Conversion surgery for stage IV gastric cancer: a multicenter retrospective study.

BACKGROUND: Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC. METHODS: A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis. RESULTS: Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011). CONCLUSIONS: CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.

[A Case of Ascending Colon Cancer with Essential Thrombocythemia].

Essential thrombocythemia(ET)is a rare myeloproliferative disorder characterized by thrombocytosis and a risk of thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Including our case, only 5 cases of c o l orectal cancer with ET have been reported in Japan. Herein, we report a case of colon cancer in an ET patient who underwent laparoscopic right hemicolectomy. Our perioperative management avoided complications such as thrombosis or bleeding. An 81-year-old woman developed bloody stools. She was previously diagnosed with ET 9 years ago. Aspirin, cilostazol, and hydroxyurea(HU)were prescribed. Colonoscopy revealed a tumor at the ascending colon. Histopathological examination showed a well-differentiated tubular adenocarcinoma. Since the patient had anemia, aspirin and cilostazol were discontinued after diagnosis. HU was discontinued from the day before surgery to 2 days after surgery. Enoxaparin was subcutaneously administered for 1 to 3 days after surgery. Aspirin and cilostazol were resumed on the fourth day post-surgery. The patient could be discharged when her condition stabilizes with no thrombosis and bleeding after 8 days.

[Surgical Resection after Chemotherapy for Ampullary Carcinoma with Synchronous Liver Metastasis--Report of a Case].

A 63-year-old woman presented with abnormalities in liver enzyme levels on laboratory studies, which were detected during a routine medical check-up. She was diagnosed with carcinoma of the ampulla of Vater with a synchronous solitary liver metastasis (S7). She was treated with gemcitabine plus S-1. After 2 courses of the chemotherapy, computed tomography revealed that the primary and metastatic tumors had not changed in size, but new lesions had not appeared. A pylorus-preserving pancreaticoduodenectomy and partial resection of the liver (S7) were performed. She received gemcitabine monotherapy for 1 year and she remains alive and well with no evidence of disease 2 year 10 months after resection.

Phase I/II trial of irinotecan and S-1 combination chemotherapy as a second-line treatment for advanced colorectal cancer.

BACKGROUND: This study attempted to determine the therapeutic dosage of irinotecan and S-1 (IRIS) as a second-line treatment for colorectal cancer (CRC). METHODS: S-1 was administered on days 1-14 of a 28-day cycle. Irinotecan was administered on days 1 and 15. The irinotecan dose was then escalated to determine the maximum-tolerated dose and the recommended dose at a fixed dosage of S-1 (80 or 65 mg·m(-2)·day(-1)). The S-1 dose was reduced to 65 mg·m(-2)·day(-1) when dose-limiting toxicities were observed at 80 mg·m(-2)· day(-1) and the irinotecan dose was increased. RESULTS: The recommended dose was 65 mg/m(2) for S-1 and 75 mg/m(2) for irinotecan. Twenty-one patients were treated at the recommended dose. The overall response rate was 28.6%. CONCLUSION: This modified IRIS regimen is considered effective with acceptable toxicities for advanced CRC resistant to treatment with 5-fluorouracil/leucovorin or uracil and tegafur/leucovorin.

Tumor-to-tumor metastasis of colon cancer metastasizing to a pancreatic neuroendocrine tumor associated with von Hippel-Lindau disease: a case report.

