A case of superficial spreading type of poorly differentiated adenocarcinoma of the stomach with invasion to the esophagus.

BACKGROUND: Invasion is more likely to occur in gastric cancer affecting larger areas. Poorly differentiated adenocarcinoma tends to invade deep. The cardiac region prefers submucosal invasion because the submucosa is coarser than the other regions. CASE PRESENTATION: A 75-year-old man presented with a chief complaint of abdominal discomfort and weight loss. Esophagogastroduodenoscopy revealed an irregular ulcerative lesion with partial redness of the upper body and lesser curve of the stomach. A continuous shallow depressed lesion invaded the abdominal esophagus by approximately 40 mm. Poorly differentiated adenocarcinomas (por, sig) were observed on biopsy. Grossly, the cancer appeared to extend into the muscle layer; however, we could not confirm invasion into the muscle layer in our biopsy tissue. We diagnosed the lesion as a superficial spreading type of advanced gastric cancer and performed a total gastrectomy, D2-lymph node dissection (spleen preservation), Roux-en-Y reconstruction, and cholecystectomy. Postoperative histopathological examination revealed extensive infiltration of poorly differentiated adenocarcinoma (90 mm × 55 mm), and all were intramucosal lesions. The final pathological diagnosis was T1a, N0, M0, and Stage IA. The postoperative course was uneventful and the patient was discharged on postoperative day (POD) 11. Five years have passed since the operation, and the patient is alive without recurrence. CONCLUSION: We encountered a case of gastric carcinoma in which poorly differentiated adenocarcinomas expanded extensively. All lesions were intramucosal.

Left thoracoscopic surgery in the prone position for a bronchogenic cyst localized to the lower thoracic esophagus: A case report.

A 60-year-old woman with an abnormality discovered during a chest X-ray was referred to the authors' hospital for diagnosis and treatment. Upon enhanced computed tomography (CT), endoscopic ultrasonography, and magnetic resonance imaging, a tumor on the left side of the lower thoracic esophagus was detected. We diagnosed mediastinum cyst. One year after the first visit, a CT examination confirmed an increase in lesion size. Therefore, surgery was performed using a left thoracoscopic approach in the prone position. Before surgery, 3D models were used for simulation. Excision was performed without leakage of the contents. The histopathological diagnosis was a bronchogenic cyst. The left thoracoscopic surgery in the prone position is an uncommon approach but is useful for resecting tumors in the left side of the lower mediastinum. The authors were well-prepared and able to perform safe and reliable surgery.

Pseudocirrhosis after chemotherapy for gastric cancer with diffuse liver metastases: A case report.

Pseudocirrhosis is a rare but important complication of metastatic cancer. We herein present the case of a patient with pseudocirrhosis occurring after a complete response to chemotherapy for metastatic gastric cancer was achieved. A 72-year-old man was diagnosed with gastric adenocarcinoma with multiple liver metastases. The patient's general condition was good, with an Eastern Cooperative Oncology Group performance status of 1. Chemotherapy with oxaliplatin and S-1 was initiated and, after four cycles, the patient noticed sudden abdominal distension. Despite the marked regression of the liver metastases, massive ascites, segmental atrophy and esophageal varices developed, findings consistent with pseudocirrhosis. The patient achieved complete response for the primary and metastatic lesions. Following endoscopic ligation of the varices, he underwent subsequent chemotherapy with S-1 only and management of his ascites for 6 months. At 12 months after initial chemotherapy, the patient appeared to be disease-free. In conclusion, clinicians should be aware of the possibility of pseudocirrhosis in cases of cancer metastasis to the liver, including metastatic gastric cancer.

Phase II Study of Preoperative Chemoradiotherapy With S-1 Plus Oxaliplatin for Locally Advanced Rectal Cancer (PerSeUS-RC01).

