Case Report Chemotherapy 2014;60:88–90 DOI: 10.1159/000371440
Received: October 10, 2014 Accepted after revision: December 8, 2014 Published online: February 14, 2015
A Case of Hepatic Portal Venous Gas in a Patient Treated with Pemetrexed and Carboplatin for Lung Cancer Yo Kawaguchi a Takuya Fujita a Jun Hanaoka b Kazuki Hayashi b a
Division of General Thoracic Surgery, Kohka Public Hospital, and b Division of General Thoracic Surgery, Department of Surgery, Shiga University of Medical Science, Shiga, Japan
Abstract Hepatic portal venous gas (HPVG) has rarely been reported in patients undergoing chemotherapy. We encountered a case of a 64-year-old man with stage IIIA lung adenocarcinoma who received adjuvant chemotherapy with pemetrexed and carboplatin and developed HPVG 1 day after the second chemotherapy. An emergency operation was performed, but the patient died 2 days after the operation because of multiple organ failure caused by sepsis. Since the patient had complained of alternating abdominal bloating and diarrhea during chemotherapy, we considered that the cause of HPVG was intestinal mucosal disruption and increased intraluminal pressure due to the chemotherapy. © 2015 S. Karger AG, Basel
Introduction
Hepatic portal venous gas (HPVG) is a potentially lifethreatening condition [1]. Therefore, it is important to immediately identify its cause. Various causes of HPVG have been reported, including bowel necrosis, digestive tract dilation and intraperitoneal abscess [1]. The mortal© 2015 S. Karger AG, Basel 0009–3157/15/0602–0088$39.50/0 E-Mail [email protected] www.karger.com/che
ity rate is high when HPVG is caused by bowel necrosis; in such cases, emergency surgery is required [2]. HPVG has rarely been reported in patients undergoing chemotherapy [3–7]. For the first time to our knowledge, we report a case of HPVG in a patient who received chemotherapy with pemetrexed and carboplatin for lung cancer. We discuss the possible mechanisms and present a comparison with previously reported cases of HPVG.
Case Report A 64-year-old man (height = 160 cm, weight = 43 kg) with stage IIIA lung adenocarcinoma received adjuvant chemotherapy with pemetrexed (500 mg/m2) and carboplatin (area under the curve from pharmacokinetic measurement = 5) at our hospital. He had a history of diabetes mellitus (HbA1c = 6.5%) and hypertension. He had also undergone total gastrectomy for stomach cancer at the age of 50 years. The neutrophil count decreased to 14 × 102/μl 8 days after administration of the first chemotherapy, but there was no fever or abdominal pain. The neutrophil count improved to within the normal range on the following day without the administration of granulocyte-macrophage colony-stimulating factor. α-Glucosidase inhibitor (α-GI) therapy with 150 mg/day miglitol was started for hyperglycemia 10 days after the first chemotherapy, and the patient started to complain of alternating abdominal bloating and diarrhea. Before the second chemotherapy, the neutrophil count was 58 × 102/ μl. One day after the second chemotherapy, the patient complained of severe abdominal pain, bloating and vomiting. Abdominal examination showed tympanic resonance on percussion and tenderness of the entire abdomen on palpation. The patient’s blood pres-
Dr. Yo Kawaguchi Division of General Thoracic Surgery Kohka Public Hospital 1256 Matsuo, Minakuchi, Kohka, Shiga 528-0074 (Japan) E-Mail kawaguchi1228 @ yahoo.co.jp
Downloaded by: University of Exeter 149.126.76.97 - 7/20/2015 10:37:17 AM
Key Words Chemotherapy · α-Glucosidase inhibitor · Hepatic portal venous gas · Lung cancer · Sepsis · Toxicity
Fig. 1. Abdominal CT scan showing a large
