Surgical Oncology

Editorial Board/Aims and Scope

2010-03-01

Surgical Oncology Reviewers: 2009

2010-03-01

Commentary: Ghrelin's role in gastrointestinal tract cancer

Talat Waseem — 2010-03-01

The article by Dr. Dimitrios Nikolopoulos et al. is a well-written review on the role of ghrelin axis in gastrointestinal malignancy. In past, this growth factor has received enormous attention regarding its role in the feeding behavior and body weight homeostasis. Recently, ghrelin has been ‘re-discovered’ in relation to its novel role in the dynamics of cellular proliferation and cellular viability in various pathological scenarios. Bulk of the data suggests that ghrelin promotes cellular proliferation in various cell types including the intestinal epithelial cells at physiological doses and prevents the cellular apoptosis during stress. Like other growth factors, the response is complementary and dependent on the magnitude of expression of ghrelin receptors and ghrelin itself, which can also act in autocrine and paracrine fashion. Like GH, EGF, GLP-2 and many others, ghrelin can affect the cellular dynamics not only in physiological conditions but also in pathological scenarios like malignancy, where the aforementioned axis has enhanced activity. Though, the response rates are significant (approx. 30–40% increase in proliferation and almost similar anti-apoptotic activity), however, ghrelin has not been proven to be essential for these cellular dynamics. Hence, the idea of using ghrelin as tumor marker does not appear fascinating as ghrelin is not specific for malignant tissues. Similarly, since cellular proliferation or apoptosis is not essentially and solely controlled by the ghrelin axis, its down-regulation or knock-down by genetic engineering does not appear promising. Besides above-mentioned factors, which negate therapeutic utility of ghrelin, elucidation of role of ghrelin axis in malignancy and other scenarios would, of course, improve our understanding of the basic human physiology and pathology.

Ghrelin's role on gastrointestinal tract cancer

Dimitrios Nikolopoulos, Stamatis Theocharis, Gregory Kouraklis — 2010-03-01

Abstract: Ghrelin is a recently identified 28-amino-acid peptide, with pituitary growth hormone releasing activities in humans and other mammals. In mammals, ghrelin plays a variety of roles, including influence on food intake, gastric motility, and acid secretion of the gastrointestinal tract. It is mainly secreted from the stomach mucosa, but it is also expressed widely in other tissues – in normal and malignant conditions – and, therefore, ghrelin may exert such variable endocrine and paracrine effects, as autocrine and/or paracrine function in cancer. Ghrelin's actions are mediated via its receptor, known as growth hormone secretagogue receptor (GHS-R), type 1a and 1b. Several endocrine and non-endocrine cancers, such as gastro-entero-pancreatic carcinoids, colorectal neoplasms, pituitary adenomas, pulmonary and thyroid tumours, as well as lung, breast, and pancreatic carcinomas express ghrelin at both mRNA and protein levels. In the current review, we summarise the available so far data with regard to: (a) the structure of the ghrelin molecule and its receptor; (b) its tissue contribution in physiologic and neoplasmatic conditions; and (c) ghrelin's possible role in carcinogenesis; specifically, in the area of gastrointestinal tract cancer. The aim of the present study is to determine whether or not ghrelin promotes the proliferation rate of the gastrointestinal tract (GIT) tumours.

Herceptin and breast cancer: An overview for surgeons

N. Patani, K. Mokbel — 2010-03-01

Abstract: Introduction: HER-2 over-expression is implicated in the pathogenesis of breast cancer and represents a key marker and determinant of patient outcome. Trastuzumab/Herceptin (TZ) is a recombinant humanised monoclonal antibody which targets HER-2. Introduction into clinical practice has significantly improved the natural history of HER-2 over-expressing tumors and has altered the standard of care for these women. This article reviews the established and emerging roles of TZ in the management of breast cancer (BC).Methods: Literature review facilitated by Medline and PubMed databases.Findings: The clinical utility of TZ was first established in the management of HER-2 over-expressing metastatic breast cancer (MBC), with improvements recognised in both the quality and quantity of life. Prospective randomized controlled trials have consistently demonstrated the efficacy of TZ for early breast cancer (EBC) in the adjuvant setting with significant improvements in disease free and overall survival. Emerging roles for TZ include neo-adjuvant therapy and the treatment of progressive disease. TZ is well tolerated and safe, however, associated cardiac dysfunction remains a significant clinical concern.Conclusion: HER-2 status is critically important in the management algorithm for BC and should be determined in all cases. Quality assurance of laboratory testing is of paramount importance. TZ has an established role in the management of HER-2 positive MBC and EBC in conjunction with conventional chemotherapy. Appropriate patient selection and monitoring for cardiac dysfunction are required.

