[A Case of Esophageal Cancer with Consciousness Disorder Due to Hyperammonemia during FP Treatment].

Hyperammonemia induced by 5-fluorouracil(5-FU)is known as a rare adverse event, but there are few reports of hyperammonemia occurring during FP(5-FU plus CDDP)treatment for esophageal cancer. We report a case of esophageal cancer with consciousness disorder due to hyperammonemia during FP treatment with an examination of some of the relevant literature. The patient was a man of approximately 70 years of age who was received FP treatment. He showed consciousness disorder on day 4. A blood test showed hyperammonemia(427µg/dL), which was considered to be the cause of his consciousness disorder. He was treated with branched chain amino acid infusion, lactulose and kanamycin and made a full recovery. An operation for esophageal cancer was performed after 3 months and he is currently followed up without recurrence. Hyperammonemia should be considered as a differential diagnosis of consciousness disorder during chemotherapy including 5-FU.

[A Case of Locally Advanced Unresectable Esophageal Cancer Treated with Nivolumab and Ipilimumab Therapy Followed by Surgery].

In cases of unresectable, locally advanced esophageal cancer, conversion surgery may be considered if chemotherapy produces favorable results and surgical resection is indicated. The use of immune checkpoint inhibitors in chemotherapy for esophageal cancer has expanded, and has increased the number of cases in which conversion surgery becomes possible. The patient in the present report had received a diagnosis of Stage Ⅳa esophageal carcinoma, and a prior nephroureterectomy discouraged the administration of platinum-based agents. Nivolumab and ipilimumab were administered as induction chemotherapy. Despite the achievement of stable disease, the patient's esophageal stricture deteriorated, necessitating surgical intervention. The resected specimen revealed that fewer than 50% of malignant cells remained viable and residual cancer cells were noticeably absent, particularly in the enlarged lymph nodes. We herein present the details of this case and discuss the literature concerning surgery following immune checkpoint inhibitor therapy.

[A Case of Synchronous Solitary Splenic Metastasis of Sigmoid Colon Cancer Treated with Laparoscopic Resection].

An 82-year-old woman presented to our hospital with chief complaints of lower abdominal pain and nausea. Contrast- enhanced CT showed ileus of sigmoid colon cancer and a solitary splenic tumor. A metallic stent was placed for the primary lesion. FDG-PET showed high FDG accumulation in the solitary splenic tumor, and synchronous solitary splenic metastasis was diagnosed. Laparoscopic sigmoid colectomy and laparoscopic splenectomy were performed without changing the intraoperative position or port arrangement. Postoperative progress was favorable. The patient was discharged 9 days after surgery, and no sign of recurrence has been observed to date, at 4 months after surgery. Solitary splenic metastasis of colorectal cancer is extremely rare. This is the first case report of synchronous solitary splenic metastasis of colorectal cancer treated with laparoscopic resection in Japan. This procedure is considered effective and minimally invasive. We review and discuss the Japanese literature on this rare disease.

Self-expandable Metal Stent as a Bridge to Surgery for Colorectal Cancer: Safety and Oncological Outcomes.

BACKGROUND/AIM: Self-expandable metal stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer (CRC) raises concerns regarding the short-term as well as oncological outcome. The present study aimed to investigate the safety of SEMS placement and risk factors of worse short-term and oncological outcomes as BTS. PATIENTS AND METHODS: Twenty-four patients with obstructive CRC who underwent SEMS placement as BTS were included. Success rate of SEMS placement and 2-year relapse-free survival (RFS) rates in stage II/III BTS patients were assessed. RESULTS: Technical and clinical success rates for SEMS placement were 100% and 87.5%, respectively. In Multivariate analyses, longer tumour length, longer interval to surgery, and angular positioning were risk factors related with the complication of stent placement. Two-year RFS rates were significantly higher in the no-complication than in the complication group (100% vs. 75%, log-rank test, p<0.01). CONCLUSION: A long tumour length, long interval between SEMS insertion and surgery, and angular positioning of the SEMS were identified as risk factors for SEMS-related complications. Moreover, SEMS insertion and/or surgery complications were associated with worse oncological outcome in CRC patients.

Methylation of bone morphogenetic protein 2 is associated with poor prognosis in colorectal cancer.