Von Hippel-Lindau disease (VHL) is frequently associated with pancreatic neuroendocrine tumors (PNETs). Here, we report a case of tumor-to-tumor metastasis in a VHL patient in whom colon cancer metastasized to the interior of a PNET. A 65-year-old man had undergone bilateral adrenalectomy for pheochromocytomas in both adrenal glands in his 50 s. Genetic screening was performed considering his family history of pheochromocytoma, and he was diagnosed with VHL. PNET was detected, for which the patient was regularly monitored by follow-up imaging. One year ago, the patient underwent right hemicolectomy to remove a tumor in the ascending colon (pT3N0M0, pStage IIA). He was admitted to our department for detailed examination because the pancreatic tumor had grown, and thus, pancreaticoduodenectomy was performed. Diagnostic imaging and histological findings indicated tumor-to-tumor metastasis, in which the patient's previous colon cancer had metastasized to and proliferated within the PNET. Colon cancer metastasizing to a PNET is extraordinarily rare and has never been reported in the literature. Thus, practitioners should be vigilant for tumor-to-tumor metastasis when performing imaging surveillance of PNETs.

Postoperative defecatory function of an ileal pouch-anal anastomosis after a restorative proctocolectomy for ulcerative colitis: evaluation using fecoflowmetry.

An ileal pouch is usually reconstructed as an alternative to a neorectum after a total proctocolectomy for ulcerative colitis (UC). However, the real defecatory function of an ileal pouch is uncertain. This study was designed to analyze the functional and clinical outcomes after a proctocolectomy and ileal pouch-anal anastomosis (IPAA) for UC using fecoflowmetry (FFM). Sixteen patients who underwent IPAA for UC between 1990 and 2005 were studied. They were evaluated by FFM, together with Kelly's clinical score (KCS), and anorectal manometric assessments were also performed. FFM showed that the fecoflow pattern (FFP) of 14 patients (87%) was the block type and of 2 patients (13%) was the segmental type. The clinical score and tolerance volume showed no improvement 1 year or more after IPAA. However, the value of the maximum fecal stream flow rate (Fmax) improved with time. FFM shows that the defecatory function improved after IPAA, and it may therefore contribute to a good long-term outcome after the surgery.

[Eighty-five-year-old patient with recurrent rectal cancer effectively treated with CapeOX chemotherapy].

We report a case of a super-elderly patient with recurrent rectal cancer effectively treated with CapeOX chemotherapy. A 85-year-old man who had a low anterior resection was diagnosed with rectal cancer in July 2009. Although peritoneal dissemination near the main tumor was disclosed during the operation, a R0 and Cur B operation was performed. After the operation, an elevation of tumor markers was detected in October. A chest-abdominal-pelvic CT scan revealed multiple liver metastases of the bilateral lobe and a metastasis of the right iliac bone. We attempted CapeOX chemotherapy from November. After 3 courses of CapeOX chemotherapy, the multiple liver metastases shrank and the bone metastasis changed to a consolidation. Although grade 1 chronic peripheral neuropathy appeared after 8 courses of chemotherapy, no other adverse event appeared. After 10 courses of CapeOX chemotherapy, the chemotherapy was changed to capecitabine at the patient's request. A chest-abdominal-pelvic CT scan after 10 courses of CapeOX chemotherapy revealed that the multiple liver metastases were shrinking. As of September 2010, the patient's PS score is 0, and he has been under treatment as an outpatient.

Comparison of a colonic J-pouch and transverse coloplasty pouch in patients with rectal cancer after an ultralow anterior resection using fecoflowmetric profiles.

PURPOSE: Because the standard straight coloanal anastomosis for low rectal cancer tends to result in unfavorable outcomes in terms of defecatory function, colonic pouch reconstruction has therefore recently been adopted in many institutions. The colonic J-pouch (CJP)- and transverse coloplasty pouch (TCP)-anal anastomoses have been adopted worldwide. However, the comparative benefits and drawbacks of the two procedures are uncertain. This study was designed to analyze the functional and clinical outcomes after an ultralow anterior resection (ULAR) using the fecoflowmetry (FFM). METHODS: Between November 1996 and July 2005, 18 patients were studied retrospectively. They were evaluated by FFM, together with Kelly's clinical score (KCS), and anorectal manometric assessments were also performed. RESULTS: The KCS directly correlated to the maximum fecal stream flow rate (Fmax). In this study, postoperative patients with good KCS as well as a high value of Fmax were seen more in the patients with CJP than in those with TCP. CONCLUSION: From the viewpoint of FFM, the patients with CJP had a more favorable functional outcome than those with TCP. FFM provided quantitative and qualitative evaluations concerning the anorectal motor activity in patients who had undergone an ULAR for rectal cancer.

