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Onco Surgery

Alternative therapy or seeking unconventional methods in cancer treatment is common in all societies including developed world. There are three main causes or areas where people look towards these alternative places for treatment for their disease.

1) Though it can offer a plethora of treatment, the scientific community does not guarantee cure. An indecisive patient is then easily lured by tall claimers.

2) Even when the patient accepts conventional treatment, he uses other therapies in the belief that these treatments are non toxic and may add an additional factor in bringing about cure by raising their body strength and disease fighting capacity.

3)The patient is reluctant to go through all the hassles of a rigorous conventional treatment and seek easier solution through alternative paths which he thinks is cheaper, easier to comply with and has no side effects.

One of the drawbacks of conventional treatment for cancer is the uncertainty attached with it, and its demanding ethics which says that the patient be told all. Conventional treatments for cancer are designed to cure the disease or slow its destructive effects, but they do little to establish a feeling of control in the patient. The patient feel dictated through a path without being able to monitor the direction and progress by himself and he develops an yearning for doing something. A cross-sectional multicentric study in Norway in hospitalized cancer patients ( Risberg T; Institute of Community Medicine, Norway, Eur J Cancer 1997 Apr;33 (4):575-80) a total of 126 ( 20% ) of the assessable 630 patients were users of non conventional therapies ( NCT ). Approximately 43 % of all patients and more than 60 % of the users of NCTs stated that they would like NCTs to be an option in hospitals belonging to the National Health Service. In a similar cross sectional study of use of alternative medicines in 100 Chinese cancer patients ( Liu JK etal, Cancer Clinical Research Center, Republic of China Jpn J Clin Oncol 1997 Feb;27 (1):37-41) found that 64 % patients used Indigenous Chinese medication. Patients of all educational levels and religious backgrounds consumed alternative medicines. Of the different reasons cited for alternative medication consumption was hope that it might be of some benefit to their well being or disease control, and may even result in a miracle cure. Sources of advice on medication were mostly from strangers ( by word of mouth ) family, friends, and the media, In another study from Australia ( Begbie SD; Sydney, NSW. Med J Aust 1996 Nov 18;165(10):545-8 ) alternative treatments ( most commonly dietary and psychological methods ) were used by 21.9 % of patients. Cost of treatment was moderate and most patients thought that they got their money s worth. In one study from our country ( SureshKumar K; Rajagopal MR, Pain and palliative care Clinic, Medical College, Calicut, Kerala., Palliat Med 1996 oct;10(4):293-8) lack of financial resources and facilities for follow up, concerns about the Welfare of the family in the absence of proper state-sponsered social security schemes, and lack of proper communication between doctors and patients were identified as major contribution factors. The availability of numerous systems of alternative medicine and a touted hope for cure even at a late stage of the disease were complimentary to the existing conditions. Moreover (Bourgeault IL,CMAJ 1996 Dec 15;155(12):1679-85) physicians themselves are unfamiliar with available alternative cancer therapies and confess that their main sources of information were their patients and the lay press. Although most physicians regard such therapies as unscientific they would respect their patients decision to use them and would not ( bother to ) discourage them. Factors found to influence the physicians reactions included the physician s own perception about the prognosis of the disease he is treating with standard treatment.

That is why perhaps, in spite of the strong presence of the whole scientific community and availability of the conventional treatment the sources of alternative medicines are becoming a thriving industry. Some are even structuring their practice on Evaluable scientific theories and carrying their fight to the home grounds of the scientific community. In USA the practice is so rampant that In response NCI had to offer to critically evaluate the claims of certain therapists. One of the famous one is the NCI sponsored clinical trial of antineoplastons, the naturally occurring substances used by Stainslaw Burzinskey , a Polish physician now practicing in USA. NCI however had to discontinue the phase II clinical trial focused on gliomas and astrocytomas on grounds of insufficient data and inadequate number of patient accrual. Burzenskey, though, to his credit has strongly refuted NCI arguments and could publish his arguments in reputed International Journal. But taking cue from the alternate sources and recognizing the potential of naturally occurring plant substances the U.S. Government is involved in numerous bioprospecting projects to develop drugs and medical products from the natural world. ( see communiqué on Biopiracy )
We in turn have not given sufficient attention to the practice of alternative medicine in our country and thus have allowed the field to mostly charlants and dopers making a loot out of the uncertain conditions and times.

