Welcome to the 12th part of educational series on GastroIntestinal Cancers. We learned in part 11 about treatment of rectal cancer, including importance of locoregional treatment in form of chemoradiation. Also, the fact that most cancers in our country present at a stage when chemoradiation should be given before surgery, rather than after surgery. Preoperative treatment in this manner would also help to avoid colostomy in many cases.
Question: First of all Dr. Chiragbhai I am interested in outcome of patient discussed last week.
Answer: Sure. I am also happy to inform you that he underwent surgery in USA, which was completed in less than two hours, and most importantly a colostomy was avoided. Thanks to a very good response with chemoradiotherapy, enough surgical margin was achieved to avoid colostomy.
Que: But isn’t it difficult to operate after chemoradiation?
Ans: Thank you for bringing out an important question. This was the concern raised after initial very small studies. However, almost all large studies and clinical experience at most centers now is same as in patient mentioned above i.e. no increase in rate of complications, blood loss, duration of surgery etc. Surgery should be done preferably within 5-10 weeks after chemoradiation is completed. Experience at our center is same.
Que: Is chemoradiation today different than in past, resulting in better results?
Ans: Yes that is also true to some extent. As there are advances in radiotherapy machines and better trained radiation oncologists and physicists, there is significantly reduced toxicity. Also, we have learned a lot more about combining chemotherapy with radiotherapy. Best option used to be infusional 5-FU, which needs to be given continuously for 6 weeks i.e. patient has to wear an infusion pump and keep it on for 24 hours a day, for total 6 weeks. A good infusion pump costs over one lakh. Also, since this is practically very difficult, enough 5-FU was frequently not given in our country. Same can be now obtained with oral prodrug of 5-FU i.e. capecitabine, a markedly convenient and safer option. Also, other medicines can now be added to radiotherapy e.g. oxaliplatin.
Que: This sounds exciting, a prodrug of 5-FU?
Ans: Yes the same old 5-FU which is active in so many diseases, is now available as an oral form. This drug gets converted to 5-FU in tumor, using its own enzyme. Most of the western world, this has replaced IV 5-FU e.g. one of the regimens used in both colon and rectal cancers is FOLFOX, which requires three days of hospitalization every two weeks. Same can be easily achieved with CapeOx regimen, where patient comes for only a two hour infusion every three weeks, followed by oral capecitabine, without any hospitalization.
Of course, there are other advances as well in chemotherapy e.g. pharmacogenomics i.e. ability to predict drug side effect, thereby reducing dose in advance. Such tests are now available in India as well e.g. UGT1A1 polymorphism test helps to predict irinotecan toxicity, DPD/TS testing helps to predict 5-FU toxicity... There are tests for other medicines as well, which are rapidly becoming commercially available, as confirmatory studies are coming out. We discussed in earlier parts about tests to detect efficacy e.g. KRAS gene test to predict efficacy of Cetuximab.
Saturday, August 22, 2009
GASTROINTESTINAL CANCER PART-11
Welcome to the eleventh part of educational series on GastroIntestinal Cancers. We learned in parts 8-9-10 about treatment of colon cancer, including the fact that many patients in stage 4 can also achieve a good prolongation of life and a significant number can also be cured.
Question: Now Dr. Chiragbhai, what about RECTAL cancer? Is there a difference in approach?
Answer: Yes. Even though, most of the treatment principles are same, especially with respect to medical management, there are some important differences.
Que: What are these differences?
Ans: They are mainly related to the fact that unlike colon cancer, there are significant differences with respect to local anatomy. Important points are: 1. Closeness of rectum to surrounding pelvic organs 2. Lack of serosa 3. Reduced ability in this region to obtain wide surgical margins.
Because of these factors, locoregional treatment is very important, rather than only systemic therapy. Advances in locoregional treatment have markedly improved results.
Que: What are these advances?
Ans: First is the change in surgical technique i.e. TME – total mesorectal excision is now standard of care and must be practiced in all patients.
Second is Adjuvant (postoperative) Chemotherapy and Radiotherapy, given concurrent further improve results. This is an integral part of most rectal cancers, except very early stages.
Que: What about loss of sphincter and permanent colostomy? Is it for every patient, and any advance in this area?
Ans: First of all, every patient does not need permanent colostomy, only for patients with tumors very close to sphincter. Secondly, colostomy care has significantly improved over years, and most patients live fairly normal life. Occasional patients do have frequent local problems, however, and can be very disturbing. Also, it is very difficult for most patients initially to accept this.
Preoperative ChemoRadiotherapy has now become standard for T3 tumors and patients with positive nodes radiologically – most of the patients in India fall in this category. This is mainly done to provide better surgical results, but it also helps in avoiding colostomy in some patients.
One of our recent patients with T3N2 disease had a doctor relative in USA, and he consulted several of his colleagues (over 20) there. Interestingly, every one of them advised preoperative chemoradiation there, emphasizing the fact that it is now a standard of care, at least in USA. We treated him here with preoperative chemoradiation. Patient is now in USA and I received news yesterday that his evaluation shows complete regression of disease radiologically. He is now due for surgery and is likely to achieve a much better surgical result and overall survival. Surgery first approach would have significantly compromised his chances. Other good news is that he would have had permanent colostomy with primary surgery, whereas now there is a good chance that he would be able to avoid this.
Question: Now Dr. Chiragbhai, what about RECTAL cancer? Is there a difference in approach?
Answer: Yes. Even though, most of the treatment principles are same, especially with respect to medical management, there are some important differences.
Que: What are these differences?
Ans: They are mainly related to the fact that unlike colon cancer, there are significant differences with respect to local anatomy. Important points are: 1. Closeness of rectum to surrounding pelvic organs 2. Lack of serosa 3. Reduced ability in this region to obtain wide surgical margins.
Because of these factors, locoregional treatment is very important, rather than only systemic therapy. Advances in locoregional treatment have markedly improved results.
Que: What are these advances?
Ans: First is the change in surgical technique i.e. TME – total mesorectal excision is now standard of care and must be practiced in all patients.
Second is Adjuvant (postoperative) Chemotherapy and Radiotherapy, given concurrent further improve results. This is an integral part of most rectal cancers, except very early stages.
Que: What about loss of sphincter and permanent colostomy? Is it for every patient, and any advance in this area?