Microwave coagulation therapy for hepatic tumors: Review of the literature and critical analysis

C. Boutros, P. Somasundar, S. Garrean, A. Saied, N.J. Espat — 2010-03-01

Abstract: Background: Surgical resection of malignant hepatic tumors has been demonstrated to increase overall survival; however, the majority of patients are not candidates for resection. For patients with unresectable tumors, various chemical and thermal ablation modalities have been developed. microwave coagulation therapy (MCT) is one such thermal ablation modality and the purpose of this review is to evaluate the presently available data for MCT and assess the level of evidence to support its clinical use.Methods: This review is limited to published studies in the English literature including at least 30 patients per study with MCT for hepatocellular cancer (HCC) or colorectal hepatic metastasis (CRHM). Patterns of local recurrence, complications and survival outcome of MCT ablation are presented and discussed including assessment of Asian experience using the 2.4GHZ device and American experience using the 914MHZ device.Conclusions: Although randomized controlled trials comparing RFA and MCT for hepatic ablation are lacking, our review (based on level 2 data) supports that MCT may be optimal when larger necrosis zones and/or ablation of multiple lesions are the objectives. The data support that the potential procedural advantage(s) noted for ablation of CRHM and HCC >3cm, is not supported for HCC <3cm; moreover MCT shares with all other ablation modalities a high rate of locoregional recurrence in HCC; likely due to the multicentricity of this disease process.

An overview of coagulation disorders in cancer patients

2010-03-01

Abstract: A diversity of coagulation disorders in cancer patients arise from tumor-specific growth characteristics, neoangiogenesis with impaired endothelial lining, defective myelopoiesis, hypoproteinemia or metastatic lesions growth with organ dysfunction. Recent investigations have found a clinically relevant correlation of coagulation disorders and tumor growth. These prompted new therapeutic strategies focused on growth factors with the aim to control tumor metastasis, particularly if used for the treatment of micrometastatic disease. However, such treatment may lead to the life threatening coagulation imbalance.A coagulation homeostasis may become further impaired after nonsurgical cancer therapy, especially after preoperative irradiation, which produces lesions precipitating both bleeding and thrombosis. Anticancer chemotherapy may affect liver function and decrease the synthesis of both procoagulation and anticoagulation factors. The most of chemotherapeutic protocols affect platelet synthesis, which arises as a principal dose-limiting side effect. It was observed both during combined systemic chemotherapy and local antitumor therapy. Although the side effects produced by chemotherapy are reversible, endothelial lesions may persist for many years after the anticancer treatment.Instead of cancer patients, there's a growing cohort of patients with nonmalignant diseases who use cytostatics in the perioperative period, and are candidates for surgical procedures not related to their malignant disease, i.e. hernia repair. In this patient population a special attention must be paid to the preoperative evaluation of coagulation status and thromboprophylaxis.This overview reminds the most common coagulation disorders in cancer patients in the perioperative period. It emphasizes the need for proper patient monitoring which may facilitate the diagnostics and treatment of cancer-related coagulation disorders in the perioperative setting.

Pregnancy after breast cancer: A need for global patient care, starting before adjuvant therapy

2010-03-01

Abstract: Breast cancer (BC) is the most frequently occurring cancer in women; early diagnosis and efficient treatments create higher event-free and overall survival rates. However, the mean age at first pregnancy continues to increase worldwide; the question of pregnancy after BC is thus raised more frequently. Chemotherapy may induce premature ovarian failure, depending largely on the woman's age and the drugs used, as well as the dosage and duration of treatment. It is important that fertility preservation strategies are addressed before chemotherapy. Pregnancy after BC may implicate a potentially higher risk of cancer recurrence, but the available literature provides reassuring data. The delay between cancer treatment and pregnancy should be discussed, depending on the initial stage of the disease. The risk of discontinuing tamoxifen prematurely should be carefully evaluated using standardised tools. The pregnancy outcome may as well be impaired by the history of cancer, leading to an increased likelihood of preterm birth and low birth weight rates. Proper follow-up and prevention should be provided based on the knowledge of these complications.Pregnancy after BC should be possible for most young BC patients in the future. This implies a global care program including multi-disciplinary teams is initiated prior to starting adjuvant treatment and particularly chemotherapy. The patient and her partner should be involved in the various steps of the process, after being properly informed.