EXORCISE BY EXCISION

Back debts
After Galen, letting out the black bile to cure diseases, practically virulent ones like malignant conditions was the main concern of physicians. And no wonders that surgical attempts with their high morbidity and mortality was viewed as acts akin to excorcism by many.

Ephrain Macdowell, an American Surgeon was the first man in recorded medical literature to have removed which he thought a malignant tumour electively in 1809. The 22 pound ovarian tumour that he removed successfully bought the patient another thirty years of fruitful life. Already in 1775 Sir Percival Pott had identified the chimney sweeper s cancer, establishing for the first time an etiological agent for the development of cancer. Before that cancer was mysterious disease which surgeons faced with much fear and anxiety and looked at it as a disease not to be meddled with. It was Galen again who invoked a stricture o noninterference because he thought cancer is a systemic disease. Ancient history though records a more balanced view. Hippocrates advised caution and selection of cases amendable to treatment, even scriptures of Egyptian Papyrus ( 3000 B.C. ) mentions surgical principles for malignant tumerous. Ancient Indian writings have abundantly described surgical therapies for tumorous growth ( 200 B.C. ). Breast cancer removal with excision of pectoral muscle was practiced by early Romans.

Developing the cutting edge ( The old story once again )

The concept and principles guiding the practice of surgical oncology have evolved gradually from the experience and thoughts of many earlier surgeons who wanted to apply the simple logic of removing all macroscopical tumours by excision to cure the disease. But that logic found limited application because of the very biological nature of the disease. In fact, if surgery could cure all diseases, non of the later researches and developments in oncology in general would have taken place. It is interesting to note how same thoughts in different disguises and refinement have appeared and disappeared in different times of history. Galen who was a strong believer in the systemic nature of cancerous disease disfavored ligature of blood vessels and used to allow bleeding from surrounding tumour vessels to flush away the black bile or malignant cells and favored pressure and cautery for haemostasis. Later surgeons replaced cautery by ligatures and now cautery is again in force. However with the people like Andreas Vesalies, the father of modern anatomy, Ambroise Pare and many alike, convened a resurgence of surgery after the Galenic period which slowly but steadfastly progressed through the next two centuries. We have seen in earlier issues how gradually with the help of pathologist anatomists the surgeons began to design their operations in conformity with their understanding of the disease process. Karl Theirsh showed by descriptive anatomy lodgment of metastatic cells in pelvic nodes and clusters of identical cells in the thoracic duct, his observation was supported by Waldeyar in 1878 by similar studies in gastrointestinal tumours. MPC Sappey anatomically described the standard regional lymphatic drainage pathways for different organs which like mathematics explained the distribution of metastatic nodes from any particular primary organ. These studies were supplemented by Von Recklinghausen in 1885 who showed that neoplastic obstruction of normal channels of lymphatics can cause opening up of collateral lymphatic pathways and rerouting of cells thus explaining metastasis at unusual sites at times. However with these studies the concept of cellular embolic theory was being erected on firm grounds and it was also realized that regional nodes are the first sanctuary where the cancerous cells are likely to be arrested foremost in their quest for spread in other parts of the body. And it was on this realization radical operations were designed in the late 19th and early 20th century. Halsted mastectomy in 1890, Criles radical neck dissection in 1906 Wertheim s hysterectomy in 1906, Mile s rectosigmoidectomy in 1908 all were designed with this conception of extirpation of regional and primary drainage area along with the excision of the primary tumour. That their theory and design was correct to a great extent so far as the initial stage of the disease is concerned has been borne out by the fact that the basic designs of these operations remain unchallenged even after a century has passed. The surgeon who dared cancer with their knives also were helped by the acceptance of autopsy procedures which greatly helped in understanding the disease progression, and then the tremendous improvement in anaesthesia, introduction of the concept of antisepsis and finally the modern era of antibiotics, blood transfusion and life support systems. Introduction of radiotherapy in 1920s and chemotherapy in 1940s are the other two boons that helped. During the early and middle part of the 20th century cancer surgery thus saw a pendulum like swing through conservative and ultra radical surgery. However as the initial enthusiasm died down it was gradually realized that all operable cases do not produce uniform results and therapists were obliged to find or define criteria which would foresee treatment outcome. We have seen how through the efforts of the Manchester group, Potrmann from Cleveland clinic, Haggenson from Colombia and later by Pierre Denoix under the aegis of UICC and uniform staging system of cancer using the T ( tumour ) N ( node ) M ( metastatis ) was developed and was combined to describe classically four clinical stages.

