Duodenal somatostatinoma associated with Von Recklinghausen’s disease

Somatostatinomas are rare, malignant, somatostatin-producing neuroendocrine tumors with a prevalence of one in 40 million. The coincidence of Von Recklinghausen’s disease and duodenal somatostatinoma has been known since 1982. We report the case of a 57-year-old female patient with Von Recklinghausen’s disease and a tumor of the pancreatic head that was diagnosed due to painless icterus. Histopathological examination after pylorus-preserving pancreatoduodenectomy revealed the existence of a duodenal somatostatinoma with lymph node metastases. Characteristics of the association of von Recklinghausen’s disease and somatostatinoma, and therapy and prognosis will be discussed. In patients with Von Recklinghausen’s disease and an ampullary tumor, a somatostatinoma should be considered. In contrast to its pancreatic counterparts, duodenal somatostatinoma is frequently associated with Von Recklinghausen’s disease, often contains psammoma bodies, is rarely associated with a recognizable “somatostatin syndrome”, and is hardly ever associated with demonstrable metastases at the time of diagnosis. Small tumors arising in the duodenum may be treated with local excision, whereas larger tumors should be treated by total excision, which may entail a partial pancreatoduodenectomy.     

59-jähriger Patient mit rezidivierendem Erröten bei blander Leberzyste

A 59-year-old patient was admitted to hospital with recurrent flush symptoms and pathologically elevated 5-hydroxyindoleacetic acid (5-HIAA) levels in urine. A known cystic lesion of the liver which had been followed for years by ultrasound examinations and was regarded as a bland hepatic cyst was identified as a metastasis of a neuroendocrine neoplasm of the ileum. In two sequential surgical interventions the primary tumor with mesenteric lymph node metastases as well as the cystic liver metastasis could be resected. After surgical treatment an R1 situation at the mesenteric site and suspicious para-aortic lymph nodes remained. The long established treatment of factor-V Leiden mutation by anticoagulation with phenprocoumon was supplemented by deep subcutaneous injection of lanreotide autogel every 4 weeks. Currently, there is no evidence for progressive disease and the patient is without clinical signs of a carcinoid syndrome.     

Pancreatic carcinoid: transcatheter arterial chemoembolization of liver metastases

Carcinoid tumors are a common disease in the gastrointestinal tract, but are extremely rare in pancreas. To our knowledge, only 33 carcinoid tumors of pancreas have been reported in the English literature. Complete surgical resection of pancreatic carcinoid contributes to prolonged survival. But distant metastases, including liver metastasis, prevent long-term survival. We report here one resected case of pancreatic carcinoid tumor with liver metastases. Postoperatively, multiple liver metastases had arisen in the bilateral lobe of the liver and were treated with transcatheter arterial chemoembolization. In this case, transcatheter chemoembolization was effective for palliation for postoperative liver metastases.     

EN BLOC REMOVAL OF A GASTRIC CARCINOID TUMOR USING ENDOSCOPIC SUBMUCOSAL DISSECTION TECHNIQUES

Endoscopic submucosal dissection (ESD) has recently been applied to the resection of gastric submucosal tumors other than carcinoid tumors. We describe a case of gastric carcinoid tumor enucleated with ESD. An 82‐year‐old woman was referred for treatment of a gastric tumor. Upper gastrointestinal endoscopy revealed a solitary submucosal tumor in the greater curvature of the gastric body. We diagnosed a carcinoid tumor by histological examination of biopsy specimens. Endoscopic ultrasound revealed a hypoechoic mass in the submucosal layer. Neither lymph node nor liver metastasis was recognized. The serum gastrin level was normal, and this tumor was classified as a type III (sporadic) carcinoid tumor. Endoscopic resection was decided on considering her age, general status, and wishes. We used ESD techniques, because the tumor was too large to be resected by conventional endoscopic mucosal resection. En bloc resection was performed. Histological examination of the 13 × 19 × 11 mm resected specimen showed that the cut end was free of tumor cells. Type III carcinoid tumor is usually treated by surgical resection with lymph node dissection. However, in high‐risk elderly patients we consider ESD to be a therapeutic option for local control of gastric carcinoid tumors.     