Ans: First of all, every patient does not need permanent colostomy, only for patients with tumors very close to sphincter. Secondly, colostomy care has significantly improved over years, and most patients live fairly normal life. Occasional patients do have frequent local problems, however, and can be very disturbing. Also, it is very difficult for most patients initially to accept this.
Preoperative ChemoRadiotherapy has now become standard for T3 tumors and patients with positive nodes radiologically – most of the patients in India fall in this category. This is mainly done to provide better surgical results, but it also helps in avoiding colostomy in some patients.
One of our recent patients with T3N2 disease had a doctor relative in USA, and he consulted several of his colleagues (over 20) there. Interestingly, every one of them advised preoperative chemoradiation there, emphasizing the fact that it is now a standard of care, at least in USA. We treated him here with preoperative chemoradiation. Patient is now in USA and I received news yesterday that his evaluation shows complete regression of disease radiologically. He is now due for surgery and is likely to achieve a much better surgical result and overall survival. Surgery first approach would have significantly compromised his chances. Other good news is that he would have had permanent colostomy with primary surgery, whereas now there is a good chance that he would be able to avoid this.
GASTROINTESTINAL CANCER PART-10
Welcome to the tenth part of educational series on GastroIntestinal Cancers. We learned in part 9 about treatment of stage 1-3, role of pathologist, chemotherapy,newer medicines for colon cancer.
Question: Now Dr. Chiragbhai, what about the stage 4 colon cancer? What palliative treatments are available?
Answer: First of all, let me remind you that colon cancer is one of the few cancer types where cure is possible in many patients, even in stage 4. This is nearly impossible in most cancer types.
Que: That is amazing. How do you do that?
Ans: Well, majority of metastatic disease in colon cancer is confined to liver, lung, peritoneum. Especially at relapse, most patients have only liver metastases. And this i.e. liver metastases are frequently amenable to complete resection. At presentation, about 10% patients have resectable metastatic disease, but the percentage is much higher at relapse.
So, if the patient has resectable disease in metastatic sites and primary, they should all be removed either in one operation or in two stages.
Que: Do you mean that all such patients can undergo surgery, and how many are cured?
Ans: Of course not all patients are resectable. And there are strict criteria for selection, since this is a major surgery.
First of all, R0 resection i.e. ability to remove all gross disease, should be possible at all disease sites. Debulking has no role. Patient fitness, surgical expertise for liver resection, and ability to manage postoperative care are also important. Disease should not be a rapidly growing one. PET scan is useful in determination of all disease sites, to avoid unnecessary resections, especially at first presentation.
About 30% of these patients are cured after such a surgery i.e. achieve a 5 year survival. This is great compared to most metastatic cancers, where 5 year survival is less than 5%.
For patients with borderline operability or clearly inoperable disease, chemotherapy preferably with a monoclonal antibody(bevacizumab or cetuximab) should be given.
23-40% (in different published series) of such patients can be converted to operable disease. Such patients frequently achieve a prolonged survival.
In fact, systemic therapy has become so effective and with so many options, that even without operation, a number of patients now survive for up to 3-4 years.
Que: This is very interesting and heartening to note that one can now cure or control such advance disease, even in stage 4.
What about certain genetic tests you had mentioned, in part 8?
Ans: Yes, this is also very interesting, since we now have ability to predict what medicine will work for which patient or tumor, based on certain tests. Something similar to antibiotic susceptibility test for various bacteria. One example is: cetuximab is a drug that works in colon cancer only if patient’s tumor has a wild type K-RAS gene i.e. if patient’s tumor shows mutation, one should not use this drug. There are few other examples which we can talk about at some other time.
Question: Now Dr. Chiragbhai, what about the stage 4 colon cancer? What palliative treatments are available?
Answer: First of all, let me remind you that colon cancer is one of the few cancer types where cure is possible in many patients, even in stage 4. This is nearly impossible in most cancer types.
Que: That is amazing. How do you do that?
Ans: Well, majority of metastatic disease in colon cancer is confined to liver, lung, peritoneum. Especially at relapse, most patients have only liver metastases. And this i.e. liver metastases are frequently amenable to complete resection. At presentation, about 10% patients have resectable metastatic disease, but the percentage is much higher at relapse.
So, if the patient has resectable disease in metastatic sites and primary, they should all be removed either in one operation or in two stages.
Que: Do you mean that all such patients can undergo surgery, and how many are cured?
Ans: Of course not all patients are resectable. And there are strict criteria for selection, since this is a major surgery.
First of all, R0 resection i.e. ability to remove all gross disease, should be possible at all disease sites. Debulking has no role. Patient fitness, surgical expertise for liver resection, and ability to manage postoperative care are also important. Disease should not be a rapidly growing one. PET scan is useful in determination of all disease sites, to avoid unnecessary resections, especially at first presentation.
About 30% of these patients are cured after such a surgery i.e. achieve a 5 year survival. This is great compared to most metastatic cancers, where 5 year survival is less than 5%.
For patients with borderline operability or clearly inoperable disease, chemotherapy preferably with a monoclonal antibody(bevacizumab or cetuximab) should be given.
23-40% (in different published series) of such patients can be converted to operable disease. Such patients frequently achieve a prolonged survival.
In fact, systemic therapy has become so effective and with so many options, that even without operation, a number of patients now survive for up to 3-4 years.
Que: This is very interesting and heartening to note that one can now cure or control such advance disease, even in stage 4.
What about certain genetic tests you had mentioned, in part 8?
Ans: Yes, this is also very interesting, since we now have ability to predict what medicine will work for which patient or tumor, based on certain tests. Something similar to antibiotic susceptibility test for various bacteria. One example is: cetuximab is a drug that works in colon cancer only if patient’s tumor has a wild type K-RAS gene i.e. if patient’s tumor shows mutation, one should not use this drug. There are few other examples which we can talk about at some other time.
GASTROINTESTINAL CANCER PART-9
Welcome to the ninth part of educational series on GastroIntestinal Cancers. We learned in part 8 about etiology, family history and early diagnosis of colon cancer.
Question: Now Dr. Chiragbhai, how do you treat colon cancer?
Answer: Treatment can be divided according to early and late stages.
For stage 1 to 3, primary treatment is surgery, basically hemi colectomy with good regional lymph node dissection. Once again, this should be done by a trained surgeon who routinely operates on colon cancer. Intra operative evaluation should include assessment of synchronous primary or metastatic disease, especially in liver and peritoneum.
