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Background
Ramucirumab is a monoclonal antibody targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Ramucirumab either alone or in combination with paclitaxel (PTX) has been found to be safe and effective for patients with previously treated advanced gastric cancer. One of the serious adverse events associated with ramucirumab is gas...
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Context 1
... pain which onset was 3 days ago. A phys- ical examination revealed left lower quadrant pain and re- bound tenderness. He had a blood pressure of 125/ 75 mmHg, body temperature of 38.2 °C, a white blood count of 4400/mm 3 , and a C-reactive protein level of 33.63. An abdominal CT-scan showed free air and fluid, but no intestinal obstruction (Fig. 1). Emergency explora- tory surgery was performed under the impression of peri- tonitis, and the surgery revealed a large amount of dirty fluid throughout the abdominal cavity. A small intestinal perforation was identified 50 cm distal from the site of jejuno-jejunal anastomosis (Roux-en-Y reconstruction) (Fig. 2), and there was no ...
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Citations
... The incidence of all-grade GI perforation with ramucirumab was 1.5%, with 29.8% mortality in another study [7]. Another case report of gastric cancer treated with ramucirumab was complicated by small intestinal metastasis and, ultimately, perforation [8]. ...
... The Food and Drug Administration recommends discontinuing ramucirumab permanently in patients who experience GI perforation. Although unclear, the proposed mechanism for GI perforation is similar to that for HCC rupture (antiangiogenesis) [8]. ...
Patient: Male, 66-year-old
Final Diagnosis: Gastrointestinal perforation • hepatocellular carcinoma
Symptoms: Altered mental state
Medication: —
Clinical Procedure: Exploratory laparotomy
Specialty: Critical Care Medicine • Gastroenterology and Hepatology • Oncology
Objective
Rare disease
Background
Hepatocellular carcinoma (HCC) is a primary liver malignant tumor that typically but not always develops in the setting of chronic liver disease, particularly in patients with cirrhosis or chronic hepatitis B virus infection. Advanced HCC portends a poor prognosis; however, recent advances in first-line and second-line treatment options yield significant survival improvements. Ruptured HCC is an uncommon presentation that occurs in approximately 3–26% of patients.
Case Report
We present a case of a patient with HCC who was undergoing treatment with the antiangiogenic monoclonal antibody ramucirumab. Subsequently, he presented with signs and symptoms of acute abdomen. The abdominal imaging revealed pneumoperitoneum with multiple abdominal and pelvic collections. The patient underwent exploratory laparotomy and was found to have necrotic liver parenchyma, which appeared to be perforated. Also, a microperforation was noted in the proximal duodenum. The pathology report from liver specimens showed fragments of hepatocellular cancer with extensive necrosis.
Conclusions
The mechanism of tumor rupture in HCC is poorly understood. The so-called vascular injury hypothesis states that collagen expansion and elastin proliferation in the arterial wall supplying the tumor could be the leading cause of HCC rupture. We believe that the process mentioned above was accelerated in our patient using the antiangiogenic factor ramucirumab. A similar antiangiogenic mechanism is also implicated in gastrointestinal hemorrhage and perforation related to this drug.
... Other cancer types that metastasized to the SB in this study were not common and were presented elsewhere only as case reports. These cancers included breast cancer [12], colon cancer, cervical cancer [13], tongue squamous cell carcinoma [14], endometrial cancer [15], bladder urothelial cell carcinoma [16], renal cell carcinoma [17], gastric cancer [18], peripheral nerve sheath sarcoma [19], primary heart sarcoma [19], and pancreatic cancer [19]. ...
BACKGROUND
The small bowel (SB) is a rare site for distant metastasis. Few recent studies have systematically reported on the clinicopathology and outcomes of SB metastasis. This study aimed to describe the clinicopathology and outcomes of SB metastasis.
