Long-term survival after combined hepatectomy and colectomy for ruptured combined hepatocellular-cholangiocarcinoma with direct colonic invasion: A case report

Abstract

BACKGROUND

Spontaneous rupture is a life-threatening complication of liver cancer. Cases involving direct tumor invasion of adjacent organs, such as the colon, pose major management challenges and are associated with extremely poor prognoses. This report describes a successful multidisciplinary approach to such a rare clinical scenario.

CASE SUMMARY

We present the case of a 69-year-old man with a giant ruptured liver cancer in the right lobe with direct colonic invasion. The patient was initially stabilized with transarterial embolization. After multidisciplinary discussion and preoperative optimization, he successfully underwent en bloc right hepatectomy combined with right colectomy, cholecystectomy, and intraoperative peritoneal chemotherapy on post-rupture day 19 (the fifth day after admission to our institution). The postoperative course was uneventful. Pathological examination confirmed a combined hepatocellular cholangiocarcinoma with focal invasion into the colonic subserosa. Subsequently, the patient received adjuvant therapy consisting of transarterial chemoembolization, lenvatinib, and tislelizumab for occult intrahepatic micrometastases detected 1.5 months postoperatively. During 42 months of follow-up, the patient’s tumor markers normalized, and surveillance imaging showed no evidence of tumor activity.

CONCLUSION

Aggressive surgical resection combined with multimodal adjuvant therapy may achieve favorable long-term survival in patients with ruptured liver cancer with colonic invasion.

Key Words: Combined hepatocellular cholangiocarcinoma; Liver cancer rupture; Colonic invasion; Combined resection; Multimodal adjuvant therapy; Hepatocellular carcinoma; Case report

Core Tip: This study reports a successful case of staged multidisciplinary management for a life-threatening ruptured liver cancer with direct colonic invasion, pathologically confirmed as combined hepatocellular cholangiocarcinoma, a rare and aggressive histological subtype. The strategy involved initial embolization, followed by combined organ resection and modern adjuvant therapy, achieving over 42 months of long-term survival. The key finding is that tumor rupture should not be considered an absolute contraindication to curative treatment, and that aggressive surgical resection integrated with modern multimodal therapy can significantly improve outcomes even in such advanced cases.

INTRODUCTION

The rupture of liver cancer is a life-threatening complication that occurs in 3%-26% of patients[1]. It is the third most common cause of death in patients with liver cancer, after tumor progression and liver failure[2], with an early mortality rate as high as 25%-75%. Potential etiologies include cirrhosis, hypertension, vascular embolism, extrahepatic metastasis, a high Child-Pugh score, external compression, and medical factors such as transarterial embolization (TAE)[3].

The primary objectives are prompt resuscitation and hemodynamic stabilization[1,2]. Hemostasis is central to emergency management[4]. Commonly used hemostatic approaches include TAE and emergency partial hepatectomy[5,6]. TAE achieves hemostasis in 53%-100% of acute cases, whereas emergency hepatectomy is highly effective but technically challenging in hemodynamically unstable patients or those with severe cirrhosis[4]. After stabilization, a comprehensive assessment is required to formulate a definitive treatment plan, and surgical resection is associated with the best long-term outcomes in patients with resectable tumors.

A major challenge is that tumor rupture with invasion of adjacent organs can render the disease unresectable, thereby eliminating the possibility of cure. Combined hepatocellular (cHCC)-cholangiocarcinoma (CCA) is a distinct histologic subtype of liver cancer with more aggressive biological behavior and a poorer prognosis than pure hepatocellular carcinoma (HCC), and reports of rupture with direct invasion of adjacent organs are exceedingly rare. This study presents a case of ruptured cHCC-CCA with direct colonic invasion. Successful surgical intervention was performed to achieve complete en bloc resection of the tumor and the involved colonic segment. Combined with subsequent comprehensive therapy, this approach resulted in a favorable outcome.

CASE PRESENTATION

Chief complaints

A 69-year-old man was admitted 2 weeks after interventional treatment for hemorrhagic rupture of a liver tumor.

History of present illness

The patient developed sudden, severe upper abdominal pain 2 weeks earlier, without any identifiable precipitating factors. Abdominal computed tomography (CT) performed at a local hospital revealed a ruptured mass measuring 13 cm × 8.8 cm in the right hepatic lobe, with evidence of active hemorrhage. Emergency TAE was performed, resulting in successful hemostasis and restoration of hemodynamic stability. At admission, the abdominal pain had resolved, and no additional symptoms were reported.

History of past illness

The patient had a history of hepatitis B infection with clinical cure and undetectable.

Personal and family history

The patient reported a long-term smoking history. No significant family history of relevant disease was documented.

Physical examination

Abdominal examination revealed a soft abdomen with mild tenderness in the right upper quadrant and no rebound tenderness. No other significant findings were noted on physical examination.

