Surgical management of liver metastases from uveal melanoma: 16 years' experience at the Institut Curie

Background

Uveal melanoma is characterised by a high prevalence of liver metastases and a poor prognosis.

Aim

To review the evolving surgical management of this challenging condition at a single institution over a 16-year period.

Patients and Methods

Between January 1991 and June 2007, among 3873 patients with uveal melanoma, 798 patients had liver metastases. We undertook a detailed retrospective review of their clinical records and surgical procedures. The data was evaluated with both uni- and multivariate statistical analysis for predictive survival indicators.

Results

255 patients underwent surgical resection. The median interval between ocular tumour diagnosis and liver surgery was 68 months (range 19–81). Liver surgery was either microscopically complete (R0; n = 76), microscopically incomplete (R1; n = 22) or macroscopically incomplete (R2; n = 157). The median overall postoperative survival was 14 months, but increased to 27 months when R0 resection was possible.With multivariate analysis, four variables were found to independently correlate with prolonged survival: an interval from primary tumour diagnosis to liver metastases >24 months, comprehensiveness of surgical resection (R0), number of metastases resected (≤4) and absence of miliary disease.

Conclusions

Surgical resection, when possible, is able to almost double the survival and appears at present the optimal way of improving the prognosis in metastatic uveal melanoma. Advances in medical treatments will be required to further improve survival.     

Circulating tumour cells during laparoscopic and open surgery for primary colonic cancer in portal and peripheral blood

Background

The objective of this study was to detect and quantify circulating tumour cells (CTC) in peripheral and portal blood of patients who had open or laparoscopic surgery for primary colonic cancer.

Methods

Patients in the laparoscopic-group were operated on in a medial to lateral approach (“vessels first”), in the open-group a lateral to medial approach was applied. The enumeration of CTC was performed with the CellSearch System. Intra-operative samples were taken paired-wise (from peripheral and portal circulation) directly after entering the abdominal cavity (T1), after mobilisation of the tumour baring segment (T2), and after tumour resection (T3). Ploidy of both the CTC and tissue of the primary tumour was determined for chromosome 1, 7, 8 and 17.

Results

Thirty-one patients were included; 18 patients had open surgery, 13 patients were operated on laparoscopically. The percentage of samples with CTC at T1 was 7% in peripheral blood and 54% in portal blood (p = 0.002). At T2, 4% and 31% respectively (p = 0.031). And at T3, 4% and 26% respectively (p = 0.125). The cumulative percentage of samples with CTC was significantly higher during open surgery as compared to the laparoscopic approach. Both the CTC and tissue of the primary tumour were diploid for chromosome 1, 7, 8 and 17.

Conclusion

The detection rate and quantity of CTC is significantly increased intra-operatively and is significantly higher in portal blood compared to peripheral blood. Significantly less CTC were detected during laparoscopic surgery probably as result of the medial to lateral approach.     

Liver resection for metastatic gastric cancer

Aims

Liver resection represents a curative treatment approach in patients suffering from liver metastases from gastric cancer. However, its value in the treatment of these patients remains controversial. This study was conducted to evaluate the safety and effectiveness of liver resection in these conditions and to identify criteria for the selection of suitable patients.

Methods

From January 1988 to December 2002, 24 patients underwent liver resection for metastatic gastric cancer. The outcome of these 24 patients was retrospectively reviewed using a prospective database. Patient, tumour and operative parameters were analyzed for their influence on long-term survival.

Results

One patient died and four patients (17%) developed complications during the postoperative course. The overall one-, three- and five-year survival was 38%, 16% and 10%, respectively. After curative resection (n = 17), the one-, three- and five-year survival rate was 53%, 22% and 15%, respectively, and patients with metachronous metastases restricted to the liver (n = 5) had a one-, three- and five-year survival of 80%, 40% and 40%, respectively. In the univariate analysis, extrahepatic manifestation showed in tendency (p = 0.069) and resection margins statistically significant (p = 0.005) influence on survival. The multivariate analysis revealed only resection margins as an independent prognostic factor for survival.

Conclusions

Long-term survival can be achieved by liver resection in well selected patients and may be considered in the multidisciplinary treatment approach of metastatic gastric cancer. Patients with metastatic disease restricted to the liver in whom a curative resection can be achieved seem to be most suitable for liver resection.     

