Gastro-duodenal ulcers and congenital abnormalities are common causes of benign pyloric stenosis. Primary gastric neoplasms, mucosal and sub-epithelial tumors, are easily detected, and sampled at endoscopy or during endosonography. Benign and malignant lesions of the adjacent pancreas or gallbladder may present as gastric outlet obstruction (GOO).

Gallbladder cancer (GBC) is listed as the sixth most common cancer affecting the gastrointestinal tract (GIT) and the most common biliary cancer.¹ GBC may be detected in the asymptomatic phase, but usually, it presents with pain, lump, and surgical jaundice. Concomitant hepatic or duodenal infiltration with GBC has variable outcomes after surgical resection.^2,3 The overall prognosis of GBC is poor with the 5-year survival rates ranging from 5% to 40% across studies^4,5 with better outcomes in incidentally detected patients and those with successful R0 resection. Vascular invasion, N2 nodes, and metastases in GBC are contraindications for attempting surgery.¹

Clinical presentation of GBC as exclusive pyloric stenosis causing GOO is rare.

A 67-year-old female patient presented with abdominal pain, anorexia, weight loss, nausea, and recurrent stale vomiting. No comorbid illnesses were reported and there was no history of gastrointestinal bleed, jaundice, or past abdominal surgery. The patient was cachectic, though vitally stable. Earlier, she had undergone gastro-duodenoscopy and a failed duodenal intubation due to tight pyloric stenosis. Biopsies taken from the pyloric area then were inconclusive for malignancy. A contrast computed tomography (CT) scan of the abdomen had revealed a massively dilated stomach with a 5 cms long wall thickening at the pylorus with stenosis. There was no evidence of lymphadenopathy or liver metastasis in the CT scan. Laboratory parameters (Table 1) revealed microcytic anemia and hypoalbuminemia.

Table 1 . Laboratory Parameters.

Date	Hb (g%)	WBC/cmm	Platelet (× 103)	MCV (fl)	INR	T. Bil (mg%)	AST (IU/mL)	ALT (IU/mL)	A Phos (IU/mL)	Alb (g%)	Creat (mg%)
05.07.2023	10.2	9,200	285	-	-	1.2	35	29	133	3.2	0.9
05.18.2023	9.4	11,400	347	77.8	0.85	-	-	-	-	-	-
05.20.2023 (post op)	13.6	17,900	244	83.9	-	-	-	-	-	-	-
01.08.2024	-	-	-	-	-	11.0	85	46	465	3.4	-

Hb, hemoglobin; WBC, white blood cell count; MCV, mean corpuscular volume; INR, international normalized ratio; T. Bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; A Phos, alkaline phosphatase; Alb, albumin; Creat, creatinine; post op, post operative.

At the time of hospital admission, the clinical picture was as aforementioned. The heart rate was 82/minute, blood pressure was 120/70 mmHg and on abdomen palpation, there was upper abdominal tenderness without lump or ascites. Naso-gastric (NG) tube drainage and lavage were undertaken over 24 hours. Endoscopic pyloric dilatation was attempted. Gastric residue was cleared and the patient was reintubated with a small caliber gastroscope. Under fluoroscopy, a guide wire was passed into the duodenum. The small scope could be negotiated over the guide wire and no luminal abnormality (Fig. 1) was seen in the duodenum up to the proximal second part. Over the guidewire, the small gastroscope was exchanged with an adult gastroscope. Pyloric dilatation with graded balloons was undertaken, serially starting from 8 mm to 12 mm in two balloon exchanges. The adult gastroscope would not cross the stenosed pylorus despite pyloric dilatation. No tumor or ulcer could be identified around the pylorus to obtain biopsies for tissue diagnosis. The patient refused consent for endoscopic ultrasonography (EUS) due to financial constraints and instead opted for direct surgical intervention. A positron emission tomography (PET) scan was undertaken preoperatively. Fluorodeoxyglucose (FDG) uptake was identified at the pyloric site (Fig. 2A) and in a solitary lymph node in the gastro-hepatic ligament. No other extra gastric FDG uptake was detected.

