Assaying ADAMTS13 Activity as a Potential Prognostic Biomarker for Sinusoidal Obstruction Syndrome in Mice.

Sinusoidal obstruction syndrome (SOS) is a serious liver disorder that occurs after liver transplantation, hematopoietic stem cell transplantation, and the administration of anticancer drugs. Since SOS is a life-threatening condition that can progress to liver failure, early detection and prompt treatment are required for the survival of patients with this condition. In this study, female CD1 mice were divided into treatment and control groups after the induction of an SOS model using monocrotaline (MCT, 270 mg/kg body weight intraperitoneally). The mice were analyzed at 0, 12, 24, and 48 h after MCT administration, and blood and liver samples were collected for assays and histopathology tests. SOS was observed in the livers 12 h after MCT injection. In addition, immunohistochemical findings demonstrated CD42b-positive platelet aggregations, positive signals for von Willebrand factor (VWF), and a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in the MCT-exposed liver sinusoid. Although ADAMTS13's plasma concentrations peaked at 12 h, its enzyme activity continuously decreased by 75% at 48 h and, inversely and proportionally, concentrations in the VWF-A2 domain, in which the cleavage site of ADAMTS13 is located, increased after MCT injection. These findings suggest that the plasma concentration and activity of ADAMTS13 could be useful biomarkers for early detection and therapeutic intervention in patients with SOS.

Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.

Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett's esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.

Interleukin-17A derived from mast cells contributes to fibrosis in gastric cancer with peritoneal dissemination.

OBJECTIVES: Interleukin-17A (IL-17A) is pro-inflammatory cytokine and acts as profibrotic factor in the fibrosis of various organs. Fibrosis tumor-like peritoneal dissemination of gastric cancer interferes with drug delivery and immune cell infiltration because of its high internal pressure. In this study, we examined the relationship between IL-17A and tissue fibrosis in peritoneal dissemination and elucidated the mechanism of fibrosis induced by IL-17A using human peritoneal mesothelial cells (HPMCs) and a mouse xenograft model. METHODS: Seventy gastric cancer patients with peritoneal dissemination were evaluated. The correlation between IL-17A and fibrosis was examined by immunofluorescence and immunohistochemistry. A fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells (HPMCs and human gastric cancer cell line MKN-45) into the dorsal side of nude mice. Mice were subsequently treated with or without IL-17A. We also examined the effect of IL-17A on HPMCs in vitro. RESULTS: There was a significant correlation between IL-17A expression, the number of mast cell tryptase (MCT)-positive cells, and the degree of fibrosis (r = 0.417, P < 0.01). In the mouse model, IL-17A enhanced tumor progression and fibrosis. HPMCs treated with IL-17A revealed changes to a spindle-like morphology, decreased E-cadherin expression, and increased α-SMA expression through STAT3 phosphorylation. Moreover, HPMCs treated with IL-17A showed increased migration. CONCLUSIONS: IL-17A derived from mast cells contributes to tumor fibrosis in peritoneal dissemination of gastric cancer. Inhibiting degranulation of mast cells might be a promising treatment strategy to control organ fibrosis.

Analysis of perioperative glucose metabolism using an artificial pancreas.

Hyperglycemia associated with insulin resistance is common in surgical patients with and without diabetes and is associated with poor surgical outcomes. Several studies have recently shown that a closed-loop blood glucose monitoring system in the form of an artificial pancreas is safe and effective for surgical patients. In this study, we analyzed the risk factors for insulin resistance in patients using an artificial pancreas. We investigated 109 patients who underwent surgical management by an artificial pancreas for 24 hours from the start of surgery during either major hepatectomy (MH), defined as resection of more than two liver segments, or pancreaticoduodenectomy (PD). The target glucose range was from 80 to 110 mg/dL using an artificial pancreas. We analyzed the risk factors for and predictors of a high insulin dose, including sarcopenia markers, according to the median 24-hour total insulin infusion. The median total insulin dose and glycemic control rate (GCR), which is the rate of achieving the target blood glucose range, per 24 hours were 78.0 IU and 30.4% in the MH group and 82.6 IU and 23.5% in the PD group, respectively. The muscle volume was the only independent factor in the high-dose subgroup, and the GCR was significantly lower in the high-dose subgroup despite a high insulin dose in both the MH and PD groups. The results of this study suggest that preoperative sarcopenia is closely associated with insulin resistance in the perioperative period. Clinicians must effectively manage sarcopenia, which may result in improved perioperative glycemic control and reduced postoperative complications.

