MLH1 germline mutation associated with Lynch syndrome in a family followed for more than 45 years.

BACKGROUND: Lynch syndrome, is an autosomal dominantly inherited disease that predisposes individuals to a high risk of colorectal cancers, and some mismatch-repair genes have been identified as causative genes. The purpose of this study was to investigate the genomic rearrangement of the gene in a family with Lynch syndrome followed for more than 45 years. CASE PRESENTATION: The family with Lynch syndrome is family N, who received colorectal cancer treatment for 45 years. The proband of family N had multiple colorectal and uterine cancers. Because the proband met the diagnostic Amsterdam criteria and was Microsatellite instability (MSI) - positive, we performed genetic testing several times. However, germline mutations in MLH1 and MSH2 genes were not found by long-distance PCR or RT-PCR/direct sequencing analysis within the 45-year follow-up. MLPA analysis showed that the genomes of the proband and proband's daughter contained a deletion from exon 4 through exon 19 in the MLH1 gene. Her son's son and her daughter's son were found to be carriers of the mutation. CONCLUSIONS: For carriers of mismatch-repair gene mutation among families with Lynch syndrome, the onset risk of associated cancers such as uterine cancer is particularly high, including colorectal cancer. The diagnosis of carriers among non-onset relatives is important for disease surveillance.

Pancreatic metastasis of papillary thyroid carcinoma preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report with review of literatures.

Pancreatic metastatic tumors from thyroid carcinoma are extremely rare. We report a case of an 80-year-old female with a pancreatic metastatic tumor derived from papillary thyroid carcinoma which was initially resected 158 months prior to detection of the metastatic pancreatic tumor. The patient has encountered cervical lymph-node metastasis on three occasions following the initial operation. Metastatic pancreatic lesions and cervical lymph nodes were first detected using 18-fluorodeoxyglucose positron-emission tomography/computed tomography, and she was preoperatively diagnosed using endoscopic ultrasound-guided fine-needle aspiration biopsy. A coin lesion, 10 mm in size, was detected in the left lung by chest computed tomography with no abnormal uptake in 18-fluorodeoxyglucose positron-emission tomography/computed tomography. Distal pancreatectomy and cervical lymph-node dissection were performed. Adjuvant chemotherapy with weekly paclitaxel was administered because anaplastic transformation had been detected in one of the cervical lymph nodes. The patient eventually died from multiple lung metastases 11 months after removing the metastatic pancreatic lesion. We reported a rare case of a pancreatic metastatic tumor from thyroid carcinoma, and found that 18-fluorodeoxyglucose positron-emission tomography/computed tomography and endoscopic ultrasound-guided fine-needle aspiration biopsy are useful for preoperatively diagnosing tumors.

[A Case of Simultaneous Recurrence of Colon Cancer at the Drain Placement and Anastomotic Sites Postoperatively].

A woman in her 70s presented to our hospital with abdominal pain and right lower abdominal mass. Colonoscopy revealed circumferential ascending colon cancer. She underwent right hemicolectomy, D3 lymphadenectomy, and ileocolonic functional end-to-end anastomosis. The tumorwas pathologically diagnosed as T4aN1M0, Stage Ⅲa. Nine months afterthe first surgery, tumor marker levels increased, and detailed examination yielded a diagnosis of isolated recurrence at the site of drain removal in the abdominal wall. The tumor was resected without exposure. Four months after the second surgery, the tumor recurred in the abdominal wall. Furthermore, colonoscopy revealed anastomotic recurrence. Both recurrent tumors at the anastomotic site and in the abdominal wall were resected. No more recurrence has been detected to date. In this case, a possible cause of recurrence is implantation of cancer cells. Sufficient consideration should be given to innovations in intraoperative maneuvers and surgical wound protection, among others.

Acinar Cell Cystadenocarcinoma of the Pancreas.

Acinar cell cystadenocarcinoma is a rare malignant epithelial neoplasm of the pancreas with a diffusely cystic, gross architecture in which the cysts are lined with neoplastic epithelial cells that demonstrate evidence of pancreatic exocrine enzyme production. This is the 10th case that has been reported in the literature. A 77-year-old male complaining of left hypochondrial pain was referred to our hospital for treatment of a pancreatic tumor. A huge, honeycomb-structured tumor was detected in the pancreatic tail. Distal pancreatectomy with total resection of the residual stomach and partial resection of the transverse colon were performed. Microscopically, there were variably sized cystic lesions in the tumor. Immunohistochemical examinations revealed that tumor cells were positive for alpha 1-antichymotrypsin and alpha 1-trypsin, showing that tumor cells had features of pancreatic acinar cells. Thus, the tumor was diagnosed as acinar cell cystadenocarcinoma. Herein, we report a rare case with acinar cell cystadenocarcinoma, which is the 10th case reported in the literature based on a PubMed search. We managed to resect the tumor completely by distal pancreatectomy with total resection of the residual stomach and partial resection of the transverse colon. The patient is still alive 26 months after surgery without any recurrence after 1 year of adjuvant chemotherapy with S-1.