Cytoreductive surgery and modified heated intraoperative intraperitoneal chemotherapy (HIPEC) for advanced and recurrent ovarian cancer – 12-year single center experience

Background

The present study reviews our 12-year results with cytoreductive surgery and HIPEC in patients with advanced primary and recurrent ovarian cancer.

Methods

During the period from January 1995 to December 2007, 56 patients (31 with primary and 25 with recurrent epithelial ovarian cancer) underwent cytoreductive surgery and HIPEC (Doxorubicin intra-operatively, and cisplatin next 1–5 postoperative days) at our department.

Results

52 (92.8%) patients had no gross residual disease after the complete surgical procedure (Sugarbaker completeness of cytoreduction CC, score 0–1), and 4 patients had macroscopic residual disease (CC-2 or CC-3) Average PCI (peritoneal cancer index) was 13.4 (4–28). Mean follow-up was 56 months (range, 1–135). The median operation time was 279 min (range 190 ± 500 min). Median total blood loss was 850 mL (range 250 ± 1550 mL). The median survival time was 34.1 months for primary, 40.1 for recurrent ovarian cancer without statistically significance difference (p > 0.05) and median disease-free survival was 26.2 months. The PCI was equal or less than 12 in 31 patients and their median survival time was statistically significant longer than median survival time of months for the 25 patients with PCI greater then 12 (p < 0.01). Morbidity and mortality rate were 17.8% (10/56) and 1.8% (1/56).

Conclusion

This series indicates that in the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival.     

Management of advanced parotid cancer. A systematic review

Background

Primary adenocarcinomas of the parotid gland are rare and account for less than 5% of all head and neck malignant neoplasms. There is considerable variation in biological behaviour within this group; low-grade tumours exhibit slow growth rates with minimal or no local invasion. High-grade tumours, however, show a high incidence of local recurrence and distant metastasis.

Aim

The purpose of this paper is to analyse the important prognostic indicators for this cancer.

Methods

A systematic review was performed involving 19 published studies from 1987 to 2005 which included 4631 patients. T stage, grade of tumour, N stage and adjuvant radiotherapy on overall (5 year) survival were analysed as prognostic indicators.

Results

T stage (p = 0.041, hazard ratio 1.8 (confidence interval 1.2–2.9)), N stage (p = 0.05, hazard ratio 1.1 (0.2–1.8)), and high-grade (p = 0.001, hazard ratio 2.1 (1.5–2.7)) were associated with a significantly worse survival. The effect of adjuvant radiotherapy was to improve overall survival: p = 0.002, hazard ratio 2.9 (1.5–4.7). The mean 5 year survival for advanced high-grade parotid cancer was 35%.

Conclusion

High-grade advanced parotid cancers are associated with a poor survival. Adjuvant radiotherapy is indicated in these tumours and this improves survival.     

Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies

Background

Treatment decisions in recurrent breast cancer are usually based on the estrogen (ER), progesterone (PgR) and HER2 receptor status of the primary tumour. Retrospective studies suggest that discordance between receptor expression of primary and recurrent breast cancer exists.

Methods

A pooled analysis of individual patient data from two large prospective studies comprising biopsy of recurrent lesions obtained from consenting patients was undertaken. Tissue was analyzed for ER, PgR by immunohistochemistry and HER2 by FISH. Receptor status of recurrent disease was compared with that of the primary tumour. Recruiting clinicians assessed whether or not receptor discordance affected subsequent systemic treatment.

Results

Two hundred and eighty-nine patients underwent biopsy. Recurrent biopsy specimens were obtained from locoregional recurrence in 48.1% and from distant metastases in 51.9%. Distant sites included skin/soft tissue (25.0%), bone/bone marrow (19.2%) and liver (15.8%). Benign disease or second primary cancer was observed in 7.6% of biopsies. Discordance in ER, PgR or HER2 between confirmed primary and recurrent breast cancer was 12.6%, 31.2% and 5.5%, respectively (all p < 0.001). Biopsy results altered management in 14.2% of patients undergoing biopsy (95% confidence intervals 10.4–18.8%, p ? 0.0001). The duration between primary and recurrent disease, the site of recurrence and the receptor profile of the primary tumour did not affect discordance rates.