[A long-term survival case of far-advanced colon cancer with Virchow's lymph node and lung metastasis that responded to multidisciplinary therapy].

The patient was a 73-year-old male. Under a diagnosis of advanced cecal colon cancer with metastasis to Virchow's and paraaortic lymph nodes and lungs, a laparoscopic-assisted ileocecal resection with D2 lymph node dissection was performed. Histological examination of the resected specimens revealed moderately-differentiated adenocarcinoma which had invaded the terminal ileum. The lesion was judged to be SI(ileum), N2, H0, P0, M1(Virchow's lymph node, No. 216, lungs), Stage IV. After the operation, he received chemotherapy with 5-FU/l-LV(RPMI method), LV/UFT, FOLFOX, FOLFIRI in succession, and cancer aggravation was generally controlled. He has survived for 3 years since operation, and shows good QOL under the treatment.

[A case of fungal pyogenic spondylitis with ulcerative colitis].

A 58-year-old man with refractory ulcerative colitis underwent subtotal colectomy 4 months after the diagnosis. He developed intense back pain and high fever 9 days after the operation. Findings of a CT scan and an MRI confirmed the diagnosis of pyogenic spondylitis, and Candida albicans was cultured from the biopsy specimen. His clinical condition gradually improved after receiving therapy with rest and antifungal agents. Physicians should be aware of the possibility of pyogenic spondylitis in patients with back pain is treated for ulcerative colitis.

A Case of Successful Treatment of Ruptured Pancreaticoduodenal Artery Aneurysm Caused by Celiac Artery Dissection.

A 52-year-old man was admitted due to severe epigastric lesion pain. Esophagus gastroduodenal endoscopy showed impaired duodenal dilatation, and contrast-enhanced computed tomography revealed a pancreaticoduodenal artery (PDA) aneurysm 13 mm in diameter below the head of the pancreas, retroperitoneal hematoma, idiopathic celiac artery (CA) dissection, and common hepatic artery disruption. Angiographic embolization with a mixture of N-butyl-1,2-cyanoacrylate and lipiodol was performed, and follow-up study showed improvement of the dilatation of the duodenum and disappearance of the aneurysm. Here we report a quite rare case of PDA aneurysm by idiopathic dissection of CA treated successfully with angiographic embolization.

Common carotid arterial thrombosis associated with ulcerative colitis.

A 26-year-old woman with ulcerative colitis was transferred to our hospital with left hemiparesis due to cerebral infarction. Cervical ultrasonography and magnetic resonance imaging angiography revealed thrombosis at the right common carotid artery and the right internal carotid artery. Antithrombotic and anticoagulant therapies were commenced. After about 2 wk of the treatment, the frequency of her diarrhea increased. She underwent emergency subtotal colectomy, but 10 d later an abundant hemorrhage from the remnant rectum occurred, so the remnant rectum was resected and an ileal pouch anal anastomosis was performed. Antithrombotic and anticoagulant therapies were continued, but neither her neurological status nor magnetic resonance imaging angiography findings showed subsequent changes. She was discharged 3 mon after operation. This is a rare case of common carotid arterial thrombosis occurring as a complication of ulcerative colitis, in which antithrombotic and anticoagulant therapies are considered to provoke a deterioration of the patient's bowel disease.

Possible role of human cytomegalovirus in pouchitis after proctocolectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis.