BACKGROUND/AIM: We report the end results of a study evaluating the safety and efficacy of preoperative chemoradiotherapy with S-1 plus oxaliplatin. PATIENTS AND METHODS: Eligible patients had histopathologically confirmed locally advanced rectal carcinoma (LARC; cT3-T4, any N). They received oral S-1 (80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and oxaliplatin by infusion (50 mg/m2/day on days 1, 8, 22, and 29) along with radiotherapy (1.8 Gy/day, total dose: 45 Gy/25 fractions). A chemotherapy gap was included in the third week of radiotherapy. The study endpoint was pathological response rate (Grade 2, 3). Secondary endpoints included rates of pathologic complete response (pCR), R0 resection, disease-free survival (DFS), overall survival (OS), local and distant recurrence, and safety and relative dose intensity. RESULTS: The study enrolled 23 patients at three Centres in Gifu, Japan. All patients received chemoradiotherapy, and 22 underwent surgery. Rates of pathological response, R0 resection, and pathological down-staging were 56.5% (13/23), 95.7% (22/23), and 63.6% (14/22), respectively. There were no grade 4 adverse events, but grade 3 events occurred in 21.7% of patients. The cumulative 3-year local recurrence rate was 8.7%. Distant metastasis occurred in 10 (43.5%) patients, 2 (8.7%) from local recurrence and 2 from secondary pancreatic cancer and lung cancer. There were 8 patients with lung metastasis, 2 with liver metastasis, one with ovarian metastasis, and one with bone metastasis. Three-year rates of DFS and OS were 51.1% (median follow-up 34.3 months) and 91.1% (45.2 months), respectively. CONCLUSION: The study showed high pathological response rate without severe toxicity and good follow-up results. Unexpectedly, however, this regimen could not control local recurrence and distant metastasis. Nevertheless, adding oxaliplatin to preoperative chemoradiotherapy with S-1 in patients with LARC appears feasible and may safely result in better local control than standard treatment. The study suggests adding treatment with induction chemotherapy in consideration of CEA level and N factor.

The Significant Role of Cyclin D1 in the Synergistic Growth-inhibitory Effect of Combined Therapy of Vandetanib with 5-Fluorouracil for Gastric Cancer.

BACKGROUND: 5-Fluorouracil (5-FU) has been a mainstay of chemotherapy for gastric cancer. Vandetanib is a tyrosine kinase inhibitor with inhibitory activity against vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR). We investigated the combination effect of vandetanib with 5-FU on gastric cancer cells. MATERIALS AND METHODS: Anticancer efficacy was assessed by 3-(4,5-dimethyl-2-tetrazolyl)-2,5-diphenyl-2H tetrazolium bromide assay of five gastric cancer cell lines, MKN1, MKN7, MKN45, MKN74, and TMK1. Signal expression was examined by western blot, and the cell-cycle distribution was assessed by flow cytometry. In vivo anticancer activity of vandetanib with/without 5-FU was tested in MKN74 cells on nude mice. RESULTS: Vandetanib inhibited the growth of all cell lines. In MKN7 and MKN74 cells, the combination of 5-FU and vandetanib had synergistic effects, but effects were only additional against the other cell lines in vitro. Combination chemotherapy in vivo also significantly inhibited tumor growth compared to single use of each drug. Flow cytometry showed vandetanib increased the proportion in the G1 phase, and in MKN74, combination therapy increased the early S phase and caused bimodal peaks in the G1 phase. The level of expression of cyclin D1 was clearly strong in MKN7 and MKN74 in the natural state, and the expression of cyclin D1, E2 promoter binding factor 1 and thymidylate synthase (TYMS) was inhibited by vandetanib, but not in MKN1 cells. The synergistic effect disappeared in MKN7 and MKN74 cells in vitro when cyclin D1 was knocked-down by siRNA. CONCLUSION: The synergistic effect of vandetanib with 5-FU is related to vandetanib-induced reduction of TYMS via down-regulation of cyclin D1. Hyperexpression of cyclin D1 might be a biomarker of the synergistic effect.

A single case of single-port access laparoscopic appendectomy during the puerperium.

Laparoscopic appendectomy is now widely practiced for the treatment of acute appendicitis. As result of increased demand for minimally invasive surgery, single-incision access was introduced and is being performed in various abdominal surgeries. Conventional laparoscopic appendectomy (LA) is gradually being performed in pregnant women. A 33-year-old woman was referred to our department at 39 weeks and 1 day of gestation due to abdominal pain. She was aware of her gastroepiploic pain even after the delivery. Though it was past 2 days, she was not recovering from right lower abdominal pain, so she was transferred to the Department of Gynecology at our hospital on the same day. Although an antibiotic was administered, the right abdominal pain did not improve, and she was referred to our department from the Department of Gynecology. We performed single-port LA (SP-LA). The total operation time was 63 minutes, and the estimated blood loss was 0 mL. She was discharged with no complications on postoperative day 7. We report our initial experience with single-port LA (SP-LA) using the glove technique for treatment of acute appendicitis in a postpartum woman. SP-LA using the glove technique was performed successfully during the puerperium without prolongation of operation time. This approach is less invasive, offers a much better cosmetic result than with conventional methods, and can be performed safely and at low cost.