Role of pathologist is also very important. Therefore, cancer histopathology experience is equally important. A good pathology review is first step in assessing quality and adequacy of surgery. Most important is to assess all margins of surgical resection, number of nodes involved, grade of tumor, lymphovascular invasion, other signs of local spread e.g. nodules in pericolic fat. Number of nodes evaluated is so important, that if there are less than 12 nodes evaluated (either not resected or not evaluated by pathologist), it is considered as incomplete resection. Such patients are given adjuvant chemotherapy as if they have positive nodes.
Que: It is interesting to note this very important role of pathologist. What is the role of other modalities in colon cancer?
Ans: Adjuvant therapy in the form of chemotherapy is very important. Role of radiotherapy is limited, only rarely required in colon cancer, however very important in rectal cancer, as we will see later.
Que: Are there any important advances in chemotherapy?
Ans: Colon cancer used to be treated by only 5-FU and Leucovorin for many years. However, in last decade there have been many new medicines, with improved efficacy and more importantly tolerability and convenience.
Adjuvant chemotherapy improves survival by about 10%-20% absolute, depending upon stage and number of positive nodes. This is very important, compared to what we achieve in other common diseases. For example, streptokinase in acute myocardial infarction improves survival by absolute 2% and primary angioplasty (PAMI) by about 4-6% at best.
5-FU/LV is still important backbone of many regimens, but addition of oxaliplatin has improved results significantly, as seen in MOSAIC trial. Capecitabine is an oral drug, which converts to 5-FU directly in tumor. This allows oral treatment, which is very convenient for patients. We have switched to use of oral treatment in over 90% of our patients, and rarely use intravenous 5-FU nowadays.
New monoclonal antibodies like Avastin (bevacizumab) and Erbitux(cetuximab) have shown significant activity in metastatic disease, and are being evaluated in adjuvant/postoperative therapy.
Question: Now Dr. Chiragbhai, how do you treat colon cancer?
Answer: Treatment can be divided according to early and late stages.
For stage 1 to 3, primary treatment is surgery, basically hemi colectomy with good regional lymph node dissection. Once again, this should be done by a trained surgeon who routinely operates on colon cancer. Intra operative evaluation should include assessment of synchronous primary or metastatic disease, especially in liver and peritoneum.
Role of pathologist is also very important. Therefore, cancer histopathology experience is equally important. A good pathology review is first step in assessing quality and adequacy of surgery. Most important is to assess all margins of surgical resection, number of nodes involved, grade of tumor, lymphovascular invasion, other signs of local spread e.g. nodules in pericolic fat. Number of nodes evaluated is so important, that if there are less than 12 nodes evaluated (either not resected or not evaluated by pathologist), it is considered as incomplete resection. Such patients are given adjuvant chemotherapy as if they have positive nodes.
Que: It is interesting to note this very important role of pathologist. What is the role of other modalities in colon cancer?
Ans: Adjuvant therapy in the form of chemotherapy is very important. Role of radiotherapy is limited, only rarely required in colon cancer, however very important in rectal cancer, as we will see later.
Que: Are there any important advances in chemotherapy?
Ans: Colon cancer used to be treated by only 5-FU and Leucovorin for many years. However, in last decade there have been many new medicines, with improved efficacy and more importantly tolerability and convenience.
Adjuvant chemotherapy improves survival by about 10%-20% absolute, depending upon stage and number of positive nodes. This is very important, compared to what we achieve in other common diseases. For example, streptokinase in acute myocardial infarction improves survival by absolute 2% and primary angioplasty (PAMI) by about 4-6% at best.
5-FU/LV is still important backbone of many regimens, but addition of oxaliplatin has improved results significantly, as seen in MOSAIC trial. Capecitabine is an oral drug, which converts to 5-FU directly in tumor. This allows oral treatment, which is very convenient for patients. We have switched to use of oral treatment in over 90% of our patients, and rarely use intravenous 5-FU nowadays.
New monoclonal antibodies like Avastin (bevacizumab) and Erbitux(cetuximab) have shown significant activity in metastatic disease, and are being evaluated in adjuvant/postoperative therapy.
GASTROINTESTINAL CANCER PART-8
Welcome to the eighth part of educational series on GastroIntestinal Cancers. We learned in previous parts that early diagnosis, complete staging, multidisciplinary evaluation, pre and post operative chemotherapy in operable patients, trained surgeon in high volume center, use of standard regimens is what can provide best possible results in stomach cancer.
Question: Now Dr. Chiragbhai, what about cancer of Colon, the next subsite?
Answer: Colon cancer is very common, especially in West. It is perhaps the most well studied GI cancer. It is a very important example of early diagnosis, importance of family history, multidisciplinary treatment, and keeping hope alive even in metastatic disease, role of gene test to decide specific therapy, and other aspects.
Que: This sounds interesting, especially about “hope” that you have mentioned. We will definitely come back to that. But what leads to colon cancer?
Ans: Colon cancer is strongly linked to family history, and lifestyle, among the known factors. Similar to breast and prostate cancer, it is much more common in West and seems related to so called western lifestyle. As we have seen in earlier discussions, we in India have adopted many of those lifestyle changes, and are therefore increasingly vulnerable to these cancers. Some possible aspects are low fiber and more fat in diet.
Family history is well studied for Western population and includes people with mildly increased risk where there is no definite syndrome but higher risk compared to average population (mostly people having only one relative with colon cancer, but no other risk factors) AND people with significantly high risk e.g. syndromes such as FAP or HNPCC. People with multiple relatives having cancer or a relative having cancer at age <50 should definitely undergo genetic counseling.
Que: What should one do for early diagnosis?
Ans: Screening recommendations for India are not possible, since we have less incidence compared to West but no studies from India addressing this issue. Therefore, at the present time, most people here follow western guidelines i.e. stool for occult blood once daily for 3 days, once every year after age of 50 OR colonoscopy once every 10 years.
Most importantly, we should remember to investigate iron deficiency anemia to find underlying cause, and thoroughly investigate any GI bleed (overt or occult) with tests including endoscopy. By following later two, we and others have made many early diagnoses.
Bright red bleeding per rectum should not be assigned to “piles bleeding” without a thorough evaluation. Such bleeding even if once, needs detailed evaluation, as a malignant tumor or polyp may not bleed repeatedly. Therefore, if bleeding has stopped spontaneously, it is not an indication to stop evaluation. But rather a warning sign from nature, that we need to follow to find out the real reason. Remember that for a chest pain, even when it has stopped after few seconds or minutes, we get complete evaluation. Not all of them are cardiac pains, same is true for GI bleeds.