AIM: To detect the presence of human cytomegalovirus (HCMV) proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: Immunohistochemistry, polymerase chain reaction (PCR) and PCR sequencing methods were utilized to test the presence of HCMV in pouch specimens taken from 34 patients in 86 endoscopies. RESULTS: HCMV genes and proteins were detected in samples from 12 (35.2%) patients. The rate of detection was significant in the endoscopies from patients diagnosed with pouchitis (5 of 12, 41.6%), according to the Japanese classification of pouchitis, in comparison to patients with normal pouch (7 of 62, 11.2%; P = 0.021). In all patients with pouchitis in which the HCMV was detected, it was the first episode of pouchitis. The virus was not detected in previous biopsies taken in normal endoscopies of these patients. During the follow-up, HCMV was detected in one patient with recurrent pouchitis and in 3 patients whose pouchitis episodes improved but whose positive endoscopic findings persisted. CONCLUSION: HCMV can take part in the inflammatory process of the pouch in some patients with ulcerative colitis who have undergone proctocolectomy with IPAA.

Angiotensin II type 2 receptor gene deficiency attenuates susceptibility to tobacco-specific nitrosamine-induced lung tumorigenesis: involvement of transforming growth factor-beta-dependent cell growth attenuation.

To clarify an involvement of angiotensin II signaling in lung neoplasia, we have examined the effect of angiotensin II receptor deficiency on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis. Male angiotensin II type 2 receptor (AT2)-null mice with an SWR/J genetic background and control wild-type mice were treated with NNK (100 mg/kg, i.p.) or saline vehicle. NNK treatment caused the development of lung tumors in all wild-type control mice (100 % tumor prevalence), but only 85% of AT2-null mice developed tumors. The tumor multiplicity in AT2-null mice (1.9 +/- 0.3) was significantly smaller than that in wild-type mice (4.1 +/- 0.9). Primary cultured lung fibroblasts prepared from both AT2-null and wild-type mice markedly increased the colony counts of A549 lung cancer cells in soft agar, but a consistently higher colony count was observed with the wild-type fibroblasts (fold increase in colony number, 5.6 +/- 0.5) than with the AT2-null fibroblasts (3.5 +/- 0.8). The underlying mechanism by which angiotensin II regulates cancer cell growth is due to the regulation of active transforming growth factor-beta (TGF-beta) production. Although the total level of TGF-beta was significantly stimulated when A549 cells were cocultured with either type of fibroblasts, the level of active TGF-beta in the conditioned medium was consistently higher with AT2-null fibroblasts than with wild-type fibroblasts. These results imply that the AT2 receptor negatively regulates the level of active TGF-beta and thus increases NNK-induced lung tumorigenesis. The AT2 receptor function in lung stromal fibroblasts may be a potential modulator of tumor susceptibility in chemical carcinogen-induced lung tumorigenesis.

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor: a case of a rare malignancy.

BACKGROUND: A gastric adenosquamous carcinoma (ASC) that produces granulocyte-colony stimulating factor (G-CSF) is an uncommon malignancy with a poor prognosis. Due to the rarity of this lesion, a standard treatment for the disease has not been established. CASE PRESENTATION: We describe a case of a 66-year-old male with a G-CSF-producing gastric ASC who presented with severe anemia and leukocytosis. A radical resection was performed, followed by a course of adjuvant chemotherapy. Histopathologic examination revealed that the tumor consisted of areas of both squamous cell carcinoma and adenocarcinoma. Immunohistochemical staining with an anti-G-CSF antibody was also positive. He was started on adjuvant capecitabine and oxaliplatin (CapeOX) 6 weeks after surgery. The patient stopped treatment after 3 months due to his own preference. Eight months following surgery, the patient was found to have diffuse lymph node, liver, and peritoneal metastases. CONCLUSIONS: G-CSF-producing gastric ASC is a rare and aggressive tumor. Because patients are usually diagnosed at an advanced stage, multidisciplinary evaluation and innovative treatments are needed. The rarity of this disease, with its aggressive features, poses a significant challenge in its treatment. In this brief case report, we summarize the management and outcomes of G-CSF-producing gastric ASC.