[Intestinal Care Using L‒Glutamine Supplement and Probiotics Can Induce a Strong Anti‒Tumor Immune Response through the Induction of Mature Tertiary Lymphoid Structures in Pancreatic Cancer Patients Receiving Preoperative Chemotherapy].

Most cancer patients receiving chemotherapy are accompanied by gut dysbiosis and intestinal mucosal barrier dysfunction to a greater or lesser degree. These disorders of the gut can easily cause bacterial translocation, resulting in the formation of immunothrombosis composed mainly of neutrophil extracellular traps and activated platelets in hepatic sinusoid in order to trap bacteria. At the same time, however, a lot of alarmin such as HMGB1, S100A8/S100A9 and VEGF‒A which are released from immunothrombosis, promote to recruit many myeloid‒derived suppressor cells(MDSCs)from bone marrow, leading to the strong immunosuppressive milieu in both liver and cancerous lesions. Therefore, intestinal care must be necessary for protection of intestinal barrier integrity during chemotherapy. Recently, we found that intestinal care using oral L‒glutamine‒ enriched supplement and probiotics including Lactobacillus casei Shirota supplement(Yakult®)and Clostridium butyricum MIYAIRI 588 strain(Miya‒BM®)could induce a strong anti‒tumor immune response through the induction of fully mature tertiary lymphoid structures in some pancreatic cancer patients who received 3 cycles of preoperative chemotherapy(gemcitabine 1,000 mg/m2 plus nab‒paclitaxel 125 mg/m2 on days 1, 8, and 15 of 28‒day cycle). In this review article, we discussed the role of intestinal care in the induction of fully mature tertiary lymphoid structures in cancer patients receiving chemotherapy.

[Four Cases of Surgical Treatment for Radiation Enteritis].

Although radiation therapy for pelvic cancer leads to improved outcomes, it may cause radiation enteritis. Radiation enteritis is classified as early and late reaction. Late reaction indicate progressive and irreversible changes caused by ischemic changes of the intestinal mucosa. Severe cases require a surgical treatment, which is challenging because of severe adhesions and a high risk of suture failure. In addition, the postoperative course may be unfavorable in some cases. We performed surgery for 4 radiation enteritis cases; however, the postoperative course was unfavorable in 2 cases because of impaired absorption and ileus of the remaining short bowel. These patients could not eat adequately after discharge; therefore, we needed to explain and make them understand the benefits and disadvantages of radiation therapy.

Comparison of prognostic impact of anatomic location of the pancreas on postoperative pancreatic fistula in laparoscopic and open gastrectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a serious complication after gastric cancer surgery. The current study aimed to investigate the significance of the anatomic location of the pancreas as a predictor for POPF in both laparoscopic gastrectomy (LG) and open gastrectomy (OG). METHODS: In total, 233 patients with gastric cancer were assessed retrospectively. We measured the maximum vertical (P-L height; PLH) and horizontal length (P-L depth; PLD) between the upper border of pancreas and the root of left gastric artery on a preoperative CT in the sagittal direction. The maximum length of the vertical line between the surface of the pancreas and the aorta (P-A length), previously reported as prognostic factor of POPF, was also measured. We investigated the correlations between these parameters and the incidence of POPF in LG and OG groups. RESULTS: Among the patients in this study, 118 underwent OG and 115 underwent LG. In LG, the median PLH and P-A length in patients with POPF were significantly longer compared with those without POPF (p = 0.026, 0.034, respectively), but not in OG. There was no significant difference in the median PLD between the patients with or without POPF in both LG and OG. The multivariate analysis demonstrated that PLH (odds ratio [OR] 4.19, 95% confidence interval [CI] 1.57-11.3, P = 0.004) and P-A length (OR 4.06, 95%CI 1.05-15.7, P = 0.042] were independent factors for predicting POPF in LG. However, intraoperative blood loss (OR 2.55, 95%CI 1.05-6.18, P = 0.038) was extracted as an independent factor in OG. The median amylase level in the drained fluid (D-Amy) were significantly higher in patients with high PLH(≥12.4 mm) or high P-A length (≥45 mm) compared with those with low PLH or low P-A length in LG. However, there were no differences in the D-Amy levels by PLH or P-A length in OG patients. CONCLUSIONS: The anatomic location of the pancreas is a specific and independent predictor of POPF in LG but not in OG. PLH is a simple parameter that can evaluate the anatomic position of the pancreas, and it may be useful for preventing POPF after LG.

