Erratum: Publisher Correction to: Severe adverse events due to dihydropyrimidine dehydrogenase deficiency in a Japanese patient with colon cancer taking capecitabine: a case report.

[This corrects the article DOI: 10.1007/s13691-018-0334-1.].

Severe adverse events due to dihydropyrimidine dehydrogenase deficiency in a Japanese patient with colon cancer taking capecitabine: a case report.

Fluoropyrimidine has been commonly used not only in unresectable cases of metastatic colorectal cancer, but also in adjuvant therapy. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down more than 80% of standard doses of 5-fluorouracil (5-FU) and capecitabine, an oral prodrug of 5-FU. The lack of enzymatic activity increases the half-life of the drug, resulting in excess drug accumulation and toxicity which may lead to life-threatening side effects. There have been several published case reports about DPD deficiency in patients with colorectal cancer in Western countries. However, case reports of DPD deficiency in Japanese patients with colorectal cancer are rare because measuring DPD activity is not covered by public medical insurance in Japan, and it is not examined in our daily clinical practice currently. Therefore, we think that it is important to accumulate such case reports for further understanding. This report describes the case of a Japanese patient with colon cancer who experienced severe side effects while taking capecitabine, due to DPD deficiency. A 68-year-old man with ascending colon cancer underwent curative laparoscopic right hemicolectomy. Because final pathologic staging was Stage IIIa, standard adjuvant chemotherapy with capecitabine (3600 mg/body/day, days 1-14, every 3 weeks) was started on postoperative day 50. After 2 weeks, he started to experience Grade 3 diarrhea and was admitted to the hospital on postoperative day 66. On day 70, the patient had Grade 4 febrile neutropenia. Antibiotics and granulocyte-colony-stimulating factor were administered until his blood tests recovered to the normal degree. After 1 week of diarrhea, antidiarrheal agents were administered, and the patient gradually recovered. During the occurrence of diarrhea, specimen cultures were negative for infection. He was discharged on day 21 of the hospital stay. DPD deficiency was suspected, and 2 weeks later the DPD activity of the peripheral blood mononucleocytes was examined. The result was 10.3 U/mg protein which was remarkedly low (reference range 22.6-183.6 U/mg protein), and DPD deficiency was diagnosed. We always must consider the possibility of DPD deficiency in patients who experience severe side effects while taking capecitabine.

Long-term follow-up after pancreatoduodenectomy with portal vein resection for a huge solid pseudopapillary neoplasm in an adolescent girl.

A 16-year-old Japanese girl with a huge 13-cm-diameter tumor in the pancreas head presented with life-threatening symptoms and findings including severe anemia, obstructive jaundice, duodenal stenosis, and serious portal vein compression. She underwent a pancreatoduodenectomy with combined resection of the portal vein. Reconstruction of the portal vein was successfully performed using an external iliac vein graft and postoperative anticoagulant therapy. Pathological examination revealed a solid pseudopapillary neoplasm of the pancreas. The patient's postoperative course was uneventful, but her menstruation ceased for 14 months. She is now alive with no evidence of recurrence 100 months postoperatively and she suffers no impairments in daily activities of life. As a treatment of solid pseudopapillary neoplasms of the pancreas, pancreatoduodenectomy combined with portal vein resection is rarely performed in adolescent patients, but is reportedly successful, with patients tolerating the operation and surviving without recurrence. An aggressive surgical attitude is recommended when dealing with this tumor type with curative resection, even in adolescent patients.

Randomized prospective trial comparing clinical outcomes 3 years after surgery by Marcy repair and Prolene Hernia System repair for adult indirect inguinal hernia.