The present study investigated aberrant methylation in colorectal cancer (CRC) and its impact on characteristics and prognosis of patients with CRC. Bone morphogenetic protein 2 (BMP2) was identified as a target gene in oligonucleotide microarray expression profiling in a previous study. Subsequently, the BMP2 methylation status was assessed in 498 patients with stage I-III CRC using methylation-specific polymerase chain reaction, and the association between BMP2 methylation status, patient characteristics and prognosis was assessed. BMP2 methylation was observed in 302/498 (60.6%) patients and was associated with positive lymph nodes and venous invasion (P<0.05). In the stage III subgroup, overall survival (OS) was significantly worse in the methylated BMP2 group compared with in the unmethylated BMP2 group (P=0.012). BMP2 methylation was identified as an independent factor for poor OS in stage III patients (P=0.041). Notably, in the left-sided stage III CRC subgroup, relapse-free survival and OS were significantly worse in the methylated BMP2 group than in the unmethylated group (P=0.048 and P=0.031, respectively). In conclusion, DNA hypermethylation of BMP2 was a poor prognostic factor in patients with stage III disease, particularly in those with left-sided stage III CRC. BMP2 methylation may be a biomarker for prognosis prediction and treatment decision-making.

[Case Report of Long-Term Clinical Efficacy of Paclitaxel plus Bevacizumab Combination Therapy for Stage â £ AdvancedBreast Cancer].

A 50-year-old woman had noted a mass in her right breast 2 years ago but did not consult a hospital. She consulted our hospital because the mass increased in size and also reddened. The tumor measured 10 cm in diameter and was palpable in the whole right breast. A core needle biopsy was performed, and invasive ductal carcinoma was diagnosed. CT showed multiple lung and liver metastases and bone scintigraphy showed bone metastases in a rib. Because the lung and liver metastases were life-threatening, paclitaxel(PTX)chemotherapy was administered weekly. Biomarkers analysis revealed ER(+), PgR(+), HER2(2+), HER2 FISH 1.27, Ki-67 30%, and bevacizumab (Bev) was added from 2 courses. After 4 courses of chemotherapy, the multiple lung and liver metastases were found to be significantly reduced on CT. Toxicities included alopecia, hypertension, and proteinuria. At this time, 3 years after the treatment started, PTX plus Bev combination therapy was also administered.

[Two Cases of Rectal Cancer with Pelvic Local Recurrence Complicated with Sepsis after Rectal Cancer Surgery Successfully Treated with Radiation Therapy].

Treatment of rectal cancer with postoperative pelvic recurrence may complicate infection and may be difficult to treat. We experienced 2 cases complicated with sepsis due to infection in the pelvic local recurrence in which radiation therapy was performed and they were shifted to outpatient molecular-targeted drug therapy. Case 1 involved a 58-year-old woman. In December 2011, colostomy and chemotherapy were performed for locally advanced rectal cancer. In June 2012, we performed low anterior resection. In January 2014, chemotherapy was started for pelvic recurrence. She discontinued treatment for 4 months due to personal circumstances. Recurrence was worsened, and infection caused sepsis and she was admitted to the hospital in February 2017. Infection was not improved with antibiotic drugs, and radiation therapy(60 Gy/30 times)was performed. Infection was improved, and panitumumab monotherapy was started and she was discharged. Case 2 involved a 61-year-old man. In February 2014, a lower anterior resection for rectal cancer was performed. In September 2015, chemotherapy was started for pelvic recurrence. In November 2016, chemotherapy was discontinued due to esophageal variceal rupture. Recurrence was worsened, and infection caused sepsis and he was admitted to the hospital in May 2017. Radiation therapy(50 Gy/20 times)was performed after colostomy. Infection was improved, and cetuximab monotherapy was started and he was discharged.

[Long-Term Survival of a Case with Brain and Lung Metastases from Resected Rectal Cancer by Gamma Knife Radiosurgery].

A 69-year-oldfemale hadund ergone low anterior resection for rectal cancer(Rb). Histological examination showedwell differentiated adenocarcinoma with lymph node metastasis. Adjuvant chemotherapy with UFT was performed postoperatively. Nineteen months later, abdominoperineal resection was performedfor anastomotic recurrence andS -1 chemotherapy was made. As 2 left lung metastases appearedat the 44 months after first surgery, capecitabine was performedfor 4 years. At the 101 months after first surgery, sensory difficulty of right lower limb appearedandMRI revealedbrain tumor(single, 18mm) in the left parietal lobe. We performedgamma knife radiosurgery for the brain metastasis andmultiagent chemotherapy for lung metastases. Although the brain metastases have relapsedtwice, gamma knife providedgoodlocal control. She is surviving without symptom of brain metastases 37 months after the detection.

[Two Cases of Colon Cancer with Severe Liver Dysfunction Due to Multiple Liver Metastases Effectively Treated with Hepatic Arterial Infusion Chemotherapy plus CetuximabFollowed by Systemic Chemotherapy].

