Cytoreductive surgery for advanced nonseminomatous germ cell tumors of testis

Cytoreductive surgery increases the cure rate in selected patients with advanced nonseminomatous germ cell tumor receiving chemotherapy. Complete resection of residual malignancy is a prerequisite for improving long-term disease-free survival after chemotherapy. Complete resection of residual tumor after three to four inductions with an optimal chemotherapy regimen is the current recommendation. Progression of disease on chemotherapy represents a contraindication to cytoreductive surgery. Residual malignant tissue is found in up to one third of patients with clinical evidence of residual disease after chemotherapy and currently constitutes a current indication for further chemotherapy. Incomplete resection of malignant tissue and elevated tumor markers after surgery are poor prognostic signs. Elevated serum tumor marker levels after chemotherapy and prior to surgery represent a relative contra-indication to surgery, and such patients should receive additional chemotherapy.     

Outcome of surgery for ileojejunal neuroendocrine tumors

Purpose

Neuroendocrine tumors (NET) of the ileum/jejunum are rare and may require different treatment options to provide long-term survival. The purpose of the study was to evaluate the outcome of surgery for ileojejunal NET.

Methods

A database of patients that underwent surgery for ileojejunal NETs between 1999 and 2010 was retrospectively analyzed regarding the clinical characteristics, surgical therapy, survival and prognostic factors.

Results

Only six of 97 patients with ileojejunal NET who underwent surgery had localized tumors (stage I/II), 29 had lymph node involvement (stage III) and 62 had distant metastases (stage IV) at the initial presentation. All stage I/II tumors were cured, in comparison to 69 % of stage III and 0 % of stage IV tumors (p = 0.01). Palliative surgery in combination with sequential multimodal treatment regimens resulted in a 5-year survival rate of 63 % in patients with stage IV tumors. A multivariate analysis showed that incomplete resection (HR 2.87; CI 1.18–6.98; p = 0.04) and distant metastases (HR 5.39; 95 % CI 1.23–23.57; p = 0.02) were associated with worse disease-specific survival.

Conclusions

Localized and regionally restricted ileojejunal NETs have an excellent prognosis after surgical treatment. Although stage IV tumors cannot be cured, an aggressive surgical approach in combination with medical or interventional treatment can provide long-term survival.     

Aggressive surgery for metastatic liver neuroendocrine tumors

BACKGROUND: Neuroendocrine tumors of the gastrointestinal tract (carcinoids, pancreatic endocrine tumors) have low malignant potential but can decrease survival rates if they spread to the liver (LNET). METHODS: The records of 16 patients with LNET primarily from gastrointestinal carcinoids treated surgically were retrospectively reviewed. RESULTS: There were 12 women and 4 men. Median age was 56 years (range 25 to 75). Thirteen (81%) had a carcinoid tumor and 5 had gastrinoma. Two patients with multiple endocrine neoplasia type 1 had both a gastric carcinoid and a jejunal gastrinoma. Eight patients (50%) had the carcinoid syndrome. Each patient had all identifiable LNET either resected or ablated. Ten patients had liver wedge resections, 1 right trisegmentectomy, 5 left hepatic lobectomies, and 2 radiofrequency ablations. Thirteen (81%) patients had concomitant bowel resections. Two patients had concomitant total gastrectomies to remove stomach primaries. The final patient had an extraintestinal pelvic primary or a liver primary. There were no operative deaths, and all 8 (100%) patients with the carcinoid syndrome had amelioration of symptoms. The 5-year actuarial survival rate was 82% with a median follow-up of 32 months. CONCLUSIONS: This study demonstrates that liver and concomitant extrahepatic surgery can be performed safely in patients with liver metastases because of carcinoids or pancreatic endocrine tumors. It results in excellent long-term survival and amelioration of symptoms. Surgery should be the first-line therapy for patients with LNET.     

