Atsushi Urakami

Gender differences in the dihydropyrimidine dehydrogenase expression of colorectal cancers

Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). DPD expression levels are believed to correlate with the 5-FU sensitivity of malignant tumors. In colorectal cancer (CRC), a few previous studies demonstrated that females could benefit more from adjuvant chemotherapy. However, it is still unknown why the effectiveness of postoperative chemotherapy is affected by gender. The objective of this study was to clarify the beneficial differences in 5-FU chemotherapy between genders in patients with the CRC based on DPD expression. Ninety-seven tumor specimens and 92 adjacent normal tissue specimens from 97 patients with the CRC and no prior therapy were obtained. The DPD expression in the tissues was quantified and analyzed based on clinicopathological factors. In the tumor tissue, the DPD expression in females was significantly lower than that in males. In the normal tissues, however, there were no significant differences in DPD expression between genders. In the treatment of CRC, cases who will benefit most because of 5-FU sensitivity; i.e. cases with lower DPD expression, must be given priority. Based on DPD expression, female gender seems to be a predictive factor for a better response to chemotherapy with 5-FU.

Lower esophageal sphincter- and vagus-preserving proximal partial gastrectomy for early cancer of the gastric cardia.

PurposeProximal gastrectomy and lymph node dissection are often performed for T1 cancer of the gastric cardia; however, direct esophagogastrostomy is frequently complicated by reflux esophagitis. We describe a simple technique for preventing esophageal reflux and discuss its results.MethodsThis technique is indicated for T1 cancer of the gastric cardia without lymphadenopathy. Partial resection, including the lesion, is performed, preserving the vagus nerve and lower esophageal sphincter (LES). Lymph node dissection is done around the left gastric, celiac, and splenic arteries. The esophagus is then anastomosed to the anterior wall in the center of the remnant stomach.ResultsWe evaluated the results of this procedure in eight patients. X-ray films showed no esophageal reflux in either the supine or the right decubitus position. None of the patients complained of reflux or other dyscrasic symptoms, and none had any feeling of microgastria. One patient had some localized erosion near the anastomosis.ConclusionsThis simple and safe technique does not result in post-gastrectomy syndrome or microgastria, and the risk of leaving cancer cells is minimal.

Laparoscopy-assisted spleen-preserving pancreatic resection for epidermoid cyst in an intrapancreatic accessory spleen.

A rare case of an epidermoid cyst originating in an intrapancreatic accessory spleen in a 50‐year‐old Japanese female is reported. A hypoechoic cystic tumor was detected incidentally by abdominal ultrasonography. It appeared to be a single cyst in the pancreatic tail with a contrasted mass lesion beside it. Laparoscopy‐assisted spleen‐preserving pancreatic tail resection was performed. Microscopic examination revealed that the cyst was surrounded by fibrous tissue and a thin layer of splenic tissue, adjacent to normal pancreatic parenchyma. The inner surface of the cyst was lined with non‐keratinizing squamous epithelium. The diagnosis of an epidermoid cyst occurring in an intrapancreatic accessory spleen was confirmed. Laparoscopy‐assisted spleen‐preserving pancreatic resection is a safe and effective procedure for benign or low‐grade malignant cystic diseases in the pancreas.

In vitro detection of cross-resistant and non-cross-resistant agents with fluorouracil for patients with colorectal cancer.