PURPOSE: The use of mesh in the surgical repair of adult indirect inguinal hernias is widely recommended in Western countries, but no randomized controlled trials have so far been reported in Japan. The purpose of the present randomized prospective trial was to compare a mesh method with non-mesh method for surgical repair of primary adult indirect inguinal hernias in which the diameter of the internal inguinal ring was up to 3.0 cm (I-1 or I-2 of Japanese Hernia Society Classification). METHODS: Patients with a primary unilateral inguinal hernia and I-1 or I-2 surgical findings were randomized to undergo either Marcy repair or Prolene Hernia System repair. Primary endpoints were recurrence, infection, and pain, with follow-up continued for 3 years postoperatively. RESULTS: Ninety-one of 479 patients with an inguinal hernia during the study period did not meet the exclusion criteria, and 46 were allocated to Marcy repair and 45 were allocated to Prolene Hernia System repair. No recurrence was observed in either group, and no significant differences were identified between the groups in any of the primary endpoints. CONCLUSION: This randomized prospective trial of I-1 and I-2 inguinal hernias suggests that Marcy repair is not inferior to PHS repair. A large-scale randomized controlled trial appears warranted to confirm whether to use mesh for Japanese adult I-1 and I-2 hernias.

T-state stabilization of hemoglobin by nitric oxide to form alpha-nitrosyl heme causes constitutive release of ATP from human erythrocytes.

Upon hypoxia, erythrocytes utilize hemoglobin (Hb) to trigger activation of glycolysis through its interaction with band 3. This process contributes to maintenance of ATP, a portion of which is released extracellularly to trigger endothelium-dependent vasorelaxation. However, whether the ATP release results either from metabolic activation of the cells secondarily or from direct regulation of the gating through Hb allostery remains unknown. This study aimed to examine if stabilization of T-state Hb could induce steady-state and hypoxia-induced alterations in glycolysis and the ATP release from erythrocytes. Treatment of deoxygenated erythrocytes with a nitric oxide (NO) donor generated alpha-NO Hb that is stabilized T-state allostery. Under these circumstances, the release of ATP was significantly elevated even under normoxia and not further enhanced upon hypoxia. These events did not coincide with activation of glycolysis of the cells, so far as judged by the fact that intracellular ATP was significantly decreased by the NO treatment. Collectively, the present study suggests that hypoxia-induced ATP release is triggered through mechanisms involving R-T transition of Hb, and the gating process might occur irrespective of hypoxia-responsive regulation of glycolysis.

[A case of advanced gastric cancer resistant to S-1 successfully treated with weekly administration of paclitaxel].

A 62-year-old female was diagnosed with type 2 advanced gastric cancer in May 2003. Pathological examination showed a poorly differentiated carcinoma. Computed tomography (CT) revealed paraaortic lymph node metastasis, duodenal metastasis and ascites due to peritoneal dissemination. Chemotherapy with CDDP+S-1 was started and continued. After the chemotherapy, there were progressive diseases. Therefore, paclitaxel (PTX) was administered at a dose of 80 mg/m2/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and CT scan revealed metastatic lymph nodes were reduced after 4 cycles. After 13 cycles, MRI revealed a solitary brain mass was detected. She was resected for a right temporal-occipital brain metastatic tumor, and local cerebral irradiation was performed. After this operation, she was diagnosed with brain metastasis from advanced gastric cancer. The procedure was interrupted for about 6 months. After rehabilitation, PTX treatment was restarted as 14th cycle. She has survived without recurrence more than 30 cycles after the resection. A weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1 resistant recurrent gastric cancer.

[Successful surgical treatment for peritoneal dissemination of liver cancer after hepatectomy--a case report].

A 58-year-old female was admitted to Ogikubo Hospital for advanced hepatocellular carcinoma in April 2007. Pathological examination showed moderately differentiated hepatocellular carcinoma. Tumor marker increased the PIVKA-II level became 129 mAU/mL after the operation. FDG-PET was showed a solitary pelvic tumor sized about 2.5 cm in diameter. No other prominent metastatic lesions were demonstrated, so that a resection of intrapelvic tumor was performed in May 2008. The report which exhibited an asynchronism recurrence of peritoneal dissemination after hepatectomy is very rare. She has survived without a recurrence more than 13 months after the resection.