Pleomorphic rhabdomyosarcoma of the liver in an adult: a rare case report.

BACKGROUND: Rhabdomyosarcoma (RMS), a malignant neoplasm that normally differentiates to form striated muscle, is the most common type of childhood soft tissue sarcoma. However, it infrequently occurs in adults and is uncommon in the liver. We herein report a case of RMS of the liver in an adult. CASE PRESENTATION: A 73-year-old woman was admitted to our institution for investigation of a hepatic mass. She had been followed for primary biliary cirrhosis for the past 20 years. A contrast-enhanced computed tomography scan of the abdomen showed a 12- × 10-cm heterogeneous low-density mass lesion containing cystic and solid components. A percutaneous liver biopsy was performed, and poorly differentiated cancer containing an RMS cell-like component was observed. The patient was diagnosed with RMS of the liver, and open surgery with right hepatic lobectomy was performed. Histopathological examination confirmed a diagnosis of pleomorphic RMS of the liver. The patient died of rapid progression of the tumor 6 months after the operation. CONCLUSIONS: The tumor site in the present case is rare. The details of this case add to the current evidence base regarding establishment of the standard diagnosis and treatment of this rare condition. We recommend consideration of RMS as a differential diagnosis for hepatic tumors.

[A Case of Stage â £Rectal Cancer with Dyskeratosis Congenita].

A 27-year-old man was diagnosed with dyskeratosis congenita from DKC1 gene mutation at 9 years of age and had been followed-up regularly.An upper gastrointestinal endoscopy performed for vomiting revealed gastric varices.Further examination resulted in a diagnosis of Stage Ⅳrectal cancer with portal hypertension, splenomegaly, liver, and lung metastasis and he was referred to our department.A laparoscopic splenectomy was performed, followed by a laparoscopic low anterior resection for rectal cancer.Subsequently, resection of the pulmonary and liver metastasis was performed, resulting in macroscopic radical resection.However, 3 months after the hepatectomy, unresectable multiple lung metastasis was detected and he received 5 courses of chemotherapy with cetuximab.A grade 3 skin rash was observed and chemotherapy was discontinued. After 5 courses, he had pneumothorax and received drainage.He had sudden respiratory failure 2 days after pleural adhesion therapy of OK-432 was performed.He was diagnosed with interstitial pneumonia induced by OK-432 and steroid pulse therapy, which resulted in his death without improvement 21 days after admission.

[A Case of Histiocytoid Breast Carcinoma Accompanied by Multiple Axillary Lymph Node Metastases].

According to previous reports in our country, histiocytoid breast carcinoma is a very rare case of its tissue type, accounting for only 0.3% of all breast cancer cases. We have neither established a diagnostic standard nor a general idea for these tumors. Previously, its inherited pathology was assumed to be a sub-form of invasive lobular carcinoma. However, some researchers indicate the presence of components that are assumed to originate from milk ducts or differentiation in the apocrine gland. In this way, origins of pathologies for these tumors seem to be complex. Previous reports suggest cases of relatively long survival times without spreading to distant sites. Recently, we encountered one case of histiocytoid breast carcinoma accompanied by multiple axillary lymph node metastases.

[A Case of Thrombotic Microangiopathy Arising from Breast Cancer Treated with Chemotherapy].

The present study reports the case of a 49-year-old woman who was diagnosed with cancer of the left breast at the age of 43 years.Following chemotherapy, the patient had undergone partial mastectomy and axillary lymphadenectomy.Postoperatively, she underwent radiotherapy and hormone therapy.Five years and 4 months after the operation, the patient developed pain in the cervical vertebrae and was diagnosed with spinal metastasis.During the period, she began experiencing fatigue and hematological investigations indicated anemia, as well as thrombocytopenia, jaundice, and schistocytes.The patient was referred to our facility for further examination and treatment.On investigation, she was diagnosed with cancer-related thrombotic microangiopathy(TMA).The patient was advised to undergo chemotherapy due to which symptoms of TMA were relieved.She continued to receive chemotherapy for the following 3 years and 2 months until her death.