Jejunal carcinoid tumor mimicking leiomyosarcoma: preoperative diagnosis by endoscopic biopsy

Primary carcinoid tumor of the jejunum is rare, and is an unusual cause of massive gastrointestinal bleeding. A case of primary jejunal carcinoid tumor in a 39-year-old woman who presented with massive hematochezia is described. Both upper and lower gastrointestinal endoscopies showed no abnormalities. An abdominal computed tomographic scan, small-bowel barium contrast studies, and small-bowel endoscopy showed a subserosal mass, of 5 × 4 cm, with a cavity suggesting central necrosis, and a deep mucosal ulceration, located in the proximal jejunum. Although these clinical presentations were strongly suggestive of a leiomyosarcoma, histologic examination of biopsy samples obtained by enteroscopy confirmed the diagnosis of jejunal carcinoid tumor. The patient underwent radical jejunal resection and recovered uneventfully. In spite of the large size of the tumor, there was one solitary lymph node metastasis, but no evidence of liver metastases. This kind of jejunal carcinoid tumor, presenting with massive gastrointestinal bleeding and a subserosal bulky growth mimicking a leiomyosarcoma, has not been reported previously. Moreover, this is a rare case of a jejunal carcinoid which was diagnosed preoperatively by small bowel-endoscopic biopsy. Received: August 9, 1999 / Accepted: April 28, 2000     

Anal metastasis from rectal adenocarcinoma

The metastasis of rectal cancer to the anus is rare. Here, we report a case of advanced rectal cancer, which had a diffuse venous invasion with anal metastasis and multiple lymph node and liver metastases. The patient was a 72-year-old woman who complained of perianal pain and fresh blood in the stools for 6 months. She had neither history of fistula-in-ano nor anal surgery. Digital examination revealed a 2-cm tumor at the 7 o’clock position, and the barium enema and colonoscopy confirmed advanced rectal cancer. Abdominal computed tomography revealed thickness of the upper rectum wall, right inguinal lymph node of 10 mm and multiple liver metastases. Laparoscopically assisted anterior resection, anal tumor resection, and right inguinal lymph node resection were performed, and the histopathological examination of the resected primary and metastatic tumors confirmed similar findings of moderately differentiated adenocarcinoma, suggestive of metastasis of the rectal cancer to the anal region. In the next procedure, she had the liver lesions resected. This case suggested the importance of the careful examination of the anus during colonoscopy, or digital examination for the detection of anal metastasis.     

Living-related liver transplantation for multiple liver metastases from rectal carcinoid tumor： A case report

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasono-graphy. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endo-scopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.     

Metastasis of primary gallbladder carcinoma in lymph node and liver

AIM: To evaluate the patterns with metastasis of gallbladder carcinoma in lymph nodes and liver. METHODS: A total of 45 patients who had radical surgery were selected. The patterns with metastasis of primary gallbladder carcinoma in lymph nodes and liver were examined histopathologically and classified as TNM staging of the American Joint Committee on Cancer. RESULTS: Of the 45 patients, 29 (64.4%) had a lymph node positive disease and 20 (44.4%) had a direct invasion of the liver. The frequency of involvement of lymph nodes was strongly influenced by the depth of the primary tumor (P= 0.0001). The postoperative survival rate of patients with negative lymph node metastasis was significantly higher than that of patients with positive lymph node metastasis (P= 0.004), but the postoperative survival rate of patients with Nl lymph node metastasis was not significantly different from that of patients with N2 lymph node metastasis (P= 0.3874). The postoperative survival rate of patients without hepatic invasion was significantly better than that of patients with hepatic invasion (P= 0.0177). CONCLUSION: Complete resection of the regional lymph nodes is important in advanced primary gallbladder carcinoma (PGC). The initial sites of liver spread are located mostly in segments IV and V. It is necessary to achieve negative surgical margins 2 cm from the tumor. In patients with hepatic hilum invasion, extended right hepatectomy with or without bile duct resection or portal vein resection is necessary for curative resection.     

Carcinoid of the papilla of Vater; a case report

A 68-year-old Japanese man, without any symptoms, was found to have a carcinoid tumor of the Ampulla of Vater. A physical examination indicated no anemia or jaundice and no abnormal findings at all in the chest or abdomen. Except for glucose intolerance, the routine laboratory data were normal. An endoscopic biopsy was performed that suggested malignant tumor cells. There were no signs of carcinoid syndrome. A pylorus-preserving pancreatoduodenectomy with extensive lymph node dissection was performed. Histological and immunohistochemical studies resulted in the diagnosis of a carcinoid of the papilla of Vater, without regional lymph node metastases. Although postoperative, an anastomotic leakage of pancreaticogastrostomy was noted; the pancreatic fistula was closed seven weeks later to use the somatostatin analogue.     