GETTING THE BEARINGS RIGHT

With new knowledge pouring in from basic science levels it was gradually realized that the roots of success and failure of cancer surgery are firmly entrenched in the basics of oncology. We have already seen how a cancerous tumour pass through Abundant genotypic changes that allows the evolving malignant clone to increase its malignant capacities. It means even after a tumour is formed it will go through many more successive changes to obtain further malignant potentialities. A small tumour will therefore signify an early life of a tumour and consequently having less number of mutational changes will be less heterogeneous in phenotypes. A small tumour will also have fewer clonogens, and if the tumour has a longer tumour doubling time it probably should have high cell loss due to having more number of differentiated cells. Smaller tumours will more likely to have preserved and apoptotic mechanism because of lesser magnitude of p53 mutations which directly correlates with the grade and stage of tumour. A smaller tumour can also mean that it will have lesser chances of acquiring the capabilities for sending out metastatic cells ( Inadequate training of the decathlon champion ! ) and even if metastasis do occur they will be oligometastasis. But that does not always mean that cutting down the volume of an estsblished big tumour will lead to therapeutic achievements, as is often argued in favour of debulking. We all know from our clinical experience that such a strategy have disastrous consequences. Firstly it allows residual tumour, which for biological reasons will have a faster growth rate, to proliferate with more mutant types, and it will have a greatly stimulated angiogenesis, a big plus factor for tumour growth and spread. It will also have a disseminated disease by multfocality. By growing big the tumour not only becomes more potent for distant spread, it also becomes less amenable to treatment for various technical, therapeutic and surgical reasons. That is why we have seen the T or the tumour size is so important a prognostic factor. We have also seen that regional nodes are the first sanctuary for the wanderlust among the tumour cells and their degree of involvement is a great prognostic factor. The present classification system, both UICC sponsored TNM system and the AJCC system work on the presumption that cancer of similar histology and site of origin share similar pattern of growth and extension and that untreated primary cancer increases progressively to cause at some point of time involvement of regional lymph nodes and metastasis at distant organs. Though this has been the simple basic model of staging, with passage of time as more and more biology is understood, some qualifying remarks have been added. For any design of surgical therapy the correct understanding of the extent and progress of the disease is important. With accumulation of more clinical experience gradually, more and more prognostically significant factors are being incorporated in the staging system other than simple description of TNM and indications are that with better understanding of the molecular biology more and more such factors which will be important enough to alter the treatment outcome within the heterogeneous group of each stage, will be incorporated. And this understanding, as it has developed and differed from time to time has swayed the practice of surgical oncology between the two extremes of ultra radical and conservative approach.

BASIC PREMISES

The basic premise on which cancer surgery stands is a disease model where the cancerous process starts as a local disease and then gradually spreads through local extension circumferentially by invading contiguous structures and then in an orderly fashion spread to regional lymph nodes and then through vascular channels to distant organ, and follow a sequence of events that is chronologically predictable.

Surgical therapy of cancer maps out the limits of the tumour and its direct spread and try to act on a zero order kinetics ( as opposed to radiation or chemotherapy which always kill in fraction ) by removing all diseases to the last cell. Automatically in clinical conditions where it cannot remove all diseases it considers itself inappropriate. It thus incorporates the following parameters.

1) MARGIN

The most important criteria of correct surgical excision is obtaining safe margin around the tumour. It not only means removal of macroscopic disease but also but removal of all potential areas of microscopic disease involvement . It is generally taken that beyond the obvious disease extensions further area of microscopic disease exist for another few centimeters and for most excision of cancerous tumours a margin of five centimeter or around is considered safe. For tumours located in such areas such as larynx or lower rectum where it is difficult to obtain such margins, lesser area has been accepted. But when expediency require such compromise it should be done with frozen section control to ensure excising through sterile areas. Theoretically excising through growing edge of the tumour, entails a greater risk of stimulated regrowth for biological reasons of faster tumour growth by reducing the doubling time from more rapid cell division, an inherent character of small volume of tumour mass, and by providing angiogenic factors which makes the environment conductive to more rapid growth. In practical clinical experience in various tumour settings the degree of involvement of margins and the proximity of tumour extension to the resection line even when it is not grossly involved has been found important. Practical experience has also taught that the standard dictum of a five centimeter margin is not always mandatory in all types of tumour.

