecystitis: a case report and the literature review.

BACKGROUND: Emphysematous cholecystitis is a severe variant of acute cholecystitis caused by anaerobic bacteria. Although intraperitoneal air as a complication has been described in association with emphysematous cholecystitis, pneumoretroperitoneum arising from emphysematous cholecystitis is extremely rare. Herein, we describe a rare case of pneumoretroperitoneum arising from emphysematous cholecystitis that was successfully treated with emergency surgery. CASE PRESENTATION: An 84-year-old male was transported to the Emergency Department of our hospital for acute abdomen. Computed tomography revealed acute cholecystitis accompanied by emphysematous change. Computed tomography also revealed massive pneumoretroperitoneum complicated with pneumobilia and gas in the hepatoduodenal ligament. Clinical findings fulfilled the diagnostic criteria for systemic inflammatory response syndrome and sepsis. Emergency surgery was carried out with a diagnosis of both emphysematous cholecystitis and gastrointestinal perforation. Intraoperative findings revealed acute gangrenous cholecystitis and pneumoretroperitoneum presenting with an odor-free foamy abscess along the loose connective tissue behind the ascending colon and mesocolon. No evidence of gastrointestinal perforation was found during surgery. Therefore, cholecystectomy and lavage drainage were performed. Bacterial culture examination isolated a single species of anaerobe, Klebsiella pneumoniae, which was considered to be the cause of emphysematous cholecystitis, pneumobilia, and pneumoretroperitoneum. CONCLUSIONS: Emphysematous cholecystitis should be considered as a possible cause of pneumoretroperitoneum. The present case is the first report of massive pneumoretroperitoneum extending to the dorsal side of the ascending mesocolon as a complication of emphysematous cholecystitis.

Metastatic gastric carcinoma from breast cancer mimicking primary linitis plastica: A case report.

Metastases to the gastrointestinal tract rarely occur in breast cancer except in invasive lobular carcinoma. The present study reports a rare case of metastatic gastric cancer from invasive ductal carcinoma (IDC) of the breast mimicking primary gastric linitis plastica. A 51-year-old premenopausal female, who had a history of partial mastectomy for right breast cancer at the age of 40, was referred to Toyama City Hospital (Toyoma, Japan) for an endoscopic diagnosis of gastric linitis plastica. Abdominal computed tomography (CT) revealed left hydronephrosis, while peritoneal metastasis and malignant ascites were not detected. Chest CT detected a left lung tumor, which had invaded the left upper bronchus. Biopsy specimens were obtained and the histopathological findings on both the gastric tumor and lung tumor demonstrated poorly differentiated adenocarcinoma, whereas the histology of the original breast cancer was IDC with a solid-tubular type. Immunohistochemistry revealed that the biopsied specimens of the gastric and lung tumors were positive for estrogen receptor (ER), progesterone receptor (PgR) and negative for human epithelial growth factor receptor-2 (HER2). These molecular characteristics indicated the case was metastatic gastric carcinoma from the breast cancer with lung metastasis, since the statuses of ER, PgR and HER2 were concordant with those of the original breast cancer. However, the possibility of primary gastric cancer could not be completely ruled out. Therefore, a total gastrectomy was performed for the purpose of both diagnosis and treatment. Pathological examination of the resected specimen provided a definite diagnosis of multiple metastatic gastric carcinomas from the breast. To the best of our knowledge, metastatic gastric cancer derived from the breast presenting as linitis plastica 11 years following the surgical removal of IDC has not been described previously.

Sigmoid colon cancer arising in a diverticulum of the colon with involvement of the urinary bladder: a case report and review of the literature.

BACKGROUND: Colon cancer can arise from the mucosa in a colonic diverticulum. Although colon diverticulum is a common disease, few cases have been previously reported on colon cancer associated with a diverticulum. We report a rare case of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder, which presented characteristic radiographic images. CASE PRESENTATION: A 73-year-old man was admitted to our hospital for macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a sigmoid colon tumor that protruded into the urinary bladder lumen. The radiographs showed a tumor with a characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer with involvement of the urinary bladder was made based on the pathological findings of the biopsied specimens. We performed sigmoidectomy and total resection of the urinary bladder with colostomy and urinary tract diversion. Histopathological findings showed the presence of a colovesical fistula due to extramurally growing colon cancer. Around the colon cancer, the normal colon mucosa was depressed sharply with lack of the muscular layer, suggesting that the colon cancer was arising from a colon diverticulum. CONCLUSION: The present case is the first report of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder. Due to an accurate preoperative radiological diagnosis, we were able to successfully perform a curative resection for sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder.