GASTROINTESTINAL CANCER PART-7
Welcome to the seventh part of educational series on GastroIntestinal Cancers. In last part, we discussed the staging of a newly diagnosed stomach cancer.
Question: Dr. Chiragbhai, how do you take care of patients with gastric cancer?
Ans: Most important first step is to have a multidisciplinary evaluation. Please note that it is a MUST in most western institutes. This type of evaluation, done with a team work, provides best chance to the patient for survival, and quality of life (according to his/her definition). In our setting also, it can be done in most cases, and in our experience, it has shown the same benefits as in west.
Since advances are rapidly occurring in every field of medicine, it is important for all specialists to work together in this deadly disease to provide best results to an individual patient. Also since frequently patients do not fall into the category of guidelines or published studies, collective experience and expertise are required to decide plan.
Que: What are the treatment options?
Ans: Surgery is the mainstay of treatment. There is enough published evidence to recommend that specific training in dealing with such cancers is extremely important. Otherwise we will never see results quoted in western literature. A surgeon who deals with cancers regularly, preferably focused in GI cancers should be the one operating. Almost all developed countries have regional surgery experts for any cancer surgery i.e. people specializing in surgery of one area e.g. GI, head and neck, breast, thoracic… More awareness of this concept will certainly lead to improved results in our country.
There are some controversies with regard to type of surgery i.e. extent of dissection D1 vs D2 vs extended D2; also about total vs subtotal gastrectomy. In short, a good margin i.e. about 4-5 cm, and minimum 15 lymph nodes removed are the least expected.
Que: How do you incorporate other modalities in treatment?
Ans: There are many emerging approaches. However, based on good data and guidelines, following are most widely accepted:
Perioperative chemotherapy i.e. before and after surgery, is preferred for most patients (based on MAGIC trial results) – standard of care in most of Europe, and many US institutes. Improves survival/cure rate by a large extent, improves complete resection rate by downsizing tumor.
Postoperative chemoradiation (in most stages) – if patient is referred after surgery. However, this treatment is difficult to tolerate for most patients, and only the most medically fit patients are able to complete course.
Locally advanced – chemoradiation – if medically fit
Metastatic – chemotherapy or supportive care alone
There are many important points to follow in planning of radiotherapy and chemotherapy. Many chemotherapy drugs and regimens are acceptable, most active and studied are ECF, DCF, and now capecitabine or oxaliplatin based.
In short, early diagnosis, complete staging, multidisciplinary evaluation, pre and post operative chemotherapy in operable patients, trained surgeon in high volume center, use of standard regimens is what can provide best possible results in stomach cancer.
Question: Dr. Chiragbhai, how do you take care of patients with gastric cancer?
Ans: Most important first step is to have a multidisciplinary evaluation. Please note that it is a MUST in most western institutes. This type of evaluation, done with a team work, provides best chance to the patient for survival, and quality of life (according to his/her definition). In our setting also, it can be done in most cases, and in our experience, it has shown the same benefits as in west.
Since advances are rapidly occurring in every field of medicine, it is important for all specialists to work together in this deadly disease to provide best results to an individual patient. Also since frequently patients do not fall into the category of guidelines or published studies, collective experience and expertise are required to decide plan.
Que: What are the treatment options?
Ans: Surgery is the mainstay of treatment. There is enough published evidence to recommend that specific training in dealing with such cancers is extremely important. Otherwise we will never see results quoted in western literature. A surgeon who deals with cancers regularly, preferably focused in GI cancers should be the one operating. Almost all developed countries have regional surgery experts for any cancer surgery i.e. people specializing in surgery of one area e.g. GI, head and neck, breast, thoracic… More awareness of this concept will certainly lead to improved results in our country.
There are some controversies with regard to type of surgery i.e. extent of dissection D1 vs D2 vs extended D2; also about total vs subtotal gastrectomy. In short, a good margin i.e. about 4-5 cm, and minimum 15 lymph nodes removed are the least expected.
Que: How do you incorporate other modalities in treatment?
Ans: There are many emerging approaches. However, based on good data and guidelines, following are most widely accepted:
Perioperative chemotherapy i.e. before and after surgery, is preferred for most patients (based on MAGIC trial results) – standard of care in most of Europe, and many US institutes. Improves survival/cure rate by a large extent, improves complete resection rate by downsizing tumor.
Postoperative chemoradiation (in most stages) – if patient is referred after surgery. However, this treatment is difficult to tolerate for most patients, and only the most medically fit patients are able to complete course.
Locally advanced – chemoradiation – if medically fit
Metastatic – chemotherapy or supportive care alone
There are many important points to follow in planning of radiotherapy and chemotherapy. Many chemotherapy drugs and regimens are acceptable, most active and studied are ECF, DCF, and now capecitabine or oxaliplatin based.
In short, early diagnosis, complete staging, multidisciplinary evaluation, pre and post operative chemotherapy in operable patients, trained surgeon in high volume center, use of standard regimens is what can provide best possible results in stomach cancer.
GASTROINTESTINAL CANCER PART-6
Welcome to the sixth part of educational series on GastroIntestinal Cancers. In last part, we had a very interesting discussion and guideline on how to make early diagnosis of GI tract cancers. We covered especially the evaluation of ANEMIA as an early sign.
Question: Dr. Chiragbhai, we have discussed risk factors for stomach cancer, and early signs. What evaluation is required for a patient who is diagnosed with stomach cancer?
Answer: Stomach cancer, as we have seen, is often diagnosed late. A good evaluation before starting treatment is important, since it can dramatically change therapy, as we will see.
Following tests are recommended:
CT scan
PET-CT, if available
EUS in few early cases
Laparoscopy
Out of above tests, most important tests in our scenario are a good quality CT scan, and laparoscopy. Both are widely available.
CT scan mainly helps to detect extent of local disease (along with endoscopy findings), lymphadenopathy-perigastric and distant, liver metastases. In one study, accuracy of PET-CT in preoperative staging was 68%, compared with 53% for CT scan alone. Newer MDCT scans, such as 64 slice CT scanners are likely to be better, however. Fortunately, PET-CT is now more widely available in India, including in Gujarat.