2) CONTIGUOUS STRUCTURES

For the same reasons of obtaining a safe margin around all visible and potential extensions of tumour, sometimes it is necessary to remove contiguous or adjacent structures. But this is guided by general surgical principles and has to take into consideration of morbidity factors consequent of reaction of such structures. Excision of jugular vein and sternocleido muscle during neck dissection are example of such excisions when primary aim of surgical excision is removal of neck nodes. Morbidity considerations have now prompted modifications which try to spare these structures. When morbidity is not great such organs like colon during a gastrectomy or even a nephrectomy is not considered taboo. Or no effort is made to save the adrenals during a nephroctomy even for a very small lower pole kidney tumour . Sometimes anatomical consideration of restoring function and continuity need greater resection than is oncologically required. For example the operation of pancreaticoduodenectomy which need to resect portion of stomach. Another example is excision of the noninvolved mandible when for certain tumours of oral cavities it is easier to do the operation with removal of mandible even when there may be no added oncological benefit.

3) SPILLAGE

Another cardinal principle is that the operating field must not be vitiated during operation by either manhandling or injuring the tumour growth. If that is done, it is possible that viable tumour cells will get spilled on to neighboring areas and if they can find a proper vascular area with some epithelial proliferative activity it is possible for them to set up colonies there and develop tumour mass. Peritoneal seedlings and Krukenberg s tumours are example of this case. Distal implantation of spilled cells are also found in colorectal carcinomas to produce intraluminal recurrences. Stomal recurrence of laryngeal cancer may be another example.

4) ENBLOCK AND RADICAL

It may be surmised that enlarged nodes must have attracted attention of earlier surgeons while removing cancerous tumours. But perhaps before Sappey their full value in disease progression was not understood. Although surgeons like Marcus Aurelius Severnius and Ambroise Pare in sixteenth century practiced removal of nodes while operating for breast cancer. A theories and conceptions gradually evolved, some part of which we have traced in our earlier issues of update in basics, finally the era of radicality arrived which pleads enblock or continuous removal of all nodes in the immediate drainage area or to make the cancer operation a complete curative one. Surgical expediency and treatment result observations have added much variation to the basic model of cancer surgery. But it can be stated again and again the foundations of the operations designed on this concept had been so strong that no modifications have bettered their therapeutic results to date in curing solid tumours ( see table )

This topic is so important that we shall deal with this separately in our next issue in a full article.

MILESTONES IN RADICAL OPERATIONS

1890 - Radical Mastectomy - W.S. Halsted
1904 - Radical Prostatectomy - H.H. Young
1906 - Radical Hysterectomy - E. Wertheim
1906 - Radical Neck Dissection - G. Crile
1908 - A.P. Resection for rectal Cancer - W.E. Miles
1913 - Oesophagectomy - F. Torek
1933 - Pneumonectomy - E. Graham
1935 - Denectomy - A.O. Whipple

TILTING THE BALANCE

Cancer surgery is perhaps the most frequently used form of immunotherapy . That is at least some people so believe. The arguments or plausible mechanisms they put forward are:

A) Inhibition of lymphocytemediated destruction of tumour sells by the soluble tumour associated antigens in the blood, shedded from a growing tumour constantly which circulate in the blood as antigen-antibody complexes.

B) Suppression of nonspecific and generalized immunity of the patient by the growing tumour. The proponents of this theory see this model in a quantitative form where the exact quantitative burden of tumour cells as pitted against body s immune system tilt the balance in either way and also assumes that this immune in competency is not only relative but also reversible. So if the tumour burden is lowered by some means, in this case by surgical excision, then the balance can be tilted in favor of body s immune system and surgery thus can act as an immunotherapy.

The data derived from the famous DNCB testing support this view. The ability to develop primary immune response to a new antigen by cancer patients was evaluated by exposing a group of patients to the contact sensitizers dinitrochlorobenzene ( DNCB) and then measuring the delayed cutaneous hypersensitive reactions. The patients who will be unable to develop sensitivity reaction or be anergic, are naturally immunoincompetent. And the persons who will develop good or pronouncedly manifested reaction are immunocompetent. Following observations were made.

1) 95 % of patients with benign disease or patients who have prolonged disease free survival from cancer are good sensitizers.