Conclusions

There is substantial discordance in receptor status between primary and recurrent breast cancer. The number needed to biopsy in order to alter treatment was 7.1. Patients with recurrent breast cancer should have tissue confirmation of receptor status of recurrent disease.     

Ultrasound and fine needle aspiration cytology of the axilla in the pre-operative identification of axillary nodal involvement in breast cancer

Aims

Pre-operative diagnosis of axillary nodal involvement in breast cancer allows one-stage axillary surgery. We evaluated the efficacy of axillary ultrasound (US) with US guided fine needle aspiration cytology (FNAC) in the diagnosis of axillary nodal involvement.

Methods

Over a 13-month period, we performed US of 369 axillae in patients with screen-detected (n = 278) and symptomatic (n = 91) invasive carcinoma of the breast, at the same time as US of the primary tumour. If abnormal lymph nodes were demonstrated, a single US guided FNAC of the most abnormal node was performed. US and FNAC results were compared with the final histology of the surgically excised lymph nodes.

Results

Among the 369 axillae studied, 102 had nodal macrometastases and 38 (37%) were identified by US guided FNAC. The rate was 33% in screen-detected and 44% in symptomatic patients. Sensitivity increased with increasing numbers of positive axillary nodes, and the more abnormal the appearances of the nodes on US.

Conclusion

US with FNAC of the most abnormal node allows pre-operative detection of a third of node positive axillae in screen-detected and over 40% of those with symptomatic breast cancer, allowing one-stage axillary surgery avoiding the sentinel node biopsy step in these patients.     

Surgical treatment of locally advanced,non-metastatic,gastrointestinal stromal tumours after treatment with imatinib

Aims

Patients with locally advanced gastrointestinal stromal tumours (GISTs) have a high risk of tumour perforation, incomplete tumour resections and often require multivisceral resections. Long-term disease-free and overall survival is usually impaired in this group of patients. Induction therapy with imatinib followed by surgery seems to be beneficial in terms of improved surgical results and long-term outcome. We report on a large cohort of locally advanced GIST patients who have been treated in four centres in the Netherlands specialized in the treatment of sarcomas.

Methods

Between August 2001 and June 2011, 57 patients underwent surgery for locally advanced GISTs after imatinib treatment. Data of all patients were retrospectively collected. Endpoints were progression-free and overall survival.

Results

The patients underwent surgery after a median of 8 (range 1–55) months of imatinib treatment. Median tumour size before treatment was 12.2 (range 5.2–30) cm and reduced to 6.2 (range 1–20) cm before surgery. No tumour perforation occurred and a surgical complete (R0) resection was achieved in 48 (84%) patients. Five-year PFS and OS were 77% and 88%. Eight patients had recurrent/metastatic disease.

Conclusions

Imatinib in locally advanced GIST is feasible and enables a high complete resection rate without tumour rupture. The combination of imatinib and surgery in patients with locally advanced GIST seems to improve PFS and OS.     

Adjuvant chemoradiation versus surgery alone for adenocarcinoma of the ampulla of Vater

Background and purpose

To examine the role of adjuvant chemoradiation (CRT) in patients with resected ampullary adenocarcinoma.

Materials and methods

The records of patients who underwent curative surgery for ampullary adenocarcinoma at a single institution between 1992 and 2007 were reviewed. Final analysis included 111 patients, 45% of which also received adjuvant CRT.

Results

Median overall survival (OS) was 36.2 months for all patients. Adverse prognostic factors for OS included T stage (T3/4 vs. T1/T2, p = 0.046), node status (positive vs. negative, p < 0.001), and histological grade (grade 3 vs. 1/2, p = 0.09). Patients receiving CRT were more likely to have advanced T-stage (p = 0.001), node positivity (p < 0.001), and poor histologic grade (p = 0.015). Patients who received CRT were also significantly younger (p = 0.001). On univariate analysis, adjuvant CRT failed to result in a significant difference in survival when compared to surgery alone (median OS: 33.4 vs. 36.2 months, p = 0.969). Patients with node-positive resections who underwent CRT had a non-significant improvement in survival (median OS: 21.6 vs. 13.0 months, p = 0.092). Thirty-three percent of patients developed distant metastasis. Common sites of distant metastasis included liver (23%) and peritoneum (7%).

