Pseudomeigs and CRS/HIPEC Results

[StDrogo]

Hello all. I've been lurking on this forum since my wife's diagnosis some nine months ago but have been too cagey to post—and am only doing so now on the off chance that someone else might find this encouraging.

In a nutshell, my thirty-three-year-old wife and I were visiting her family in Australia over the summer last year; we normally live in Venice but were in the process of relocating to Berlin. We were consulting a Catholic fertility doctor at the time (we've been trying to conceive since our marriage four years ago exactly today), and based on some somewhat odd endocrine blood panel results we were contemplating remaining in Australia for a few extra months to sort out what was going on. I returned to Italy at the end of January to sort out some bureaucracy and planned to return in six weeks. However, the day after Valentine's day my wife called me in excruciating abdominal pain after a Yoga session asking whether she should go to the ER for evaluation; naturally, I told her she should go, but since she had always enjoyed pristine health and exceptional athleticism I wasn't unduly concerned—my worst case scenario at the time was an ectopic pregnancy.

A couple of days later, however, she called me harrowed to the bone. CT-imagery had revealed an enormous multiloculated mass in her left ovary, massive ascites, and slightly right-sided bilateral hydrothorax. Her CA-125 was 105, and CA19-9 was 36. Being a medical editor, I naturally connected the dots and assumed stage IV ovarian cancer with a median life expectancy of 20 weeks or so. At the time, however, I had recently been working on some material pertaining to gynecological malignancies and chose to be buoyed by the hydrothorax, which wasn't consistent with even the normal presentation of late-stage ovarian cancer and seemed somewhat suggestive of a benign etiology like Meigs' syndrome. I tried not to let my distress show as best I could—though the tech in radiology had already made a pretty serious blunder by going on to my wife about how she had "lived a good life"—and boarded the earliest flight from Venice to Australia.

I greeted my wife at the airport in a rather dire way; she was in a wheelchair, profoundly emaciated, and her belly severely distended. We met with the gyne team a couple of days later, and they were all pretty pessimistic. Results from the ascitic cytology came back negative the following week, and suddenly everyone changed their tune; the consultants agreed that it was probably Meigs' syndrome caused by an ovarian cystadenofibroma. Her surgery was scheduled for the following week, and we elected to forgo frozen section pathology and pursue fertility sparing surgery if at all possible.

The surgery for the ovarian tumor was fairly uneventful; they drained approximately eight liters of ascites and removed the left ovary and mass (which measured 160 mm x 220 mm) and corresponding fallopian tube and took a couple of biopsies from some inflamed portions of her omentum and pouch of Douglas. All looked well, and she was discharged on the third postoperative day.

The following week, her gyne doctors called to inform us that pathology had come back suspicious of colon cancer but that based on the clinical findings (unilateral and greater than 120 mm in maximal dimensions) it was most likely a borderline ovarian primary of intestinal type; the other biopsies and peritoneal lavages were absent any sign of malignancy. They scheduled her for a routine colonoscopy/endoscopy in a few weeks time to be sure. I was very skeptical based on the CK7-/CK20+ immunohistochemical phenotype of the ovarian mass and asked our priest to confer extreme unction on my wife, which he did.

The postoperative course before the colonoscopy did not go according to plan. She was nauseated and vomiting the whole time; I suspected an ileus or serious adhesions, but she continued to pass stool and gas and wasn't febrile so nothing was done. I was concerned at one point that she was complaining about intense spasming pain in her shoulders, which sounded a lot like gas pains, but that was shrugged off. By the day of our pre-op meeting with the head of the colorectal unit, my wife was looking profoundly cachectic and was very tachycardic (pulse between 140 and 160). Though still skeptical of a colonic primary, they agreed to do some diagnostics after percussing her abdomen. Eventually, at around 10:30 p.m., they did a CT scan and discovered free gas and significant purulent peritonitis. Those results arrived at around 11:30 p.m.; a MET call was made, most of the the surgeons from her previous operation along with half a dozen new ones congregated around her bedside, I called our priest (who arrived in twelve minutes flat—he had previously been an ER doctor, so knew his way around the hospital well), and my wife was whisked off for emergency surgery just after midnight. A few hours later, I received a call from her previous gyne surgeon that they had discovered two liters of purulent peritonitis, ultimately identified a stenosing mass in her splenic flexure, and had resected 60 cm of her colon. The operation ended up lasting around 6.5 hours. Fortunately, I have a good friend who was working in the ER that night who managed to cajole the staff in recovery to let me see my wife immediately.

Fast forwarding a bit, pathology came back again. They tested a phial of blood from back in February, and her baseline CEA was 10. Unsurprisingly, the stenosing mass in the splenic flexure was the primary. Of 16 identifiable lymph nodes resected, one was possibly positive. All other biopsies were negative, so that left us with a diagnosis of t4an1am1a. There were two pinprick perforations caused by ischemia proximal but 2 cm distant from the primary site. Though I had been working on a book on novel treatment modalities for colorectal cancer at the time (a weird coincidence), I was unfamiliar with any manifestation of colon cancer like this. An oncologist and a senior surgeon visited us shortly to inform us that my wife would die in short order, which greatly discouraged my wife—they were insistent that she had peritoneal carcinomatosis, though I adamantly refuted them on the basis of the utter lack of pathological or surgical findings to support the opinion. I promptly set out to do some research on my wife's presentation. I ended up discovering only 19 cases of pseudo-Meigs' from a colorectal primary and only four unilateral cases. Interestingly, though nowhere near any kind of statistical significance, the majority evinced long-term survival. Despite the possible proximal lymph node metastasis, reasoning from the same-sidedness of the colonic primary and the ovarian met, I reckoned that a transcoelomic mode of metastasis was most probable and started thinking about prophylactic HIPEC in the hopes of eliminating any remaining microscopic disease. Fortunately, the head of medical oncology we met with in a few weeks seemed to know his stuff and agreed to refer us to one of the few HIPEC surgeons in Australia, who also agreed to take on my wife's case.