Life-Threatening Gastrointestinal Mucosal Necrosis during Methotrexate Treatment for Rheumatoid Arthritis.

Methotrexate (MTX), a folic acid antagonist, is widely used in the treatment of neoplasms, psoriasis and rheumatoid arthritis. Despite its efficacy, MTX sometimes finds limited application because of its adverse effects, including renal or liver impairment, bone marrow toxicity and gastrointestinal mucosal injury. Intestinal mucositis, bleeding and peptic ulcers are well-known gastrointestinal adverse effects of MTX, although cases of fatal mucosal necrosis induced by MTX are extremely rare. Here, we report the case of an 82-year-old Japanese woman who developed severe gastrointestinal mucosal necrosis after 8 years of treatment with low-dose MTX (8 mg/week). In the drug lymphocyte stimulation test, MTX showed a strong positive reaction, with a stimulation index of 443% against normal controls. Physicians must be aware of potential drug-induced adverse effects in patients with chronic diseases who are on long-term medication.

Impact of inflammation-metaplasia-adenocarcinoma sequence and prevention in surgical rat models.

The incidence of esophageal cancer continues to rise in the Western world. Prior studies have suggested that gastroduodenal content reflux from gastroesophageal reflux disease induces the inflammation-mediated progression from hyperplasia to metaplasia, and to adenocarcinoma. We further investigated the sequential development of esophageal adenocarcinoma (EADC) with the use of an established surgical rat model. The present paper will describe the impact of the inflammation-metaplasia-adenocarcinoma sequence and chemoprevention in surgical rat models. A clinically relevant rat reflux model was used to investigate the cause of carcinogenesis, the sequential development of adenocarcinoma and chemoprevention with the use of a proton pump inhibitor. We found that duodenal reflux plays an important role in the inflammation-induced transformation of esophageal mucosa to adenocarcinoma. We were able to inhibit this transformation with rabeprazole, a proton pump inhibitor. Duodenal reflux promotes inflammation in the esophagus. The inflammation-metaplasia-adenocarcinoma sequence is important in the progression and development of EADC. Carcinogenesis can be prevented with chemoprevention agents such as rabeprazole. These results will need to be validated in clinical trials.

[A case of advanced colon cancer successfully treated with combination therapy of cetuximab and oxaliplatin, leucovorin, and 5-fluorouracil].

A 65-year-old woman was referred to our hospital for examination of anemia. Colonoscopy showed a type 1 tumor in the ascending colon with nearly complete stenosis that was diagnosed as a tubular adenocarcinoma. Computed tomography (CT) revealed swelling of the regional, periaortic, and celiac lymph nodes and lymphangitis carcinomatosa. The patient was diagnosed as having Stage IV ascending colon cancer, and neoadjuvant chemotherapy was administered to avoid non-curative resection. The patient was treated with cetuximab and oxaliplatin, Leucovorin, and 5-fluorouracil( mFOLFOX6) combination chemotherapy. After 6 courses of chemotherapy, the primary lesion and multiple lymph node swellings greatly reduced in size and lymphangitis carcinomatosa improved. Accordingly, right colectomy with D3 nodal dissection was performed. The patient was recurrence free at her 8-month follow-up examination. Neoadjuvant chemotherapy with molecular targeted drugs is useful in the treatment of patients with unresectable primary cancer.

[A case of locally advanced rectal cancer successfully treated by laparoscopic intersphincteric resection and effective neoadjuvant chemoradiation therapy].