A case report on efficacy of Abound™ for anti-EGFR antibody-associated skin disorder in metastatic colon cancer.

BACKGROUND: Panitumumab is a full human epidermal growth factor receptor (EGFR) monoclonal antibody, an agent for metastatic colorectal cancer therapy. One of the most general adverse events of anti-EGFR monoclonal antibody therapy is skin disorder. At the present time, although prophylaxis of skin disorder is important for continuation of cancer therapy, there are no effective precautionary treatments. CASE PRESENTATION: A 73-year-old male with sigmoid colon cancer and synchronous lung metastasis was treated with panitumumab, an alone anti-EGFR monoclonal antibody as the third-line therapy.During the nine courses of the therapy, the response was stable disease (SD), but skin disorder gradually appeared obviously (CTCAE version 4.0: Grade 2). After 1 month of administration of Abound™, symptoms of the skin disorder improved (CTCAE version 4.0: Grade 1), thus the antibody therapy could be continued. CONCLUSION: We report that Abound™ was apparently effective in the treatment for anti-EGFR antibody-associated skin disorder. In the future, Abound™ could be expected as an agent for skin disorder as one of the side effects of colorectal cancer therapy.

Efforts to advance surgical treatments for patients with familial adenomatous polyposis for 40 years in a cancer hospital.

BACKGROUND/AIMS: There have been numerous studies on surgical procedures for familial adenomatous polyposis (FAP), but the evolution in surgical treatments as they pertain to the major perioperative item, i.e., complications, as well as advantages and disadvantages of surgery, in only one institution have not been reported. We examined this surgical treatment evolution in FAP patients. METHODOLOGY: We enrolled 67 FAP patients who had undergone surgery and classified them into three groups, i.e., early phase (1965 to 1977), intermediate phase (1978 to 1987), and late phase (1988 to 2004). We assessed clinicopathological findings and outcomes in these three groups. RESULTS: With the passage of time, surgical techniques and therapeutic benefits improved, but the overall survival rates of early and late phase patients were significantly better than that of intermediate phase patients. CONCLUSION: As the surgical techniques improved, patient stress diminished but outcomes in the late period were not always better than in the early period. Surveillance has been enhanced by the increased prevalence of colonoscopy and genetic research has also contributed to better disease management. It is necessary to research the prognosis of FAP patients in the future.

Decreased FANCJ caused by 5FU contributes to the increased sensitivity to oxaliplatin in gastric cancer cells.

BACKGROUND: Oxaliplatin is effective against many types of cancer, and the combination of 5-fluorouracil (5FU) and oxaliplatin is synergistically effective against gastric cancer, as well as colon cancer. The FANCJ protein is one of the Fanconi anemia (FA) gene products, and its interaction with the tumor suppressor BRCA1 is required for DNA double-strand break (DSB) repair. FANCJ also functions in interstrand crosslinks (ICLs) repair by linking to mismatch repair protein complex MLH1-PMS2 (MutLα). While oxaliplatin causes ICLs, 5FU is considered to cause DSBs. Therefore, we investigated the importance of FANCJ in the synergistic effects of oxaliplatin and 5FU in MKN45 gastric cancer cells and the derived 5FU-resistant cell line, MKN45/F2R. METHODS: MKN1, TMK1, MKN45, and MKN45/F2R (5FU-resistant) gastric cancer cells were treated with 5FU and/or oxaliplatin. The signaling pathway was evaluated by a western blotting analysis and reverse transcription polymerase chain reaction (RT-PCR). Drug resistance was evaluated by the 3-(4,5-dimethyl-2-tetrazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. RESULTS: In MKN45 cells, the combination of 5FU and oxaliplatin had synergistic effects. DSBs appeared when the cells were treated with 5FU. FANCJ was down-regulated, and BRCA1 was induced in a dose- and time-dependent manner. MKN45 cells showed increased sensitivity to oxaliplatin when FANCJ was knocked down by short interfering (si) RNA. However, these findings were not observed in MKN45/F2R 5FU-resistant cells. CONCLUSION: These results strongly suggest that the decrease in FANCJ caused by 5FU treatment leads to an increase in sensitivity to oxaliplatin, thus indicating that the FANCJ protein plays an important role in the synergism of the combination of 5FU and oxaliplatin.