Survival benefit of multimodal local therapy for repeat recurrence of thoracic esophageal squamous cell carcinoma after esophagectomy.

BACKGROUND: This study was performed to clarify the optimal therapeutic strategy for recurrent disease after esophagectomy. METHODS: We investigated the prognosis of 37 patients who developed recurrence among 128 patients who underwent curative thoracoscopic esophagectomy (TE) at Kanazawa University Hospital. The prognostic factors after recurrence were examined by univariate and multivariate analyses. RESULTS: Of these 37 recurrences, 29 patients underwent local therapy (surgery, 10 patients; surgery followed by radiation, 2 patients; radiation, 17 patients). Radiation includes intensity-modulated radiation therapy, chemoradiation, and simple radiation therapy. Seventeen patients (58.6%) were considered to have undergone successful therapy by disappearance or diminishment of the targeted region without regrowth. Eleven of 17 patients (64.7%) showed repeat recurrence at another site. Multiple local therapy was performed for repeat recurrence or uncontrollable first therapy. Finally, 57 local therapies were performed. Using multimodal local therapy, 37 (64.9%) of 57 recurrences were successfully managed. The 12 patients treated by surgery as the initial therapy showed the most favorable survival. Seventeen patients who underwent successful initial therapy showed better survival than others. Multiple or miscellaneous organ metastasis, abdominal lymphatic recurrence and best supportive care at recurrence were statistically significant negative variables for survival after recurrence. Performance of surgery and successful therapy as the initial recurrence were statistically significant positive variables for survival after recurrence. Multivariate analysis showed that successful therapy at the initial recurrence was the only independent variable for survival after recurrence. CONCLUSIONS: Multimodal local therapy for repeat recurrence after TE contributes to the improvement of survival after recurrence.

Oral cryotherapy for prophylaxis of oral mucositis caused by docetaxel, cisplatin, and fluorouracil chemotherapy for esophageal cancer.

BACKGROUND: Chemotherapy, including preoperative chemotherapy, plays an important role in the treatment of esophageal cancer. However, although docetaxel, cisplatin, and fluorouracil (DCF) therapy has a powerful antitumor effect, the associated adverse events make it difficult to maintain the patient's general condition. Oral mucositis is an important adverse effect of chemotherapy, and its severity, frequency, and impact on patient quality of life should not be underestimated. This study evaluated the role of oral cryotherapy for prophylaxis of oral mucositis caused by DCF therapy. METHODS: We retrospectively examined the incidence and severity of adverse events, including mucositis, in 72 patients with esophageal cancer treated with DCF. Fifty-eight patients received cryotherapy during docetaxel administration and 14 received no cryotherapy. RESULTS: The incidence of mucositis of all grades and grade 3 was significantly lower in the cryotherapy group compared with the no-cryotherapy group (24.1% vs. 71.4%, P < 0.001 and 0% vs. 28.6%, P = 0.001, respectively). The incidence of anorexia of all grades and grade 3 was also significantly lower in the cryotherapy group (22.4% vs. 57.1%, P = 0.037 and 0% vs. 28.6%, P = 0.010, respectively). CONCLUSION: Adjunctive oral cryotherapy is effective for the prophylaxis and relief of oral mucositis and anorexia caused by chemotherapy.

Use of esophageal stent for the treatment of postoperative gastrointestinal-airway fistula after esophagectomy.

A gastrointestinal-airway fistula (GAF) after esophagectomy is a very serious postoperative complication that can cause severe respiratory complications due to digestive juice inflow. Generally, GAF is managed by invasive surgical treatment; less-invasive treatment has yet to be established. We performed esophageal stent placement (ESP) in three cases of GAF after esophagectomy. We assessed the usefulness of ESP through our clinical experience. All GAFs were successfully managed by ESP procedures. After the procedure, the stent positioning and expansion were appropriately evaluated by radiological assessments over time. The stent was removed after endoscopic confirmation of fistula closure on days 8, 23, and 71. Only one patient with a long-term indwelling stent developed a manageable secondary gastrobronchial fistula as a procedure-related complication. In conclusion, ESP was shown to be a less-invasive and effective therapeutic modality for the treatment of GAF.

Importance of human peritoneal mesothelial cells in the progression, fibrosis, and control of gastric cancer: inhibition of growth and fibrosis by tranilast.