Double selective shunting for esophagogastric and rectal varices in portal hypertension due to congenital hepatic polycystic disease.

A 55-year-old woman with ascites, pancytopenia by hypersplenism, recurrent hemorrhagic esophagogastric varices, and large rectal varices due to congenital hepatic polycystic disease underwent splenectomy and simultaneous double selective shunt; a left gastric venacaval direct shunt for esophagogastric varices and a sigmoid venous left ovarian vein shunt for rectal varices. Her preoperative Child-Pugh grade was A (score 6). Postoperative course was uneventful. Serum NH3 level decreased from 90 micrograms/dL to 36 micrograms/dL after shunt surgery. She was discharged on the 21st postoperative day. The remarkable improvement of both the esophagogastric varices and the rectal varices was demonstrated by postoperative fiberscope. We strongly consider sigmoid venous left ovarian shunting to be as selective as the Inokuchi shunt preventing encephalopathy and an effective surgical approach to anorectal varices.

Diagnosis of ischemic small bowel disease by measurement of serum intestinal fatty acid-binding protein in patients with acute abdomen: a multicenter, observer-blinded validation study.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP) is a low-molecular-mass (15 kDa) cytosolic protein found exclusively in the epithelial cells of the small bowel mucosa. We aimed to evaluate the clinical usefulness of serum I-FABP measurement for the diagnosis of ischemic small bowel disease. METHODS: Patients with a clinical diagnosis of acute abdomen were recruited for this multicenter trial at one university hospital and nine city hospitals over a 13-month period. Serum I-FABP levels were measured in 361 eligible patients by an enzyme-linked immunosorbent assay using a specific monoclonal antibody. RESULTS: Of the 361 patients, 242 underwent surgery, and small bowel ischemia was diagnosed in 52 patients. The mean serum I-FABP level in the patients with small bowel ischemia was 40.7 ± 117.9 ng/ml, which was significantly higher than that in patients with non-ischemic small bowel disease (5.8 ± 15.6 ng/ml) and those with non-small bowel disease (1.8 ± 1.7 ng/ml). The serum I-FABP cutoff level for the diagnosis of small bowel ischemia was 3.1 ng/ml. Serum I-FABP was more efficient than conventional biochemical markers, in terms of sensitivity and positive and negative predictive values, in the diagnosis of small bowel ischemia. However, its specificity was slightly lower than that of creatinine phosphokinase or lactate dehydrogenase. The positive and negative likelihood ratios of serum I-FABP were 3.01 and 0.29, respectively. CONCLUSION: Serum I-FABP measurement is a non-invasive method that is potentially useful for the efficient identification of patients with acute abdomen who are at risk of small bowel ischemia.

Angiotensin II bi-directionally regulates cyclooxygenase-2 expression in intestinal epithelial cells.

We previously demonstrated that angiotensin II (Ang II) receptor signaling is involved in azoxymethane-induced mouse colon tumorigenesis. In order to clarify the role of Ang II in COX-2 expression in the intestinal epithelium, the receptor subtype-specific effect on COX-2 expression in a rat intestinal epithelial cell line (RIE-1) has been investigated. Ang II dose- and time-dependently increased the expression of COX-2, but not COX-1 mRNA and protein. This stimulation was completely blocked by the AT(1) receptor antagonist but not the AT(2) receptor antagonist. Ang II and lipopolysaccharide (LPS) additively induced COX-2 protein in RIE-1 cells, whereas the LPS-induced COX-2 expression was significantly attenuated by low concentrations of Ang II or the AT(2) agonistic peptide CGP-42112A only in AT(2) over-expressed cells. These data indicate that Ang II bi-directionally regulates COX-2 expression via both AT(1) and AT(2) receptors. Control of COX-2 expression through Ang II signaling may have significance in cytokine-induced COX-2 induction and colon tumorigenesis.