In one study, 657 patients with potentially resectable stomach cancer underwent laparoscopy before surgery. 31% of these patients were found to have metastatic disease. Thus laparoscopic staging helped to avoid a major surgery and related morbidity in these patients. Also, it allowed earlier initiation of palliative therapy.
Thus, at least a routine good CT scan and laparoscopy would help to avoid many “open and close” surgeries and palliative resections, and use patient’s limited resources for right treatment.
Que: Oh! Thank you for that clarity. Since laparoscopy is an invasive procedure, and rarely required in other cancers for staging, we never think of it for staging work up. This discussion was quite enlightening for me at least. What is your next step?
Ans: Now that we have completed staging the patient, patient will have either resectable OR non resectable tumor.
Non resectability could be secondary to distant spread/metastatic disease (which includes peritoneal spread) OR locally advanced disease.
Question: Dr. Chiragbhai, we have discussed risk factors for stomach cancer, and early signs. What evaluation is required for a patient who is diagnosed with stomach cancer?
Answer: Stomach cancer, as we have seen, is often diagnosed late. A good evaluation before starting treatment is important, since it can dramatically change therapy, as we will see.
Following tests are recommended:
CT scan
PET-CT, if available
EUS in few early cases
Laparoscopy
Out of above tests, most important tests in our scenario are a good quality CT scan, and laparoscopy. Both are widely available.
CT scan mainly helps to detect extent of local disease (along with endoscopy findings), lymphadenopathy-perigastric and distant, liver metastases. In one study, accuracy of PET-CT in preoperative staging was 68%, compared with 53% for CT scan alone. Newer MDCT scans, such as 64 slice CT scanners are likely to be better, however. Fortunately, PET-CT is now more widely available in India, including in Gujarat.
In one study, 657 patients with potentially resectable stomach cancer underwent laparoscopy before surgery. 31% of these patients were found to have metastatic disease. Thus laparoscopic staging helped to avoid a major surgery and related morbidity in these patients. Also, it allowed earlier initiation of palliative therapy.
Thus, at least a routine good CT scan and laparoscopy would help to avoid many “open and close” surgeries and palliative resections, and use patient’s limited resources for right treatment.
Que: Oh! Thank you for that clarity. Since laparoscopy is an invasive procedure, and rarely required in other cancers for staging, we never think of it for staging work up. This discussion was quite enlightening for me at least. What is your next step?
Ans: Now that we have completed staging the patient, patient will have either resectable OR non resectable tumor.
Non resectability could be secondary to distant spread/metastatic disease (which includes peritoneal spread) OR locally advanced disease.
GASTROINTESTINAL CANCER PART-5
Welcome to the fifth part of educational series on GastroIntestinal Cancers. We completed discussion about evaluation and treatment of Esophageal Cancer.
Question: Now Dr. Chiragbhai, what about cancer of Stomach, the next subsite?
Answer: Stomach cancer is very common in India, once again with significant regional variation as in other GI subsites. Also, for unknown reasons, it has declined significantly in West and now represents a much smaller proportion of all cancers there, also proximal tumors are more common in West. In rest of the world, however, it remains one of the most common cancer, including number 1 in Japan.
Que: What are the known risk factors?
Ans: Known risk factors include:
Helicobacter pylori infection
Smoking
High salt intake
Hereditary – only 1-3% patients
Que: Why is the mortality so high in stomach cancer?
Ans: Once again, it is more because of late diagnosis. In Japan, where earlier diagnosis is done because of aggressive screening, mortality is much lower than in other countries. Since symptoms are nonspecific i.e. early satiety, nausea, vomiting, anemia, and sometimes bleeding, patients are not investigated till late.
Que: What should our readers keep in mind to make an early diagnosis?
Ans: There is a tendency for empiric treatment without diagnosis, for many of the above noted symptoms. Also, patients frequently change doctors when invasive or expensive tests are advised.
Frequent counseling and awareness among both doctors and patients, and wider availability of tests, will help to change this situation. For example, chest pain is now more thoroughly investigated with non invasive and invasive tests to detect heart disease. Even though there is a potential for excessive work up, over diagnosis, and sometimes test related complications, it has certainly helped many patients with early detection of heart disease. In spite of all these limitations, most educated patients, including most doctors themselves, prefer to undergo these tests rather than miss a heart disease. Similar change of mindset is required for cancer related tests, including endoscopy, CT scans and biopsy.
It is important to highlight the fact that a significant proportion of almost all cancers are now curable if detected early. This is the reason why we should be doing evaluation. And this is not a wishful thinking, as one can see published literature in the era of internet, and data from various patient support groups. There are a few million people with cancer in USA alone who were treated several years ago, and hence are now considered cured. Such patients, many of them celebrities or leaders, have also helped to change mindset in USA. Even with such late diagnoses in India, if you ask around, you are very likely to find at least one person who has been cancer free for many years. We can increase this number of cured patients substantially if we make more early diagnoses.
Even today some doctors and many educated people ask me this question, if cancer can ever be cured. This question is a reflection of our poor job in highlighting the fact that many patients have already been cured. The question should be “how many more can be cured?”
Que: Chiragbhai, can you give some detailed recommendations for our readers?
Ans: Let us start with one of the above noted symptom of stomach cancer i.e. anemia, which happens to be an important symptom for many GI cancers.
Anemia in an adult over 40 (more so in men) should be thoroughly investigated, as it may be first sign of many serious diseases e.g. cancer of upper or lower GI tract, myeloma as well as non malignant diseases like early kidney failure, hypothyroidism etc. Stool for occult blood should be tested for 3 consecutive days, and GI endoscopy must be done if even one day is positive. GI endoscopy should also be done if there is no other obvious reason (such as clear cut poor nutrition history), even if stool for occult blood is negative, as blood loss from tumor may be intermittent.
Treatment of iron deficiency anemia with Iron supplement is only half treatment, without finding out the reason for developing iron deficiency. This is very important since iron deficiency anemia related to chronic blood loss from a cancer will also respond to iron supplement, for few months. However if not picked up at that time, it will present at a late stage in few months.
Severe anemia (Hb less than 8 g/dl) without very obvious cause should also be evaluated thoroughly. Blood transfusion or other empiric treatment without finding out the underlying reason should be considered completely inadequate and poor medical care. In most of the western countries, if a cancer is missed because of such empiric treatment, patient may go to court and will almost certainly win the case.