Intranuclear accumulation of galectin-3 is an independent prognostic factor for patients with distal cholangiocarcinoma.

Galectin-3 has been reported to be associated with the prognosis of patients with various malignancies; however, it has not yet been investigated in patients with extrahepatic cholangiocarcinoma (EHCC). Expression of galectin-3 was retrospectively examined in 58 patients with EHCC: 21 with perihilar cholangiocarcinoma and 37 with distal cholangiocarcinoma (DCC). The Cox proportional hazard model was used to identify independent prognostic factors. Intranuclear accumulation of galectin-3 (gal-3-INA) was associated with poorer overall survival (OS) in all patients (P=0.003), as well as in patients with DCC (P=0.004). Patients with gal-3-INA also exhibited a poorer disease-free survival (DFS) than those without gal-3-INA in all patients with EHCC (P<0.001), and in patients with DCC (P<0.001). Gal-3-INA was an independent prognostic factor of OS and DFS in all patients [OS: Hazard ratio (HR), 4.470; 95% confidence interval (CI), 1.759-11.357; P=0.002; and DFS: HR, 5.116; 95% CI, 2.025-12.925; P=0.001]. Gal-3-INA was also an independent prognostic factor in patients with DCC (OS: HR, 2.979; 95% CI, 1.035-8.570; P=0.043; and DFS: HR, 6.773; 95% CI, 1.558-29.439; P=0.011). In the analysis of patients with DCC, the number of patients with high galectin-3 expression (P=0.038), recurrence (P<0.001), distant metastases (P<0.001), R0 status (P=0.029) or microscopic vascular invasion (P=0.019) was significantly higher in the gal-3-INA-positive group than in the gal-3-INA-negative group. In conclusion, gal-3-INA was identified as a strong prognostic factor for OS and DFS in patients with DCC.

Concomitant existence of pheochromocytoma in a patient with multiple endocrine neoplasia type 1.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant inherited disorder that is classically characterized by the presence of neoplastic lesions of the parathyroid glands, the anterior pituitary gland, and the pancreas. However, MEN1 with concomitant pheochromocytoma is extremely rare. CASE REPORT: We report a case of MEN1 concomitant with pheochromocytoma. A 44-year-old Japanese man, who had undergone total parathyroidectomy due to primary hyperparathyroidism at the age of 18, was referred to our hospital with a complaint of a large abdominal tumor. He was diagnosed as having a giant insulinoma (maximum diameter 18 cm) in the pancreatic tail, five other non-functional neuroendocrine tumors in the pancreatic body and tail, multiple liver metastases of pancreatic neuroendocrine tumors, a pituitary prolactinoma, non-functional adrenal cortical adenomas, a pheochromocytoma in addition to a subcutaneous neurofibroma, and a cutaneous fibroma. The genetic screening revealed a deletion mutation at codons 83-84 in exon 2 of the MEN1 gene. He underwent distal pancreatectomy, splenectomy, cholecystectomy, right adrenalectomy, abdominal subcutaneous tumor excision, and cutaneous tumor biopsy for the purpose of tumor volume reduction. Extended right posterior segmentectomy with partial hepatectomy of S2, S3, and S8 was performed to resect residual tumors 9 months after the initial surgery. Although a newly formed liver metastasis was found 19 months after the hepatectomy, he is still alive 4 years and 4 months after the initial surgery. CONCLUSIONS: We reported an extremely rare case of giant insulinoma and simultaneous occurrence of pheochromocytoma and adrenal cortical adenoma in the ipsilateral adrenal gland in a patient clinically and genetically diagnosed as having MEN1.

MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm.