A 74-year-old woman was diagnosed as having lower rectal cancer. Colonoscopy revealed a type 2 circular tumor over 15 cm from the port side close to the dentate line. The patient was diagnosed as having a moderately differentiated adenocarcinoma by biopsy. Computed tomography (CT) and fluorodeoxyglucose (FDG)-positron emission tomography (PET) revealed thickening of the wall from near the anus to the rectosigmoid junction and an increase in the concentration of the surrounding adipose tissue as well as swelling of the left internal iliac lymph nodes with FDG accumulation. The patient was diagnosed as having cSE, cN3, cM0, cStage IIIb rectal cancer. Because the tumor was very close to the anus with advanced extramural invasion and because the patient desired anal sphincter preservation, we performed preoperative chemoradiation therapy( CRT) combined with capecitabine plus oxaliplatin( XELOX) and bevacizumab( BV). Radiation therapy was performed with a linear accelerator( LINAC) for stereotactic radiation therapy( Novalis®). Partial response (PR) was achieved by this therapy. Five weeks after CRT, the patient underwent laparoscopic-assisted intersphincteric resection( total ISR). Pathological examination revealed minimal residual cancer cells( Grade 2, pPR, pA, N0, M0, pPM0, pDM0, pRM0, pStage II). Increased implementation of anus-preserving surgery can be expected owing to the successful control of regional and distant metastases by neoadjuvant CRT. Based on these encouraging findings, we should consider the challenges posed by neoadjuvant CRT for the treatment of lower rectal cancer.

Locally advanced breast cancer made amenable to radical surgery after a combination of systemic therapy and Mohs paste: two case reports.

INTRODUCTION: Chemotherapy and other systemic therapies are the primary treatments for patients with unresectable, locally advanced breast cancer. The clinical application of supportive care using Mohs paste has become widespread for the purpose of improving patients' quality of life. Here, we report two cases of locally advanced breast cancer, for which the patients underwent radical surgery after a combination of systemic therapy and Mohs chemosurgery. CASE PRESENTATIONS: Patient 1 was a 90-year-old Japanese woman with right breast cancer diagnosed as stage IIIB (T4bN1M0). The treatment included Mohs paste application and hormonal therapies. Patient 2 was a 60-year-old Japanese woman with right breast cancer diagnosed as stage IIIB (T4cN2aM0). Her treatment included Mohs paste application, together with chemotherapy (four cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, and four cycles of docetaxel). In both cases, a reduction in the primary tumor volume was observed, and radical mastectomy and axillary lymph node dissection were possible without relaxation incision or skin flap. CONCLUSION: We report patients with no distant metastases who were able to undergo radical resection after a combination of systemic therapy and Mohs chemosurgery. For locally advanced breast cancer, Mohs chemosurgery, in addition to multidisciplinary treatment, is useful.

Cholecystomucoclasis: revaluation of safety and validity in aged populations.

BACKGROUND: We evaluated the safety and validity of cholecystomucoclasis (CM) and compared its intraoperative characteristics with those of standard cholecystectomy (SC). METHODS: We enrolled 174 patients who underwent cholecystectomy and retrospectively evaluated the outcomes of patients in the SC and CM groups. RESULTS: Significant differences in age (71.1 vs. 61.9 years), American Society of Anesthesiologists physical status (ASA-PS), and serum C-reactive protein levels (CRP) (18.1 vs. 4.7 mg/dL) were observed between the CM and SC groups. Conversely, no significant differences were observed in the operation time (129 vs. 108 min), amount of blood loss (147 vs. 80 mL), intraoperative complications (0% vs. 5.7%), or duration of hospital stay (13.2 vs. 8.9 days) between the 2 groups. A high conversion rate (35.3%), postoperative complications (33%), and frequent drain insertions (94%) were observed in the CM group. CONCLUSIONS: CM is a safe and valid surgical procedure and surgeons should not hesitate to transition to CM for patients who are of advanced age, in poor general condition (high ASA classification), or have high levels of serum CRP.

Xanthogranulomatous gastritis mimicking malignant GIST on F-18 FDG PET.