2) Amongst cancer patients only 72 % could be sensitized. 28 % who remained anergic were found to develop incurable or progressive disease.

3) This co-relation between impaired cell mediated immune reaction and progress of the disease is more pronounced in certain histologic types like epidermoid carcinomas of cervix or head and neck cancers. It is interesting that later same tumour types were found to be strongly associated with H.papilloma virus infection.

The other application of cytoreductive surgery in clinical practice is found in tumours where some other form of therapy is very effective, like the germ cell tumours or ovarian carcinomas, visceral lymphoid malignancies and some sarcomas where the bulk of the tumour is too great for the other therapy to work. There by removing the main mass or in other words by reducing the number of tumour cells it is possible to help the other definitive therapy.

BALANCING THE OPPOSITE OF IDEAS

Surgical treatment of solid tumours have resulted in both encouraging and discouraging results in varying conditions. Sometimes the results are good but the attendant morbidity and complications are found to be unwelcome resulting in poor patient compliance. In the opposite side scope of further improving the results have been seen by extending the limits of surgery ignoring the massiveness and repeat endeavors of surgical reactions. Paradoxically this axiom applies to both responsive an unresponsive tumours to radiotherapy and chemotherapy. In tumours sensitive to radiotherapy and chemotherapy there is scope of further improving the results by adjuvant therapy after surgical resection and in tumours not sensitive to such therapies surgery remains the only option of minimizing the disease. Modifications and developments have thus taken place in either direction,

A) towards minimally invasive surgery for lesser complications and better compliance and

B) More extensive reaction both locally and at distant sites.

A) MINIMALLY INVASIVE SURGERY

A of factors have contributed to the development of minimally invasive surgery. Initial results with conservative surgery in breast and rectal cancer have encouraged the surgeons to keep in hold the basic oncological surgical principles o enblock radical reaction of malignanttumours and yet expect the same results of more extensive therapies. Detection of early cases with increased awareness and sophisticated investigation facilities have helped in developing this approach.

One of the first to exploit the possibilities in this direction was the Endoscopic removal of glottic cancers with the help of Lasers ( Zeitels 1995 ). This has been facilitated by a half century of technological developments; the surgical microscope, the CO2 laser, improved laryngoscope, and endotracheal anesthesia. Selected small-volume cancers can be curatively resected, whereas excisional biopsy can be performed on larger neoplasms. With this cost effective minimally-invasive surgical approach, there is less disturbance of normal tissue, thereby minimizing morbidity rate and hospitalization . However the long term and overall benefits of minimally invasive surgeries in the total scenario of oncological problems are yet to be justified except in some select areas. To determine the long-term outcome after curative resection of ( Hase K 1995 ) colorectal cancers that extend only into the sub mucosal, a group from National Defence College, Japan followed 79 patients with minimally invasive sumucosal cancers of colon and rectum for five year and found that 13.9 patients had positive nodes with 72.7 percent cumulative five year survival. This study identified few histological criteria which will indicate necessity of appropriate bowel resections with lymph node dissection even for minimal disease in colonic cancers. Early gastric cancer is now treated successfully by Endoscopic mucosal resection ( EMR ). This technique at times is further supplemented by Transgastrostomal Endoscopic surgery in difficult tumour locations or when the size of the tumour is bigger than 20 mm providing an easy and convenient method of gastric tumour operation. A technique similar and easier than that of laparoscopic resection especially for a lesion on the posterior side of the stomach ( Ohta J 1997 ). Since the introduction of minimally invasive surgical techniques in thoracic surgery in 1990, video-assisted thoracic surgery ( VATS ) has become an optional approach for many thoracic operations. In a study involving two hundred thoracic surgeons in North America majority of respondents thought that VATS was an acceptable approach for the diagnosis of the indeterminate pulmonary nodule and for anterior and posterior mediastinal masses , limited lung cancer treatment, and benign esophageal disease ( Mack M J 1997 ). A group from Milan have reported their experience with thoracoscopic oesophagectomy. Between 1991 and 1995, 18 patients affected by a respectable intramural tumor of the oesophagus underwent oesophagectomy. The results of the present series, and those reported by other authors, do no seem to indicate evident advantages at present for the minimally invasive procedure during resection of the oesophagus for cancer. Another group from university of Munich ( Born P.,1996 ) have reported their experience with patients having both duodenal and biliary obstruction in whom endoscopic drainage is not feasible requiring gastroenterostomy plus bilodigestive anastamosis. This group have used permanent precutaneous transheptic biliary drainage ( PTBD ) and open or laparoscopic gastroenterostomy. But the reported benefit in presence of advanced disease is small and complications rate are high. ( Minor complications in 47.6% of cases. Thirty day mortality was 23.8%, Mean survival and hospital stay were 4.9 months ( SD 3.6 ) and 21.5 days ( SD 7.3 ) respectively ). For laparoscopic excisions of malignant tumours concerns have been expressed about increased incidence of implanted malignancy at trocar sites. And if the underlying mechanism involved is the aerosolization of cancer cells away from the original malignancy onto adjacent noncancerous tissue by carbon dioxide in addition to the direct implantations of cancer cells by spillage during manipulations and delivery, then it is also possible to cause general dissemination of the disease by laparoscopic surgery.