Figure 1. Endoscopy images. (A) Guide wire negotiation across tight pyloric stenosis. (B) Small caliber scope intubated over a guide wire into the deep duodenum. (C) Balloon dilatation undertaken through the scope over the guide wire.

Figure 2. PET CT preoperative and at recurrence. (A) FDG uptake before surgery: Pyloric canal uptake and no hepato-biliary abnormality. (B) FDG uptake in a recurrent mass (arrow) in the proximal CBD with intrahepatic biliary dilation. (C) FDG uptake in the porta hepatis lesion (arrow). (D) FDG uptake in the aortocaval lymph node (arrow). PET, positron emission tomography; CT, computed tomography; FDG, fluorodeoxyglucose; CBD, common bile duct.

Total parenteral nutrition and multi-vitamin supplements were administered for five days before surgery, with concurrent NG tube lavage and drainage.

Operative findings

There were no peritoneal deposits or palpable metastases on the liver. A tumor extending into the pylorus was palpable in the first part of the duodenum causing GOO. The duodenum and the pylorus were stuck at the porta hepatis with fibrotic tissue around it. No significant lymphadenopathy was encountered around the lymph node stations 1–12. A biopsy sample taken for frozen section evaluation from the antrum, distal to the gastric incision, revealed a sub-epithelial malignancy, and the gastric mucosa was free of tumor (Fig. 3A–3C). A shrivelled gallbladder (GB) and fibrosis at the Hartmann’s pouch without common bile duct (CBD) dilation were observed. No palpable gallbladder tumor or porta lymph nodes were detected. Thus, intraoperatively the organ of origin of neoplasm remained uncertain. The patient was subsequently operated on for D2 gastrectomy, gastrojejunostomy with N1 node resection, and cholecystectomy.

Figure 3. Histopathology: Stomach wall and gallbladder. (A) Frozen section from the stomach wall showing normal mucosa (H&E stain, × 400). (B) Frozen section: Atypical clusters (arrow) in the gastric submucosa (H&E stain, × 400). (C) Frozen section: Singly scattered cells (arrows) infiltrating the gastric muscularis propria (H&E stain, × 200). (D) Wall of gallbladder showing a tumour arising from the mucosa, arranged in a cribriform pattern (H&E stain, × 400). (E) Higher magnification of tumour arising from gallbladder mucosa (H&E stain, × 200). (F) Tumour cells infiltrating the serosa (arrow), up to the cauterised margin (H&E stain, × 400). (G) Higher magnification showing tumour cells in the clusters and the glands with perineural invasion (arrow) (H&E stain, × 200).

She had an uneventful post-operative course and started tolerating oral feeds.

The final histopathology (Fig. 3D–3F) diagnosis was a poorly differentiated gallbladder adenocarcinoma (pT3N0) with gastric infiltration extending up to the muscularis propria, without gastric mucosal involvement. On immuno-histochemistry staining (Fig. 4) of the gallbladder as well as the stomach tumor cells, diffuse and strong positivity was seen for CK7 and CK19. Tumor cells were negative for CK20 and CDX2. The resected margins of the stomach and duodenum were free of tumor, but the cauterized margin of the gallbladder revealed tumor infiltration on microscopy. The patient disapproved of re-exploration and declined to take post-operative adjuvant chemotherapy.

Figure 4. Immunohistochemistry: Gallbladder and stomach wall. (A) Wall of gallbladder showing CK7 positive tumor cells, × 40. (B) Wall of stomach showing CK7 positive tumor cells, × 40. (C) Wall of gallbladder showing CK19 positive tumor cells, × 40. (D) Wall of stomach showing CK19 positive tumor cells, × 40. (E) Wall of gallbladder negative for CK20, × 40. (F) Wall of stomach negative for CK20, × 40. (G) Wall of gallbladder negative for CDX2, × 40. (H) Wall of stomach negative for CDX2, × 40.