Extracellular signal-regulated kinase and Akt activation play a critical role in the process of hepatocyte growth factor-induced epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) has recently been studied to elucidate mechanisms of the liver metastatic process. We investigated EMT in the process of liver metastasis and the effects of chemotherapy on EMT cells as therapeutic strategy for colorectal liver metastasis. We used the CT26 murine colorectal carcinoma cell line to create an in vivo mouse liver metastasis model. Liver tumors were stained immuno-histochemically. Expression of proteins associated with TGF-ß/Smad and hepatocyte growth factor (HGF)/c-Met pathways were investigated by western blotting. Cells with c-Met mRNA knockdown by siRNA techniques showed clearly reduced liver metastases compared with regular cells at 21 days. TGF-ß and HGF induced EMT expression, but signal transduction was quite different. TGF-ß induced ERK, but not Akt phosphory-lation. HGF mediated both ERK and Akt phosphorylation. Akt inhibitor blocked Akt phosphorylation but did not affect TGF-ß-induced activation of ERK, Snail and Slug. U-0126 did not reduce Snail activity by TGF-ß at a concentration to block ERK phosphorylation. However, Akt inhibitor and U-0126 completely inhibited HGF-induced Slug activation. 5-FU mediated cell death in the EMT process induced by TGF-ß more effectively than HGF. ERK/Akt signaling, but not the Smad pathway, may be one of the main processes in HGF-induced EMT, despite the Smad pathway, but not ERK/Akt, being critical for TGF-ß-induced EMT. The MAPK/Akt pathway is indispensable in HGF/c-Met signaling. The ERK/Akt pathway particularly may be critical in the HGF-induced EMT process. However, long-term use of chemotherapeutic agents may induce drug resistance and distant metastases through EMT-related signaling pathway activation.

Growth inhibition of unresectable tumors induced by hepatic cryoablation: report of two cases.

The efficacy of percutaneous cryosurgery (PCS) as a treatment strategy for unresected liver tumor was evaluated in two cases. The first patient was a 64-year-old man who was found to have multiple liver tumors after undergoing gastrectomy for gastric cancer (T3, N0, M0, Stage II). Two PCS treatments under local anesthesia decreased the size of both the treated and untreated tumors. The second patient was a 61-year-old man in whom multiple liver tumors were discovered after hepatectomy for metastases of a duodenal gastrointestinal stromal tumor, which also had been treated surgically. A third surgery was performed for mass reduction. The patient showed stable improvement after surgery, and PCS combined with administration of polysaccharide-Kureha was selected to treat the unresectable tumors. PCS was performed once a week with an overnight hospital stay. After nine PCS treatment, the remarkable reduction in the size and number of liver tumors was observed, even among non-treated tumors. The patient remains in good condition without tumors 21 months after treatment.

Volvulus of the gall bladder diagnosed by ultrasonography, computed tomography, coronal magnetic resonance imaging and magnetic resonance cholangio-pancreatography.

A 54-year-old woman was admitted to our hospital with the complaint of right upper quadrant pain. Upon physical examination the vital signs of the patient were within normal ranges. Ultrasonography and computed tomography (CT) examination of the abdomen was obtained, which demonstrated a large dilatated cystic structure, measuring approximately 68.6 mm multiply 48.6 mm, with marked distension and inflammation. Additionally, the enhanced CT was characterized by the non-enhanced wall of the gallbladder. As the third examination in this study, magnetic resonance imaging (MRI), namely coronal MRI and magnetic resonance cholangio-pancreatogra (MRCP), were performed. The MRCP demonstrated a dilatation of the gallbladder but detected no neck of the gallbladder. Simple cholecystectomy was performed. Macroscopic findings included a distended and gangrenous gallbladder, and closer examination revealed a counterclockwise torsion of 360 degrees on the gallbladder mesentery. Coronal MRI and MRCP showing characteristic radiography may be useful in making a definitive diagnosis.