Liver metastases of a minute rectal carcinoid less than 5mm in diameter: a case report

We report a case of liver metastases of a minute rectal carcinoid less than 5mm in diameter, which was found during the postoperative follow-up course of a stomach cancer patient. For the early stomach cancer, laparoscope-assisted distal gastrectomy with lymph node dissection was performed on August 26, 1998. Later, abdominal CT revealed space-occupying lesions in the liver (S2). Metastatic tumors of the stomach cancer were suspected, but further examination revealed that the lesions were metastatic tumors due to a rectal carcinoid tumor. Ten months later, metastatic carcinoid tumors were found in the liver (S1, S5, S6, S7, S8). Subsegmentectomy of the liver (S7) and microwave coagulation therapy (S1, S5, S6, S8) were performed. Carcinoid tumors metastatic to the lymph nodes, liver, and other areas have been reported, but all were larger than 20mm in diameter. In this case, the primary tumor was less than 5mm in diameter, which is extremely rare. This patient was successfully treated with lateral segmentectomy, subsegmentectomy (S7), microwave coagulation therapy of the liver, and transanal extirpation. She is presently in a good condition and has had no recurrence of the carcinoid tumor from ten months after the last hepatectomy.     

Primary hepatic carcinoid tumor with metachronous lymph node metastasis after long-term follow up

A case of hepatic carcinoid tumor occurring in a 71-year-old man is reported. The tumor was diagnosed initially as a hepatocellular carcinoma, and was then shown after resection histologically to be a carcinoid tumor. The tumor cells formed small nests and trabeculae separated by fibrous septa and were positive for Grimelius staining. Immunohistochemically, most of the tumor cells stained positive with chromogranin A and neuron-specific enolase. After a follow up for 5 years and 7 months, the patient developed tumors in lymph nodes between the remnant liver and the lesser curvature of the stomach with no tumors in other organs. Histologically, the tumor cells in the lymph nodes demonstrated a pattern of the immunostainings consistent with carcinoid tumor. After lymphadenectomy, the patient is free from recurrence in the regional lymph nodes for more than 1 year. This case is con-sidered to be a primary hepatic carcinoid tumor with metachronous lymph node metastasis.     

Early colonic carcinoma with extensive lymph node metastases: case report and review of literature

An 81-year-old woman had an early carcinoma invading focally into the upper submucosa of the middle-transverse colon, which was accompanied by extensive lymph node metastases and resulted in a poor prognosis. Although her tumor was small and flat, a rim of pale yellow-speckled mucosa adjacent to the tumor enabled its earlier detection. To further study the exceptional lymph node metastases we studied the expression of intestinal trefoil factor and sialyl Tn antigen immunohistochemically on the resected specimen. Their simultaneous expression in lymph node metastasis further supports the aggressive nature of this tumor.     

Typical and atypical pulmonary carcinoids : outcome in patients presenting with regional lymph node involvement

STUDY OBJECTIVE: Typical pulmonary carcinoid tumors are well-differentiated neuroendocrine tumors that are associated with good patient survival rates, while atypical carcinoid tumors are more aggressive and have worse patient survival rates. Because these tumors rarely involve the thoracic lymph nodes at presentation, it is currently unknown to what extent the presence of thoracic lymph node metastases at the time of diagnosis influences patient survival. METHODS: A computerized search of the medical records for pulmonary carcinoid tumor at the Mayo Clinic from 1976 to 1997 revealed 517 patients, from which we identified 36 patients with pulmonary carcinoid tumors involving regional thoracic lymph nodes but without distant disease. For each patient, we reviewed the tumor histology, stage, and outcome. In addition, because the histologic criteria for the diagnosis of carcinoid tumors had changed significantly during the time of the study, we reexamined all of the histologic specimens using the current World Health Organization (WHO) criteria for classifying pulmonary neuroendocrine tumors. RESULTS: After reclassification with the WHO criteria for neuroendocrine tumors, 23 patients had typical carcinoid tumors with thoracic lymph node involvement. At the last follow-up, 19 patients had no evidence of disease (NED), 2 patients had developed systemic metastases (SM) and are still alive, and 2 patients had died. Eleven patients had atypical carcinoid tumors with thoracic lymph node involvement. At the last follow-up, four patients had NED, seven patients had developed SM within a median time of 17 months, and six patients with SM died shortly thereafter (median survival time, 25.5 months), while one is still alive. Two patients had been reclassified with large cell neuroendocrine carcinoma at the time of this review; both of these patients had developed SM (at 4 months and 21 months after diagnosis) and had died (at 15 months and 21 months after diagnosis, respectively). CONCLUSIONS: These data suggest that patients with atypical pulmonary carcinoid tumors with regional lymph node metastases have a high likelihood of developing recurrent disease if treated with surgical resection alone and have significantly worse outcome (p < 0.001) compared to those patients with typical carcinoid tumors with thoracic lymph node involvement.     