Cytoreductive surgery in patients with advanced-stage carcinoid tumors

The role of aggressive surgical resections as well as criteria for resectability in patients with advanced carcinoid tumors is not clearly defined. Thirty patients (17 male and 13 female) who were previously diagnosed to have "unresectable carcinoid disease" were treated using a multimodality approach over a period of 2 years. Extensive liver involvement was present in 28 of 30 (93%) of the cases. Small bowel involvement was noted in 22 of 30 (73%), and peritoneal/retroperitoneal/mesenteric invasion was observed in 15 of 30 (50%) of the cases. Three patients had remote metastases (brain, bone, and eye). Twenty of 30 (66%) patients had carcinoid syndrome with severely disabling symptoms. Eight patients (26%) had small bowel obstruction. All patients underwent at least one surgical exploration/intervention. Radiofrequency ablation (RFA) of one or more liver lesions was performed as an adjunct in 22 of 30 (73%) patients. Six patients (20%) had a second surgical procedure. There were 11 complications in eight patients (27%) after the initial operation. Median hospital stay for patients who underwent RFA only, RFA/liver resection, and liver resection with abdominal tumor debulking were 2, 4, 8, and 16 days respectively. Twenty-five of 30 patients (83%) showed symptomatic improvement. Mean pre- and postoperative Karnofsky physical performance scores were 55 and 85 respectively (P < 0.02). Small bowel obstruction was due to adhesions in five patients. All patients with intestinal obstruction had complete relief of their symptoms postoperatively. 5-Hydroxyindolacetic acid levels decreased by 50 per cent in all patients with follow-up determinations available. Aggressive surgical exploration and tumor debulking could be performed with significantly improved symptomatic outcome and relatively minor complications. Longer follow-up is needed for assessment of effect on survival.     

Cytoreductive surgery for ovarian cancer

Cytoreductive surgery is a crucial component of the management of cancer of the ovary. Surgical cytoreduction of ovarian cancer volume has been associated with an increase in survival in all settings in which it has been studied. This association seems strongest, and the benefits of aggressive surgery are generally greatest, in patients with chemosensitive disease. Effective surgical management of ovarian cancer, therefore, requires competence in surgical anatomy and cytoreductive techniques and a thorough understanding of the patient's disease status and therapeutic goals.     

Metastatic neuroendocrine hepatic tumors: resection improves survival

BACKGROUND: The optimal treatment for hepatic metastases from neuroendocrine tumors remains controversial because of the often indolent nature of these tumors. We sought to determine the effect of 3 major treatment modalities including medical therapy, hepatic artery embolization, and surgical resection, ablation, or both in patients with liver-only neuroendocrine metastases, with the hypothesis that surgical treatment is associated with improvement in survival. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: Patients with metastatic liver-only neuroendocrine tumors were identified from hospital records. INTERVENTIONS: Patients were subdivided into those receiving medical therapy, hepatic artery embolization, or surgical management. MAIN OUTCOME MEASURES: Effect of treatment on survival and palliation of symptoms was analyzed. RESULTS: From January 1996 through May 2004, 48 patients with liver-only neuroendocrine metastases were identified (median follow-up, 20 months), including 36 carcinoid and 12 islet cell tumors. Seventeen patients were treated conservatively, which consisted of octreotide (n = 7), observation (n = 6), or systemic chemotherapy (n = 4). Hepatic artery embolization was performed in 18 patients. Thirteen patients underwent surgical therapy, including anatomical liver resection (n = 6), ablation (n = 4), or combined resection and ablation (n = 3). No difference was noted in the percentage of liver involved with tumor between the 3 groups. An association of improved survival was noted in patients treated surgically, with a 3-year survival of 83% for patients treated by surgical resection, compared with 31% in patients treated with medical therapy or embolization (P = .01). No difference in palliation of symptoms was noted among the 3 treatment groups (P = .2). CONCLUSION: In patients with liver-only neuroendocrine metastases, surgical therapy using resection, ablation, or both is associated with improved survival.     

Primary and secondary hepatic manifestation of neuroendocrine tumors

BACKGROUND: In comparison with most other malignancies, in the treatment of metastatic neuroendocrine tumors one also has to consider endocrine symptoms and natural progression of disease. Since hepatic metastasis predominates and endocrine symptoms correlate with functional tumor mass, hepatic resection may improve prognosis or even cure patients. PATIENTS AND METHODS: We reviewed 41 consecutive patients with metastatic neuroendocrine tumors and four patients with primary hepatic disease presenting between 1989 and 1999. The neuroendocrine tumors were classified according to their origin, pattern of metastasis, endocrine activity, and histology. Operative therapy including hepatic resections of different extent, liver transplantation, and removal of the primary tumor was analyzed. The median survival after initial diagnosis and after hepatic resection were major parameters of outcome. RESULTS: There were 26 low-grade malignant, 12 high-grade malignant, 2 biphasically differentiated neuroendocrine carcinomas, and 5 pancreatic endocrine tumors. Hepatic resections were performed in 25 patients, resections of the primary tumor in 40 patients. The median survival after initial diagnosis was 49 months; 50.5 months in patients with hepatic resection versus 47 months in those with no liver surgery. CONCLUSION: Hepatic resection improved the outcome of patients with liver metastasis due to neuroendocrine tumors tendentiously but not significantly.     