Impacted obturator hernia treated successfully with a Kugel repair: report of two cases.

Obturator hernia repair has traditionally been performed via an intra-abdominal approach, although laparoscopy is also emerging as a feasible alternative. On the other hand, the Kugel method is a minimally invasive and effective form of repair of groin hernia, but there have been few reports on its use for an incarcerated obturator hernia. We describe how we used the Kugel method to repair an obturator hernia in two patients. Both patients presented with acute intestinal obstruction, necessitating emergency surgery. Via a preperitoneal approach, the impacted obturator hernia was carefully released and the obturator canal defect was repaired with a Kugel patch. One patient recommenced oral intake on postoperative day (POD) 1, and was discharged on POD 5. The other patient's postoperative course was complicated by ileus, prolonging the hospital stay to 14 days. There has been no sign of recurrent disease for 6 and 21 months, respectively. The Kugel method offers several advantages, such as a short operative time (76-82 min), small scar (3 cm), and early postoperative ambulation (POD 1), thus minimizing the hospital stay. Further study is needed to confirm the usefulness of this procedure for an incarcerated obturator hernia.

Perineal hernia as a rare complication after laparoscopic abdominoperineal resection: report of a case.

We report what seems to be the second documented case of perineal hernia after laparoscopic abdominoperineal resection (APR) and describe its successful repair with transperineal intraperitoneal mesh. An 89-year-old woman complained of a large, painful perineal swelling 4 months after APR for rectal cancer. Computed tomography (CT) showed small intestine protruding through the pelvic floor into the perineal area. However, opening of the hernia sac revealed no intra-abdominal adhesions. An oval, 8 x 12 cm Bard Composix Kugel Patch (Davol, Cranston, RI, USA) was inserted into the intraperitoneal space and secured over the defect in the pelvic floor; then firmly attached to the pelvic wall with 16 interrupted nonabsorbable sutures. There has been no sign of hernia recurrence in 10 months of follow-up. We speculate that because laparoscopic surgery is minimally invasive, fewer postoperative adhesions in the abdominal cavity can result in the small bowel sliding more readily into the perineal area. Based on our experience, perineal hernia after laparoscopic APR can be repaired easily and effectively with a Composix Kugel Patch.

Recurrent pancreatitis caused by ampullary carcinoma and minor papilla adenoma in familial polyposis: report of a case.

We report a case of relapsing pancreatitis in familial adenomatous polyposis (FAP) with severe duodenal adenomatosis (Spigelman's stage IV). A 58-year-old man who had undergone total colectomy for FAP 18 years earlier was hospitalized for carcinoma arising from the residual rectum. He had experienced several episodes of upper abdominal pain and ultrasonography and computed tomography (CT) showed diffuse calcification of the atrophic pancreas, suggestive of chronic pancreatitis. He had severe diabetes mellitus, but had no symptoms of pancreatic exocrine dysfunction. Upper endoscopy showed multiple duodenal adenomas including carcinoma involving the papilla of Vater. To remove these duodenal adenomas and ampullary carcinoma and prevent recurrent pancreatitis, we performed pancreaticoduodenectomy. On pathologic examination, the major duodenal papilla was completely obstructed by the carcinoma, and the minor papilla was also involved by the adenoma. The patient has no evidence of disease and has experienced no pancreatitis in 3 years of follow-up.

Clinicopathological features and surgical outcome of isolated metastasis of renal cell carcinoma.

