Signet Ring Cell Carcinoma + Malignant Ascites, T4N3Mx - Looking for feedback

[Ron-guteleute]

Hello everyone,

my father was diagnosed with Signet Ring Cell Carcinoma of the colon (pathology of the tissue T4N3Mx) and malignant asites. The tumor (8cm) was located in cecum near the ileocecal valave. 6 of 16 LN came back positive, including the distant superior mesenteric LN. He had an extended right hemicolectomy. The surgeon said that all macroscopic cancer tissue was removed. Unfortunately to make it worse, there was also ascites in pelvis which was positive for malignant cells, which I guess makes it Stage IV.

Short chronology of the recent events:

Apr-2022: Routine CT scan, all fine
Jun-2022: Bowl camps, fullness, constipation, IBS like symptoms. Ultrasound: all fine. Wight loss (7 kg)
Jul-2022: PET Scan all clear, minimal ascites in pelvis, CEA 1.8
Aug-2022: Using anti bowl spasms medications.
Sep-2022: CT scan 8cm tumor in cecum, minimal ascites. CEA 1.7. No suspicion on malignant ascites due to prior history of ascites (liverchirrosis)
Sep-2022: Surgery: Right extended hemicolectomy, many enlarged lymph nodes observed, ileum obstructed, no peri mets visible. No liver mets visible. Very slow recovery after surgery.
Oct-2022: Pathology: T4N3Mx, malignant ascites, colon origin (CK7-/CK20+/CDX2+/-).
Oct-2022: KRAS test on the way, in order to add Cetuximab.

We have met with the Oncologist, based on statistics the prognosis is quite shocking, however she is a bit optimist that FOLOFOX+Cetuximab could be a bit effective (hopefully). We'll do other molecular test if needed. Avastin (bevacizumab) is also being considered but not recommended after surgery as it can cause anastomosis leak.

I've read a lot about Signet Ring Cell Carcinoma, its poor prognosis, extremely aggressive with poor response to chemo. I'm feeling a bit comfort and lucky that I found this forum, needless to say I'm in the same boat as may of you. I was shocked and speechless when I red the pathology reports.

Malignant ascites have complicated the prognosis to quite worse. I fear that malignant ascites will lead to the inevitable peritonimum mets, progressing even during chemo.

I would highly appreciate if you could share some similar experiences or your stories about the treatment and the outcomes.

Many thanks,
R.

[rp1954]

As you know, SRCC as primary colorectal cancer is a rare subtype, less than 1%, usually with varied poor treatment results. Also concerning is the ascites aspect, often a sign of shorter time horizons to work with.

Ascites, associated with low albumin levels, may be more common in SRCC.
the albumin level was significantly lower in the PSRCCR group than in the non-SRCC group, 3.4 vs 4.3
https://bmcgastroenterol.biomedcentral. ... 22-02258-1

One odd aspect, perhaps a little hopeful is that low CEA value, is apparently uncommon within CRC SRCC.

What you need to do is achieve some combination of chemical components that slow or kill SRCC cells in various locations, the more locations the better, AND try to improve/preserve immune function and quality of life.

You've got several possible directions
1. Collect several conventional recommendations for treatment, you may see variation and get added bits of information each time.
2. Look for complementary treatments to regular treatments
3. Look for alternative treatments with varying kinds of medical or biological basis
4. Look for conventional trials

We found conventional blood testing very limited in scope and not so useful for comparative access to the world's medical literature, as well as dealing with practical problems sooner. In a situation like your father's, you need a baseline yesterday (tomorrow, call the labs' 800#) if you are going to get much beyond Step 1, which I label standard, "Std".
My prior discussion of immediate recommendations, Day1, Week1
We found a lot of answers (and questions) in the expanded bloodwork.

To get beyond, Step 1, you need to try to achieve the extra steps each day, and not stop for long on insurance approvals. Our first year, we just paid cash on smaller stuff without the delays fighting or begging - I realized both of us might suffer serious damage fooling with insurance bs.

We found a lot of low hanging answers this way that were useful, some critically so, but not readily available in Std.

Some of us have found good results and quality of life via daily oral chemo enhanced by generics and supplements beyond what is possible in standard chemo schedules. e.g. what some of us call the ADAPT+++ approach.