HPVG was first described by Wolf and Evans [8] in 1955 in infants with necrotizing enterocolitis. Kinoshita et al. [1] reviewed 182 cases of HPVG and found that it had different causes, including bowel necrosis (43%), digestive tract dilation (12%), intraperitoneal abscess (11%), ulcerative colitis (4%), gastric ulcer (4%), Crohn’s disease (4%), complications of endoscopic procedures (4%), intraperitoneal tumor (3%) and others (15%). They also reported an overall mortality rate of 39%, but this rate increased when HPVG was caused by bowel necrosis (75%). In the present case, the causes of HPVG were bowel necrosis by chemotherapy and digestive tract dilation. As thrombosis or narrowing of the mesenteric artery was not observed, we excluded ischemic enterocolitis and nonocclusive mesenteric ischemia as the causes of bowel necrosis. The pathogenesis of HPVG remains unclear, but two possible mechanisms have been proposed: (1) escape of
gas into the portal vein due to increased pressure in the bowel lumen and (2) invasion of gas-forming bacteria in the portal vein. Evidence of both these causes has been noted in many cases of HPVG [1]. Five cases of HPVG following chemotherapy have been reported in the literature. The drugs involved were irinotecan and cisplatin for esophageal cancer [3], oxaliplatin, cetuximab and bevacizumab for rectal cancer [4], paclitaxel, carboplatin and bevacizumab for lung cancer [5], cetuximab, oxaliplatin, tegafur-uracil and folinic acid for rectal cancer [6] and irinotecan for ovarian cancer [7]. To our knowledge, the present report is the first description of HPVG in a patient treated with pemetrexed and carboplatin. However, Buchinger et al. [9] reported pemetrexed-induced severe neutropenic enteritis, so pemetrexed might be a potential cause of enterocolitis and bowel necrosis. In addition, other chemotherapy drugs may induce enterocolitis [10]. Makiyama et al. [11] also reported HPVG caused by α-GI therapy. In their case, the mechanism of HPVG was probably the escape of gas due to increased pressure in the bowel lumen and circulation of this gas in the portal vein. The primary side effects of α-GI therapy, which occur in about 20% of patients, are gastrointestinal symptoms, especially bloating, abdominal discomfort, diarrhea and flatulence [12]. α-GI therapy causes intestinal gas production via the fermentation of carbohydrates by the intestinal flora. This resulted in an increased intraluminal pressure, and the gas flowed into the portal vein, thereby causing HPVG. In our case, intestinal mucosal disruption due to chemotherapy and increased intraluminal pressure due to α-GI facilitated easy entry of the gas into the intestinal vessels and eventually resulted in HPVG. In animal experiments, Yamaguchi [13] confirmed that HPVG occurred easily when the intraluminal pressure in the intestinal tract increased with mucosal disruption, and these findings support the mechanism of HPVG development in our case.
HPVG in a Pemetrexed- and Carboplatin-Treated Patient
Chemotherapy 2014;60:88–90 DOI: 10.1159/000371440
sure was 102/62 mm Hg, heart rate was 150 beats/min, and body temperature was 35.9 ° C. Hematological examination showed a white blood cell count of 222 × 102/μl, a neutrophil count of 192 × 102/μl, a lactate dehydrogenase level of 141 IU/l and a C-reactive protein level of 0.2 mg/dl. Blood coagulation was normal. Arterial blood gas analysis indicated a pH of 7.36, PCO2 of 35.1 mm Hg, PO2 of 98.0 mm Hg, lactate level of 3.57 mg/dl and base excess of –6.1 mmol/l. An abdominal computed tomography (CT) scan showed a large amount of gas in the small bowel and colon. Contrast-enhanced CT showed HPVG and mesenteric venous gas (fig. 1). Although thrombosis or narrowing of blood vessels was not observed in the mesenteric artery, several parts of the wall of the small intestine showed low contrast. HPVG with bowel necrosis was diagnosed. An emergency operation was performed, and diffuse necrotic changes were seen in the small intestinal wall. The necrotic parts of the small intestine could not be resected due to extensive necrotic lesions. The gas in the small intestine was drained to reduce the intraluminal pressure during the operation. The patient died 2 days after the operation because of multiple organ failure caused by sepsis.