BACKGROUND/AIMS: The benefit of pancreatic resection for metastatic renal cell carcinoma (RCC) is poorly defined. Here, we investigate the clinicopathological features and surgical outcome of patients with pancreatic metastasis from RCC. METHODOLOGY: Among a total of 131 patients who underwent pancreatic resection at our center between November 2000 and November 2005, four patients (three men, one woman) with a median age of 57 years (range: 52-80 years) at the time of pancreatic tumor presentation, had histologically confirmed metastatic RCC to the pancreas. The medical records, imaging data, surgical records, and pathology findings of these patients were reviewed retrospectively. RESULTS: All patients underwent radical nephrectomy for primary RCC. The pathologic stage was TNM stage T2N0M0 (n = 1) or T3aN0M0 (n = 2) (no data were available on one patient). RCCs developed in the right (n = 2) or left (n = 2) kidney. The median interval between nephrectomy and detection of pancreatic metastasis was 84 months (range: 0-285 months). All patients were asymptomatic, and the pancreatic masses with a median tumor diameter of 2.0 cm (range: 1.5-4.0 cm) were detected during routine follow-up or screening examinations. All pancreatic tumors were smooth, well-demarcated, and hypervascular on imaging studies. None of them showed evidence of associated extrapancreatic disease. Complete resection with an adequate margin of safety was achieved by distal pancreatectomy (n = 3) or pylorus-preserving pancreatoduodenectomy (n = 1). Within a median follow-up period of 39 months (range: 4-41 months) after the surgery, three patients were alive with no evidence of recurrence, and one patient was alive with evidence of recurrence. The median survival from nephrectomy was 103 months (range: 40-326 months). CONCLUSIONS: RCCs may demonstrate very late metastasis to the pancreas, thus the possibility of pancreatic metastasis should be considered when a patient with a pancreatic tumor has a history of RCC, despite the interval since nephrectomy. The experience gained in this study suggests that pancreatic metastasectomy should be attempted for RCC patients without extrapancreatic disease.

Signet-ring cell carcinoma of the ampulla of Vater: report of a case.

Signet-ring cell carcinoma (SRCC) of the ampulla of Vater is uncommon, and only 13 cases have been previously described. We herein report a rare case of a 43-year-old woman with SRCC in the ampulla of Vater. Although this histologic type of cancer generally predicts a poor prognosis elsewhere in the gastrointestinal tract, the present patient has survived with no evidence of recurrence for 7.5 years. The patient was hospitalized for pruritus and jaundice. She underwent a pancreaticoduodenectomy with an extended lymphadenectomy for ampullary carcinoma. This neoplasm was classified as AcdbBi, 2.0 x 1.8 cm, ulcerative type, Panc(0), Du(2), T(2)N(0)M(-), Stage II according to the Japanese Classification on Cancer of the Biliary Tract. Unfortunately, previous reports of ampullary SRCC have been limited to short-term follow-ups with a median period of only 12 months (range, 6-134 months), and long-term survival (more than 5 years) was only documented in two cases without lymph node metastasis (including the present case). In conclusion, the experience gained in the present and previous cases suggests that long-term survival is possible following a curative resection in selected patients with ampullary SRCC without nodal involvement. Due to the lack of sufficient evidence, additional reports are warranted to determine whether SRCC also portends a poor prognosis in patients with ampullary cancer.

Neoplastic endocrine differentiation of pancreatic ductal adenocarcinoma in a metastatic lymph node: report of a case.

The occurrence of non-neoplastic, scattered endocrine cells in pancreatic ductal adenocarcinoma (DAC) is thought to be a general phenomenon. Conversely, neoplastic endocrine differentiation (NED) of pancreatic DAC is extremely unusual. We report a case of NED in a metastatic lymph node from pancreatic DAC. This case is distinct because the main tumor of the pancreas was composed purely of DAC without endocrine differentiation, and the NED was found in only one of four metastatic peripancreatic lymph nodes. To our knowledge, no other such case has ever been reported. The patient was a 61-year-old woman who underwent pylorus-preserving pancreaticoduodenectomy for pancreatic head cancer. Some authors reported that pancreatic DAC with endocrine differentiation was associated with a better prognosis than DAC without endocrine differentiation. However, more cases must be studied to investigate the impact of NED of metastatic lymph nodes in pancreatic DAC.

Intrahepatic cholangiocarcinoma with old infestation of Schistosoma japonicum: report of a case.

