Hepatic resection for metastatic gastrointestinal and pancreatic neuroendocrine tumours: outcome and prognostic predictors

Background. Treatment modalities for hepatic metastases from neuroendocrine tumours (NETs) include surgery, somatostatin analogues and arterial embolization. The aims of this study were to evaluate the outcome of patients following surgery and to identify prognostic predictors of recurrent disease. Patients and methods. This was a retrospective clinico-pathological analysis of patients managed with hepatic NET metastases over a 13-year period (January 1994 to December 2006). Results. Eighteen patients with hepatic metastases from NET were identified with a median age of 53 years (range 31–75). The localization of the primary tumour was the terminal ileum (n=8), pancreas (n=7), appendix (n=2) or duodenum (n=1). Twelve patients had synchronous disease and six patients developed metachronous hepatic tumours over a median period of 20 months (range 6–144). Presenting symptoms included abdominal pain (n=13), recurrent diarrhoea (n=7) and flushing (n=7). Fifteen patients underwent surgery with complete cytoreduction and three patients had partial cytoreduction. The overall 2- and 5-year actuarial survival rates were 94% and 86%, respectively. The 2- and 5-year disease-free rates following hepatic resection with complete cytoreduction were both 66%. Partial or complete control of endocrine-related symptoms was achieved in all patients with functioning tumours following surgery. Recurrent disease occurred in four patients following complete cytoreductive surgery. Resection margin involvement was associated with developing recurrent disease (p=0.041). Conclusion. Surgical resection for hepatic NET metastases results in good long-term survival in selected patients and resection margin involvement was associated with recurrent disease.     

Combined liver and pancreas resection with biochemotherapy for metastatic ocular melanoma

Systemic therapy alone for metastatic melanoma is relatively ineffective, and surgical resection of metastases to a solitary site remains the best single treatment to improve survival. While cytoreductive surgery plus chemotherapy play a significant role in the management of advanced ovarian cancer, the precise role of surgery as an adjunct to systemic therapy for melanoma metastatic to multiple sites is not well defined. We report a patient with ocular melanoma metastatic to liver and pancreas treated by cytoreductive surgery consisting of mesohepatic resection, distal pancreatectomy, and portal node dissection, followed by biochemotherapy with dacarbazine and interferon alpha. The concept of cytoreductive surgery is reviewed, with particular attention to its use in the management of metastatic melanoma. The patient's postoperative course was unremarkable and she remains alive and asymptomatic with no detectable disease at 20 months' follow‐up. Cytoreductive surgery as a part of an aggressive multidisciplinary approach may play a role in the treatment of cutaneous and ocular melanoma metastatic to multiple visceral sites. Data from well‐designed, innovative clinical trials of cytoreductive surgery and biochemotherapy are required to determine the effectiveness of this multidisciplinary approach.     

老年妇女上皮性卵巢癌的临床特点及预后

目的评价老年妇女上皮性卵巢癌治疗方法对预后的影响。方法对卵巢上皮癌１５３例进行回顾性分析。结果老年组（３３例）比非老年组（１２０例）肿瘤细胞分化差，减瘤术多，系统化疗≥８个疗程者不多，５年生存率低，两组比较差异有显著性（Ｐ值＜０．０５）。结论对老年患者只要一般情况允许，可以进行满意的瘤细胞减灭性手术及系统的化疗，从而提高患者生存率。     

Surgical management of patients with peritoneal carcinomatosis of gastrointestinal origin

Peritoneal carcinomatosis is found in approximately 15 % of patients with colorectal cancer during the course of their disease, and is associated with a poor prognosis. Even more patients with gastric cancer develop peritoneal seeding. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) have been introduced in the past decade and have led to 5-year survival rates of 30 to 40 % for selected patients with colorectal cancer and peritoneal carcinomatosis. These numbers have been demonstrated by many retrospective analyses and by prospective Phase II studies. The clinical assessment to select patients who will benefit from the combined therapy and achievement of complete macroscopic cytoreduction both play a crucial role. Less favourabale results have been achieved for patients suffering from stage IV gastric cancer with peritoneal seeding. Promising results were demonstrated for postoperative intraperitoneal chemotherapy following curative gastrectomy. Patients with hepatic, biliary and pancreatic cancers and peritoneal carcinomatosis do not benefit from cytoreductive surgery. There is a need for further multicentre, prospective trials analysing the use of hyperthermic intraperitoneal chemotherapy. They should be conducted in the specialised centres by interdisciplinary teams.     