Xanthogranulomatous gastritis (XGG) is a rare inflammatory lesion of the stomach, with only 11 reported cases worldwide. Furthermore, reports on the use of detailed diagnostic imaging in XGG are not available. Herein, we describe a case of XGG with detailed diagnostic imaging mimicking malignant gastrointestinal stromal tumor (GIST) in light of the current literature. A 79-year-old woman who presented with epigastric pain was referred to our hospital. Upper gastrointestinal endoscopy revealed an elevated lesion similar to a submucosal tumor (SMT). F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed intense FDG uptake in the mass. Additional imaging studies revealed a malignant GIST, which was suspected of having infiltrated the left lobe of the liver. Open surgery was carried out, but tumorous lesions were not found. For exact histopathological diagnosis, partial resection of the thickening gastric wall was performed, and XGG was diagnosed. We conclude that benign conditions, including XGG, should be considered when intense FDG uptake in SMT is found.

Stenotic ischemic colitis treated with laparoscopy-assisted surgery.

Ischemic colitis is the most common type of intestinal ischemia. The etiology of this condition is multifactorial, and the diagnosis is based on a combination of clinical symptoms, as well as endoscopic and histological findings. Although conservative therapy is effective in most cases, surgery still plays a key role in the treatment of ischemic colitis. Here, we describe a case of a 73-year-old man in whom laparoscopy-assisted left colectomy was performed 80 d after the onset of ischemic colitis. He recovered completely after surgery, and the pathological findings were consistent with ischemic colitis. To the best of our knowledge, there are no detailed reports of laparoscopic surgery for chronic segmental stenotic ischemic colitis. We discussed the usefulness of laparoscopic surgery, comparing it with endoscopic treatment, and we propose an optimal treatment strategy from a viewpoint of stenosis length and duration of disease.

Barrett's esophagus and animal models.

The following on Barrett's esophagus (BE) and animal models contains commentaries on the factors of BE carcinogenesis; a duodenoesophageal reflux model; translation of targeted therapies for esophageal adenocarcinoma; and novel target regimens selected through a proteomics screen.

Portal and superior mesenteric venous thrombosis treated with thrombolytic therapy via the superior mesenteric artery and vein.

A 61-year-old man was hospitalized for treatment of portal and superior mesenteric venous thrombosis (PSMVT). We selected interventional radiology (IVR) because there were no signs of intestinal necrosis. The thrombosis was significantly reduced and the patient made progress after we performed thrombectomy via catheter aspiration, and thrombolytic therapy via both the superior mesenteric artery and vein. Even if there are no signs of intestinal necrosis, treatment which prevents intestinal necrosis is vital. In the present case, single-stage IVR therapy via both the superior mesenteric artery and vein improved the therapeutic outcome of PSMVT.

False-Positive Mediastinal Lymphadenopathy on 18F-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography after Rectal Cancer Resection: A Case Report of Thoracoscopic Surgery in the Prone Position.

(18)F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (integrated FDG PET/CT) has been used to diagnose recurrence and differentiate postoperative changes from lymph node metastasis in colorectal cancer, although its accuracy is questionable. We report a prone thoracoscopic surgery for a rectal cancer patient in which false-positive mediastinal lymph nodes were found on FDG-PET/CT. A 60-year-old man underwent a laparoscopic high anterior resection and D3 lymph node dissection for rectal cancer. The histopathological diagnosis was moderately differentiated adenocarcinoma of the rectum, stage IIIB (pT3N1M0), necessitating oral fluoropyrimidine agent S-1. After the primary surgery, a solitary mediastinal lymph node measuring 30 mm in diameter was detected, and abnormal accumulation was confirmed by FDG-PET/CT (SUV(max), 11.7). Thoracoscopic resection was performed in the prone position, but histopathological results showed no metastasis. He was subsequently diagnosed with reactive lymphadenitis. The patient was discharged on postoperative day 4 in good condition and is alive without recurrence 12 months after surgery. PET/CT is useful for the detection of colorectal cancer recurrence; however, it does have a high false-positive rate for mediastinal lymph nodes. There is a limit to its diagnostic accuracy, and one must determine the indication for surgical treatment carefully. Surgery in the prone position is a useful and minimally invasive approach to the mediastinum and allows aggressive resection to be performed.

Inflammation-related carcinogenesis and prevention in esophageal adenocarcinoma using rat duodenoesophageal reflux models.

Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.