Laboratory examinations

Notable findings included the following: Alpha-fetoprotein, 1727 ng/mL (reference range, 0-9 ng/mL); protein induced by vitamin K absence-II, 5595 mAU/mL (0-40 mAU/mL); carcinoembryonic antigen, 4.21 ng/mL (0-3 ng/mL); hemoglobin, 85 g/L (130-175 g/L); white blood cell count, 8.77 × 10⁹/L [(3.5-9.5) × 10⁹/L]; platelet count, 351 × 10⁹/L [(125-350) × 10⁹/L]; prothrombin time, 12.3 seconds (10-14 seconds); total bilirubin, 19.2 μmol/L (2.0-20.4 μmol/L); and albumin, 30 g/L (40-55 g/L).

Imaging examinations

Chest CT showed chronic bronchitis and emphysema. Contrast-enhanced abdominal CT revealed a large heterogeneous mass measuring 21 cm × 9 cm × 14 cm in the right hepatic lobe (Figure 1). The mass demonstrated internal high-density material, gas foci, heterogeneous enhancement, and obliteration of the adjacent fat planes, findings consistent with ruptured liver cancer with hemorrhage, necrosis, and superimposed infection.

Figure 1 Abdominal contrast-enhanced computed tomography showed a large heterogeneous right hepatic lobe mass with internal high-density material, gas shadows, heterogeneous enhancement, and blurred adjacent fat planes. Orange arrow: Liver mass; White arrow: Duodenum; Blue arrow: Colon.

FINAL DIAGNOSIS

Ruptured liver cancer with hemorrhage and secondary infection [China Liver Cancer Staging stage Ib; Barcelona Clinic Liver Cancer stage A1; American Joint Committee on Cancer stage IIIB (T4bN0M0)]. The Child-Pugh classification was A.

TREATMENT

The patient received supportive care, including albumin infusion, hepatoprotective therapy, antibiotic treatment, and expectorant therapy. Multidisciplinary team evaluation determined that surgical resection was feasible, and open resection of the liver mass was planned. Given the high risk of recurrence, the surgical strategy included intraoperative peritoneal lavage with distilled water and chemotherapy, followed by adjuvant transarterial chemoembolization (TACE), targeted therapy, and immunotherapy. Preoperative planning accounted for anticipated severe adhesions and the potential need for en bloc colonic resection.

After adequate bowel preparation and optimization with blood products, an exploratory laparotomy was performed on the fifth day after admission (19 days after rupture). Intraoperative exploration revealed an exophytic ruptured tumor involving hepatic segments 5 and 6, with dense adhesions to the right abdominal wall, retroperitoneum, and right colon, as well as compression of the descending duodenum. No peritoneal metastases were identified. En bloc resection included partial hepatectomy, right hemicolectomy, omentectomy, and cholecystectomy, followed by ileotransverse anastomosis. Subsequently, intraoperative intraperitoneal chemotherapy was administered using 2000 mL of distilled water containing 5-fluorouracil (1 g) and cisplatin (100 mg) for 30 minutes.

OUTCOME AND FOLLOW-UP

The operative time was 5 hours, and the estimated blood loss was 2000 mL. This necessitated the transfusion of 8 units of packed red blood cells, 800 mL of fresh frozen plasma, and 10 units of cryoprecipitate. The gross specimen is shown in Figure 2. The final pathological diagnosis was moderately differentiated cHCC-CCA with necrosis and tumor rupture (HCC accounting for 70% and CCA for 30%). The lesion invaded the colonic subserosa. There was no fistula between the tumor and the colonic lumen, indicating that the gas seen within the tumor on preoperative CT was caused by tumor necrosis and secondary infection. The Ki-67 proliferation index was 20% in the HCC component and 70% in the CCA component. The margins were negative, and there was no evidence of microvascular invasion (M0) or lymph node metastasis.

Figure 2 Gross specimen revealed the tumor adherent to the colon, with surface ulceration and an indistinct border.

The postoperative course was uneventful except for a transient right pneumothorax, which resolved after closed thoracic drainage. The patient was discharged on postoperative day 15. Adjuvant TACE was performed 1.5 months after surgery, during which three suspicious lesions were identified and subsequently treated with lipiodol embolization (Figure 3). Systemic therapy with lenvatinib (8 mg daily) and tislelizumab (200 mg every 3 weeks) was then initiated. Ten months after the start of combined therapy, the patient developed grade 2 skin rash, grade 2 diarrhea and nausea, and grade 3 drug-induced hypothyroidism (thyroid stimulating hormone > 100 mIU/L) according to CTCAE v5.0 criteria. After 2 months of symptomatic treatment, thyroid function showed partial improvement, whereas the cutaneous and gastrointestinal symptoms improved only minimally, with persistent fatigue and anorexia that impaired quality of life. A multidisciplinary consultation, therefore, led to discontinuation of tislelizumab and to a reduction in lenvatinib to half the daily dose for maintenance therapy. Approximately 3 months after the regimen adjustment, the aforementioned symptoms resolved, and thyroid function returned to normal.

