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Modern Management of Colorectal Cancer
- William J Fawcett, Jeffrey T Lordon, Nial F Quiney, Nariman D Karanjia, Timothy A Rockall (26 October 2007)
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Should we consider also an alternate pathway beside Adenoma- carcinoma model of Vogelstins in pathogenesis of colorectal carcinoma?
- Professor Pranab Kumar Bhattacharya MD(cal) Path, FIC Path(ind), Bhattacharya Rupak Bsc(cal)MSc(JU), 7/51 Purbapalli, Sodepur Kol-110Bhattacharya Upasana DPS Kolkata Mouumita Bera MD (PGT) Patho, IPGMER, Sarkar Diptendra MS, DNB.FRCS(Eng) Asst. Prof. Surgery, IPGMER, Chakraborty Anindya MS(cal) Surgery(uro IPGMER, (27 November 2007)
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William J Fawcett, Consultant Anaesthetist Royal Surrey County Hospital, Guildford GU2 7XX, Jeffrey T Lordon, Nial F Quiney, Nariman D Karanjia, Timothy A Rockall
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Dear Sir We read with interest the review of the management colorectal cancer [1] but were disappointed that significant aspects of current treatment received little or no mention. There is no mention is made of the role of laparoscopic large bowel resection for colorectal cancers. This technique has become increasingly widely used in both the UK and abroad, and is now recommended as an alternative to open surgery by NICE [2]. A recent study [3] shows that laparoscopic surgery allows rapid mobilisation of the patient, an earlier return of bowel function, lower complication rates and a much earlier discharge from hospital (4 days vs. 11 days). Secondly, liver resection, for uni-lobar or bi-lobar colorectal tumour metastases has revolutionised treatment of the condition yet only merits one sentence. Up to 50% of patients with colorectal cancers develop liver metastases following diagnosis. Chemotherapy has been shown to extend median survival. However without liver resection, five year survivors are extremely rare. Indeed some units are achieving a five year survival of 46% with low mortality (2.1%) and morbidity rates [4]. The use of neo-adjuvant chemotherapy prior to liver resection, avoidance of peri- operative blood transfusion and meticulous surgical technique may all have contributed to this success story. WJ Fawcett, Consultant Anaesthetist
Departments of Anaesthesia and Surgery, Royal County Hospital, Guildford GU2 7XX References 1. Ballinger AB, Anggiansah C. Colorectal cancer. BMJ 2007;335:715- 718 2. NICE guidance - Laparoscopic surgery for the treatment of colorectal cancer http://guidance.nice.org.uk/TA105. 3. Laparoscopic colorectal surgery – results from 200 patients. Scala A, Huang A, Dowson HMP, Rockall TA. Colorectal Disease 2007;9:701-705 4. Lordon JT, Karanjia ND, Quiney N, Fawcett WJ, Worthington TR, Remington J. A ten year prospective audit of liver resection for colorectal metastases in a tertiary referral unit. British Journal of Surgery 2007;94:2 Competing interests: None declared |
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Professor Pranab Kumar Bhattacharya MD(cal) Path, FIC Path(ind), Professor of Pathology, Incharge of Histopathology Unit, Blood Bank&;VCTC,Cytogenetics Institute of Post Graduate Medical Education& Research-244A AJC Bose Road, Kolkata-20 West Bengal, I, Bhattacharya Rupak Bsc(cal)MSc(JU), 7/51 Purbapalli, Sodepur Kol-110Bhattacharya Upasana DPS Kolkata Mouumita Bera MD (PGT) Patho, IPGMER, Sarkar Diptendra MS, DNB.FRCS(Eng) Asst. Prof. Surgery, IPGMER, Chakraborty Anindya MS(cal) Surgery(uro IPGMER,
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Colorectal cancer is the commonest malignancy of GI tract of old age and most lethal cancer in males (after lung and prostate cancer) and in females (after lung and breast) with male female ratio 2.9:1. The average age of detection is around 60 years though 6-8% of colorectal cancer arises below age 40. Though exact etiology of colorectal cancer is not known, there is evidence that there is both an inherited and environmental component of which lynch syndrome or, hereditary non polyposis colorectal cancer (HNPCC, Lynch syndrome-Type1 & type II), or, familial adenometous polyposis(FAP) Peutz Jeghers, Familial Juvenile polyposis, Hamartomatous Polyposis syndromes, adenomatous polyposis ,ulcerative colitis, chron’s disease, diet play a significant factor. The usual histological variety of colorectal cancer is well to moderately differentiated columnar cell adenocarcinoma