The combination of docetaxel and cisplatin plus fluorouracil as neoadjuvant chemotherapy in the treatment of T4 stage gastric cancer

Ming-Gao Guo, Qi Zheng, Zhe Cheng, Yu Wang, Chang-Ning Feng, Zhe Yang — 2010-03-01

Abstract: The prognosis of local advanced gastric carcinoma is very poor. We evaluated the impact on survival and the effects induced by the triple combination docetaxel–cisplatin–fluorouracil (DCF) as neoadjuvant chemotherapy in 24 T4 stage gastric tumor patients. They received 2–3 cycles DCF chemotherapy, followed by radical gastric resection. Tumor downstaging detected by CT was obtained in 17 out of 24 patients. The overall 3-year survival rate was 68.2%. Patients who received R0 resection (19/22) showed a 3-year survival rate of 78.9%. T downstaged patients (17/22) showed a higher 3-year survival rate of 82.4%. Those who responded to the triple combination of docetaxel–cisplatin–fluorouracil, exhibited T downstaging and subsequently received an R0 resection had a definitely better chance of a cure as compared to surgery alone, according to a complete 3-year follow-up.

Prognostic role of lymphatic vessel invasion in early gastric cancer: A retrospective study of 188 cases

2010-03-01

Abstract: Background: Lymphatic vessel invasion is an important prognostic factor for the gastric cancer without lymph node metastasis. However, the studies on early gastric cancers is still sparse. Therefore, we carried out this study to determine clinicopathological and surgical prognostic factors, especially lymphatic vessel invasion, for early gastric cancers.Methods: Clinicopathological characteristics and prognostic outcomes of 188 patients who received a gastrectomy for early gastric cancer between 1980 and 2000 were retrospectively evaluated based on the subclassification of pN category. A multivariate analysis was performed by using the Cox regression model, where lymphatic vessel invasion and other potential prognostic factors were included.Results: Of the 188 patients, 158 had T1N0M0 and 30 T1N1M0 cancers. In patients with T1N0M0 cancers, the survival rate was significantly lower in those with lymphatic vessel invasion than in those without (χ2=4.025, P=0.045). However, in patients with T1N1M0 cancers, the survival rates were not significantly different between those with and those without lymphatic vessel invasion (χ2=0.253, P=0.615). The multivariate analysis identified that age (P=0.033) and lymph node metastasis (P=0.019) were independent prognostic factors for all early gastric cancers. However, age (P=0.042), tumor location (P=0.032), and lymphatic vessel invasion (P=0.010) were the independent prognostic factors for T1N0M0 cancers.Conclusions: Lymphatic vessel invasion was an independent prognostic factor for T1N0M0 early gastric cancers, and thus may be a potential prominent factor that should be considered to be included in the category of lymphoid metastasis (both lymph node metastasis and lymphatic vessel invasion) in patients with early gastric cancer.

Intramammary lymph node metastasis predicts poorer survival in breast cancer patients

Brian V. Hogan, Mark B. Peter, Hrishikesh Shenoy, Kieran Horgan, Abeer Shaaban — 2010-03-01

Abstract: Involvement of an intramammary lymph node with metastatic breast cancer is an uncommon clinical or radiological presentation. Previously reported series of patients are small in number and the clinical advice is unclear.We identified 100 patients on our pathology database with intramammary lymph nodes in association with a primary breast cancer. Ten were identified pre-operatively on breast imaging and 90 were first discovered on pathological assessment of excised breast tissue. Twenty one contained metastasis. Factors that predicted for intramammary node metastasis were increasing age (p=0.017), lymphovascular invasion (p=0.002) and grade of tumour (p=0.012). The presence of metastasis within the intramammary lymph node was associated with a poorer disease free survival (p=0.007) and reduced overall survival (p=0.035). Sixty seven percent of patients with intramammary node metastasis had further axillary metastases. One patient had an intramammary node metastasis but uninvolved axillary sentinel node. She presented 19 months later with an axillary nodal recurrence.The presence of intramammary lymph node metastasis is associated with poorer outcome in breast cancer patients. Pre-operative detection of intramammary lymph node metastasis is helpful to guide breast and axillary surgeries. Intramammary lymph node metastasis predicts strongly for axillary metastatic disease and axillary node clearance is recommended.

Options of restorative pancreaticoenteric anastomosis following pancreaticoduodenectomy: A review

Mallika Tewari, Priya Hazrah, Vinay Kumar, Hari S. Shukla — 2010-03-01

Abstract: Pancreatic fistula (PF), haemorrhage and delayed gastric emptying are some of the common causes of morbidity and PF is the single most important cause of mortality following pancreaticoduodenectomy (PD). Authors, who claim to have reduced leak rates, recommend modifications of the standard technique of pancreaticojejunostomy (PJ) that are often complex and difficult to standardize for wider applications. Most individual studies, multicenter retrospective analysis and certain prospective studies report a lower leak rate with pancreaticogastrostomy (PG) when compared with PJ. However, the only three randomized controlled clinical trials (RCTs) to date have failed to demonstrate the superiority of either technique. Here we discuss the various aspects of pancreaticoenteric anastomosis following pylorus preserving pancreaticoduodenectomy (PPD) and the standard pancreaticoduodenectomy (PD).