Despite strict criteria for the observation of intraductal papillary mucinous neoplasm (IPMN), it remains difficult to distinguish invasive IPMN from non-invasive IPMN. The aim of the present study was to identify an indicator of invasive IPMN. The present study retrospectively evaluated 53 patients (28 with non-invasive and 25 with invasive IPMN) who underwent resection of IPMN, and examined the usefulness of the MIB-1 labeling index as an indicator of invasive IPMN. The MIB-1 labeling indexes in patients with invasive IPMN were significantly higher compared with those with non-invasive IPMN (P<0.001). A receiver operating characteristic curve revealed that the area under the curve was 0.822. These results suggested that a cut-off level for the MIB-1 labeling index should be set to 15.5% to distinguish invasive from non-invasive IPMN. A multivariate analysis using a logistic regression model revealed the MIB-1 labeling index (hazard ratio, 18.692; 95% confidential interval, 4.171-83.760; P<0.001) and the existence of mural nodules (hazard ratio, 6.187, 95% confidential interval, 1.039-36.861; P=0.045) were predictive factors for invasive IPMN. However, no statistically significant differences were observed between patients with a lower MIB-1 labeling index and patients with a higher MIB-1 labeling index (P=0.798). The MIB-1 labeling index must be considered as a candidate for the classification of IPMN.

[A Long-Term Survival Case of Unresectable Hilar Bile Duct Cancer Treated with Gemcitabine].

A 69-year-old woman was diagnosed with liver dysfunction on blood testing in a nearby clinic. Computed tomography revealed stenosis of the hilar bile duct. Accordingly, an endoscopic nasobiliary drainage tube was inserted in the left hepatic duct and she was referred to our hospital for diagnostic examinations and treatment. The endoscopic retrograde cholangiopancreatography findings revealed obstruction of the cystic duct and stenosis of the hilar bile duct due to inflammation of the cystic duct or inflammation of the clamping type by cholecystitis. Considering the possibility of malignant tumor, surgical operation was performed. Radical resection was considered impossible and we instead performed cholecystectomy and resection of a bile duct wall specimen for diagnosis. The pathological diagnosis was poorly differentiated tubular adenocarcinoma. The patient was treated with gemcitabine as systemic chemotherapy for unresectable hilar bile duct cancer. Currently, 78 months after the start of chemotherapy, the patient is alive and well, without tumor progression.

Our contrivances to diminish complications after pylorus-preserving pancreaticoduodenectomy.

The objective of this study is to diminish postoperative complications after pylorus-preserving pancreaticoduodenectomy. Pylorus-preserving pancreaticoduodenectomy is still associated with major complications, especially leakage at pancreatojejunostomy and delayed gastric emptying. Traditional pylorus-preserving pancreaticoduodenectomy was performed in group A, while the novel procedure, an antecolic vertical duodenojejunostomy and internal pancreatic drainage with omental wrapping, was performed in group B (n = 40 each). We compared the following characteristics between the 2 groups: operation time, blood loss, time required before removal of nasogastric tube and resumption of food intake, length of hospital stay, and postoperative complications. The novel procedure required less time and was associated with less blood loss (both P < 0.0001). In the comparison of the 2 groups, group B showed less time for removal of nasogastric tubes and resumption of food intake, shorter hospital stays, and fewer postoperative complications (all P < 0.0001). The novel procedure appears to be a safe and effective alternative to traditional pancreaticoduodenectomy techniques.

[Treating Side Effects of FOLFIRINOX--A Study of the Effect of Hange-Shashin-To on Preventing Diarrhea].

OBJECTIVES: FOLFIRINOX is an effective therapy for unresectable advanced pancreatic cancer. However, FOLFIRINOX has side effects of blood and gastrointestinal toxicity. Diarrhea, one of the side effects of CPT-11, sometimes becomes serious. We studied whether Hange-shashin-to could prevent diarrhea caused by CPT-11. METHODS: Seven patients who were diagnosed with unresectable pancreatic cancer, either Stage Ⅳor recurrent disease, were enrolled. They took 2.5 g of Hange-shashin-to before each meal starting one day before FOLFIRINOX, and continued taking it for one week. We examined the occurrence of diarrhea by using CTCAE retrospectively. RESULTS: The median age was 61 years. The median number of chemotherapy courses was 4. The frequency of diarrhea was lower, compared to the results of ACCORD11 trial and the domestic phaseⅡ clinical trials. In addition, Grade 3 or more serious diarrhea was not observed, even in the patients with genetic polymorphisms of UGT1A1. CONCLUSION: The incidence of diarrhea in patients treated with Hange-shashin-to in our department was lower compared to the ACCORD11 trial and domestic phase Ⅱ clinical trials. Hange-shashin-to is useful to allay the severity of diarrhea caused by CPT-11 in FOLFIRINOX therapy.