secreting variable amount of mucin. The tumor cells represent a combination of columnar and of goblet cell with occasional participation of endocrine cell and exceptional occurrence paneth cells. There are consistent inflammatory cells & desmoplastic reactions at the edge of the tumor, most of the inflammatory cells are T cell lymphocytes. The tumor may be limited in the mucosa (insitu) or may be invasive. It may also be invading all layers of bowel and extending into peri-rectal spaces, permeating the peri-neural space & invading veins. Besides other variants adeno carcinomas are also fond in colorectal cancer. They are mucinous carcinoma (15%- mostly found in rectum), Signet ring type (affecting young people), squamous differentiation, clear cell change, chorio-carcinomatous differentiation, small cell carcinoma, carcinoid tumor, malignant lymphoma & malignant melanoma are also seen In a recent study at IPGMER, kolkata, for last 2 years periods [from 2004-06] 18 cases of colorectal cancer below the age 40 years, all came from lower socio-economic strata, showed 8 cases (44%) were in age group 11 -20 years, 6 cases(33%) in age group 21-30 years and 4 cases(22%) in age of 31-40 years and most younger patient were in 2nd decade of life (44%) M:F ratio is 1.25:1, having upper rectum cases 5(27%) mid rectum3(17%) and lower rectum10(56%) involving recto sigmoid junction is the commonest site. All these patients are vegetarian, non alcoholic and 13 cases were Hindu in religion and only 2 patients (11%) had a family history. Both patients had one parent affected who was histological proven Adenocarcinoma of Colon. Though meat diet augments colorectal carcinoma, in our series 100% were purely vegetarian and used to have fiber diet. Presenting symptoms were bleeding per rectum (94.5%), alteration of bowel habit(77.7%), Pain abdomen (27.8%) ,Pain lower back (11.1%) ,mucoid stool (33.3%), tenesmus(44.4%) ,loss of weight(50%), pain on defecations(27.7%) and jaundice(5.5%). On clinical examination 72% showed clinically palpable growth, Pallor(66%), Histopathologically 16 cases were diagnosed by first author as adenocarcinoma and only 2 cases came out as villous adenoma with superimposed adeno carcinoma. We did not find any cases of Lymphoma or malignant melanoma or STUMP in this age group. PreOP CEA value above 15 ng and 6 cases CEA level were less 10ng/ml. The mean CEA value increased with Dukes staging and 16 .6% cases were in stage A, 27% I stage B , 38% in stage C and 16% in Dukes stage-D. The percentage of patients with CEA>10ng/ml was 100% at stage D. Highest mean CEA level was found in poorly differentiated adeno carcinoma. In Mucin secreting type the mean value of CEA was 108, in moderately differentiated the mean value was 37, in well differentiated -15 and in poorly differentiated it was 126ng. Colorectal cancer is though in our study found to be higher in men, it is slightly higher in women than in men, it is common in individuals more than age 50, we in a random sampling study found the incidence in kolkata, west Bengal, india, is also high in younger population bellow age 40. Screening for asymptomatic population for presence of adenomatous polyp will help not only to detect the disease at early but in favorable stage, can prevent the disease by removing pre malignant lesions. Combined Occult Fecal blood Testing [at least 3 consecutive stool avoiding food like meat, Broccoli, Turnips, radishes, Cantalpupe, NSSAIDs, Vitc, Fe , 2 days prior of testing] and flexible sigmoidoscopy or colonoscopy[sensitivity 90% in trained gastroenterologist] must be done to be considered by the state government level spreading the scope for these tests at state general hospital level. Colorectal cancer is now understood to be a genetic disorder-a term not synonymous with hereditary but implies that the transformation of a normal cell to a malignant cell is achieved through step by step accumulation of genetic alteration. The inherited colon cancer syndrome accounts for only 1-3% of colorectal cancer in population. Several studies have shown that first degree relatives of patients with colo- rectal cancer have 2-3 fold increased risk of colon cancer when compared with control population [1-2] It is widely accepted that majority of colorectal cancer develop within a pre existing adenoma (Adenoma- carcinoma model of Vogelstin[3]). The model proposed by Vogelstin and coworkers in1988 [3] alterations involving APC, K-ras, tumor suppressor loci on 18q and TP53 are pre-requisites for progression for normal colonic mucosa through adenoma to carcinoma based on Darwinian concept of evolution of cancer in a hostile environment resulting DNA damage. This model [3] is associated with LOH at multiple loci including 5q,17p and 18q and therefore fits well neoplasm classified as chromosomal instability(CIN) or micro satellite stable.