Discussion
89
Downloaded by: University of Exeter 149.126.76.97 - 7/20/2015 10:37:17 AM
amount of gas in the small intestine and hepatic portal vein and mesenteric venous gas.
Conclusion
Increased intraluminal pressure increases the risk of HPVG during chemotherapy. When patients complain of bloating, not only due to α-GI therapy but also due to
conditions such as constipation and diabetes, this symptom should be corrected before chemotherapy is administered. If chemotherapy must be administered for patients with this symptom, abdominal symptoms should be carefully monitored.
References
90
5 Ortega J, Hayes JM, Antonia S: Hepatic portal venous gas in a patient with metastatic nonsmall cell lung cancer on bevacizumab therapy: a case report and review of the literature. Cancer Chemother Pharmacol 2009; 65: 187– 190. 6 Clemente G, Chiarla C, Giovannini I, De Rose AM, Astone A, Barone C, Nuzzo G: Gas in a portal circulation and pneumatosis cystoides intestinalis during chemotherapy for advanced rectal cancer. Curr Med Res Opin 2010;26:707–711. 7 Iwata N, Adachi H, Nakayama S: A case of portal venous gas with septic shock in a patient treated with irinotecan for ovarian cancer. Jpn J Gynecol Oncol 2011;29:730–735. 8 Wolf JN, Evans WA: Gas in the portal veins of the liver in infants: a roentgenographic demonstration with postmortem anatomical correlation. Am J Roentgenol Radium Ther Nucl Med 1955;74:486–488. 9 Buchinger K, Stahel R, Niggemeier V, Gubler C, Franzen D: Pemetrexed-induced neutropenic enteritis and severe cutaneous hyperpigmentation in a patient with malignant pleural mesothelioma. Lung Cancer 2013; 80: 347–349.
Chemotherapy 2014;60:88–90 DOI: 10.1159/000371440
10 Kim MJ, Kim SH, Kang JH, Kim HG, Cho YJ, Jeong YY, Kim HC, Lee JD, Hwang YS, Kim MG, Choi JY, Lee G: Phase II trial of biweekly chemotherapy with docetaxel and cisplatin in high-risk patients with unresectable nonsmall cell lung cancer. Chemotherapy 2013; 59:159–166. 11 Makiyama H, Kataoka R, Tauchi M, Sumitomo H, Fujita R: Do alpha-glucosidase inhibitors have the potential to induce portal venous gas? Two clinical case reports. Intern Med 2014;53:691–694. 12 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M: Acarbose for prevention of type 2 diabetes mellitus: the STOPNIDDM randomised trial. Lancet 2002; 359: 2072–2077. 13 Yamaguchi T: Experimental studies on the etiology of gas in the portal venous system. Jpn J Gastroenterol Surg 1980;13:1260–1270.
Kawaguchi/Fujita/Hanaoka/Hayashi
Downloaded by: University of Exeter 149.126.76.97 - 7/20/2015 10:37:17 AM
1 Kinoshita H, Shinozaki M, Tanimura H, Umemoto Y, Sakaguchi S, Takifuji K, Kawasaki S, Hayashi H, Yamaue H: Clinical features and management of hepatic portal venous gas: four case reports and cumulative review of the literature. Arch Surg 2001; 136: 1410–1414. 2 Nelson LA, Millington MT, Sahani D, Chung TR, Bauer C, Hertl M, Warshaw LA, Conrad C: Hepatic portal venous gas. The ABCs of management. Arch Surg 2009;144:575–581. 3 Kung D, Raun DT, Chan RK, Ericsson ML, Saund MS: Pneumatosis intestinalis and portal venous gas without bowel ischemia in a patient treated with irinotecan and cisplatin. Dig Dis Sci 2008;53:217–219. 4 Zalinski S, Scatton O, Jacmin S, Tacher V, Brezault C, Soubrane O: Portal venous gas following chemotherapy for colorectal cancer liver metastasis. Eur J Surg Oncol 2009; 35: 557–560.