Clinical implications of pleural effusions in ovarian cancer

The pleural cavity constitutes the most frequent extra‐abdominal metastatic site in ovarian carcinoma (OC). In patients with OC and pleural effusions, a positive fluid cytology is required for a stage IV diagnosis. Unfortunately, about 30% of malignant pleural effusions exhibit false‐negative cytological pleural fluid results. In those circumstances, exploratory video‐assisted thoracoscopic surgery (VATS) serves as a diagnostic, staging and even therapeutic modality. Maximal (no visible disease) or, at least, optimal (no residual implant greater than 1 cm) cytoreduction should be the primary surgical goal in stage IV OC patients. This is due to residual tumour after cytoreductive surgery being one of the most important factors impacting on survival. Although malignant pleural effusions do not preclude abdominal surgical debulking, excision of gross pleural nodules may be necessary to achieve optimal cytoreduction. VATS quantifies pleural tumour burden and allows for intrathoracic cytoreduction or, if the latter is not feasible, ensures that abdominal surgery is not unnecessarily performed on women in whom gross tumour would still remain in the pleural space afterwards. Taxane‐platinum neoadjuvant chemotherapy should be offered to this group. Patients with tumour extension into the pleural space have a median overall survival of 2 years.     

Secondary cytoreductive surgery in the patient with recurrent ovarian cancer is often beneficial

The majority of women with ovarian cancer will present at an advanced stage and ultimately experience a recrudescence of tumor. Recent data indicates that secondary cytoreductive surgery is feasible, well tolerated and associated with significant prolongation of survival in selected patients with recurrent ovarian cancer.     

Cytoreductive surgery in advanced endocrine tumours of the pancreas

Surgery still plays an important role even in advanced endocrine tumours of the pancreas, owing to their biological behaviour. Sometimes it is possible to attempt a radical approach, but more often only cytoreduction is feasible. In fact, when the malignancy is not completely resectable on account of vessel involvement or extensive liver metastases, surgical reduction of the tumour burden (debulking) can be proposed, aimed at improving the clinical conditions and survival of these patients. Forty-one patients suffering from advanced endocrine tumour of the pancreas were observed from 1985 to 1996. In 13 patients, the disease was locally advanced as far as concerns lymph node metastases and/or vessel involvement, while the other 28 patients presented liver metastases. In the former group, we performed 6 radical resections, in the latter we submitted 2 patients to radical resection and 12 patients to cytoreductive surgery, with complete removal of the pancreatic malignancy. The overall survival of the resected patients was 87% (7/8). Three patients (37.5%) are alive and free of disease, while the other 4 have subsequently developed liver metastases. One patient died with hepatic recurrence. Half the patients (6/12) undergoing cytoreductive surgery are alive, 3 with stable and 3 with progressive disease. The other 6 patients have died due to liver progression of the disease. As data in the literature concerning the role of debulking as regards the survival are conflicting, we have modified our surgical approach in patients with advanced disease. We perform cytoreductive surgery whenever complete removal of the pancreatic tumour is feasible. The rationale of this approach is to leave only a liver with residual disease, with a view to giving targeted adjuvant treatment.     