(MSS). However mutation of APC, K-ras and TP53 is far from inevitable. Combining the mutational data of multiple laboratories the frequency of APC, K-Ras and TP53 mutation in Colorectal cancer is 58%,36% and 52% respectively[4]In MSI cancer lOH is observed relatively infrequently but it is conceivable that both copies of tumor suppressor genes APC and TP53 could be inactivated by somatic mutation. In fact the frequency of APC and TP53 mutation is low in sporadic MSI cancer 39% and 18% respectively and frequency of K –ras mutation is still lower 11%(5,6&7). With all respects to Vogelstein Model of Adenoma Carcinoma sequence, the authors here want to high light the fact there remains short comings to Vogelstein model like a) missing mutations b) higher frequency to certain genetic alteration in as adenoma versus carcinoma. In fact in our study we had only 2 cases of villous Adenoma that came out to have carcinoma favoring adeno carcinoma sequences of Vogelstein in sporadic colorectal cancer. This lead us to think whether there is any alternative pathways exist called ‘polyp- cancer sequence?’ There may be also alternative path ways a) Rapidly progressing or aggressive adenomas- They are HNPCC- showing high grade dysplasia or villocity- and an individual adenoma is not only likely to transform into carcinoma but will do in a short time frame, probably due to genetic instability 2) flat or depressed adenomas that are overlooked at endoscope – mostly found in Japanese subjects and difficult to detect by endoscopies. And histopathology shows high grade dysplasia and sub mucosal invasion3) de- novo carcinoma –Cancer arising within and destroying small flat adenomas4) serrated path way- in other epithelial polyps namely Juvenile, Peutz- Jeghers, hyperplasic- which are traditionally classified as non neoplastic lacking any malignant potential Genetic alterations in SMD4 and ST11 in Peutz jeghers polyps K-Ras mutation, low and occasional Micro satellite instability in Hyperplasic polyp has been demonstrated by multiple workers References 1) Fuchus.CS, Giovannucci EL, Colditz G etaL “ A PROSPECTIVE STUDY OF FAMILY HISTORY AND RISK OF COLORECTAL CANCER “ New Eng. J. Med- 1994:331:1669-74 2)Burt R.W” screening of patients with positive family history of colorectal cancer” Gastrointest.Endosc. Cln. NA 1997;7;65-79 3)3) Vogelstein B, Fearon ER, Hammilton SR etal” Genetic alterations during colorectal tumor development” New.Eng. J. Med. 1988:319:525-32 4 Jereny R Jass “ pathogenesis of Colorectal cancer” Surg. Clin. N. Am 2002;82;891-904 5)5) Shitoh K, Konishi F, Miyaki m etal” Pathogenesis of non-familial colorectal carcinoma with high microsatellite instability” J. Clin. PaTHOL.2000:53:841-45 6) Fujiwara T, Stoker JM, watanable T Et al” Accumulated clonal alterations in familial & sporadic colorectal carcinomas with widespread instability in microsatellite sequences” Am. J. Pathol 1198:153:1063-78 7)Konishi M, Kikuchi-yanoshita R Tanaka K et al “ molecular nature of colon tumors in hereditary non polyposis colon cancer, familial polyposis, and sporadic colon cancer” gastroenterology 1996:111;307-17 Authors -: 1)Professor PranabKrBhattacharyaMD(Path)CalFIC path(Ind.),
Professor, Dept. of pathology, In charge of Histopathology Unit, in charge
of Cytogenetics, Ex-In charge of 24 hours Ronald Ross Malaria clinic,
Technical Supervisor In charge of Blood Bank, Institute of Post Graduate
Medical Education& Research (IPGMER) 244A AJC Bose Road, K0lkata-
700020, West Bengal , India
2) Mr. Rupak Bhattacharya BSc(cal), MSc(JU)
7/51 Purbapalli Po= Sodepur ,Dist.- 24 parganas(North),West Bengal ,Pin
700110, India
3)Miss Upasana Bhattacharya
Delhi Public School, Rubipark, Kolkata
4)Dr. Moumita Bera MD(PGT) Pathology Institute of Post Graduate Medical Education &research 244A AJC Bose Road, KOlkata-20, West Bengal, India 5)Dr. Diptenddra Sarkar MS(cal)DNB ,FRCS(Eng)
6) Dr. Aninda kumar Chakraborty MBBS(cal), MS(cal), Dept of Surgery(uro) Institute of Post Graduate Medical Education &research 244A AJC Bose Road, KOlkata-20, West Bengal, India Competing interests: None declared |
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