Metastatic Colorectal Cancer: How a Negative Ascitic Tap Was Solved by Diagnostic Laparoscopy and PIPAC

A 58-year-old post-menopausal woman presented at MACS Clinic, Bangalore, with one month of unintentional weight loss totalling 8 kilograms, complete loss of appetite, persistent dull abdominal pain, vomiting, and progressive abdominal distension. Her past medical history included long-standing rheumatoid arthritis and hypothyroidism, both stable on treatment. She had no family history of malignancy and no prior abdominal surgery.

On clinical examination, her abdomen was tense and distended, consistent with significant free fluid. An abdominal ultrasound confirmed gross ascites. In a post-menopausal woman with new-onset ascites and constitutional symptoms, the differential diagnosis narrows sharply to two leading possibilities, advanced liver disease and peritoneal carcinomatosis from a hidden primary cancer. The patient was admitted for urgent multidisciplinary evaluation.

Contrast-enhanced CT of the abdomen and pelvis revealed an enlarged liver with venous collaterals, three small hepatic lesions reported as probable haemangiomas, gross ascites, omental thickening, and bilateral pleural effusions. A whole-body PET-CT was performed for staging and showed FDG-avid deposits across the omentum, mesentery, and peritoneum, a hot lesion within the liver, and extensive skeletal involvement spanning the left pterygoid bone, right humerus, multiple ribs, dorsal and lumbar vertebrae, sacrum, both iliac bones, and both femurs. The pterygoid lesion recorded a maximum SUV of 18.69.

Three separate diagnostic ascitic taps were performed. All three returned negative for malignant cells on cytology. GeneXpert testing for tuberculosis was also negative, and acid-fast bacilli were not seen on smear. Tumour markers were unhelpful in the conventional sense, with CA 19-9 within normal limits and CEA only borderline elevated. CA-125 was raised at 191, but pre-operative imaging showed no ovarian primary. Faced with cancer-pattern imaging and three clean cytology reports, the patient was referred to Dr. Sandeep Nayak, Senior Surgical Oncologist at MACS Clinic, for definitive tissue diagnosis.

Metastatic colorectal adenocarcinoma with peritoneal carcinomatosis (Peritoneal Cancer Index 32), hepatic deposits, and widespread skeletal metastases. Confirmed on diagnostic laparoscopy with frozen-section biopsy and immunohistochemistry showing a colorectal immunoprofile (CK20 positive, CDX2 positive, SATB2 positive; CK7, PAX8, and WT1 negative).

Peritoneal carcinomatosis is the seeding of cancer across the lining of the abdominal cavity, and it is one of the hardest forms of metastatic disease to diagnose by minimally invasive means. Ascitic fluid cytology, the most commonly used first-line test, has a sensitivity of only around 60 to 70 per cent in this setting. Roughly one in three patients with proven peritoneal malignancy will have a clean cytology report, often because tumour deposits remain firmly anchored to peritoneal surfaces and shed few free cells into the fluid. In this patient, three negative taps could easily have led to an empirical diagnosis of tuberculous peritonitis and months of inappropriate treatment before the truth surfaced.

Diagnostic laparoscopy with directed biopsy and a complete immunohistochemistry panel is the test that ends the uncertainty. In this case, the IHC profile localised the primary to the lower gastrointestinal tract with high confidence, and a sigmoid primary became visible on follow-up imaging once peritoneal disease shrank with treatment.

Faced with imaging strongly suggestive of peritoneal malignancy and three negative ascitic cytology reports, Dr. Sandeep Nayak proceeded directly to diagnostic laparoscopy. Through three small ports, the team systematically inspected the peritoneal cavity and quantified disease burden using the Peritoneal Cancer Index, a structured 0 to 39 score that grades tumour bulk across thirteen abdominal regions. Findings included four and a half litres of straw-coloured ascites, a hardened omental cake, tumour deposits across both diaphragmatic surfaces, the falciform ligament, the pelvic peritoneum, the surface of both ovaries, the bowel mesentery, and the serosa of the small intestine. Mesenteric scarring had clumped the terminal ileum together. The Peritoneal Cancer Index was scored at 32, indicating extensive disease.

Frozen-section biopsies returned within minutes confirming adenocarcinoma. Immunohistochemistry was then performed to localise the primary site. The tumour stained positive for CK20, CDX2, and SATB2 and negative for CK7, PAX8, and WT1, a pattern strongly indicative of a lower gastrointestinal, almost certainly colonic, origin. The negative CK7 and PAX8 effectively excluded a primary ovarian or upper-gastrointestinal source despite the elevated CA-125.

On the same operating table, before the patient was woken from anaesthesia, the team delivered Pressurised Intraperitoneal Aerosol Chemotherapy (PIPAC). PIPAC is a technique developed in Germany in 2011 in which a fine aerosol of chemotherapy is sprayed into the pressurised abdomen through the existing laparoscopy ports. The pressure drives the drug into peritoneal tumour deposits that intravenous chemotherapy struggles to penetrate, and the doses used are a small fraction of systemic doses, keeping toxicity minimal. Doxorubicin and cisplatin were used in this case. PIPAC is not curative on its own, but in patients with bulky peritoneal disease it can shrink omental and peritoneal tumour, reduce ascites production, and create a window for systemic therapy to take effect. A chemoport was placed in the right subclavian vein in the same sitting to support upcoming systemic treatment.

“PIPAC is not a cure for peritoneal disease. It is a bridge. In a patient with this volume of carcinomatosis, treating the peritoneal compartment on the day of diagnosis changes what systemic therapy can then achieve.”

— Dr. Sandeep Nayak, Surgical Oncologist, MACS Clinic

While the patient recovered, her tumour was sent for next-generation sequencing and a separate germline test was performed on her own DNA. The molecular workup returned a KRAS p.(G12V) driver mutation, a TP53 p.(R213X) nonsense mutation, a CDKN2A p.(D84N) variant, intact mismatch repair (pMMR), and PD-L1 CPS of 10. The KRAS mutation ruled out anti-EGFR antibodies such as cetuximab and panitumumab. The pMMR status ruled out pembrolizumab-based immunotherapy despite the PD-L1 expression. Bevacizumab combined with a fluoropyrimidine doublet was therefore the rational backbone.

The germline test detected a heterozygous variant in DPYD, the gene that codes for dihydropyrimidine dehydrogenase, the enzyme that breaks down 5-fluorouracil. Patients carrying clinically relevant DPYD variants cannot metabolise 5-FU efficiently, and standard doses can cause life-threatening toxicity within weeks of the first cycle. Roughly 3 to 8 per cent of patients carry such variants. International guidelines recommend testing every patient before they receive 5-FU, although this remains uneven in routine practice in India. On the strength of this result, cycle one of mFOLFOX6 was delivered at 80 per cent of standard dose with close monitoring. The patient tolerated it well, cycle two was escalated to 100 per cent, and from cycle three onwards the regimen settled at 90 per cent, a therapeutic dose that did not breach her metabolic threshold. Bevacizumab was given alongside chemotherapy, and monthly zoledronic acid was added for her skeletal metastases.