We report a rare case of intrahepatic cholangiocarcinoma associated with old infestation of Schistosoma japonicum. The patient was a 76-year-old Japanese man who had lived his childhood in an endemic area of this parasite. He presented with jaundice and computed tomography showed a 4-cm, hypodense tumor in segment VIII of the liver. Microscopically, the resected mass was composed of well-differentiated adenocarcinoma cells. Fibrosis and inflammation were seen around the dilated peripheral portal veins embolized with dead S. japonicum eggs. Our search of the literature found only one other case of cholangiocarcinoma coincident with S. japonicum, suggesting that it is not a risk factor for cholangiocarcinoma, although the inflammation and fibrosis caused by the S. japonicum eggshells may predispose to carcinogenesis. However, there is no evidence supporting this hypothesis. More data are necessary to evaluate the differences in clinicopathological findings between cholangiocarcinoma concomitant with S. japonicum and the usual type of cholangiocarcinoma.

Successful pancreatectomy with en-bloc resection of the celiac artery and portal vein for pancreatic endocrine carcinoma.

Invasion to the celiac axis and portal vein is one reason for the unresectability of pancreatic carcinoma of the body and tail. Some authors advocate a radical distal pancreatectomy with en-bloc resection of the celiac artery and portal vein. However, long-term survival is still rare. We report here on a very rare, long-term survivor of a locally-advanced endocrine carcinoma of the body of the pancreas that was treated by distal pancreatectomy with en-bloc resection of the celiac artery and portal vein. The patient recovered well postoperatively, and has survived for 55 months without evidence of recurrence. The experience gained in the present case suggests that radical pancreatectomy with en-bloc resection of the celiac artery and portal vein is a potential approach that might increase tumor resectability and improve the prognosis of patients with locally-advanced endocrine carcinomas of the pancreas.

Adult colonic intussusception caused by cecum adenoma: successful treatment by emergency laparoscopy: report of a case.

Although intestinal intussusception is relatively common in children, in adults it remains a rare clinical entity. We report an emergency laparoscopy for an adult case of colonic intussusception caused by cecum adenoma. In the present case, owing to a successful reduction via laparoscopy, the extensive intussusception could be treated with a more limited resection (wedge resection) instead of an en-bloc wide resection (right hemicolectomy). Because of the theoretical risk of perforations which could lead to the seeding of tumor cells and microorganisms into the intra-abdominal cavity, most surgeons advocate an en-bloc resection without reduction. The experience gained from the present case suggests that laparoscopy may therefore be a useful diagnostic or therapeutic tool for selected cases of adult intussusception. The choice of using either a laparoscopic approach or an open approach depends on the clinical condition of a patient, the location and extent of intussusception, the possibility of underlying disease, and the availability of surgeons with sufficient laparoscopic expertise. Additional reports may help standardize the management of this uncommon disease.

Pseudoaneurysm of the cystic artery secondary to cholecystitis as a cause of hemobilia: report of a case.

Spontaneous intracholecystic bleeding is very rare. We report herein a very rare case of a pseudoaneurysm of the cystic artery due to acute cholecystitis. A 58-year-old man presented at the emergency department complaining of colicky pain in the right upper quadrant. Dynamic magnetic resonance imaging demonstrated an early-enhanced pooling of contrast material (suggestive of a pseudoaneurysm of the cystic artery) inside the neck of the gallbladder. After the proximal control of the hepatic artery, the patient underwent a cholecystectomy and a ligation of the cystic artery. The resected specimen of the gallbladder showed evidence of a massive intracholecystic hematoma. Proximal to the impacted gallstone in the neck, a 2-cm diameter saccular-type pseudoaneurysm was identified. Although a pseudoaneurysm of the cystic artery is very rare, it should be included in the differential diagnosis of hemobilia. Once the pseudoaneurysm is confirmed, its embolization before a cholecystectomy (which can be attempted laparoscopically) may be useful to ensure the safety of the patient.