肝脏原发性神经内分泌肿瘤19例分析

目的总结肝脏原发性神经内分泌肿瘤（PHNET）患者的临床症状、影像学及实验室检查、手术治疗方式及预后情况,探讨其诊断、治疗及预后状况。 方法回顾性分析新疆医科大学第一附属医院2015年1月至2021年12月收治的19例PHNET患者的临床资料、影像学检查特点、诊治过程、病理学结果及治疗转归。 结果19例PHNET患者中位年龄47岁,其中男8例,女11例;上腹部疼痛8例,腹胀2例,体检发现8例,发热伴皮疹为主诉入院1例;CA19-9升高2例,CA125升高2例,AFP均无异常。肿瘤分级G1 2例,G2 13例,G3 4例。肿瘤平均大小为（6.68±3.11）cm,均显示突触素和嗜铬粒蛋白染色阳性。平均随访时间为（42.21±30.03）个月,行肝切除术的14例患者中因肿瘤复发死亡1例,未行外科手术治疗的5例中死亡3例,R0切除患者预后明显较好。 结论PHNET是一种非常罕见的肿瘤,临床特征无特异性,其最终诊断主要依靠病理和免疫组织化学检查。排除其他部位的转移后,根治性切除是PHNET的最佳治疗方案。     

Liver transplantation for metastatic neuroendocrine tumors.

OBJECTIVE: This article describes the experience with liver transplantation in patients with irresectable neuroendocrine hepatic metastases. SUMMARY BACKGROUND DATA: Liver transplantation has become an established therapy in primary liver cancer. On contrast, there is little experience with liver transplantation in secondary hepatic tumors. So far, in the majority of patients being transplanted for irresectable liver metastases, long-term results have been disappointing because of early tumor recurrence. Because of their biologically less aggressive nature, the metastases of neuroendocrine tumors could represent a justified indication for liver grafting. METHODS: In a retrospective study, the data of 12 patients who underwent liver transplantation for irresectable neuroendocrine hepatic metastases were analyzed regarding survival, tumor recurrence, and symptomatic relief. RESULTS: Nine of 12 patients currently are alive with a median survival of 55 months (range, 11.0 days to 103.5 months). The operative mortality was 1 of 12, 2 patients died because of septic complications or tumor recurrences or both 6.5 months and 68.0 months after transplantation. all patients had good symptomatic relief after hepatectomy and transplantation. Four of the nine patients who are alive have no evidence of tumor with a follow-up of 2.0, 57.0, 58.0, and 103.5 months after transplantation. CONCLUSIONS: In selected patients, liver transplantation for irresectable neuroendocrine hepatic metastases may provide not only long-term palliation but even cure. Regarding the shortage of donor organs, liver grafting for neuroendocrine metastases should be considered solely in patients without evidence of extrahepatic tumor manifestation and in whom all other treatment methods are no longer effective.     

Cytoreductive surgery in testicular cancer

Summary The role of cytoreductive surgery in testicular cancer has shifted from one of primary therapy to one of an adjunct to chemotherapy. In this setting, surgery restages the disease. It provides therapeutic benefit to many and determines the need for additional chemotherapy. Because of the heterogeneity of the tissue in the retroperitoneum, a thorough dissection is needed to reassess the patient adequately. Thoroughness is especially important in the case of teratoma. If active carcinoma is found in it, additional salvage chemotherapy is usually required. If teratoma without carcinoma is present, careful observation is required because of the propensity for local or distent later recurrence. The role of further chemotherapy in this group is not well defined. If neither carcinoma nor teratoma is present, the patient can be observed, because there is only a small likelihood of recurrence.     