Therapeutic innovations in the management of peritoneal carcinomatosis from digestive origin: cytoreductive surgery and intraperitoneal chemotherapy

PURPOSE: Peritoneal carcinomatosis and particularly those from digestive origin has long been considered as an automatically terminal disease in abdominal cancer patients. CURRENT KNOWLEDGE AND KEY POINTS: Over the past decade, new locoregional treatments combining cytoreductive surgery, peritonectomy procedures with perioperative intraperitoneal chemotherapy (with or without hyperthermia) have been developed by specialized teams. Because of its high but acceptable mortality and morbidity, this aggressive but comprehensive therapeutic strategy requires accurate and strict patient's selection into multidisciplinary and specialized teams. It may allow prolonged survival and cure for patients with pseudomyxoma peritonei, peritoneal mesothelioma, carcinomatosis from colorectal or gastric cancer. Qualitative and quantitative prognostic indicators are needed to assess a patient's eligibility, including tumor histopathology, assessment of carcinomatosis extent or completeness of cytoreduction which appears to be the most important. PERSPECTIVES: Combination of cytoreductive surgery with perioperative intraperitoneal chemotherapy appears to be an adapted therapeutic approach for patients strictly selected, with peritoneal carcinomatosis. Phase III studies are now needed for the validation and the evaluation of the type of intraperitoneal chemotherapy.     

The role of neoadjuvant chemotherapy and interval laparotomy in advanced ovarian cancer

Radical debulking surgery allows for optimal cytoreduction in less than 50% of patients with advanced ovarian cancer. In spite of highly efficient chemotherapeutic regimens, the prognosis of patients with residual tumor masses larger than 1 cm in diameter following staging laparotomy is very poor. This observation led to the initiation of numerous trials evaluating the feasibility and efficiency of the use of primary chemotherapy followed by interval laparotomy in women with advanced ovarian cancer. The available data is presented and discussed in this review.     

Gemcitabine: current role and future options in the treatment of ovarian cancer

Epithelial ovarian cancer is the gynecological malignancy with the highest mortality. The standard therapeutic approach for patients with advanced-stage epithelial ovarian cancer has been cytoreductive surgery followed by combination chemotherapy. Despite improvements in outcome via carboplatin/paclitaxel based chemotherapy, 30% of patients with ovarian cancer fail to respond to primary therapy; moreover, 55-75% of responders relapse within 1 or 2 years from the end of primary treatment and die of the disease within 5 years from their initial diagnosis. Gemcitabine has been shown to be active as a single agent and in combination with other drugs, including carboplatin and paclitaxel, in the treatment of patients with recurrent ovarian cancer. It is currently under evaluation in new combinations for initial therapy in ovarian cancer patients.     

Ten years’ disease-free survival of advanced epithelial ovarian cancer treated by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: A case report and literature review

Rationale:One of the most distinctive features of epithelial ovarian cancer is tendency to disseminate into peritoneal cavity to form peritoneal carcinomatosis, indicating advanced disease with poor prognosis.Patient concerns:A fifty-year-old patient had a chief complaint of an abdominal distension lasting 1 month.Diagnoses:The patient was diagnosed with advanced epithelial ovarian cancer with peritoneal carcinomatosis by computed tomography scan, tumor markers, endoscopy examination, and pathology.Interventions:The patient was treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy followed by 8 cycles of systemic chemotherapy.Outcomes:Till March 9, 2020, the patient has disease-free survival over 10 years.Lessons:The application of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy combined with systematic chemotherapy may improve survival dramatically for the patients with epithelial ovarian cancer and peritoneal carcinomatosis and should be considered as an option of a relatively new regime.     

Ovarian cancer

Ovarian cancer accounts for 4% of all cancers in women and is the leading cause of death from gynaecologic malignancies. Because early-stage ovarian cancer is generally asymptomatic, approximately 75% of women present with advanced disease at diagnosis. Survival is highly dependent on stage of disease: 5-year survival in patients with early-stage is 80-90% compared to 25% for patients with advanced-stage disease. For all patients, a comprehensive surgical staging should be performed to obtain the histological confirmation of diagnosis and to evaluate the extent of disease. Patients with early-stage should both be optimally staged and be treated with adjuvant platinum-based chemotherapy if they have a medium or high-risk tumour. For advanced disease the currently recommended management is primary cytoreductive surgery followed by platinum-paclitaxel combination chemotherapy. Appropriate salvage therapy is based on the timing and nature of recurrence and the extent of prior chemotherapy. Surgical resection should be considered in patients with long-term remission, especially in those with isolated recurrences and good performance status. Platinum-based combination represents the standard second-line chemotherapy in patients with platinum-sensitive relapsed ovarian cancer. Salvage chemotherapy in platinum-refractory patients usually results in low response rates and short survival.     

Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian cancer peritoneal carcinomatosis: systematic review of current results

Background  

Advanced and recurrent ovarian cancer results in extensive spread of tumor on the peritoneal surfaces of the abdomen and pelvis. We collectively review studies in the literature that report the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer peritoneal carcinomatosis.     

腹膜转移的结肠癌患者MDT诊治二例

本文描述了2例异时性腹膜转移的结肠癌病例的多学科诊治过程。1例多发转移,1例单发转移。这两例患者经MDT讨论后都首先采用了肿瘤减灭术联合腹腔热灌注化疗的治疗模式（cytoreductive surgery,CRS/hyperthermic intraperitoneal peroperative chemotherapy,HIPEC）,单发转移的患者目前获得了12个月的无病生存期（disease-free survival,DFS）,而多发转移的患者也获得了12个多月的总生存期（overall survival,OS）。目前发现与结直肠癌腹膜转移患者OS相关的因素包括肿瘤减灭术（CRS）完全程度和肿瘤累及的范围（腹膜转移癌指数）等。因此,对于结直肠癌的腹膜转移患者,评估病变范围极其重要,对于较局限的腹膜转移,多学科的综合诊治和积极的治疗手段能改善这部分患者的生存时间和生存质量。     

Peritoneal carcinomatosis of unknown primary site in women. A distinctive subset of adenocarcinoma

STUDY OBJECTIVE: To define the clinical features and results of systemic treatment in women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surfaces. DESIGN: Retrospective analysis of 18 patients treated at a single institution between 1978 and 1984. PATIENTS: All 18 women had abdominal carcinomatosis and had no primary site identified at laparotomy. Nine patients had limited residual tumor (maximal tumor diameter, 3 cm or less) after initial cytoreductive surgery, and 9 patients had extensive residual disease. INTERVENTIONS: In general, patients were treated according to standard guidelines for treatment of advanced ovarian carcinoma. All patients had initial laparotomy with attempted cytoreduction; of these 18 patients, 16 subsequently received cisplatin-based chemotherapy. Patients were restaged either clinically (10 patients) or with second-look surgery (8 patients). RESULTS: The median survival for all patients was 23 months. Five patients had complete response to chemotherapy, and three patients remain disease-free 41, 59, and 77 months after diagnosis. Patients with limited residual disease had longer median survival than did those with extensive residual disease (31 months compared with 11 months). CONCLUSIONS: Women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surface should be distinguished from other patients with adenocarcinoma of unknown primary site because they have a more indolent disease course, a higher response rate to systemic therapy, and a chance for long-term, disease-free survival after therapy. Although optimal treatment is undefined, we recommend that these patients be treated using the guidelines established for therapy of advanced ovarian carcinoma, including initial surgical cytoreduction followed by cisplatin-based combination chemotherapy.     

Multimodality treatment of peritoneal carcinomatosis from colorectal cancer: first results of a new German centre for peritoneal surface malignancies

