Recently, genes encoding the succinate dehydrogenase subunit have been identified as the genes responsible for hereditary pheochromocytoma. Subsequent studies have demonstrated that pheochromocytoma/paraganglioma due to germline mutations of those genes are much more frequent than previously expected; a novel clinical entity “hereditary pheocyromocytoma/paraganglioma syndrome（HPPS）” has been established. A clinical and genetic study of Japanese HPPS patients has been initiated the fubdubgs are expected to facilitate better
Great progress has been achieved in the fields, especially genetics in pheochromocytoma. Before 2000, 10% of patients were believed to have a hereditary disease. After 2000, however, around 30% of pheochromocytoma patients assumed to have a hereditary disease following reason. 1）Nuclear genes encoding two mitochondrial complex II subunit proteins, SDHD and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas（ Hereditary pheochromocytoma/ paraganglioma syndrome）, in 5% of familial cases. respectively. 2）It is reported that 10% of apparently sporadic patients have unexpected germline mutation. Also, growing evidence suggest that mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis. However, these findings were obtained mainly from USA and Europe. Therefore, it remains uncertain whether these genes play a pathological role in populations outside these geographic locations. To overcome this problem, we set up multi-institute studies to determine diagnostic value of genetic testing in our country. In the present study, analysis of blood taken from 25 cases of malignant pheochromocytomas in Japanese subjects （13 abdominal paraganglioma and 12 adrenal pheochromocytomas） led to the identification of nine SDHB mutations. It should be noted that 7 SDHB mutations were detected in 13 abdominal paraganglioma-derived malignant cases （7/13）, whereas 2 SDHB mutation was observed in 10 malignant cases derived from adrenal pheochromocytoma （2/10）, in agreement with previous reports.
Pheochromocytoma （paraganglioma） is defined as a catecholamine-producing tumor originating from chromaffin cells in the adrenal medulla or extra-adrenal sympathetic ganglions. The diagnosis and treatment of pheochromocytoma is thought to be relatively simpler than those of other hormone-producing tumors. However, patients with this tumor may develop certain clinical conditions （e.g., hypertension crisis） that may be lifethreatening. In addition more than 10% of pheochromocytoma patients are diagnosed with malignant, although reliable histopathological criteria for predicting malignant behavior have not yet been established. Therefore, we review the current status and problems associated with the diagnosis, pharmacological treatment and radiotherapy of benign or malignant pheochromocytoma, and describe our experiences in this regard.
In the 1950’s, perioperative mortality rates ranging from 20 to 45% used to be reported for pheochromocytomas. However, since usage of α1-blockers perioperative mortality rate dropped to 3 to 4% in 1970’s. Also, important developments which have contributed to this major reduction in perioperative mortality rate are better imaging techniques for accurate preoperative tumour localization. It is important for physicians, surgeons and anesthesiologists to cooperate closely. Laparoscopic adrenalectomy has become the gold standard for removing adrenal masses because of their minimal invasiveness. Pheochromocytomas are no exceptions, and many reports say laparoscopic surgery is minimally invasive and safe to treat tumors smaller than 6cm in diameter. Hereditary pheochromocytomas show different frequencies of becoming malignant or multiple depending on each respective hereditary syndrome. Therefore, treatments for these would vary accordingly. Pheochromocytomas such as MEM2, VHL, and PGL1 are frequently multiple and rarely malignant. It is necessary to try to maintain adrenal function, and be careful to avoid lifelong corticosteroid replacement and acute adrenal insufficiency.
Diagnosis, treatment, and molecular mechanism of Lynch syndrome have been advanced by the development of ICG-HNPCC by InSiGHT. Although germline mutation of mismatch repair genes hasbeen identified as playing a causative role in Lynch syndrome, Lynch syndrome is still the subject of investigation, However, it is difficult to accumulate evidence by prospective randomized studies because of the nature of this syndrome. However, a Japanese version of the guidelines for treatment of Lynch syndrome is required by general clinicians, and the significance and difficultes establishing such guidelines are discussed.
Purpose: We evaluated the surgical treatment and long-term outcome of patients with familial adenomatous polyposis（FAP）who underwent restorative proctocolectomy. The timing of surgery, and selection of surgical procedure, must be carefully decided, considering the lifetime cancer risk of each patient while maintaining quality of life（QOL）at the highest level possible. Materials and Methods: Between 1970 and 2005, we encountered 73 patients with FAP in 16 families. Thirty patients were treated by total colectomy with ileo-rectal anastomosis（IRA）for patients with sparse rectal polyposis without cancer. Twenty-two patients were treated by proctocolectomy with ileal Jpouch anal canal anastomosis （IACA）, and 8 patients were treated by proctocolectomy with ileal J-pouch anal anastomosis（IAA）. Results: Mean follow-up after IRA was 21.7 years. Nine of the 30 （30%） treated by IRA developed cancer in the residual rectum. Five of 9 developed advanced cancer, and 5 died of cancer in the residual rectum. However, none of patients treated by IACA or IAA developed rectal cancer. The mean age at the development of colorectal cancer was 42.3 years in patients with system A（codon 2–479）or system B （codon 348–785） of APC gene mutation. The mean age at the development of colorectal cancer in patients with system C（codon 658–1283）and system D（codon 1099–1700）was 28.8 years. Conclusions: These cases suggest that we should perform restorative proctocolectomy by IACA for patients with system A–B, and by IAA for patients with system C–D.
【Purpose】The incidence of colorectal cancers on colonoscopy was compared with that of upper gastrointestinal tract cancers on gastroduodenoscopy in patients with Lynch syndrome. The clinical significance of colonoscopy and gastroduodenoscopy as surveillance procedures was examined.【Materials and Methods】 Forty-two patients with Lynch syndrome who were followed up for more than 2 years as of the end of December 2009 were studied. Endoscopic findings during the last 5 years were evaluated, the incidence of gastrointestinal cancers was calculated, and the clinical and pathological findings of adenomas and cancers were studied.【Results and Discussion】Cancers of the colorectum （5 cases, 7 lesions）, stomach （4 cases, 5 lesions） and duodenum （2 cases, 2 lesions） were detected during follow-up. In addition, 57 colorectal adenomas were detectid and were removed by colonoscopic resection. The frequency of detecting cancers per endoscopic examination was 3.1 ％ for colonoscopy and 4.2 ％ for gastroduodenoscopy. The incidence of colorectal cancers was lower than that of gastric and duodenal cancers. This finding suggests that the resection of precancerous lesions such as colorectal adenomas effectively reduced the occurrence of colorectal cancers. Surgical treatment was required in 2 patients, both of whom had not undergone colonoscopy for more than 24 months before lesion detection. Therefore, annual colonoscopy is recommended for surveillance in patients with Lynch syndrome. On the other hand, early detection of gastric cancer was more difficult: although gastroscopy was performed with 1–2 year interval, all but one lesion had submucosal or deeper invasion. The frequency of finding early lesions was lower than that of colonoscopy. However, annual gastroduodenoscopy is now needed for the surveillance and early detection of upper gastrointestinal tract lesions in patients with Lynch syndrome.