Received: October 10, 2014 Accepted after revision: December 8, 2014 Published online: February 14, 2015
A Case of Hepatic Portal Venous Gas in a Patient Treated with Pemetrexed and Carboplatin for Lung Cancer Yo Kawaguchi a Takuya Fujita a Jun Hanaoka b Kazuki Hayashi b a
Division of General Thoracic Surgery, Kohka Public Hospital, and b Division of General Thoracic Surgery, Department of Surgery, Shiga University of Medical Science, Shiga, Japan
Abstract Hepatic portal venous gas (HPVG) has rarely been reported in patients undergoing chemotherapy. We encountered a case of a 64-year-old man with stage IIIA lung adenocarcinoma who received adjuvant chemotherapy with pemetrexed and carboplatin and developed HPVG 1 day after the second chemotherapy. An emergency operation was performed, but the patient died 2 days after the operation because of multiple organ failure caused by sepsis. Since the patient had complained of alternating abdominal bloating and diarrhea during chemotherapy, we considered that the cause of HPVG was intestinal mucosal disruption and increased intraluminal pressure due to the chemotherapy. © 2015 S. Karger AG, Basel
Introduction
Hepatic portal venous gas (HPVG) is a potentially lifethreatening condition [1]. Therefore, it is important to immediately identify its cause. Various causes of HPVG have been reported, including bowel necrosis, digestive tract dilation and intraperitoneal abscess [1]. The mortal© 2015 S. Karger AG, Basel 0009–3157/15/0602–0088$39.50/0 E-Mail [email protected] www.karger.com/che
ity rate is high when HPVG is caused by bowel necrosis; in such cases, emergency surgery is required [2]. HPVG has rarely been reported in patients undergoing chemotherapy [3–7]. For the first time to our knowledge, we report a case of HPVG in a patient who received chemotherapy with pemetrexed and carboplatin for lung cancer. We discuss the possible mechanisms and present a comparison with previously reported cases of HPVG.
Case Report A 64-year-old man (height = 160 cm, weight = 43 kg) with stage IIIA lung adenocarcinoma received adjuvant chemotherapy with pemetrexed (500 mg/m2) and carboplatin (area under the curve from pharmacokinetic measurement = 5) at our hospital. He had a history of diabetes mellitus (HbA1c = 6.5%) and hypertension. He had also undergone total gastrectomy for stomach cancer at the age of 50 years. The neutrophil count decreased to 14 × 102/μl 8 days after administration of the first chemotherapy, but there was no fever or abdominal pain. The neutrophil count improved to within the normal range on the following day without the administration of granulocyte-macrophage colony-stimulating factor. α-Glucosidase inhibitor (α-GI) therapy with 150 mg/day miglitol was started for hyperglycemia 10 days after the first chemotherapy, and the patient started to complain of alternating abdominal bloating and diarrhea. Before the second chemotherapy, the neutrophil count was 58 × 102/ μl. One day after the second chemotherapy, the patient complained of severe abdominal pain, bloating and vomiting. Abdominal examination showed tympanic resonance on percussion and tenderness of the entire abdomen on palpation. The patient’s blood pres-
Dr. Yo Kawaguchi Division of General Thoracic Surgery Kohka Public Hospital 1256 Matsuo, Minakuchi, Kohka, Shiga 528-0074 (Japan) E-Mail kawaguchi1228 @ yahoo.co.jp
Downloaded by: University of Exeter 149.126.76.97 - 7/20/2015 10:37:17 AM
Key Words Chemotherapy · α-Glucosidase inhibitor · Hepatic portal venous gas · Lung cancer · Sepsis · Toxicity
Fig. 1. Abdominal CT scan showing a large