Carcinoid heart disease in patients without hepatic metastases

Most carcinoid tumors originate in the gut. Carcinoid heart disease typically occurs when tumor progression results in the formation of hepatic metastases, which allow vasoactive substances to reach the heart without being metabolized in the liver. Except for patients with primary ovarian carcinoid tumors, the occurrence of carcinoid heart disease without hepatic metastases has been reported only anecdotally. From a retrospective analysis of 265 patients, 4 patients were identified who developed carcinoid heart disease in the absence of liver metastases or primary tumors located in the ovaries. All 4 patients had metastases to the retroperitoneal lymph nodes and had carcinoid syndrome. The reasons for referral to cardiac evaluation by transthoracic echocardiography were findings on auscultation in 3 patients and exertional dyspnea in 1 patient. In conclusion, cardiac symptoms or findings on auscultation should prompt further evaluation by transthoracic echocardiography in these patients, although the classic prerequisites for development of carcinoid heart disease are lacking.     

Minute gastric carcinoid tumor with regional lymph node metastasis： A case report and review of literature

We have encountered an unusual case of gastric carcinoid tumor. Gastroscopic examination of this 32-year-old male patient showed a smooth protrusion at the greater curvature of the gastric body with a central depression, identified by subsequent biopsy as carcinoma. The patient had a normal serum gastrin level and was negative for anti-parietal cell antibody. Histological examination of the resected gastric tissues showed that the tumor was a carcinoid, 0.3 cm x 0.3 cm in size with only one regional lymph node metastasis. We reviewed the pathogenesis, clinical presentation, diagnosis and treatment of gastric carcinoids and raise the possibility of being a lymph vessel-related metastasis even for a minute carcinoid tumor. Sentinel lymph node biopsy is recommended for surgery of minute carcinoid tumors.     

A patient with gallbladder cancer with paraaortic lymph node and hepatic metastases who has survived for more than 13 years after the primary extended radical operation

Gallbladder cancer is a disease with poor prognosis, especially when it is associated with distant metastasis. Here we report a rare case of a patient with gallbladder cancer with extensive local and distant lymph node metastases and multiple liver metastases who has survived for more than 13 years through aggressive treatments. A 54-year-old woman developed right upper quadrant pain. Computed tomography (CT) revealed a papillary tumor in the gallbladder. Low-density tumors in segments 4, 5, and 8 of the liver and extensive paraaortic lymph node swelling were observed. She underwent central hepatic bisectionectomy and paraaortic lymphadenectomy. Two months later, hepatic metastases were found in segments 2, 3, 6, and 7, and percutaneous ethanol injection and transcatheter arterial chemoembolization were performed. Twelve months after the first surgery, CT revealed lymph node swelling around the right external iliac artery and behind the left renal vein. Metastatic lymph node dissection and resection and reconstruction of the right external iliac artery and vein with artificial graft replacements were performed. Two months later, CT revealed a paraesophageal lymph node swelling, which was treated by radiotherapy. At present, 13 years after the first surgery, and 11 years after the last radiotherapy, she is alive without any sign of recurrence.     

Flow cytometric examination of p53 protein in primary tumors and metastases to the liver and lymph nodes of colorectal cancer

PURPOSE AND METHODS: To confirm prognostic significance of overexpression of p53 in cases of colorectal cancer, expression of p53 protein was examined by flow cytometry in 113 cases of colorectal cancer and its metastasis to the liver and lymph nodes. RESULTS: Overexpression of p53 was found in 44 (39 percent) of the 113 primary tumors. There were no significant correlations among the level of p53 protein in the primary tumor, clinicopathologic features, and prognosis of colorectal cancer. Overexpression of p53 protein was detected in 72 percent (18/25) of liver metastases and in 40 percent (10/25) of lymph node métastases. Frequency of samples that were positive for p53 was significantly higher for liver metastases than for primary tumors and lymph node metastases (P<0.01). By comparing overexpression of p53 in primary tumors with that in corresponding secondary tumors, a decrease of more than 5 percent in the fluorescence index, compared with primary tumor, was not found in liver metastasis but was found in 20 percent of lymph node metastases. Incidence of cases with lower level expression of p53, compared with primary tumor, was significantly higher in lymph node metastases (32 percent) than in liver metastases (8 percent;P<0.05). CONCLUSIONS: From these results, it seems possible that overexpression of p53 may not be a good prognostic indicator of colorectal cancer and may be influenced by environments of the tumor.Presented at the meeting of the Japanese Gastroenterological Surgery, Fukui City, Japan, July 20 and 21, 1995.     