Conclusions

Adjuvant chemoradiation following curative resection for ampullary adenocarcinoma did not lead to a statistically significant benefit in overall survival. A significant proportion of patients still developed distant metastatic disease suggesting a need for more effective systemic adjuvant therapy.     

Extra-abdominal primary fibromatosis: Aggressive management could be avoided in a subgroup of patients

Objective

To evaluate the impact of surgery as first-line treatment on event-free survival (EFS) of primary aggressive fibromatosis.

Patients and methods

Treatments were categorized into: surgery with or without radiotherapy and nonsurgical strategies with systemic treatment alone or wait and see policy. Eighty-nine patients had initial resection of their primary tumour followed by postoperative radiotherapy in 13 cases. Twenty-three did not undergo surgery but received systemic treatment or watch and wait policy.

Results

Median follow-up was 76 months. Overall 3 years EFS was 49%. In the univariate analysis, patients with microscopically complete surgery had a similar outcome to patients in the no-surgery group (3 years EFS of 65% and 68%, respectively). Gender, age, tumour size, treatment period and strategy (surgery versus no-surgery) were not statistically significant. Quality of resection according to margins and the tumour site were the only prognostic factors. There was a significant correlation between tumour site and quality of surgery (p = 0.0002).

Conclusions

A subset of patients with extra-abdominal fibromatosis could be managed with a nonaggressive policy, as growth arrest concerned 2/3 of nonoperated patients. When surgery is finally necessary, it should be performed with the aim of achieving negative margins.     

Patent blue staining as a method to improve lymph node detection in rectal cancer following neoadjuvant treatment

Introduction

Lymph node involvement is one of the most important prognostic factors in rectal cancer. After neoadjuvant treatment the number of retrieved lymph nodes is often reported to be low which impairs reliable tumour staging. This study examines the effect of patent blue staining on the number of harvested lymph nodes and evaluates whether a higher number of retrieved lymph nodes is of prognostic significance.

Patients and methods

Between March 2007 and December 2010, 295 consecutive patients with locally advanced rectal cancer following neoadjuvant treatment were included. Specimens were either not stained (NB), injected with patent blue into the mesorectum (MB) or directly into the inferior mesenteric artery (AB). Data were retrieved from a prospective database.

Results

The number of evaluated lymph nodes was significantly higher in the stained specimens: mean 6.8 in the NB group (n = 89), 11.5 in the MB group (n = 86) and 17.4 in the AB group (n = 106) (p < 0.001). The percentage of patients with a minimum of 12 lymph nodes increased from 15.5% (NB) to 44.2% (MB) to 74.5% (AB) (p < 0.001). The three-year cancer specific survival for the lymph node ratio (LNR) was 95% (0), 94.4% (0.01–0.1), 80.1% (0.11–0.4) and 63.7% (0.41–1).

Conclusion

The use of patent blue in patients who underwent rectal cancer surgery after neoadjuvant treatment significantly enhanced lymph node harvest. Injection into the inferior mesenteric artery was most effective. This relatively simple and generally applicable method can help to improve lymph node detection which lowers the LNR and allows adequate tumour staging.     

Primary tumour resection and survival in the palliative management of metastatic colorectal cancer

Aim

To examine whether surgical resection of the primary tumour confers a survival benefit and to identify the predictive factors of outcome in patients presenting with asymptomatic metastatic colorectal cancer (CRC).

Materials and methods

A review of a hospital database in a tertiary institution over a 6-year period (1999–2005) revealed 70 patients with asymptomatic primary CRC and unresectable liver metastases treated initially by systemic chemotherapy. A multivariate regression analysis model was used to determine the relative influence of multiple tumours, single/multiple liver metastases, tumour site, differentiation, response of liver and primary tumour to chemotherapy, biochemical response to chemotherapy, age at presentation, performance status and surgical intervention for the CRC primary.

Results

In 67 cases (3 lost to follow-up), 63 had multiple and 4 single surgically irresectable liver metastases. A total of 41 deaths were recorded. All patients received systemic chemotherapy and surgery was performed for bowel obstruction, bleeding or stable disease (n = 32). Surgery (OR 0.26; p = 0.00013) and clinical response of the primary tumour (OR 0.53; p = 0.012) were independently associated with prolonged survival. Proximal tumours (OR 2.61; p = 0.0075) and multiple primaries (OR 3.37; p = 0.02) were associated with poor outcome.