HPVG was first described by Wolf and Evans [8] in 1955 in infants with necrotizing enterocolitis. Kinoshita et al. [1] reviewed 182 cases of HPVG and found that it had different causes, including bowel necrosis (43%), digestive tract dilation (12%), intraperitoneal abscess (11%), ulcerative colitis (4%), gastric ulcer (4%), Crohn’s disease (4%), complications of endoscopic procedures (4%), intraperitoneal tumor (3%) and others (15%). They also reported an overall mortality rate of 39%, but this rate increased when HPVG was caused by bowel necrosis (75%). In the present case, the causes of HPVG were bowel necrosis by chemotherapy and digestive tract dilation. As thrombosis or narrowing of the mesenteric artery was not observed, we excluded ischemic enterocolitis and nonocclusive mesenteric ischemia as the causes of bowel necrosis. The pathogenesis of HPVG remains unclear, but two possible mechanisms have been proposed: (1) escape of
gas into the portal vein due to increased pressure in the bowel lumen and (2) invasion of gas-forming bacteria in the portal vein. Evidence of both these causes has been noted in many cases of HPVG [1]. Five cases of HPVG following chemotherapy have been reported in the literature. The drugs involved were irinotecan and cisplatin for esophageal cancer [3], oxaliplatin, cetuximab and bevacizumab for rectal cancer [4], paclitaxel, carboplatin and bevacizumab for lung cancer [5], cetuximab, oxaliplatin, tegafur-uracil and folinic acid for rectal cancer [6] and irinotecan for ovarian cancer [7]. To our knowledge, the present report is the first description of HPVG in a patient treated with pemetrexed and carboplatin. However, Buchinger et al. [9] reported pemetrexed-induced severe neutropenic enteritis, so pemetrexed might be a potential cause of enterocolitis and bowel necrosis. In addition, other chemotherapy drugs may induce enterocolitis [10]. Makiyama et al. [11] also reported HPVG caused by α-GI therapy. In their case, the mechanism of HPVG was probably the escape of gas due to increased pressure in the bowel lumen and circulation of this gas in the portal vein. The primary side effects of α-GI therapy, which occur in about 20% of patients, are gastrointestinal symptoms, especially bloating, abdominal discomfort, diarrhea and flatulence [12]. α-GI therapy causes intestinal gas production via the fermentation of carbohydrates by the intestinal flora. This resulted in an increased intraluminal pressure, and the gas flowed into the portal vein, thereby causing HPVG. In our case, intestinal mucosal disruption due to chemotherapy and increased intraluminal pressure due to α-GI facilitated easy entry of the gas into the intestinal vessels and eventually resulted in HPVG. In animal experiments, Yamaguchi [13] confirmed that HPVG occurred easily when the intraluminal pressure in the intestinal tract increased with mucosal disruption, and these findings support the mechanism of HPVG development in our case.
HPVG in a Pemetrexed- and Carboplatin-Treated Patient
Chemotherapy 2014;60:88–90 DOI: 10.1159/000371440
sure was 102/62 mm Hg, heart rate was 150 beats/min, and body temperature was 35.9 ° C. Hematological examination showed a white blood cell count of 222 × 102/μl, a neutrophil count of 192 × 102/μl, a lactate dehydrogenase level of 141 IU/l and a C-reactive protein level of 0.2 mg/dl. Blood coagulation was normal. Arterial blood gas analysis indicated a pH of 7.36, PCO2 of 35.1 mm Hg, PO2 of 98.0 mm Hg, lactate level of 3.57 mg/dl and base excess of –6.1 mmol/l. An abdominal computed tomography (CT) scan showed a large amount of gas in the small bowel and colon. Contrast-enhanced CT showed HPVG and mesenteric venous gas (fig. 1). Although thrombosis or narrowing of blood vessels was not observed in the mesenteric artery, several parts of the wall of the small intestine showed low contrast. HPVG with bowel necrosis was diagnosed. An emergency operation was performed, and diffuse necrotic changes were seen in the small intestinal wall. The necrotic parts of the small intestine could not be resected due to extensive necrotic lesions. The gas in the small intestine was drained to reduce the intraluminal pressure during the operation. The patient died 2 days after the operation because of multiple organ failure caused by sepsis.