BACKGROUND: Scirrhous gastric cancer is an intractable disease with a high incidence of peritoneal dissemination and obstructive symptoms (e.g., ileus, jaundice, and hydronephrosis) arising from accompanying marked fibrosis. Microenvironmental interactions between cancer cells and cancer-associated fibroblasts are the suggested cause of the disease. We elucidated the mechanisms of tumor growth and fibrosis using human peritoneal mesothelial cells (HPMCs) and investigated the effects of tranilast treatment on cells and a xenograft mouse model of fibrosis. METHODS: HPMCs were isolated from surgically excised omentum and their interaction with MKN-45 gastric cancer cells was investigated using co-culture. Furthermore, a fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells into the dorsal side of nude mice to form large fibrotic tumors. Mice were subsequently treated with or without tranilast. RESULTS: The morphology of HPMCs treated with transforming growth factor (TGF)-ß1 changed from cobblestone to spindle-type. Moreover, E-cadherin was weakly expressed whereas high levels of α-smooth muscle actin expression were observed. TGF-ß-mediated epithelial-mesenchymal transition-like changes in HPMCs were inhibited in a dose-dependent manner following tranilast treatment through inhibition of Smad2 phosphorylation. In the mouse model, tumor size decreased significantly and fibrosis was inhibited in the tranilast treatment group compared with that in the control group. CONCLUSIONS: Tranilast acts on the TGF-ß/Smad pathway to inhibit interactions between cancer cells and cancer-associated fibroblasts, thereby inhibiting tumor growth and fibrosis. This study supports the hypothesis that tranilast represents a novel strategy to prevent fibrous tumor establishment represented by peritoneal dissemination.

Phosphodiesterase III inhibitor attenuates rat sinusoidal obstruction syndrome through inhibition of platelet aggregation in Disse's space.

BACKGROUND AND AIM: Sinusoidal obstruction syndrome (SOS) is a serious drug-induced liver injury. However, the pathophysiology of the disease remains unclear. This study investigated the effects of cilostazol (CZ), a phosphodiesterase III inhibitor, in a monocrotaline (MCT)-induced rat model of SOS. METHODS: Male Wistar rats were administrated MCT to induce SOS. Rats were divided into control, MCT, and MCT + CZ groups. In the MCT + CZ group, CZ was administered at 48 h, 24 h, and 30 min prior to and 8 h and 24 h after MCT administration. The MCT group was treated with water instead of CZ. At 48 h after MCT administration, blood and liver samples were collected to assess biochemistry and liver histology. Expression of rat endothelial cell antigen, CD34, CD41, P-selectin, and caspase-3 in the liver were analyzed. Plasminogen activator inhibitor-1 (PAI-1) in hepatocytes was analyzed using western blotting and polymerase chain reaction. RESULTS: In the MCT group, macroscopic findings showed a dark-red liver surface. Histological findings showed sinusoidal dilatation, coagulative necrosis of hepatocytes, and endothelial damage of the central vein. These changes were attenuated in the MCT + CZ group. Elevated serum transaminase and decreased platelet counts were observed in the MCT + CZ group compared with those in the MCT group. Treatment with CZ reduced MCT-induced damage to the liver sinusoidal endothelial cells, inhibited extravasated platelet aggregation, and suppressed hepatocyte apoptosis around the central vein. CZ attenuated hepatic PAI-1 protein and mRNA levels. CONCLUSIONS: Cilostazol attenuated MCT-induced SOS by preventing damage to liver sinusoidal endothelial cells and extravasated platelet aggregation. Hepatic PAI-1 levels were suppressed with CZ treatment.

Contribution of equilibrative nucleoside transporters 1 and 2 to gemcitabine uptake in pancreatic cancer cells.