BackgroundFluorouracil-based chemotherapy, such as that with 5-fluorouracil (5-FU)/leucovorin, is standard as first-line chemotherapy for advanced colorectal cancer (CRC) in Japan. However, the best agent for second-line chemotherapy after fluorouracil failure is yet to be determined. This study was undertaken to find an appropriate agent for second-line chemotherapy.MethodsSeventy-five tumor specimens from CRC patients with no prior chemotherapy were obtained operatively and their chemosensitivity to five anticancer agents; i.e., 5-FU, mitomycin C (MMC), cisplatin, docetaxel, and an active metabolite of irinotecan (SN-38), was analyzed in an in vitro chemosensitivity test. In this method, the degree of chemosensitivity was expressed as the percent T/C ratio, where T was the total volume of the tumor colonies in the treated group and C was that of the control group. Pearsons correlation coefficients were used to assess the relationship between two agents.ResultsFifty-eight specimens (colon, 28; rectum, 30) were successfully analyzed. Positive correlations with 5-FU chemosensitivity were verified for the chemosensitivity of MMC, cisplatin, and docetaxel. No correlation with 5-FU chemosensitivity was verified for SN-38 chemosensitivity. Although the functional mechanism of each of the agents differs from that of 5-FU, with the exception of irinotecan, they all had a spectrum closely similar to the 5-FU spectrum.ConclusionOnly irinotecan exhibited a spectrum independent of that of 5-FU, thus indicating that it could be an appropriate agent for second-line chemotherapy after fluorouracil failure.

Spontaneous splenic rupture complicating granulomatosis with polyangiitis (Wegener's granulomatosis).

Dear Editor, Granulomatosis with polyangiitis (GPA; Wegener’s granulomatosis) is a systemic vasculitis that primarily affects the upper respiratory tract, lungs and kidneys of most patients and only occasionally involves the spleen. The pathologic splenic changes associated with GPA include necrotizing granulomatous inflammation, vasculitis, fibrinoid change of blood vessels and infarction. Although extremely rare, with only three published cases to date, spontaneous splenic rupture may occur as a complication in GPA. Here, we report a fourth case of spontaneous splenic rupture, which occurred during treatment for GPA with corticosteroids. A 47-year-old woman presented in September 2010 with a 4-month history of fever and refractory sinusitis. She had paranasal sinus pain with purulent and bloody nasal discharge and swelling of the face. She also reported having right anterior uveitis requiring treatment with corticosteroid eye drops. Examination of her respiratory and abdominal systems was unremarkable. Laboratory tests showed a leukocyte count of 8380/lL, hemoglobin 11.1 g/dL, hematocrit 36.8%, platelet count 23.9 9 10/lL, and serum C-reactive protein (CRP) 4.37 mg/dL (normal < 0.30). Liver function tests showed aspartate aminotransferase level of 15 IU/L, alanine aminotransferase 12 IU/L, alkaline phosphatase 271 IU/L, and total bilirubin 0.3 mg/dL. Renal function tests were normal. A serological test was positive for proteinase 3 – antineutrophil cytoplasmic antibodies (PR3-ANCA) with a titer of 37 IU/L (normal < 10). Antinuclear antibody was negative. Urine examinations were normal. Computed tomography (CT) scan showed extensive mucosal thickening in the bilateral maxillary sinuses. Plain X-ray and high-resolution CT scan of the chest showed no pulmonary disease. On the basis of the findings of antibiotic-resistant sinusitis, uveitis and PR3-ANCA positivity, she was suspected as having a limited form of GPA. She was started on prednisolone (30 mg/day) and low-dose weekly oral methotrexate (8 mg/week) and within a few days her fever disappeared and sinusitis and inflammatory laboratory data were improved. Neither anticoagulants nor antiplatelet agents were given to the patient to prevent steroid-induced thrombosis. When tapering the steroid dose to 17.5 mg/day in December 2010, the patient complained of pain in the left upper quadrant and fever. Serum CRP was elevated at 12.31 mg/dL, leukocyte count was 12 930/lL, and the PR3-ANCA level was 12 IU/L. Contrast-enhanced CT scan showed a well-defined hypodense area within the spleen, with some enhanced small patches within the larger hypodense area (Fig. 1a). The provisional diagnosis was splenic infarction. Cardiac ultrasonography to detect vegetations was normal. Pulmonary and abdominal CT scan and upper and lower intestinal endoscopy showed no features of malignant disease with potential to cause thromboembolic events. Abdominal pain and inflammatory laboratory abnormalities improved comparatively quickly with prophylactic antibiotic treatment. In February 2011, while taking prednisolone 12.5 mg/day, the patient presented with intractable abdominal pain and fever. Laboratory findings were CRP 21.36 mg/dL and leukocyte count 15 260/lL. Contrast-enhanced CT scan revealed splenic rupture (Fig. 1b) and she underwent emergency laparoscopic splenectomy. Pathological findings showed massive necrosis at the rupture site (Fig. 2a), with a palisaded granuloma in the vicinity of the necrotic area (Fig. 2b). The patient’s postoperative course was uneventful and she was subsequently discharged feeling quite well. A search of the PubMed database identified only three documented cases of spontaneous splenic rupture in GPA. In all three cases rupture was the first presenting sign of GPA. The present case is unique in that splenic rupture developed after the diagnosis of GPA and during treatment with corticosteroids. Histological findings revealed extensive splenic necrosis and a palisaded granuloma, which alongside the appearance on CT scan,