Yes, there are many women and young people in India, for whom diagnosis is mostly nutritional or menorrhagia even with severe anemia. But as mentioned above, it should be obvious stated cause, and not a presumption.
Importantly remember to investigate following subsets: all of them will not have an underlying cancer, but some will do, and many others will have another significant underlying disease. Just like we investigate almost every pain in chest or nearby region not to miss one case of heart disease, following should be evaluated not to miss a cancer in potentially curative stage (especially when there is no obvious cause like poor nutrition or menorrhagia).
Men with anemia, especially over 35-40.
Women with anemia over age 35-40.
Any one with new anemia i.e. documented normal Hb within last two years.
Iron deficiency anemia, in an adult, even with negative stool for occult blood.
Positive stool for occult blood, even if only one of 3 days.
Bleeding from upper or lower GI tract, even if only once (in absence of very obvious cause like piles)
Non specific GI symptoms persisting for more than 4 weeks (not evaluated in last two years), or change in pattern of old chronic symptoms, or increasing in severity, or associated with significant weight loss.
Question: Now Dr. Chiragbhai, what about cancer of Stomach, the next subsite?
Answer: Stomach cancer is very common in India, once again with significant regional variation as in other GI subsites. Also, for unknown reasons, it has declined significantly in West and now represents a much smaller proportion of all cancers there, also proximal tumors are more common in West. In rest of the world, however, it remains one of the most common cancer, including number 1 in Japan.
Que: What are the known risk factors?
Ans: Known risk factors include:
Helicobacter pylori infection
Smoking
High salt intake
Hereditary – only 1-3% patients
Que: Why is the mortality so high in stomach cancer?
Ans: Once again, it is more because of late diagnosis. In Japan, where earlier diagnosis is done because of aggressive screening, mortality is much lower than in other countries. Since symptoms are nonspecific i.e. early satiety, nausea, vomiting, anemia, and sometimes bleeding, patients are not investigated till late.
Que: What should our readers keep in mind to make an early diagnosis?
Ans: There is a tendency for empiric treatment without diagnosis, for many of the above noted symptoms. Also, patients frequently change doctors when invasive or expensive tests are advised.
Frequent counseling and awareness among both doctors and patients, and wider availability of tests, will help to change this situation. For example, chest pain is now more thoroughly investigated with non invasive and invasive tests to detect heart disease. Even though there is a potential for excessive work up, over diagnosis, and sometimes test related complications, it has certainly helped many patients with early detection of heart disease. In spite of all these limitations, most educated patients, including most doctors themselves, prefer to undergo these tests rather than miss a heart disease. Similar change of mindset is required for cancer related tests, including endoscopy, CT scans and biopsy.
It is important to highlight the fact that a significant proportion of almost all cancers are now curable if detected early. This is the reason why we should be doing evaluation. And this is not a wishful thinking, as one can see published literature in the era of internet, and data from various patient support groups. There are a few million people with cancer in USA alone who were treated several years ago, and hence are now considered cured. Such patients, many of them celebrities or leaders, have also helped to change mindset in USA. Even with such late diagnoses in India, if you ask around, you are very likely to find at least one person who has been cancer free for many years. We can increase this number of cured patients substantially if we make more early diagnoses.
Even today some doctors and many educated people ask me this question, if cancer can ever be cured. This question is a reflection of our poor job in highlighting the fact that many patients have already been cured. The question should be “how many more can be cured?”
Que: Chiragbhai, can you give some detailed recommendations for our readers?
Ans: Let us start with one of the above noted symptom of stomach cancer i.e. anemia, which happens to be an important symptom for many GI cancers.
Anemia in an adult over 40 (more so in men) should be thoroughly investigated, as it may be first sign of many serious diseases e.g. cancer of upper or lower GI tract, myeloma as well as non malignant diseases like early kidney failure, hypothyroidism etc. Stool for occult blood should be tested for 3 consecutive days, and GI endoscopy must be done if even one day is positive. GI endoscopy should also be done if there is no other obvious reason (such as clear cut poor nutrition history), even if stool for occult blood is negative, as blood loss from tumor may be intermittent.
Treatment of iron deficiency anemia with Iron supplement is only half treatment, without finding out the reason for developing iron deficiency. This is very important since iron deficiency anemia related to chronic blood loss from a cancer will also respond to iron supplement, for few months. However if not picked up at that time, it will present at a late stage in few months.
Severe anemia (Hb less than 8 g/dl) without very obvious cause should also be evaluated thoroughly. Blood transfusion or other empiric treatment without finding out the underlying reason should be considered completely inadequate and poor medical care. In most of the western countries, if a cancer is missed because of such empiric treatment, patient may go to court and will almost certainly win the case.
Yes, there are many women and young people in India, for whom diagnosis is mostly nutritional or menorrhagia even with severe anemia. But as mentioned above, it should be obvious stated cause, and not a presumption.
Importantly remember to investigate following subsets: all of them will not have an underlying cancer, but some will do, and many others will have another significant underlying disease. Just like we investigate almost every pain in chest or nearby region not to miss one case of heart disease, following should be evaluated not to miss a cancer in potentially curative stage (especially when there is no obvious cause like poor nutrition or menorrhagia).
Men with anemia, especially over 35-40.
Women with anemia over age 35-40.
Any one with new anemia i.e. documented normal Hb within last two years.
Iron deficiency anemia, in an adult, even with negative stool for occult blood.
Positive stool for occult blood, even if only one of 3 days.
Bleeding from upper or lower GI tract, even if only once (in absence of very obvious cause like piles)
Non specific GI symptoms persisting for more than 4 weeks (not evaluated in last two years), or change in pattern of old chronic symptoms, or increasing in severity, or associated with significant weight loss.
GASTROINTESTINAL CANCER PART-4
Welcome to the fourth part of educational series on GastroIntestinal Cancers.
Question: Now Dr. Chiragbhai, we discussed about Barrett’s esophagus and about evaluation of a patient with esophagus cancer. What are the treatment approaches?
Answer: Traditionally, surgery has been the mainstay of treatment. However, recently more and more patients are being treated with chemotherapy plus radiotherapy without surgery, or triple treatment including surgery as well.
Que: Can you tell us more about how to choose between treatment options?