Conclusions

Surgical resection and response of the primary tumour to chemotherapy may be associated with improved survival, but proximal or multiple cancers predict poor outcome in patients with asymptomatic CRC and unresectable metastatic disease.     

Surgical treatment of combined hepatic and pulmonary colorectal cancer metastases

Aims

Surgical resection of combined hepatic and pulmonary metastases remains controversial in light of limited supportive evidence. This study aimed to audit our initial experience with this aggressive surgical strategy.

Methods

Between 1997 and 2006 we assessed 19 patients with colorectal cancer metastases for combined liver and lung metastasectomy, of whom 16 patients underwent surgery. We retrospectively reviewed perioperative and survival data.

Results

Synchronous liver metastases were present in three out of 16 patients at time of diagnosis of the primary tumour, and one out of 16 patients had synchronous lung and liver metastases with the primary tumour. Of those 12 patients who developed metachronous metastases five patients developed liver metastases first, one patient developed pulmonary metastases first, and six patients developed synchronous liver and lung metastases. Thirty nine operations were performed on 16 patients. The median hospital stay was 5.5 (2–10) days for the pulmonary and 7 (1–23) days for the hepatic resections. There were no in-hospital deaths. Chemotherapy was given to five patients prior to metastasectomy and nine received adjuvant chemotherapy following metastasectomy. Median survival from diagnosis of metastatic disease was 44 months (8–87 months). Estimated 1-year survival from diagnosis of metastatic disease was 94%, estimated 5-year survival was 20%.

Conclusion

We believe an aggressive but selective surgical approach to combined hepatic and pulmonary colorectal metastases is justified by limited resource requirements and encouraging survival.     

Diagnosis and multi-disciplinary management of hepatic metastases from gastrointestinal stromal tumour (GIST)

Aim

To explore the present application of diagnosis and management of hepatic metastases from GIST.

Methods

We performed a systematic review of the literature for studies concerning hepatic metastases from GIST. A literature search was performed using the Medline/PubMed databases to identify publications relevant to the review published from January 1998 to December 2008. Totally 113 relevant articles were retrieved. Abstracts from recent ASCO symposia were hand searched for relevant articles. After the primary filtration, articles on review and with repetitive content were excluded. The articles on clinical research, which were issued in authorized journals, were selected. At last, totally 69 articles were included for review.

Findings

The rate of liver metastases was reported as 15.9% in primary GISTs. The recurrence rate following surgical resection for hepatic metastases from GIST had been reported as 70–77%. For metastatic GIST patients with tyrosine kinase inhibitor (TKI) treatment, it demonstrated rates of CR, PR and SD respectively of 5.84%, 50.7%, and 32.4%. Combining repeated surgery with TKI treatment, R0/R1 resection rates range in various series between 48 and 82%. For those patients with unresectable disease confined to the liver or unable to tolerate liver resection due to co-morbidity or advanced age, RFA, HACE, TKI therapy, or even liver transplantation, can also improve survival.

Conclusions

The liver is a common metastatic site for gastrointestinal stromal tumour (GIST). Appropriate initial evaluation remains paramount for selecting the correct management strategy. Multi-disciplinary management (which includes pathology, medical oncology, surgical oncology, and imaging expertise) of this disease is important for both curative and palliative treatment in these patients. Combining repeated surgery with TKI treatment may be the most effective management for GIST patients with liver metastases.     

A small mammal model of tumour implantation,dissemination and growth factor expression after partial hepatectomy

Background

Surgical resection remains the most effective therapy for metastatic colorectal cancer confined to the liver, although the extrahepatic recurrence rate is high.

Aim of the study

To develop a mammal model in order to investigate by which mechanisms liver surgery affects distant tumour recurrence.

Methods

In this animal study the effect of partial hepatectomy (phX) on the development of tumour noduli in the lungs was evaluated. CC531 rat colon carcinoma cells were inoculated i.v. 24 h before, during or 24 h after surgery. Rat serum was obtained at different time-points after phX and added to in vitro CC531 cell cultures. Finally, phX was compared with an ileum resection (ilX).