We resolved on 12 cycles of adjuvant FOLFOX followed by a second-look laparotomy and CRS/HIPEC in December with or without manifest disease. Though I'm a dyed in the wool Pyrrhonist when it comes to wishy-washy alternative medicine, I ended up familiarizing myself with all of Valter Longo of USC's research on fasting and differential stress sensitization. Since my wife and I are orthodox Catholics and normally follow a Byzantine diet in line with the liturgical cycle of the year, I didn't figure she would have too much difficulty water fasting for five days out of every two weeks during her chemotherapy. Since my wife was a mere 43 kg at the time, we chose not to inform her oncologist (who would've completely correctly quashed the idea). Caveat: I am not recommending such extreme fasting to anyone. We wanted to be as aggressive with this disease, even recklessly aggressive, as we could. I couldn't convince myself that prophylactic oophorectomy of her remaining ovary would actually meaningfully affect overall or disease-free survival—nor could the medical oncologist and HIPEC surgeon—so we agreed to preserve it absent obvious macroscopic infestation.

Chemotherapy went uneventfully, though the first two days were always hell since she never took any of the dexamethasone (I was concerned about upsetting the potentially beneficial effects of fasting and the alternative metabolic pathways it putatively induces). Encouragingly, in spite of the severe fasting, she continued to put on 2–3 kg of weight every other week. Until the last few cycles, she had no clinically relevant toxicities and any neuropathy was minor. Around the seventh cycle, she developed isolated thrombocytopenia and I had her stop taking the cimetidine I had asked her oncologist to prescribe her early on (I was worried that she was having an immune reaction to it). That didn't make a difference, so on the basis of some really preliminary studies on treating dengue fever–induced thrombocytopenia, she took some papaya leaf extract, which did seem to make a significant difference in her platelet count, and she was able to resume the full dose of oxaliplatin for the next couple of cycles. By the end of her treatment, she was up to 63 kg (we wanted her to put on some extra weight for the planned HIPEC in December). All CT imagery revealed no evidence of disease—even the peritoneal stranding from the previous surgeries had disappeared (though we knew it wasn't very good at visualizing small peritoneal nodules)—and her CEA had remained at around .5 since April.

CRS/HIPEC was scheduled for December 13. Pre-op assessment went well. However, my wife's platelet count was still depressed, so the oncologist at the HIPEC center decided to not administer any IV chemo during the operation (the perfusion agent was oxaliplatin); they did, however, increase the intra-abdominal perfusion time from 30 minutes to 90, though. I wasn't too fussed about the decision to not administer IV 5-fu/leucovorin since I figured it was probably wishful thinking, assuming a relatively low peritoneal carcinomatosis index and considering the avascularity of the peritoneal surface, to suppose that the 5-fu was actually going to manage to get to where it needed to go in order to hypothetically potentiate the cytotoxic activity of the oxaliplatin. Anyway, my wife went into theatre first thing in the morning, and I expected a call at some point. After a few hours, though a complete wreck, I figured no news was good news since if her PCI were too high they would've called me to inform me that they were terminating the operation. Eventually, after about 7.5 hours in theatre, the surgeon called me to inform me that they were relieved to find minimal disease, only two small nodules less than 5 mm in the left lower peritoneum and a suspicious lesion in the left lobe of her liver. Mysteriously, there were practically no adhesions to impede the examination. The stoma reversal proceeded without incident, and my wife's remaining ovary was unremarkable, so the surgeon restrained himself. My wife's presumed PCI was 1, but I was distressed about the possibility of hepatic involvement.

Anyway, her postop recovery went remarkably smoothly. Though she didn't have an epidural, she refused most pain meds (she has a very high pain tolerance and didn't want to do anything to hinder the recovery of her gut). I had her walking and exercising within a couple of days of the operation, though we had to fight the hospital staff at every turn to get them to comply with our wishes. Remarkably, her gut was also working better than ever and she was passing gas and stool within a couple of days. Within a few days, my wife's GP called me wanting to discuss the pathology results. As I was fixated on getting my wife out of hospital as soon as possible, I was reluctant, but the GP insisted that I would want to discuss the results as none of the biopsies revealed any evidence of malignancy. The presumed metastatic nodules were in fact a foreign body giant cell reaction to vegetable matter from her gut perforation at the beginning of the year—well, there was also a small area of focal nodular hyperplasia in her liver, presumably from the oxaliplatin. Obviously, we were elated by this news, as assuming a transcoelomic mode of metastasis to the ovary, based on some of Sugarbaker's studies and the most recent research on second-look laparotomy with HIPEC, macroscopically PC-free patients in my wife's scenario enjoy similar OS and PFS odds as stage II patients.

She has now been home for around a week, and apart from some mild abdominal tenderness is basically back to normal—the fact that she's eating almost normally with normal gut function/bowel movements (not too frequent, even though she only has her sigmoid colon and has had an ileostomy for eight months) is incredible to me, but I'll take it! Apologies for the lengthy post, but I figured I should probably post something in case someone else comes down with a similarly weird and dire case as my wife. Merry Christmas!

[susie0915]

Wow! That is quite a story. I'm so glad your wife is doing well, but sad she had to go through so much to get to this point. Merry Christmas to both you and your wife. I'll pray she continues to do well. She is very lucky to have your as such as support as well as your knowledge.