Different gene expression profiles in metastasizing midgut carcinoid tumors

The genetic events leading the progression of midgut carcinoid tumors are largely unknown. The disease course varies from patient to patient, and there is a lack of reliable prognostic markers. In order to identify genes involved in tumor progression, gene expression profiling was performed on tumor specimens. Samples comprised 18 primary tumors, 17 lymph node (LN) metastases, and seven liver metastases from a total of 19 patients. Patients were grouped according to clinical data and histopathology into indolent or progressive course. RNA was subjected to a spotted oligo microarray and B-statistics were performed. Differentially expressed genes were verified using quantitative real-time PCR. Self-organizing maps demonstrated three clusters: 11 primary tumors separated in one cluster, five LN metastases in another cluster, whereas all seven liver metastases, seven primary, and 12 LN metastases formed a third cluster. There was no correlation between indolent and progressive behavior. The primary tumors with Ki67 >5%, with low frequency of the carcinoid syndrome, and a tendency toward shorter survival grouped together. Primary tumors differed in expression profile from their associated LN metastases; thus, there is evidence for genetic changes from primary tumors to metastases. ACTG2, GREM2, REG3A, TUSC2, RUNX1, TPH1, TGFBR2, and CDH6 were differentially expressed between clusters and subgroups of tumors. The expression profile that assembles tumors as being genetically similar on the RNA expression level may not be concordant with the clinical disease course. This study reveals differences in gene expression profiles and novel genes that may be of importance in midgut carcinoid tumor progression.     

阑尾肿瘤急诊手术后追加外科手术的价值评估

目的探讨以阑尾炎起病的阑尾肿瘤行急诊手术后追加右半结肠切除术的临床意义以及对预后的影响。 方法收集32例阑尾肿瘤急诊手术后再行补救性右半结肠切除术患者的病例资料,分析其临床病理特征,并对预后进行评价。 结果32例患者均以阑尾炎起病,其中30例于外院行单纯阑尾切除术,2例行阑尾及回盲部切除术。术后中国医学科学院肿瘤医院病理会诊15例为类癌（类癌组）,17例为腺癌、黏液腺癌或者印戒细胞癌（非类癌组）,均在本院接受补救性右半结肠切除术。术后类癌组均未发现有癌残留及淋巴结转移,非类癌组有11例（64.7%）发现癌残留或者淋巴结转移。全组患者中位随访时间为60.5（12~156）月,其中类癌组均无复发、转移或死亡;非类癌组有6例出现疾病进展,4例因肿瘤死亡,其5年无病生存率（DFS）及总生存率（OS）分别为67.6%和68.6%。 结论对于以阑尾炎起病的阑尾肿瘤行急诊手术后病理结果提示类癌者,追加右半结肠根治术后可获得良好的长期预后。而对于腺癌、黏液腺癌或者印戒细胞癌者,有较高的肿瘤残存或淋巴结转移率,应及早追加右半结肠根治术,以决定最终的病理分期,指导后续辅助治疗,进而提高预后。     

乙肝表面抗原等因素对结直肠癌肝转移的影响

目的本研究将探讨乙肝表面抗原（HBsAg）等多项临床因素对结直肠癌肝转移的影响,为进一步治疗结直肠癌肝转移提供新的研究思路及方向。 方法回顾性分析青岛大学医学院附属医院2010年1月至2011年6月病理证明的结直肠癌患者892例。收集患者的相关临床资料（包括乙肝表面抗原、年龄、术前相关实验室检查、术后病理结果等）,研究是否会影响肝转移的发生。 结果结直肠癌是否发生肝转移两组患者在性别、年龄、肿瘤发生部位、大小、病理组织类型、是否造口、血清白蛋白、总胆红素及谷草转氨酶等方面相比,差异均无统计学意义（χ²=0.359,Z=-1.631,χ²=0.003,χ²=1.223,χ²=0.619,χ²=0.516,Z=-3.235,Z=-0.106,Z=-0.328;均P>0.05）。HBsAg阳性较阴性患者发生肝转移几率明显降低,差异有统计学意义（χ²=5.809,P<0.05）。另外,肝转移与分化水平（χ²=14.165,P<0.01）、浸润程度（χ²=17.808,P<0.01）以及淋巴结转移数目（χ²=41.798,P<0.01）有关,差异均有统计学意义。多因素logistic回归分析结果表示乙肝病毒表面阳性患者肝转移发生低,而低分化、浸润程度高、淋巴结转移多者肝转移率高。 结论乙型肝炎病毒表面抗原阳性会降低肝转移的发生几率。分化程度越低、浸润程度越高、淋巴结转移数多,越容易发生肝转移。