Results

phX leads to increased tumour noduli in the lungs, compared to Sham operation (p = 0.002), but only when performed directly before the injection of tumour cells and not when performed 24 h before or after the inoculation. Comparable results were obtained for ilX. No growth stimulation of tumour cells after incubation with rat serum, obtained at different time-points after phX, could be detected in vitro.

Conclusion

Not only phX, but also surgery, in general promotes distant tumour recurrence exerting the effect during the early phase of tumour cell adhesion and not during tumour outgrowth.     

Primary and locally recurrent retroperitoneal soft-tissue sarcoma: Local control and survival

Aim

To evaluate local control for long-term prognosis in retroperitoneal soft-tissue sarcoma (primary tumors (PT) and local recurrence (LR)).

Methods

A total of 110 patients underwent surgery between 1988 and 2002. Prospectively gathered clinicopathological data were analyzed. Kaplan–Meier estimations and Cox regression analyses were performed.

Results

Resectability was 90%, being comparable for PT (n = 71) and LR (n = 39). Morbidity, mortality, blood loss, and operation time did not differ for PT or LR (24% vs. 31%, p = 0.41; 7.0% vs. 5.1%, p = 1.0; 1000 ml vs. 1500 ml, p = 0.17; 240 min vs. 255 min, p = 0.13). Hospitalization was comparable in both groups (median, 12 days (PT) and 13 days (LR)). Follow-up was 89 months (median, IQR 37–112 months). Local 3- and 5-year control rates after complete resection of PT were 66% and 59% (19% and 9% for LR, p < 0.001). The mean number of operations were 1.4 for PT and 2.4 for LR (p = 0.0047). The 5-year survival rates after complete resection were 51% for PT and 43% for LR (p = 0.39). The 5-year survival rates were 65%, 4%, and 0% for complete resection, incomplete resection, and exploration, respectively (p < 0.001). Multivariate analysis showed high-grade and blood loss with a poor prognosis.

Conclusions

Comparable resectability rates and perioperative outcome were observed for surgery of PT and LR. Consequent reoperation leads to respectable long-term survival rates after resection of LR. The prognosis in retroperitoneal sarcomas varies significantly according to resectability, grade and blood loss.     

Disease-related surgery in patients with distant metastatic breast cancer

Introduction

This study evaluates the frequency of and indications for disease-related surgical procedures in the palliative breast cancer (BC) situation.

Patients & methods

Based on a cohort of women who were treated for newly diagnosed BC during a 20-year period (1990–2009), we analyzed 340 patients who developed distant metastatic disease (DMD) until 2011 and died (i.e. still ongoing palliative disease courses were not included).

Results

One hundred and twenty-seven surgical procedures were performed in 100 patients (29.4% of all patients with metastatic disease). The most common site for surgery was breast (n = 60, 47.2%). The primary tumor was removed at first diagnosis of DMD in 43 patients (33.9%); sixteen operations (12.6%) were performed for local recurrence. In 37 patients, 50 surgical procedures (39.4%) were necessary to stabilize osseous structures due to metastases. Procedures were rarely performed on other common metastatic sites: lung: n = 1 (0.8%); liver: n = 1 (0.8%), brain: n = 4 (3.1%). When excluding surgery for primary breast tumors at initial diagnosis of DMD from analysis, 34 of 84 surgeries (40.4%) were performed in the first third of survival follow-up (i.e. period of metastatic disease survival); operations in the last two-thirds each totaled 29.8% (n = 25). The median survival after surgery was 16 months (range: 0.5–89 months).

Conclusions

In a cohort of BC patients who had primary or developed secondary DMD, nearly one third of the patients received disease-related surgical procedures during their palliative disease course. This high rate of operations shows that surgery has a clearly established role in the palliative therapy concept.     

Anticancer effect of tetrandrine on primary cancer cells isolated from ascites and pleural fluids

Objective

The present study was designed to examine the effect of tetrandrine on primary cancer cells isolated from the ascites or pleural fluids of patients with metastatic cancers.