[MadMed]

Hi R.
I'm sorry about your father's situation. There's no way of hiding it, it's bad. I am one of the lucky few SRCC. We make as rp said 1% of CRC, so there's very, very little data on our specific subtype.
Here's a few of my notes through out my own experience.

• I am not surprised how quickly things went haywire, in my own experience, i went from a small polyp to a 3 cm blocking rectal mass in 2 1/2 months. My Drs still can't comprehend it.
• Most SRCC are caught very late because it seems to work so fast, like a frenzy, from nothing in April to stage 4 in August.
• There's a notion that chemo does not work. It's not 100% true. I am an example where chemo reduced the tumor by 85%. Specifically FOLFIRINOX. Note that mine was of the mucinous type and Irinotecan does a number on that.
• CEA was useless in my case, it was always around 1.
• When I started, there are a few board members (BeckyH, Dori) that were SRCC and survived it, that gave me hope. I hope it does the same for you.

RP gave you some good advice, I can add a couple. Get an NCI accredited center. Get second opinions on everything. Move fast, don't delay, this subtype works fast.
If your Dad can handle FOLFIRINOX, get it. It is a rough regiment but may give your Dad a good shot.

This seems like a new cancer rather than the original gastric one ? Is that true ? Was the original cancer SRCC ?
I wish you the best, this thing is hateful!

[Peregrine]

Hi Ron,

Welcome to the forum, and I 'm sorry to hear about your dad's situation. Here are some of my thoughts on the situation.

• Assessment of comorbidities
  In order to determine if your dad can handle the strong chemo treatments recommended by rp1954 and MadMed, I think that a prior assessment needs to be made of any current comorbidities that exist that could pose a problem for implementing such treatments. This means making a list of all non-cancer health issues currently under treatment (e.g., diabetes, hypertension, high cholesterol, etc.) as well as other health problems that exist and that probably should already have been under treatment (e.g., obesity, nicotine addiction, alcohol abuse, etc.)
  
  This needs to be done in order to help determine what kinds of strong treatment can be applied now without causing multiple problems.
  .
  Once you find a good doctor who understands the situation and all of the constraints involved, then he/she can map out some sort of regimen that will help extend the life expectancy as much as possible. That's my suggestion.
  .
• Life expectancy for SRCC with peritoneal mets
  .
  
  "The 5-year survival of patients with PM induced by CRC is only 20%~25%, the median survival time is only 6~9 months, and the 1-year survival rate of patients with malignant ascites is less than 10% .
  
  Ref.[ 4, 5 ]
  4. van Gestel YR, de Hingh IH, van Herk-sukel MP, et al.
  Patterns of metachronous metastases after curative treatment of colorectal cancer.
  Cancer Epidemiol. 2014;38(4):448–454. doi:10.1016/j.canep.2014.04.004
  
  5. Mo S, Cai G.
  Multidisciplinary treatment for colorectal peritoneal metastases: review of the literature.
  Gastroenterol Res Pract. 2016;2016:1516259. doi:10.1155/2016/1516259
  

[Rock_Robster]

I’m sorry for the news, but I’m glad you’ve found this forum.

One question/clarification on MadMed’s (very good) post - did you do FOLFIRINOX or FOLFOXIRI? Same drugs but different protocol, I believe (with the former more commonly used in pancreatic cancer).

[MadMed]

Hi RR,
I went back to onc notes to make sure:

He started neoadjuvant FOLFOX on 5/13/2021. We switched to FOLFIRINOX from cycle 2 onwards and completed a total of 8 cycles of neoadjuvant chemotherapy on 9/2/2021.

If I understand the difference, there’s a 5FU bolus in FOLFIRINOX. I did get that.

[Ron-guteleute]

What you need to do is achieve some combination of chemical components that slow or kill SRCC cells in various locations, the more locations the better, AND try to improve/preserve immune function and quality of life.

You've got several possible directions
1. Collect several conventional recommendations for treatment, you may see variation and get added bits of information each time.
2. Look for complementary treatments to regular treatments
3. Look for alternative treatments with varying kinds of medical or biological basis
4. Look for conventional trials
...
To get beyond, Step 1, you need to try to achieve the extra steps each day, and not stop for long on insurance approvals. Our first year, we just paid cash on smaller stuff without the delays fighting or begging - I realized both of us might suffer serious damage fooling with insurance bs.