Figure 3 Transarterial chemoembolization detected three suspicious lesions. Imaging performed 3 months after surgery showed satisfactory lipiodol deposition. Orange arrow: Dorsal portion of hepatic segment 8; White arrow: Paracaval portion of caudate lobe; Blue arrow: Segment 7.

Carbohydrate antigen 19-9 (CA199) was added to routine postoperative tumor marker surveillance after the pathological diagnosis of cHCC-CCA. During 42 months of postoperative follow-up, the occult micrometastases showed no significant blood flow and exhibited a gradual trend toward shrinkage (Figure 4), and all tumor markers (alpha-fetoprotein, protein induced by vitamin K absence-II, carcinoembryonic antigen, and CA199) normalized (Figure 5).

Figure 4 At the 42-month postoperative follow-up, the three occult micrometastases showed no significant blood flow or enhancement on magnetic resonance imaging during both arterial and portal venous phases, with gradual shrinkage. Computed tomography confirmed satisfactory lipiodol deposition within some tumors. Orange arrow: Dorsal portion of hepatic segment 8; White arrow: Paracaval portion lesion; Blue arrow: Segment 7 lesion.

Figure 5 Changes in tumor markers. Preoperative carbohydrate antigen 19-9 was not tested. AFP: Alpha-fetoprotein; PIVKA-II: Protein induced by vitamin K absence-II; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 19-9.

DISCUSSION

Ruptured liver cancer represents a distinct clinical entity. The main treatment options include conservative management, interventional therapy, ablation, surgical resection, and comprehensive adjuvant therapy. Among these modalities, ablation and surgical resection are associated with relatively better prognoses.

The prognosis of ruptured liver cancer is generally poor, partly because of the risk of peritoneal seeding. According to the American Joint Committee on Cancer tumor-node-metastasis staging system (8^th edition), tumor rupture automatically upstages the tumor to T4[7], which is associated with worse survival[8]. Nevertheless, several studies have shown that overall survival in patients with ruptured liver cancer is comparable to that in nonruptured patients at the same T stage[1,9]. A 2014 nationwide Japanese survey proposed that although rupture adversely affects baseline survival, its effect is not sufficient to outweigh other tumor-related parameters. Therefore, it may be reasonable to upstage a ruptured tumor by 0.5 stages to 2 stages beyond its baseline stage[10]. Accordingly, we argue that tumor rupture should not be automatically equated with end-stage disease and that active treatment remains highly relevant. After stabilization, a comprehensive patient assessment is essential. For resectable tumors, most studies recommend surgical resection as the preferred approach for achieving long-term survival[1,10,11].

Given the risk of peritoneal implantation associated with delayed surgery, the timing of surgery is critical. A study from Tongji Hospital proposed an 8-day window after rupture for hepatectomy to reduce peritoneal metastasis and improve outcomes[12]. Our team also supports the principle of early intervention. However, this patient was transferred to our institution 2 weeks after the initial TAE and presented with anemia, hypoalbuminemia, and pulmonary infection, all of which required preoperative optimization, resulting in surgery beyond the recommended timeframe. To mitigate the increased risk of peritoneal seeding, intraoperative peritoneal lavage with distilled water and chemotherapeutic agents was performed prophylactically, although evidence supporting this intervention remains limited, based on studies suggesting that it may reduce the risk of implantation in ruptured liver cancer[1,13,14]. Fortunately, no peritoneal implantation has been detected to date. This finding suggests that a delayed but well-prepared operation, combined with targeted perioperative strategies to counteract seeding risk, may be more beneficial overall than a hasty procedure performed without adequate preparation. Although timing is important, the patient’s systemic condition, thorough preoperative assessment, and appropriate perioperative risk mitigation are equally vital.

Cases of liver cancer with direct colonic invasion are rarely reported[15-17]. Reported management strategies include surgery and TAE. The overall prognosis is poor, with an average survival of approximately 4 months[15]. However, surgical resection appears to be associated with improved survival and may be the most effective treatment for gastrointestinal invasion by liver cancer[15,16]. In this case, the dense adhesion between the ruptured tumor and the colon, which could not be distinguished from direct invasion, indicated advanced disease. Nevertheless, given the preserved liver function and thorough preoperative bowel preparation, combined en bloc multiorgan resection was feasible. En bloc resection is a key oncologic principle because it helps prevent tumor cell spillage and peritoneal implantation by enabling the complete removal of the tumor and invaded adjacent tissue in a single specimen, thereby minimizing residual disease. This approach removed a substantial volume of necrotic tumor tissue, potentially reducing the risk of infection and increasing the patient's chance of cure and prognosis. Effective control of early occult micrometastases with multimodal adjuvant therapy contributed to survival beyond 42 months to date.