Methods

Primary cancer cells were isolated from the pleural fluids (n = 13) or ascites (n = 21) of patients. Compared with culture cell lines, the response of these cancer cells to tetrandrine and chemotherapeutic agents commonly used in clinical practice were determined by WST-8 assay. Tetrandrine-induced apoptosis in primary cancer cells was determined by Annexin V-FITC assay. Quantitative RT-PCR was used to examine the role of apoptotic associated genes in the anticancer effect of tetrandrine.

Results

The primary cancer cells isolated from effusions showed sensitivity to tetrandrine with IC₅₀ values of 38.23 ± 25.77 μM, similar to the IC₅₀ in established cell lines. Patients with gastric cancers were more sensitive to tetrandrine than patients with lung cancers (P = 0.04). Four cancer cells isolated from effusions were resistant to tetrandrine, which also had increased tolerance to docetaxel, cisplatin and 5-fluorouracil. We also observed a weak but significant correlation between sensitivity to tetrandrine and cellular expression of bcl-2 (P = 0.035, r = −0.364).

Conclusions

Using cancer cells isolated from the ascites or pleural fluids, this study shows the potential anticancer effect of tetrandrine against primary cancer cells.     

Predictors and prognostic significance of operative complications in patients with hepatocellular carcinoma who underwent hepatic resection

Aims

The morbidity rate of hepatic resection for hepatocellular carcinoma (HCC) remains high. To clarify predictors and the prognostic significance of operative complications in patients with HCC, we conducted a comparative retrospective analysis of 291 patients with HCC who underwent hepatic resection.

Methods

Operative complications included hyperbilirubinemia, ascites, hemorrhage, respiratory and cardiovascular diseases, bile leakage and abscess formation, renal failure, wound infection, and pleural effusion. Predictors of operative complications and their prognostic value for long-term survival were studied by univariate and multivariate analyses.

Results

Mortality and morbidity rates were 7.2% and 42.6%. The main operative complications were ascites (n = 30), intraabdominal abscess (n = 25), hyperbilirubinemia (n = 19), wound infection (n = 16), pleural effusion (n = 10) and intraabdominal hemorrhage (n = 9). By a multivariate logistic regression model, Child–Pugh class B and increased operative blood loss (≥1200 ml) were independent predictors of postoperative complications. Among 243 patients without operative death, the 5-year overall survival rate was significantly lower in patients with operative complications (34.3%) than in those without these complications (48.7%). By the multivariate Cox proportional hazards model, the presence of operative complications was an independent predictor of poor overall survival as well as presence of portal invasion.

Conclusions

Child–Pugh class B and operative blood loss ≥1200 ml were independent predictors of complications after hepatic resection for HCC. Long-term survival is poorer in patients with postoperative complications. Decreasing operative blood loss may result in fewer postoperative complications and better long-term survival of HCC patients.     

Rigid sigmoidoscopy and MRI are not interchangeable in determining the position of rectal cancers

Purpose

1) To analyse for interchangeability of rigid sigmoidoscopy and MRI in determining the distance from anus to tumour, and to determine if anterior/posterior location influences this difference. 2) To analyse the effect of preoperative chemo-radiotherapy on the distance from anus to tumour.

Methods

Retrospective investigation of endoscopy reports and MRI series of 144 consecutive patients operated for rectal cancer.

Results

The mean distance from the anal verge to the tumour measured by sigmoidoscopy was 82 mm and by MRI 61 mm (p < 0.01). For tumours in the anterior quadrant this difference was 30 mm and for tumours located in the posterior quadrant only 12 mm. The distributions of the cancers as low, middle and high differ by more than 10% between the two methods. The coefficient of correlation between measurements was 0.9 but the variation was not acceptable. The length of the tumours decreased by 16 mm after neoadjuvant treatment, but the distance from tumour to anus increased by only 4 mm.

Conclusion

1) MRI and sigmoidoscopy are not interchangeable in determining the distance from anus to tumour simply by correcting for the length of the anal canal. It has not been determined if measurements from MRI or sigmoidoscopy are more accurate, but current evidence concerning the effect of neoadjuvant irradiation at different positions in the rectum is based upon rigid sigmoidoscopy. 2) The gain in tumour free distance above the anus induced by neoadjuvant treatment is small. Facilitation of sphincter-saving surgery should not be an argument for neoadjuvant treatment.