Case 1: An 80-year-old man was diagnosed with cecal cancer plus multiple liver metastases and peritoneal disseminations. He underwent surgical resection of the primary tumor to prevent bowel obstruction. Initially, hepatic arterial infusion(HAI) plus cetuximab(Cmab)was administered to reduce the size of the metastatic tumors and prevent liver failure. A partial response(PR)was observed in the liver metastases after 12 courses of treatment and S-1 plus oxaliplatin(SOX)plus bevacizumab was started. Case 2: A 44-year-old man was diagnosed with sigmoid colon cancer with multiple liver, lung and bone metastases, and with obstructive jaundice and cholangitis due to severe liver hilum lymph node metastases. His performance status(PS)score was 3 because of severe liver damage. Initially, he underwent endoscopic nasobiliary drainage for obstructive jaundice, and HAI plus Cmab was started to prevent liver dysfunction and to control all metastases. A PR in the metastatic liver tumors was observed after 18 courses. His PS increased to 1 and he was treated with mFOLFOX6 plus Cmab. HAI plus Cmab might be a treatment option for patients who have RAS-wild type tumors with severe liver dysfunction due to multiple liver metastases; HAI is intended to have few side effects and has a high local control rate.

[A Case of Metastasis to the Base of the Skull after Rectal Cancer Operation with Symptom Management via Radiotherapy].

In 2009, A 67-year-old woman underwent high anterior resection for rectal cancer(RS, type 2, pT3, pN1, cM0, pStage III a). U FT/LV was administered for 6 months as adjuvant chemotherapy after the operation. Because peritoneum dissemination and pelvic lymph node metastasis developed 9 months after the operation, CapeOX plus Bmab therapy was started, and we monitored the cancer partial response for the next 6 years. Six years and 9 months after the operation, we detected metastasis to the sacrum; thus, radiotherapy was started. Seven years after the first operation, we detected pulmonary, liver, distant lymph node, and subcutaneous metastasis. Additionally, in the next month, she complained of double vision and dysarthria, and metastasis to the base of the skull was diagnosed via head MRI scanning. We started radiotherapy, and the symptoms gradually improved. Although we started IRIS plus Bmab therapy for pulmonary, liver, distant lymph node, and subcutaneous metastasis, it became a progressive disease(PD). She passed away 7 years and 6 months after the first operation. In this case, radiotherapy was useful for symptom management of metastasis to the base of the skull after surgery for rectal cancer, which is an extremely rare occurrence.

[Resection of Pancreatic Metastasis from Renal Cell Carcinoma 21 Years after Nephrectomy].

We report a case where resection was performed for pancreatic metastasis from renal cell carcinoma 21 years after nephrectomy. A 72-year-old man had undergone total gastrectomy with distal pancreatomy and splenectomy for gastric cancer, and right nephrectomy for primary renal cell carcinoma in 1993. Incidentally, a CT scan performed in 2014 revealed a tumor in the head of the pancreas. Enhanced MRI suggested that the tumor contained some fat tissue. The tumor in the pancreatic body had sharp margins; therefore, we performed subtotal pancreatectomy. The tumor was considered pancreatic metastasis from renal cell carcinoma. Pathological findings indicated clear-cell type carcinoma(G1-G2), which is very similar to renal cell carcinoma. We diagnosed pancreatic metastasis from renal cell carcinoma. The patient has remained well, with no recurrence 20 months after the pancreatectomy.

[A Case of Brain Metastases from Pancreatic Cancer That Had Been Treated Effectively with FOLFIRINOX].

We report a case of multiple brain metastases from pancreatic cancer, which had responded remarkably to FOLFIRINOX. A 47-year-old man had hypovascular tumors, 25 mm on the body and 23 mm on the uncus of the pancreas; multiple liver metastases; and skin metastasis. A diagnosis of unresectable pancreatic cancer, cT4N3M1 (HEP, LYM, PUL, SKI), cStage Ⅳb was made. We chose FOLFIRINOX for treatment because of his young age and good performance status. After 6 courses, he showed decreasing tumor marker levels, an almost complete disappearance of the primary lesion, and reduced liver metastases. After 8 courses, abnormal behaviors were noted and we performed a head contrast-enhanced MRI, which revealed diffuse enhancement of the cerebral and cerebellar hemisphere. Multiple brain metastases from pancreatic cancer were diagnosed. We made the shift to palliative treatment, but his general condition was worsening and he died a month later, 7 months after the first diagnosis.