Liver transplantation for neuroendocrine tumors

Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible, it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen symptomatic patients with unresectable NET liver metastases who had failed medical management were listed for transplantation. Two patients listed for transplantation underwent prior right lobectomies. Three patients were listed but did not undergo transplantation: one was lost to follow-up, one died 14 months after listing, and one remains waiting over 4 years. Eleven patients underwent liver transplantation, three with living donor grafts. There were four men (36.4%) and seven women (63.6%) who had a mean age of 51.2 ± 6.3 years. Three patients had distal pancreatectomies and one patient had a Whipple procedure at the time of transplantation. There were six nonfunctioning tumors (54.6%), three carcinoid tumors (27.3%), and two (18.2%) Vipomas. In one patient, with fulminant hepatic failure, the NET was an incidental finding in the explant. The 1- and 5-year survival among transplanted patients is 73% and 36%, respectively, with a mean follow-up of 34 ± 40 months (range 0 to 119 months). Of the three patients surviving more than 5 years, only one was disease free. In carefully selected patients with metastatic NETs, liver transplantation may be an appropriate option. Presented in part at the Fourth Americas Congress of the American Hepato-Pancreatico-Biliary Association, Miami, Florida, February 28, 2003.     

Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors

BACKGROUND: We reviewed 36 patients with liver metastases from islet cell tumors of the pancreas (n = 18) and carcinoid tumors (n = 18) who were treated with surgical resection (n = 16) or hepatic chemoembolization (n = 20). METHODS: All resections were complete and included 4 lobectomies, 6 segmental resections, and 6 wedge resections. There were no operative deaths. RESULTS: Median survival has not yet been reached, and the actuarial 5-year survival rate is 70%. Prognostic variables associated with improved disease-free survival included prior resection of the primary tumor and 4 or fewer metastases resected (P <.05). With an average of 3 chemoembolization procedures per patient, 17 of 20 patients (90%) demonstrated either a significant radiographic response (n = 5), stabilization of tumor mass (n = 2), or improvement of clinical symptoms (n = 10). Factors related to a sustained response (more then 1 year) included surgical resection of the primary tumor, 4 or more chemoembolization procedures, and liver metastases of 5 cm or smaller. Median survival after treatment was 32 months (range, 7-63 months), and the actuarial 5-year survival rate was 40%. CONCLUSIONS: Surgical resection of metastatic neuroendocrine tumors provides the best chance for extended survival. Chemoembolization effectively improves clinical symptoms and, in selected patients, may provide sustained tumor control.     

Radioguided surgery in the treatment of gastro-entero-pancreatic neuroendocrine tumors]

Neuroendocrine tumors are rare neoplasms. In most cases conventional imaging techniques (US,CT,RMN) are not able to identify primitive tumors. This fact conditions the approach to the treatment of these tumors. 111In-Pentetreotide scintigraphy (Octreoscan) permits to visualize occult primary tumor by somatostatin receptors, changing the clinical history of patients. This method can be used in guided surgery with a hand-held gamma probe allowing to improve the detection of occult tumor (inverse square law), giving to the patient further possibilities of survival. Intraoperative gamma probe was still utilized with success in the management of other tumors, as relapsed colorectal cancer, while reports about gamma probe in neuroendocrine tumors are poor because of the rarity of disease. In two cases we have utilized a gamma probe (ORIS model 2) in neuroendocrine tumors: in a case we have observed liver recurring localizations originating from pancreas, with high proliferative index (Ki-67 = 2033 x 10 HPF), and in a case liver metastatic carcinoid of lung. The difference between tumor and background counts was significant exceeds 2 standard deviation count rate. Gamma probe permits a radical cure in many cases and completes intraoperative ultrasound in order to provide the surgeon with other information on the intraoperative staging of the patient.     

Synaptophysin. A new marker for pancreatic neuroendocrine tumors

Synaptophysin (SYP) is a glycoprotein recently isolated from presynaptic vesicles of bovine neurons. Initial studies have demonstrated its presence in neurons in the brain, spinal cord and retina, and in adrenal medullary cells. A subsequent study demonstrated it in pancreatic islet cells and certain neuroendocrine (NE) neoplasms, including several pancreatic islet cell tumors. Based on these preliminary observations, we examined, by immunohistochemistry, conventionally fixed, paraffin sections of 57 pancreatic endocrine tumors with a monoclonal antibody to SYP. Furthermore, we compared the SYP immunoreactivity of 30 of these same tumors with that of neuron-specific enolase (NSE) and of chromogranin (CG). SYP was demonstrated in all but one of the 57 tumors. In the comparative study, for which material was available in only 30 cases, SYP and NSE were present in 29 of the tumors, whereas CG was seen in only 15 cases. We conclude that SYP is a highly sensitive and useful marker for pancreatic NE neoplasms. Moreover, in view of the increasingly evident limited specificity of NSE, SYP should be considered the marker of choice for pancreatic NE neoplasms.