We found a lot of low hanging answers this way that were useful, some critically so, but not readily available in Std.
...
.

Many thanks RP for your comprehensive answer, I've also checked your other post, very helpful indeed!

[Ron-guteleute]

Hi R.
I'm sorry about your father's situation. There's no way of hiding it, it's bad. I am one of the lucky few SRCC. We make as rp said 1% of CRC, so there's very, very little data on our specific subtype.
...
RP gave you some good advice, I can add a couple. Get an NCI accredited center. Get second opinions on everything. Move fast, don't delay, this subtype works fast.
If your Dad can handle FOLFIRINOX, get it. It is a rough regiment but may give your Dad a good shot.

This seems like a new cancer rather than the original gastric one ? Is that true ? Was the original cancer SRCC ?
I wish you the best, this thing is hateful!

Thank you MadMed, this is giving me some hope! I'll start asking 2nd opinions as much as I can. I fear adding Irinotecan on top of FOLFOX would make the therapy quote toxic for my father, as he already suffer from liver cirrhosis (his ALT/AST has elevated frequently in the recent years) and from diabetis mellitus type II, however I'd definitely bring this up to the Oncologist.

This is a new tumor of colon origin, the previous gastric cancer was Adenocarcinoma (Poorly differentiated G3).

Many thanks!

[Peregrine]

"...Oct-2022: KRAS test on the way, in order to add Cetuximab...

Ron -

You probably already know that you can't add Cetuximab unless there are no KRAS mutations in the tumor, i.e., unless the tumor is coded by the pathologist as KRAS-'wild type'.

However, what I wanted to ask right now is whether your father's test for KRAS was a comprehensive KRAS/NRAS/BRAF test that also includes results for BRAF mutations, in particular, the BRAF V600E mutation.

This is because BRAF V600E mutations typically occur in tumors in the right colon, next to the caecum and appendix, and when they do occur it tends to complicate the treatment plan considerably.

Could you check with the oncologist to see what kind of KRAS test they did? If the test didn't test for the BRAF V600E mutation, then maybe they should do another test to test for that mutation specifically, since it is a very important mutation to know about when attempting to treat right-side colon cancers.

BRAF V600E mutations in right-side colon cancer: Heterogeneity detected by liquid biopsy

"Conclusion: BRAFV600E mutations are observed in right-side colon cancer at high frequency, especially in the cecum. BRAFV600E mutations can be detected in plasma and the detection rate is high in patients with advanced cancer.

https://pubmed.ncbi.nlm.nih.gov/35172933/

[Peregrine]

Ron --
As everybody has mentioned so far, time is of the essence right now. It's important to act quickly and do something effective now before things get really out of control.

But you need to have good advice to begin with. How are you doing on finding good doctors and good cancer hospitals near where you are? When will you be able to get some second opinions, and when will you be able to test for even more biomarkers to get a better picture of your father's specific SRCC profile?

Also, a few more questions ...

1.What country are you in? Does your country have some cancer hospitals that are considered centers of exellence?

2. What is your father's body mass index (BMI)?

3. What kinds of medications is your father on right now? And for what purpose?

4. What is your father's current state of mind? What does he think of all of the prognoses and about the different treatment approaches that might be taken right now, even the ones that might be somewhat toxic and unpleasant? It should be noted that stress, anxiety, depression, etc., have a bad effect on the immune system. Your father needs to have a good, functional immume system to help fight off this new cancer.

5. Is your mother available to give your father some emotional support?

6. What are your father's wishes concerning what should be done right now and in the immediate future? Your father is the patient, and it is his right to have his wishes respected.

7. etc., etc. ...

8. P.S. - You need to post more messages to this board so that you can eventually be promoted from "Newly Registered User" to a higher status where your messages can appear immediately after you click on the Submit button without having to spend time in the queue for later review by the Moderators. Newly Registered Users normally have to post from 5 to 10+ good messages or replies to the main board before their status will be upgraded.