Ans: A number of factors are involved, but most important are: 1. Site of disease and resectability 2. Patient Fitness 3. Patient Preference 4. Availability of Expertise – surgical vs. chemoradiotherapy
Site: For Upper 1/3 chemoradiotherapy is preferred. For Middle 1/3 either surgery or chemoradiotherapy can be offered. For Lower 1/3 surgery is frequently preferred.
Patient should be explained advantages and disadvantages of both approaches. Local expertise should also be kept in mind, e.g. surgery for esophagus cancer is a challenging one, and surgeon’s skill level and experience are important in deciding outcome.
Surgery can be transthoracic or transhiatal, both have their advantages and disadvantages, and more important is surgeon’s familiarity and comfort level with either approach.
Postoperative treatment is recommended for high risk patients e.g. microscopic or macroscopic residual disease, and few other factors.
Que: What about triple or trimodality therapy?
Ans: Trimodality therapy refers to a combination of all 3 approaches i.e. chemotherapy, radiotherapy and surgery. Considering modest overall survival with either approaches alone, studies were done to combine all three. Results are not consistent in randomized trials, but suggestive in some studies and meta-analysis to favor trimodality therapy i.e. chemoradiotheapy followed by surgery. However, this should be undertaken only with most expert team, and in very fit patients, as the mortality can be significantly high.
Que: Are there any differences with regard to lower 1/3 esophagus or G-E junction tumors, as they are frequently studied as part of stomach tumors as well?
Ans: Yes, they are treated somewhat differently e.g. Based on intergroup study by McDonald et al, postoperative chemoradiation is offered to such patients. Also, practice in Europe is different based on MAGIC trial. This includes perioperative chemotherapy i.e. 3 cycles of ECF chemotherapy, followed by surgery, followed by 3 more cycles of ECF.
Que: Is there a role for preoperative chemotherapy without radiotherapy?
Ans: There are at least two major positive studies i.e. MRC group and French group studies. Both showed increase in PFS and overall survival with preoperative chemotherapy without radiotherapy. RTOG trial did not show benefit.
GASTROINTESTINAL CANCER PART-3
Welcome to the third part of educational series on GastroIntestinal Cancers. In last issue of GMJ, we learned about risk factors, especially tobacco and alcohol. We also learned about tests for early diagnosis.
Question: Now Dr. Chiragbhai, you had mentioned about discussing each subsite of GI cancer in detail. What should we start with?
Answer: Esophagus. It is very common in Gujarat, in both men and women, as we saw in first part of this series.
There are two main histologies: Squamous Cell Carcinoma AND Adenocarcinoma.
SCC is mainly related to use of tobacco and alcohol.
Adenocarcinoma is mainly related to Barrett’s esophagus and GERD (gastroesophageal reflux disease). GERD known as reflux disease is more commonly seen in obese patients in West, but is an increasing common symptom in India.
However, many patients do not have any of these risk factors.
Que: What is Barrett’s esophagus?
Ans: This is a condition where normal mucosa at gastroesophageal junction is converted from squamous to columnar epithelium. This metaplasia frequently progresses to dysplasia and then cancer.
Que: How do you monitor this risk of cancer in patients with Barrett’s esophagus?
Ans: Patients with Barrett’s esophagus are managed medically e.g. using proton pump inhibitors. Patients with severe symptoms of reflux need upper GI endoscopy. Monitoring frequency is debated. Every 1-3 years, endoscopy is performed. More frequent endoscopy is done for those who develop low grade dysplasia. Esophagectomy is recommended for high grade dysplasia, as over 50% of such patients already have adenocarcinoma.
Que: What is the screening test for other patients?
Ans: There is no good test for other patients. Patients with uncomplicated GERD do not need repeated endoscopy. Most important is to intervene early if there is increase in severity of reflux symptoms, or development of dysphagia, weight loss.
Widespread monitoring with screening endoscopy is done in Japan, but this approach has not been found to be useful in other countries.
Que: What tests are recommended for a patient with suspected cancer?
Ans: Upper GI endoscopy with biopsy from suspected area, CT scan of chest and abdomen are basic tests. Wherever feasible, PET-CT is preferred, as it can detect disease spread early and hence avoid unnecessary local treatment. EUS (endoscopic ultrasound) is also useful in accurate staging, perhaps less important with availability of PET-CT.
Question: Now Dr. Chiragbhai, you had mentioned about discussing each subsite of GI cancer in detail. What should we start with?
Answer: Esophagus. It is very common in Gujarat, in both men and women, as we saw in first part of this series.
There are two main histologies: Squamous Cell Carcinoma AND Adenocarcinoma.
SCC is mainly related to use of tobacco and alcohol.
Adenocarcinoma is mainly related to Barrett’s esophagus and GERD (gastroesophageal reflux disease). GERD known as reflux disease is more commonly seen in obese patients in West, but is an increasing common symptom in India.
However, many patients do not have any of these risk factors.
Que: What is Barrett’s esophagus?
Ans: This is a condition where normal mucosa at gastroesophageal junction is converted from squamous to columnar epithelium. This metaplasia frequently progresses to dysplasia and then cancer.
Que: How do you monitor this risk of cancer in patients with Barrett’s esophagus?
Ans: Patients with Barrett’s esophagus are managed medically e.g. using proton pump inhibitors. Patients with severe symptoms of reflux need upper GI endoscopy. Monitoring frequency is debated. Every 1-3 years, endoscopy is performed. More frequent endoscopy is done for those who develop low grade dysplasia. Esophagectomy is recommended for high grade dysplasia, as over 50% of such patients already have adenocarcinoma.
Que: What is the screening test for other patients?
Ans: There is no good test for other patients. Patients with uncomplicated GERD do not need repeated endoscopy. Most important is to intervene early if there is increase in severity of reflux symptoms, or development of dysphagia, weight loss.
Widespread monitoring with screening endoscopy is done in Japan, but this approach has not been found to be useful in other countries.
Que: What tests are recommended for a patient with suspected cancer?
Ans: Upper GI endoscopy with biopsy from suspected area, CT scan of chest and abdomen are basic tests. Wherever feasible, PET-CT is preferred, as it can detect disease spread early and hence avoid unnecessary local treatment. EUS (endoscopic ultrasound) is also useful in accurate staging, perhaps less important with availability of PET-CT.