Discussion
89
Downloaded by: University of Exeter 149.126.76.97 - 7/20/2015 10:37:17 AM
amount of gas in the small intestine and hepatic portal vein and mesenteric venous gas.
Conclusion
Increased intraluminal pressure increases the risk of HPVG during chemotherapy. When patients complain of bloating, not only due to α-GI therapy but also due to
conditions such as constipation and diabetes, this symptom should be corrected before chemotherapy is administered. If chemotherapy must be administered for patients with this symptom, abdominal symptoms should be carefully monitored.
References
90
5 Ortega J, Hayes JM, Antonia S: Hepatic portal venous gas in a patient with metastatic nonsmall cell lung cancer on bevacizumab therapy: a case report and review of the literature. Cancer Chemother Pharmacol 2009; 65: 187– 190. 6 Clemente G, Chiarla C, Giovannini I, De Rose AM, Astone A, Barone C, Nuzzo G: Gas in a portal circulation and pneumatosis cystoides intestinalis during chemotherapy for advanced rectal cancer. Curr Med Res Opin 2010;26:707–711. 7 Iwata N, Adachi H, Nakayama S: A case of portal venous gas with septic shock in a patient treated with irinotecan for ovarian cancer. Jpn J Gynecol Oncol 2011;29:730–735. 8 Wolf JN, Evans WA: Gas in the portal veins of the liver in infants: a roentgenographic demonstration with postmortem anatomical correlation. Am J Roentgenol Radium Ther Nucl Med 1955;74:486–488. 9 Buchinger K, Stahel R, Niggemeier V, Gubler C, Franzen D: Pemetrexed-induced neutropenic enteritis and severe cutaneous hyperpigmentation in a patient with malignant pleural mesothelioma. Lung Cancer 2013; 80: 347–349.
Chemotherapy 2014;60:88–90 DOI: 10.1159/000371440
10 Kim MJ, Kim SH, Kang JH, Kim HG, Cho YJ, Jeong YY, Kim HC, Lee JD, Hwang YS, Kim MG, Choi JY, Lee G: Phase II trial of biweekly chemotherapy with docetaxel and cisplatin in high-risk patients with unresectable nonsmall cell lung cancer. Chemotherapy 2013; 59:159–166. 11 Makiyama H, Kataoka R, Tauchi M, Sumitomo H, Fujita R: Do alpha-glucosidase inhibitors have the potential to induce portal venous gas? Two clinical case reports. Intern Med 2014;53:691–694. 12 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M: Acarbose for prevention of type 2 diabetes mellitus: the STOPNIDDM randomised trial. Lancet 2002; 359: 2072–2077. 13 Yamaguchi T: Experimental studies on the etiology of gas in the portal venous system. Jpn J Gastroenterol Surg 1980;13:1260–1270.
Kawaguchi/Fujita/Hanaoka/Hayashi
Downloaded by: University of Exeter 149.126.76.97 - 7/20/2015 10:37:17 AM
1 Kinoshita H, Shinozaki M, Tanimura H, Umemoto Y, Sakaguchi S, Takifuji K, Kawasaki S, Hayashi H, Yamaue H: Clinical features and management of hepatic portal venous gas: four case reports and cumulative review of the literature. Arch Surg 2001; 136: 1410–1414. 2 Nelson LA, Millington MT, Sahani D, Chung TR, Bauer C, Hertl M, Warshaw LA, Conrad C: Hepatic portal venous gas. The ABCs of management. Arch Surg 2009;144:575–581. 3 Kung D, Raun DT, Chan RK, Ericsson ML, Saund MS: Pneumatosis intestinalis and portal venous gas without bowel ischemia in a patient treated with irinotecan and cisplatin. Dig Dis Sci 2008;53:217–219. 4 Zalinski S, Scatton O, Jacmin S, Tacher V, Brezault C, Soubrane O: Portal venous gas following chemotherapy for colorectal cancer liver metastasis. Eur J Surg Oncol 2009; 35: 557–560.