Hepatic arterial infusion (HAI) chemotherapy is expected to be a more effective and safer method to treat the hepatic metastasis of pancreatic cancer than intravenous (iv) administration because of higher tumor exposure and lower systemic exposure. To clarify the uptake mechanism of nucleoside anticancer drugs, including gemcitabine (GEM), in pancreatic cancer, we investigated the uptakes of radiolabeled uridine (a general substrate of nucleoside transporters) and GEM in pancreatic cancer cell lines MIA-PaCa2 and As-PC1. Uridine uptake was inhibited by non-labeled GEM and also by S-(4-nitrobenzyl)-6-thioinosine (NBMPR; an inhibitor of equilibrative nucleoside transporters, ENTs) in a concentration-dependent manner, suggesting that ENTs contribute to uridine uptake in pancreatic cancer cells. As for GEM, saturable uptake was mediated by high- and low-affinity components with Km values of micromolar and millimolar orders, respectively. Uptake was inhibited in a concentration-dependent manner by NBMPR and was sodium ion-independent. Moreover, the concentration dependence of uptake in the presence of 0.1 µM NBMPR showed a single low-affinity site. These results indicated that the high- and low-affinity sites correspond to hENT1 and hENT2, respectively. The results indicated that at clinically relevant hepatic concentrations of GEM in GEM-HAI therapy, the metastatic tumor exposure of GEM is predominantly determined by hENT2 under unsaturated conditions, suggesting that hENT2 expression in metastatic tumor would be a candidate biomarker for indicating anticancer therapy with GEM-HAI.

[A Case of Pathological Complete Response Induced by Preoperative Chemotherapy with Gemcitabine plus Nab-Paclitaxel in a Patient with Pancreatic Cancer on Hemodialysis].

A 59-year-old man was admitted to our hospital for further investigation of abnormal uptake in the pancreatic body on positron emission tomography-computed tomography(PET-CT). He had chronic renal failure due to diabetic nephropathy, and had been on maintenance hemodialysis since he was 45-years-old. He was diagnosed with pancreatic body cancer(cT1c, cN0, cM0, cStageⅠa)and was treated preoperatively with neoadjuvant chemotherapy(gemcitabine plus nab-paclitaxel). After 2 courses, we performed distal pancreatectomy. Histopathological examination revealed no viable tumor cells(pathological complete response). The postoperative course was uneventful, and he is alive without recurrence at 6 months after surgery, without adjuvant chemotherapy. Our findings suggest that gemcitabine plus nab-paclitaxel is a useful treatment for patients with pancreatic cancer on hemodialysis.

[A Case of Spontaneous Esophageal Rupture That Required Operation during Adjuvant Chemotherapy for Transverse Colon Cancer].

A 75-year-old male underwent adjuvant chemotherapy with tegafur uracil(UFT)plus Leucovorin(LV)after surgery for transverse colon cancer(pT3pN0M0, ly1, v2, pStageⅡ). Although he had diarrhea(Grade 3)and vomiting(Grade 2)from day 15, he continued to take the medicine at his own discretion. He visited a hospital because of acute renal failure from severe dehydration. He went into shock after evacuation, and the computed tomography(CT)finding suggested a diagnosis of spontaneous esophageal rupture at the lower esophagus. We made a diagnosis of intrathoracic perforation of the esophagus by using thoracic drainage. Then, we performed an operation for mediastinal drainage via a transabdominal approach and the lesser omentum. He started ingestion from POD36 and transferred to another hospital on POD85. He had no disease recurrence in our outpatient care. We think that the spontaneous esophageal rupture occurred because of the frequent vomiting caused by the continued chemotherapy despite the severe side effects. Treatments must be selected by considering patients' life background and medical compliance, and common guidance in taking medications must be provided to elderly patients at the start of chemotherapy.

[A Case of Colon Cancer with Brain, Liver and Lung Metastasis Successfully Treated with Bevacizumab plus Xelox Therapy].

The patient was a 57-year-old woman. Preclinical examination of malignant lymphoma revealed 0-I sp type of early rectal cancer in the upper rectum, 20 cm from the anal margin. Endoscopic mucosal resection was performed and positive deep margins were pathologically diagnosed. Additional intestinal resection with lymph node dissection was deemed necessary, but ABVD therapy was initiated because the clinical stage of the malignant lymphoma was Stage III b or higher. Two months after detecting elevated CEA, S8 liver metastasis was pointed out, and examination of weakness of the right upper limb revealed nodular, multifocal brain metastasis. After chemotherapy for malignant lymphoma, bevacizumab(BV)plus Xelox therapy was initiated. After administering 4 courses, partial loss of multiple brain metastases and reduction of the liver metastatic lesion were confirmed; therefore, partial resection of the liver via laparoscopy was performed. After surgery, BV plus Xelox therapy was resumed, but since the lower lobular lung metastasis was confirmed after 8 courses, partial resection of the left lower lobe with thoracoscopy was performed. After lung resection, BV plus FOLFIRI therapy was administered, and 12 months after the onset of treatment for brain metastasis, recurrence was not detected.