GASTROINTESTINAL CANCER PART-2
Welcome to the second part of educational series on GastroIntestinal Cancers. In last issue of GMJ, we started series on GI cancers, and learned that it is very common and since it is in both sexes, overall numbers are very high. Also, there is a wide regional variation in incidence of different GI cancers. We also noted SIGNS AND SYMPTOMS FOR EARLY DIAGNOSIS.
Question: Now Dr. Chiragbhai, we learned about basics of early diagnosis last time. But what leads to GI cancers?
Answer: GI cancers include seven major subsites. And as we saw last time, there is a wide variation in regional incidence, indicating differences in risk factors. Each subsite behaves like a different cancer, with minimum commonalities. Accordingly known risk factors are also different. Many risk factors are unknown or poorly understood.
Que: What are the known risk factors?
Ans: It is very interesting to note that that risk factors range from infection to addiction to diet to genetics. It is truly very diverse. We will see them in more detail as we take up each subsite separately.
Esophagus – tobacco, alcohol, barrett’s esophagus
Stomach – diet, helicobacter pylori infection, tobacco
Colorectal – diet, genetic syndromes
Liver – Hepatitis B/C, alcohol, aflatoxin B1
Pancreas – little is known
Que: That is truly a wide variation. However diet and tobacco/alcohol seem to be commoner.
Ans: Yes, if we can stay away from tobacco and alcohol, that alone would reduce GI cancer burden remarkably. These are very strong risk factors, and are avoidable. But these habits are difficult to leave. Therefore, it is better to focus on our children and youth, so they do not start these habits.
Diet, of the so called Western type, is also an important risk factor. Our traditional diet is proven to be safer for many cancer prevention, as well as cardiovascular risk reduction – which is high in fiber, and low in fat. Fruits are also important.
Que: Is there any test for healthy people for early diagnosis, as in breast cancer?
Ans: Unfortunately there is no good test. We have to depend on early evaluation of symptoms/signs. For colorectal cancers, stool for occult blood and sigmoidoscopy/colonoscopy are regularly recommended tests in West. They are being used in India also, but their utility is not proven here for mass screening, considering significant differences in incidence/regional variation/other factors.
Question: Now Dr. Chiragbhai, we learned about basics of early diagnosis last time. But what leads to GI cancers?
Answer: GI cancers include seven major subsites. And as we saw last time, there is a wide variation in regional incidence, indicating differences in risk factors. Each subsite behaves like a different cancer, with minimum commonalities. Accordingly known risk factors are also different. Many risk factors are unknown or poorly understood.
Que: What are the known risk factors?
Ans: It is very interesting to note that that risk factors range from infection to addiction to diet to genetics. It is truly very diverse. We will see them in more detail as we take up each subsite separately.
Esophagus – tobacco, alcohol, barrett’s esophagus
Stomach – diet, helicobacter pylori infection, tobacco
Colorectal – diet, genetic syndromes
Liver – Hepatitis B/C, alcohol, aflatoxin B1
Pancreas – little is known
Que: That is truly a wide variation. However diet and tobacco/alcohol seem to be commoner.
Ans: Yes, if we can stay away from tobacco and alcohol, that alone would reduce GI cancer burden remarkably. These are very strong risk factors, and are avoidable. But these habits are difficult to leave. Therefore, it is better to focus on our children and youth, so they do not start these habits.
Diet, of the so called Western type, is also an important risk factor. Our traditional diet is proven to be safer for many cancer prevention, as well as cardiovascular risk reduction – which is high in fiber, and low in fat. Fruits are also important.
Que: Is there any test for healthy people for early diagnosis, as in breast cancer?
Ans: Unfortunately there is no good test. We have to depend on early evaluation of symptoms/signs. For colorectal cancers, stool for occult blood and sigmoidoscopy/colonoscopy are regularly recommended tests in West. They are being used in India also, but their utility is not proven here for mass screening, considering significant differences in incidence/regional variation/other factors.
GASTROINTESTINAL CANCER PART-1
Welcome to the first part of educational series on GastroIntestinal Cancers. In last issue of GMJ, concluding 14th part of Breast Cancer series was published.
Question: Thank you Dr. Chiragbhai Shah. Our readers learned a lot from your series on breast cancer. It helped to clarify concepts for many and provided significant awareness on this issue. I am glad that you have decided to continue writing. May I ask why you have chosen this topic, and not your current interest i.e. stem cell transplant?
Answer: Thank you. I am also happy to continue writing for this highly educated group of readers. Many of whom inspire me with their excellent work in respective fields. This is my small effort to create awareness and provide information to assist busy doctors in making right decisions for their patients.
My goal therefore is to first choose topics of wider interest, with more incidence, more impact on mortality and morbidity. As you have mentioned, stem cell transplant is my recent interest but I take care of many more patients with solid tumors like breast, GI, head/neck and other cancers and they are equally challenging and important.
Que: How important is this topic?
Ans: GI cancers include esophagus, stomach, intestine, colon, rectum, anal canal, hepatobiliary, pancreas.
Nationally, Stomach is second most common cancer. In Gujarat, esophagus is 5th most common cancer in both men and women. Thus, if all GI cancers are taken together, they account for a large number. Interestingly, there is significant regional variation, e.g. esophagus is first in men in Nagpur registry, gall bladder cancer is significantly more common in North India, Stomach more common in South India.
Also, most are diagnosed late and are difficult to treat.
Que: Why are they diagnosed late?
Ans: Many of these present with nonspecific GI symptoms and hence ignored for long. Imaging studies/endoscopy for diagnosis are often done late or are not widely available or are not interpreted properly.
Important symptoms/signs/clues like GI bleed, melena, persistent (over 3-4 weeks) abdominal pain, dysphagia, altered bowel habits – new persistent constipation or diarrhea, jaundice, iron deficiency anemia in an adult especially men, positive stool for occult blood, weight loss should be evaluated thoroughly. These do not always mean a GI cancer, but frequently lead to an early diagnosis, which is so important for saving a life.
Que: What tests are recommended for early diagnosis?
Ans: Most important is not to ignore above noted signals. Thereafter, tests depend upon specific subsite. However I would like to mention that a good sonography, and/or endoscopy can diagnose most cases early. Barium studies can be used as initial tool (although not enough) only if endoscopy is not available. When feasible, CT scan is a better test. Newer imaging modalities provide additional benefit. Importantly, tumor markers should not be used for initial diagnosis, except in case of primary liver cancer. Just remember SONOGRAPHY/CT and ENDOSCOPY.
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