METHODS
A retrospective study involving patients diagnosed with SB metastasis at a single medical center between January 2009 and December 2019 was conducted. Patients with secondary SB cancer with direct invasion or peritoneal carcinomatosis by a primary tumor were excluded. The demographic characteristics of the patients, clinical patterns of primary cancer and SB metastasis, and outcomes were analyzed.
RESULTS
During the 10-year period, we identified 31 patients eligible for analysis. The female:male ratio was 8:24, and the median patient age was 63.5 years. Metastasis of lung cancer to the SB was noted most frequently. Most patients presented with abdominal pain, gastrointestinal bleeding, or abnormal imaging findings. The interval between primary cancer and SB metastasis was 19.2 months. Sole SB metastasis was noted in 20 patients (64.5%). Twenty-two (70.1%) patients underwent surgical intervention. The median survival was 6.6 months.
Conclusions
Distant metastasis of other primary cancers to the SB is noted extremely rarely. The presence of SB metastasis indicated extremely poor prognosis. Surgery plays an important role in ameliorating critical symptoms However, surgery does not confer survival benefits.
... Nonetheless, based on our experience in this patient, tumour lysis syndrome with severe adverse complications must be taken into consideration when more and more efficient agents are approved for clinical use. Among them, in our opinion, anti-angiogenic monoclonal antibody ramucirumab, with its potential risk of wound healing impairment and gastrointestinal perforation [37,38], is an example in case of treating a massive gastric tumour like our patient's. ...
A 56-year-old man was diagnosed to have a huge gastric cancer extending from the lesser curvature of the stomach to the pancreas with multiple hepatic and peritoneal metastases. Two days after completing chemotherapy with cisplatin plus high dose leucovorin and fluorouracil, drastic necrotising tumour lysis led to gastric perforation and septic shock most likely due to bacterial peritonitis. The image of tumour lysis looked like an emphysematous pancreatitis. Afterwards, immunohistochemical study of the tumour specimen confirmed moderate positivity of dihydropyrimidine dehydrogenase and absence of Bcl-2 expression. The incomplete expression of dihydropyrimidine dehydrogenase and total deficiency of Bcl-2 are considered to be the main underlying causes of such extraordinary chemosensitivity and so severe a tumour lysis phenomenon. Pre-emptive intensive survey of possible biomarkers of chemosensitivity is thus highly recommended upon treating a massive gastric cancer.
Background
Treatment for acute abdomen during chemotherapy is frequently difficult because of the complicated status of the patients, and there have been only a few case series summarizing the outcomes of emergent surgery during chemotherapy. The aim of this study was to clarify the clinical outcomes of emergency surgery for acute abdomen during chemotherapy and identify predictive factors associated with mortality.
Methods
We retrospectively analyzed the records of patients who underwent emergency surgery for acute abdomen within 30-days after anti-cancer drugs administration between 2009 and 2020.
Results
Thirty patients were identified. The primary malignancies were hematological (n = 7), colorectal (n = 4), lung (n = 4), stomach (n = 2), breast (n = 2), prostate (n = 2) and others (n = 5). Fifteen patients were treated with the regimen, including molecular-targeted anti-cancer drugs (Bevacizumab: 8 cases, Rituximab: 4, Ramucirumab: 2, and Gefitinib: 1). Indications for emergency surgery were perforation of the gastrointestinal tract (n = 24), appendicitis (n = 3), bowel obstruction (n = 2), and gallbladder perforation (n = 1). Severe morbidity (Clavien-Dindo IIIa or more) occurred in 8 cases (27%), and there were 6 in-hospital deaths (20%). Significant factors related to in-hospital death were age >70 years old (P = 0.029), poor performance status (ECOG score 1 or 2) (P = 0.0088), and serum albumin level <2.6 g/dl (P = 0.026). The incidence of acute abdomen (odds ratio 5.31, P = 0.00017) was significantly higher in the patients receiving anti-VEGF drugs than in those without anti-VEGF drugs.
Conclusion
This study identified three predictive factors associated with in-hospital death after emergency surgery during chemotherapy: an older age, poor performance status, and low serum albumin level.