Background The presence of peritoneal carcinomatosis arising from colorectal cancer is associated with a poor prognosis. It was the purpose of this study to analyze morbidity, mortality, and survival after major cytoreductive surgery and intraperitoneal chemotherapy. Materials and methods Thirty-two patients with peritoneal carcinomatosis were operated between April 2004 and June 2006 with the aim of complete macroscopical cytoreduction. All had a primary colorectal carcinoma. Surgery in these patients was followed by hyperthermic intraperitoneal chemotherapy (HIPEC) consisting of mitomycin C and doxorubicin. Data were analyzed retrospectively. Results Of all patients, 16 had appendix and 16 non-appendiceal colorectal carcinoma. A macroscopically complete cytoreduction was achieved in 24 patients by parietal and visceral peritonectomy procedures. All resections were combined with HIPEC. Overall morbidity was 34%. Most frequent surgical complications were intestinal obstruction (4/32), enteric fistula (2/32), pancreatitis (2/32), and bile leakage (2/32). One patient presented grade 4 renal toxicity. There was no hospital mortality. The median follow-up was 12 months. The 1-year overall survival rate is 96%. All patients after complete cytoreduction are still alive. Conclusions Cytoreductive surgery combined with HIPEC is associated with an acceptable morbidity and low mortality. Complete cytoreduction may improve survival, particularly in well-selected patients having a low tumor volume and no extra-abdominal metastases.     

Gonadal vein graft for hepatic artery reconstruction.

BACKGROUND/AIMS: Resection of hepatic arteries is often obligatory on resecting pancreatic, gastric and hepatobiliary malignancies. Hepatic artery reconstruction is required to preserve liver function and blood flow to the bile duct. We applied the gonadal vein to hepatic artery reconstruction. METHODOLOGY: Hepatic artery reconstruction using a gonadal vein graft was performed in two patients: one with gallbladder cancer and the other with recurrent gastric cancer. RESULTS: The right ovarian vein, 2 mm in diameter and 4 cm in length, was grafted for reconstruction between the proper hepatic and the posterior hepatic artery in one patient who underwent modified central hepatic bisegmetectomy and common bile duct resection. The left spermatic vein, 3 mm in diameter and 6 cm in length, was grafted for reconstruction between the celiac artery and the right hepatic artery in the other, who underwent upper abdominal exenteration. The former graft was occluded due to tumor invasion at 4 months after surgery, the latter one was patent at 8 weeks after surgery. CONCLUSIONS: The gonadal vein had an ideal diameter and sufficient length to accomplish hepatic arterial reconstruction. The gonadal vein graft will be a new and preferable addition to the selection of an optimal graft for hepatic arterial reconstruction.     

Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis

This article is to offer a concise review on the use of cytoreductive surgery （CRS） plus intraperitoneal hyperthermic chemotherapy （IPHC） for the treatment of peritoneal carcinomatosis （PC）. Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 too. With the establishment of several phase Ⅱ studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase Ⅲ studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.     

Adjunctive radiofrequency ablation of metastatic neuroendocrine cancer to the liver complements surgical resection

Background:

Resection of liver metastases from neuroendocrine cancer (NEC) prolongs survival and provides durable symptom relief. Not all hepatic lesions are amenable to resection, particularly when there is multifocal involvement. In this study, it was hypothesized that ablation of concomitant non-resectable NEC liver metastases is safe and salvages patients who would not have been selected for cytoreductive surgery.

Methods:

Patients who underwent adjuvant ablation of NEC liver metastases between 1995 and 2008 were reviewed. NEC was classified by patient and tumour characteristics. Regression and Kaplan–Meier models were used to compare variables and generate survival curves.

Results:

Ninety-four patients underwent hepatic resection and intra-operative ablation of metastatic NEC. The median number of lesions ablated was 3, and median size was 1.4 cm. One abscess occurred at an ablation site. Local recurrence was detected in four patients (3.8%). Overall survival was 80% and 59% at 5 and 10 years. Age, gender, tumour type, grade, primary site and need for repeat ablation had no significant association with survival. The Ki67 proliferative index was a significant predictor of decreased survival. Symptom-free survival was 34% at 3 years and 16% at 5 years, independent of the tumour grade.

Conclusion:

Concurrent ablation of NEC metastases to the liver not amenable to resection is safe and increases the candidacy of patients for cytoreductive surgery. Ablation performed intra-operatively and repeated post-operatively as needed provides significant symptom control regardless of the tumour grade.