On telephonic follow-up, eight months after surgery, we were informed that she had presented to the local physician with jaundice (Fig. 5) and pruritus. She had developed local recurrence and extrahepatic biliary obstruction. In comparison to the pre-operative PET scan (Fig. 2A), the follow-up PET scan (Fig. 2B–2D) revealed FDG uptake in a soft tissue mass in the proximal CBD, intrahepatic biliary dilation, with more FDG uptake in the portocaval, retrocaval, and aortocaval lymph nodes. The patient was recommended for percutaneous transhepatic biliary drainage in her hometown. The decision for subsequent palliative chemo-radiation was pending the outcome of biliary drainage.

Figure 5. Liver biochemistry (pre-operative versus at recurrence). (A) Rise in T. Bil from 1.2 mg/dL pre-operatively to 11.0 mg/dL at recurrence. (B) Significant elevation of A. Phos with a modest rise in AST & ALT at recurrence. T. Bil, total bilirubin; Alb, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; A. Phos, alkaline phosphatase.

Ethics statement

The case was discussed in a clinical meeting among local gastroenterologists in February 2024. The study was approved by the local Institutional Review Board (IRB) (KEMHRC/RVM/EC/138 dated 04.08.2024). The IRB confirmed informed consent.

GBC is a fatal malignancy as most of the patients present in an advanced stage and have poor survival. Right hypochondriac pain mimicking cholelithiasis or cholecystitis followed by obstructive jaundice are the common presentations.⁴ Advanced cases of GBC usually present as malignant biliary obstruction. GBC may be occasionally detected on routine ultrasound evaluation or as an unexpected intraoperative finding. The 5-year post-resection survival in the early stage of GBC is 65%, but less than 10% of GBCs are limited to the T1 stage at diagnosis.¹ Gall stones are associated with 90% of GBC⁴ and an incidental GBC is histologically detected in 0.3% to 3% of gallbladder specimens post cholecystectomy.¹ In such cases, if the resected margin is positive for malignancy in the specimen, re-exploration is recommended for R0 resection.^1,4 Palliative chemo-radiation¹ or immunotherapy⁶ are options available for a select few patients with inoperable GBC.

Due to proximity, the liver and duodenum are variably involved in GBC. Few studies have reported successful segmental hepatectomy or pancreato-duodenectomy as a part of R0 resection.^2,3 Currently there is no supportive data to recommend neo-adjuvant chemo-radiation in advanced GBC.⁷

Friedman et al⁸ first reported GBC causing pyloro-duodenal stenosis without jaundice. GBC cases with retrograde duodenal intussusception⁹ and pyloro-duodenal stenosis¹⁰ are reported. Our patient with GOO resembled benign pyloric stenosis at endoscopy. No duodenal infiltration was observed with a small caliber video scope. Both the CT scan and the preoperative PET scan failed to detect the GB tumor and a sub-epithelial gastric malignancy was suspected. Intra-operatively there was uncertainty about the organ of tumor origin. The frozen section evaluation had revealed malignant cells in the gastric muscularis propria and the submucosa, but the mucosa was spared. R0 resection was missed as the primary organ of the tumor origin could not be ascertained intraoperatively and the resected margin of the gallbladder remained positive. The patient had declined to undergo re-exploration or adjuvant chemotherapy and developed local recurrence eight months after surgery.

In conclusion, exclusive pyloric stenosis is a rare presentation of GBC. Imaging modalities may have limitations when the gallbladder is shrivelled, often missing the diagnosis. A strong index of suspicion is needed when tight pyloric stenosis is encountered, more so if the response to endoscopic dilatation is sub-optimal. Considering the limitations of pre-operative diagnosis, intra-operative frozen section biopsy plays a leading role in the diagnosis and surgical decision. Ideally, R0 resection should be the aim, which may demand a re-exploration in the cases of incidental GBC.

None.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

No potential conflict of interest relevant to this article was reported.