Breast cancer chemoresistance: Emerging importance of cancer stem cells

Suebwong Chuthapisith, Jennifer Eremin, Mohamed El-Sheemey, Oleg Eremin — 2010-03-01

Abstract: Cancer stem cells (CSCs) have recently been documented in solid tumours. Evidence has suggested that CSCs are involved in carcinogenesis, tumour invasion and metastases, and resistance to various forms of therapies, including chemotherapy. Breast CSCs are characterised by the expression of CD44 but lack of CD24 (CD44+/CD24− cells). The mechanisms involved in chemoresistance of breast CSCs are complex and not clearly defined. Overexpression of ABC transporters, detoxification enzymes (aldehyde dehydrogenase), low cell turn over rate and the ability to activate the DNA check point response are possibly all involved. Innovative therapies, based on a better understanding of CSCs, should lead to enhanced and long-term cure rates in breast cancer.

Endometriosis related to family history of malignancies in the Yale series

2010-03-01

Abstract: Objective: Recent studies reported that endometriosis could behave as a neoplasmatic process. The purpose of this study is to investigate the family risk of ovarian, colon and prostate cancer in women with endometriosis.Study design: A search of medical records at the Yale New Haven Hospital from 1996 to 2002 identified 348 women with endometriosis and 179 women without endometriosis. All the cases were diagnosed by laparoscopy. Demographic characteristics were evaluated in women with positive or negative family history of cancers in women with endometriosis.Results: The overall risk of patients with endometriosis and positive family history of cancers was 7.7 (95% confidence interval 3.8–15.7) (χ2=39.8, P<0.001). Significant excess was observed for ovarian cancer in first- and second-degree relatives (OR=10.5, 95% CI (2.5–44.2), χ2=14.3, P<0.001), colon cancer (OR=7.5, 95% CI (2.7–21.1), χ2=18.2, P<0.001) and prostate cancer (OR=4.5, 95% CI (14–15.3), χ2=6.1, P<0.001). We found similar results in first- and second-degree relatives with ovarian and colon cancer. Moreover, we found similar results regarding the demographic characteristics in women with positive family history of cancers and in women with negative history.Conclusions: These data suggest a familial association of endometriosis with ovarian, colon and prostate cancers. This evidence could support the genetics and molecular similarities between endometriosis and cancer. Future studies will be important to determine a clear genetic link between endometriosis and cancer.

A meta-analysis of chemotherapy regimen Fluorouracil/Leucovorin/Oxaliplatin Compared with Fluorouracil/Leucovorin in treating advanced colorectal cancer

Mian Ling Chen, Chi Hua Fang, Liu Sen Liang, Li Hua Dai, Xiao Kang Wang — 2010-03-01

Abstract: Background: We performed a meta-analysis to evaluate the efficacy and safety of Fluorouracil (FU)/Leucovorin (LV)/Oxaliplatin compared to FU/LV in treating advanced colorectal cancer.Methods: Two independent researchers identified and extracted all relevant literature using MEDLINE and the Cochrane Library Database. The regimens included arm A (FU/LV) and arm B (FU/LV/Oxaliplatin) with no other chemotherapy agent.Results: Five randomized controlled trials (RCTs) fulfilled the requirements. All RCTs showed superiority of FU/LV/Oxaliplatin to FU/LV when measuring RR (response rate) and PFS (progression-free survival); no significant improvement in OS (overall survival) was observed. This meta-analysis shows a better RR for the FU/LV/Oxaliplatin group (OR 4.02, 95% CI 2.37–6.82, p<0.00001). The incidence of grade 3/4 toxicities, including neutropenia, thrombocytopenia, vomiting, neurological toxicity, toxicity-related dose modification and discontinuation was higher in the FU/LV/Oxaliplatin group, while the incidence of anemia, nausea and diarrhea was not different.Conclusion: FU/LV/Oxaliplatin offers better efficacy (RR and PFS) than FU/LV in the treatment of advanced colorectal cancer. The incidence of grade 3/4 toxicities, i.e. neutropenia, thrombocytopenia, vomiting, neurological toxicity, is significantly higher in the FU/LV/Oxaliplatin than in the FU/LV group but these are manageable or reversible.

Supportive care in heart failure

Jeffrey B. Ball — 2010-03-01

This book is one of a series which details the support of patients with a variety of long term conditions. Supportive care is necessarily multidisciplinary and holistic and relates to the care both of patients suffering chronic life threatening illnesses and their families. In addition to physical complaints it also addresses the psychological, social and spiritual concerns of patients and their families. Supportive care has long been established for cancer patients and grew from the development of palliative care services for such patients in the terminal phase of their illness.