[An inflammatory pseudotumor of the liver mimicking a metastatic lesion of gallbladder cancer - a case report].

An inflammatory pseudotumor (IPT) of the liver is a rare benign disorder.As its characteristics based on computer tomography and magnetic resonance imaging findings are still unclear, it is difficult to distinguish IPT from malignant diseases of the liver.Herein, we report a case of IPT of the liver concurrent with advanced gallbladder cancer, which we could not diagnose preoperatively.First, we performed lateral segmentectomy of the liver.Second, a radical operation for gallbladder cancer was performed after confirming that the hepatic tumor was IPT via intraoperative pathological diagnosis.Therefore, modalities less invasive than surgical resection should be innovated, even though surgical resection is accurate.

IgG4-related intrahepatic sclerosing cholangitis resulting in sepsis caused by secondary suppurative inflammation: report of a case.

We report a case of pre-disseminated intravascular coagulation caused by secondary suppurative inflammation in a patient with immunoglobulin (Ig) G4-related sclerosing cholangitis. The patient was a 78-year-old man in whom a localized stenosis of the intrahepatic bile duct was found without any other bile duct stricture or symptoms. He underwent surgical resection 6 months later for acute severe cholangitis and sepsis caused by bile duct obstruction. The resected specimen contained an abscess and nodulary mass in the liver. Immunohistochemical analysis revealed IgG4-positive plasma cell infiltration, whereby we diagnosed IgG4-related sclerosing cholangitis. As IgG4-related sclerosing cholangitis limited to within the intrahepatic portion is extremely rare, we present this case with a review of the literature.

[A case of metastatic liver carcinoma treated with radiofrequency ablation and hepatectomy].

We report a case of metastatic liver carcinoma treated by radiofrequency ablation (RFA) and hepatectomy. A 53-year-old man suffering from sigmoid colon carcinoma and unresectable multiple liver metastases was treated with capecitabine and oxaliplatin and bevacizumab. After the seventh course, tumor reduction was confirmed but liver dysfunction meant that it was difficult to continue the same regimen. Because preoperative evaluation of liver function showed a high risk of postoperative liver failure, a combination of partial hepatectomy and RFA was planned in order to reduce the amount of liver resection. High anterior resection, partial hepatectomy and RFA were performed as planned. He underwent S-1 therapy following 7 courses of irinotecan, S-1, and bevacizumab therapy. To date, no recurrence has been observed 18 months after the operation. A combination of hepatectomy and RFA is expected to be an effective local treatment for multiple liver metastases of colorectal cancer, although the evidence is currently insufficient.

Description of pylorus-preserving pancreaticoduodenectomy in elderly patients.

BACKGROUND/AIMS: The aim of this paper is to examine the safety and feasibility of pylorus-preserving pancreaticoduodenectomy in elderly patients. METHODOLOGY: The study population consisted of 40 consecutive patients. They were divided into two groups: Group A (<75 years old) and Group B (=75 years old). Reconstruction with a vertical duodenojejunostomy and internal pancreatic drainage with an omental wrapping was performed on the patients in both the groups. RESULTS: Less time was required to complete the operations in Group B (280±20min) than in Group A (386±88min; p=0.0006). Intraoperative blood loss in Group B was significantly lesser (365±109g) than that in Group A (629±249g; p=0.0026). No statistically significant difference was observed between both groups, in terms of the length of time required until food intake resumed and length of hospital stay. Although the rate of postoperative complication was higher in Group B (10.0%), no statistically significant difference was observed. CONCLUSIONS: Pylorus-preserving pancreaticoduodenectomy with a vertical duodenojejunostomy and internal pancreatic drainage with an omental wrapping seems safe and can be performed on elderly patients without a significant risk of complications.

Emergency operation for phlegmonous gastritis.

Phlegmonous gastritis is a rare inflammatory lesion in which bacterial infection occurs in the gastric wall. A case of phlegmonous gastritis producing an intramural filling defect in the stomach is presented. Endoscopy showed edematous and reddened gastric mucosa with a mass lesion in the gastric body and antrum. An abdominal CT scan showed diffuse and irregular thickening of the gastric wall. At emergency operation, a total gastrectomy with splenectomy was performed. The most important differential diagnosis is carcinoma, especially scirrhous-type gastric cancer. Radiographic findings of phlegmonous gastritis resemble those of scirrhous gastric cancer. More frequent recognition of this disease, early diagnosis and prompt institution of treatment is essential.