Key factors contributing to this favorable outcome

Initial stabilization with bridge therapy: TAE effectively served as a bridge to radical surgery by achieving initial hemostasis and aligning with modern standards for the management of ruptured liver cancer. This initial control was crucial in enabling the transition to definitive surgical intervention.

Anatomically localized disease despite rupture: The rupture was contained by the surrounding anatomic structures, preventing widespread peritoneal dissemination. Furthermore, colonic involvement was histologically limited to the subserosal layer, making en bloc resection both feasible and oncologically sound.

Meticulous preoperative optimization and surgical timing: Anticipation of possible organ invasion prompted thorough preoperative bowel preparation. Surgery was scheduled promptly once the patient’s systemic condition had been optimized, thereby balancing the need for timely intervention with the necessity of physiologic readiness to reduce operative risk and potential seeding.

Adherence to the R0 resection principle: Despite the technical complexity, adherence to the en bloc resection principle ensured complete removal of the tumor together with the involved colonic segment. This approach minimized residual disease and was fundamental to achieving both macroscopic and microscopic radicality.

Comprehensive postoperative adjuvant therapy: The combination of TACE, targeted therapy, and immunotherapy was crucial for controlling micrometastases. This multimodal approach[18,19] successfully controlled the disease over the long term. Although immune-related adverse events occurred, they were managed effectively without compromising overall therapeutic efficacy, highlighting the integral role of supportive care in modern oncology.

A critical finding in this case was the postoperative diagnosis of cHCC-CCA, which differed from the preoperative clinical diagnosis of HCC. Compared with HCC, cHCC-CCA exhibits more aggressive malignant behavior and is associated with a poorer prognosis[20]. Reports of tumor rupture in such cases are exceedingly rare. This case illustrates that even with this more aggressive histology, the comprehensive strategy described here can be effective. Surgery remains central, supported by timely intervention, thorough assessment, meticulous preparation, and multimodal adjuvant therapy, offering improved prospects for selected patients.

It is noteworthy that the lesions detected 1.5 months postoperatively likely represented the rapid progression of residual tumor or pre-existing occult micrometastases that were undetectable on preoperative imaging, rather than true recurrence. Preoperative evaluation included only contrast-enhanced CT rather than magnetic resonance imaging (MRI), which is more sensitive for small hepatic lesions, because the patient’s anxiety prevented completion of the examination, and the long wait time for MRI appointments would have delayed urgent surgery. MRI was completed only postoperatively with family accompaniment. This accelerated progression of micrometastases was closely associated with the high proliferative activity of the CCA component (Ki-67, 70%), which was far greater than that of the HCC component (20%). This pathologic feature also justified the adoption of aggressive multimodal adjuvant therapy, and effective control of these highly proliferative micrometastases by this regimen was key to the patient’s long-term survival beyond 42 months, highlighting the importance of individualized adjuvant therapy based on pathologic subtype in cHCC-CCA.

This study has several inherent limitations that warrant consideration. The absence of preoperative CA199 testing and MRI may have resulted in inadequate assessment of tumor status, and the lack of intraoperative peritoneal lavage cytology results provides insufficient direct objective evidence to support intraperitoneal perfusion chemotherapy. These are important aspects to optimize in the management of similar cases going forward. The early postoperative detection of occult micrometastases suggests the likely presence of pre-existing micrometastases, which might have been detectable with more sensitive preoperative imaging. As a single-case report, the conclusions are inherently limited in statistical power and generalizability. Finally, the lack of consensus on treatment for cHCC-CCA poses a therapeutic dilemma. Although the selected HCC-oriented adjuvant regimen was associated with an excellent outcome, the potential value of adding standard chemotherapy for the CCA component (e.g., gemcitabine/cisplatin) remains a valid question for multidisciplinary discussion in future cases.

CONCLUSION

This case illustrates that a staged multidisciplinary strategy, comprising initial hemostasis with TAE followed by planned en bloc resection (including involved adjacent organs) and multimodal adjuvant therapy, can achieve excellent long-term survival even in complex cases of ruptured liver cancer (including cHCC-CCA) with direct colonic invasion. It highlights that tumor rupture alone should not be considered a contraindication to curative-intent treatment and highlights the critical importance of multidisciplinary team collaboration, thorough preparation, and integrated management for aggressive tumor types. This case provides valuable clinical insight into the diagnosis and treatment of rare ruptured cHCC-CCA with adjacent organ invasion.

ACKNOWLEDGEMENTS

We would like to express our gratitude to the patient for granting permission for the case report.