Determination of a second-line chemotherapy agent for patients with colorectal cancer (CRC) after fluorouracil failure

3638 Background: Fluorouracil-based chemotherapy, such as with 5-FU/leucovorin, is standard as first-line chemotherapy for advanced CRCs. However, the best agent for chemotherapy after fluorouracil failure is still unknown. The primary objective of this study was to determine the best agent for second-line chemotherapy. METHODS Seventy-eight tumor specimens from CRC patients with no prior chemotherapy were obtained operatively and their sensitivity against five anticancer drugs, 5-FU, Mitomycin C, Cisplatine, Decetaxel and CPT-11, in an in vitro chemosensitivity test using CD-DST methods was analyzed. The chemosensitivity was expressed as the percentage T/C ratio, where T was the total volume of the treated group and C was that of the control group. Pearsons correlation coefficients were used to assess the relationship. P<0.05; statistically significant. A statistically significant correlation between two drugs was defined as a correlation of cross-resistance between them. Conversely, non-positive correlation was defined a correlation of no cross-resistance between them, with each of them having an independent spectrum. RESULTS Fifty-four specimens (colon, 30; rectum, 24) were successfully analyzed. The mean T/C ratios of 5-FU, Mitomycin C, Cisplatine, Decetaxel and CPT-11 were 79.1%, 69.9%, 81.2%, 59.4% and 63.8%, respectively. Although each of the agents has a different functional mechanism from that of 5-FU, with the exception CPT-11, all of them had a closely positive correlation with 5-FU. CONCLUSIONS Only CPT-11 expressed an independent spectrum from 5-FU, thus indicating it to be the best agent for second-line chemotherapy after fluorouracil failure. [Figure: see text] No significant financial relationships to disclose.

A pitfall of MRCP for preoperative cholangiography: report of a case

bowel are usually discovered in the late stage. Thus, the 5-yr survival rate for patients with small bowel cancer is poor, averaging 30% (2–4). Among small bowel tumors, 35% of benign tumors and 17% of malignant tumors are located in the duodenum (2). With the development of new endoscopic techniques such as strip biopsy, it has become possible to achieve adequate tumor resection including not only pedunculated or sessile lesions but also flat or erosive lesions. Because strip biopsy permits the resection of large specimens, it is useful not only for therapy but also for assessing the pathological characteristics and degree of invasion of lesions. Although strip biopsy has a number of limitations, patients who are not candidates for surgery because of severe underlying disease or refusal to grant consent are good candidates for this procedure. Because the duodenum mucosa is quite thin, endoscopic resection is associated with a high risk of perforation. However, the risk of this complication can be minimized in strip biopsy procedures by injecting saline solution into the submucosa to lift the lesion away from underlying tissues as well as to prevent excessive spread of the electrocoagulation effect (5). The excellent clinical outcome observed in the case presented here strongly suggests that strip biopsy may prove to be useful for the treatment of early duodenal cancer.