9. P.P.S - Have you discussed the possibility that your father's type of SRCC might be hereditary? Have you yourself been tested for the CDH1 gene mutation? https://www.mskcc.org/news/6-things-know-about-cdh1-gene-mutation-and-stomach

[Ron-guteleute]

Ron --
As everybody has mentioned so far, time is of the essence right now. It's important to act quickly and do something effective now before things get really out of control.

But you need to have good advice to begin with. How are you doing on finding good doctors and good cancer hospitals near where you are? When will you be able to get some second opinions, and when will you be able to test for even more biomarkers to get a better picture of your father's specific SRCC profile?

Indeed, thank you Peregrine for emphasizing it once again. My father lives in non-EU country in Europe, so I guess they are not at the NCI or CCC levels like in the US or Germany. However I live in Germany and I have asked for a 2nd opinion in one the top 10 Hospitals, Comprehensive Cancer Center (CCC) which is NCI alike. Hopefully I'll get an appointment next week. I'll also ask on another CCC well known University Hospital a week or two weeks later.

As soon as KRAS results are ready (most probably in 2-3 weeks), we'll discuss again with the oncologist for other genomic/mutation tests. I guess this topic will also come up during the 2nd opinion consultation in Germany.

2. What is your father's body mass index (BMI)?

It is 15.3 kg/m2 which is quite under wight. My father was struggling to gain weight since the gastrectomy 3 years ago, and during this time before and after surgery he lost some weight (10kg). During the last weeks has been gaining some weight slowly (around 1.5 kg).

3. What kinds of medications is your father on right now? And for what purpose?

He takes small doses of Insulin (once per day) because of Diabetes Mellitus II. This type of diabetes is usually treated with metformin, however my father's liver does not tolerate the toxicity of this medication.

4. What is your father's current state of mind? What does he think of all of the prognoses and about the different treatment approaches that might be taken right now, even the ones that might be somewhat toxic and unpleasant? It should be noted that stress, anxiety, depression, etc., have a bad effect on the immune system. Your father needs to have a good, functional immume system to help fight off this new cancer.

Right now he is normal, however the first weeks of the recovery (from the hemicolectomy) were quite stressful (due to diarrhea, weakness, lack of movement...). We're trying to cheer him up and giving hope, optimism and courage so he could have a strong start with the chemo.

5. Is your mother available to give your father some emotional support?

My mother is a born optimist.

[Ron-guteleute]

9. P.P.S - Have you discussed the possibility that your father's type of SRCC might be hereditary? Have you yourself been tested for the CDH1 gene mutation? https://www.mskcc.org/news/6-things-know-about-cdh1-gene-mutation-and-stomach

That's interesting, I remember coming across this article 3 years ago when my father was diagnosed with stomach cancer (Adenocarcinoma G3 but not SRC). I'll do more research about it.

Thank you!

[Peregrine]

Earlier I forgot to mention the problem with high doses of paracetamol and possible liver damage. Paracetamol, a pain medication, is also known as acetaminophen and is marketed as Tylenol, or Panadol etc., etc. in other countries.

You can read about this problem in the links below:

https://coloncancersupport.colonclub.com/viewtopic.php?f=1&t=61855&p=490666#p490666

Liver injury induced by paracetamol and challenges associated with intentional and unintentional use

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336293/

I mention this because whatever strong chemo regimen your father will be taking next might trigger pain and discomfort, and he might be tempted to engage in self-medication with an over-the-counter pain medication like paracetamol. Instead, he should find a doctor who knows a lot about pain medications and can prescribe appropriate medications that won't cause these kinds of problems.

[Peregrine]

Ron -

In case the malignant pelvic ascites actually become peritoneal mets, here are some references to procedures for dealing with peritoneal mets:

Special procedures for dealing with mCRC mets to the peritoneum

Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC)
https://www.webmd.com/cancer/what-is-pipac
.
Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
https://www.uchicagomedicine.org/cancer/types-treatments/hipec?

Cytoreductive Surgery (CRS)
https://en.m.wikipedia.org/wiki/Cytoreductive_surgery

[Peregrine]

Ron -

Another question: Did they remove the ileocecal valve when they did the extended right hemicolectomy? If so, other digestive problems are likely to emerge and require specialized treatments.

Permanent SIBO due to removal of ileocecal valve
https://connect.mayoclinic.org/discussion/permanent-sibo-due-to-removal-of-ileocecal-valve/