B) EXTENSIVE SURGERY

This can go into two directions

1) extensive local surgery
2) excision of disease at distant site.

1) EXTENSIVE LOCAL SURGERY

2) Partly encouraged by long term survival following good loco-regional control and partly by the improved methods of reconstruction and efficacy of chemotherapy to contain further progression of some diseases after debulking , in some areas extensive local surgery are now performed when so indicated. Where biology of the disease allow such approach,resection of locally important structures has been done, more so when methods of reconstructing that important structure is available. For example in differentiated carcinomas of thyroid excision of even carotid in squamous cell carcinomas of head and neck region will be considered as a sign of inoperability. Radical operation for gall bladder and bile duct carcinomas have been designed which combine panercaticoduodenetomy with hepatic resections. Extensive resections of skull base radio resistant tumours are becoming common. A group ( Spitize 1997 ) from university of Southern California have reported that it is possible to excise even the inferior vena cava during retroperitoneal lymph node dissection for germ cell tumours. 19 men who underwent retroperitoneal lymph node dissection for stage B3 ( N3 ) or C ( N3,M+ ) germ cell tumor after induction chemotherapy had resection ofinferior venecava because of extensive thrombosis or direct involvement of the vessel wall by a tumor. The inferior vena cava was resected from just below the renal veins to beyond the level of disease involvement. Complete resection of retro peritoneal disease was accomplished in all patients without immediate mortality. Seven patients had long term survival. Even organ transplant is now being practiced for locally advanced but not disseminated disease like liver cancers. A group from Ontario, Canada, has reported 83 % survival and no recurrance following liver transplant in pediatric patients. ( Superina R 1996 ).

3) SURGEY FOR METASTATIC DISEASE

Large series are now available in literature where commendable results have been reported after excision of metastatic disease. It started with excision of metachronous liver metastatic sites in even lung and brain. In a follow up study of 1209 patients with lever metastasis from colorectal carcinoma, the acturial 5 years and 10 year survival for 173 patients who had curative resection of liver secondaries were 40% and 27% respectively.( Scheele J., 1990 )

In a group of 139 patients who underwent pulmonary resection for metastatic colorectal carcinoma overall 5 and 20 year survival ( McAfee M K 1992 ). Apart from colorectal cancers, such policy is now abundantly employed in soft tissue sarcomas, melanomas, germ all tumours and even breast cancers. Favourable prognostic factors are metachronous metastasis, single or less than 3 lessons, single organ involvement, long disease free interval between primary and metastatic disease, greater tumour doubling time and known and predictable natural history of the disease.

GENE THERAPY

The concept of gene therapy for non-genic cancers has recently been expounded and more than hundred clinical trials are taking place. This involves targeting the delivery of potentially therapeutic genes to tumour sites and regulating their _expression within the tumour micro environment. We shall discuss this in our article on gene therapy in a later issue. For the present it can be stated that surgery can play a preventive role by prophylactic removal of organs which are genetically predisposed to a strong possibility of development of cancer at a later date. Established examples are for medullary carcinoma of thyroid, familial breast and ovarian cancers.

CIRCULATING CANCER CELLS

Histological, immunological, and molecular methods have been used for detecting micro metastases in solid tumours by simple blood test. Some methods, such as, reverse transcriptase-polymerase chain reaction ( RT-OCR ) for the detection of circulating tumour cells have been suggested as potential techniques for staging of cancer.