Carcinosarcoma of the gallbladder: A case report and review of the literature

A rare case of a huge carcinosarcoma of the gallbladder is presented. Despite a tumor thrombus in the portal vein, this tumor was resected successfully by extended right hepatic lobectomy with right caudate lobectomy and gastroduodenectomy. However, hepatic metastases developed rapidly, and the patient died only 3 months after surgery. Macroscopically, a whitish tumor filled the body and neck of the gallbladder and involved the right lobe and left medial segment of the liver, stomach, and duodenum. Microscopically, the neoplasm consisted of both carcinomatous and sarcomatous components. The former contained adenocarcinoma and squamous cell carcinoma, which were observed in the wall of the gallbladder. The latter comprised the bulk of the mass and contained malignant cartilage and osteoid. Immunohistochemically, the sarcomatous cells reacted to antibodies for epithelial membrane antigen and cytokeratin, but were negative for vimentin antibody, Although stromal differentiation into osteoid and cartilage was noted, the sarcomatous component was felt to be derived from mesenchymal metaplasia of the carcinomatous cells. Only 14 cases of carcinosarcoma of the gallbladder have been reported in the English language literature since 1967.     

Long-term survival case of esophageal carcinosarcoma coexisting with alcoholic liver cirrhosis successfully treated by staged operation: A case report

IntroductionPatients with esophageal cancers including carcinosarcoma sometimes have underlying liver cirrhosis because of a history of heavy drinking. It is definitely required to determine the appropriate surgical strategy and to manage the patients promptly when performing esophagectomy for the esophageal carcinosarcoma coexisting with alcoholic liver cirrhosis.Presentation of caseA 56-year-old male patient with a history of chest pain and difficulty swallowing was admitted to our hospital. He had a history of drinking 250 g of alcohol per day. Endoscopy revealed an irregular protruding tumor on the left wall of the lower-third thoracic esophagus. Computed tomography showed a tumor lesion in the lower-third thoracic esophagus; the images also showed irregularities on the surface of the liver, suggestive of coexisting alcoholic liver cirrhosis. The preoperative diagnosis was T3N2M0, Stage III esophageal leiomyosarcoma. In consideration of the underlying alcoholic liver cirrhosis, a staged operation was planned for this patient as a curative treatment. The patient had an uneventful postoperative clinical course and was discharged on the 47th day after the first surgery. Final histopathological diagnosis was T2N0M0, Stage II esophageal carcinosarcoma. The patient is alive without recurrence three years after surgery.DiscussionThis is the first report of long-term survival case of esophageal carcinosarcoma with alcoholic liver cirrhosis that was treated successfully by staged operation.ConclusionsDespite coexisting with alcoholic liver cirrhosis, staged operation could reduce the surgical invasiveness, so that very good short-term outcome and long-term survival was obtained in the patient with esophageal carcinosarcoma.     

Primary carcinosarcoma of the liver: clinicopathologic features of 5 cases and a review of the literature

Carcinosarcoma of the liver is very rare worldwide. The terminology and pathogenesis of hepatic carcinosarcoma remain controversial issues. In this article, we studied the clinicopathologic features of 5 cases of hepatic carcinosarcomas (matching the World Health Organization definition), analyzed the clinical data, histologic and immunohistochemical (IHC) results, and discussed the terminology, pathologic differential diagnoses, pathogenesis, and prognosis. The patients were 40 to 68 years old, and included 4 males and 1 female. All patients were Hepatitis B surface antigen positive with para-tumorous cirrhosis. The largest dimensions of the neoplasms ranged from 6.0 to 14.0 cm. Satellite nodules, portal vein tumor thrombi, direct invasion into local tissues (right diaphragm, right adrenal gland, and gastric wall) as well as metastatic foci in lungs and abdominal lymph nodes were identified. Pathologically, the neoplasms consisted of carcinomatous and sarcomatous components. The carcinomatous components were exclusively conventional hepatocellular carcinomas in all 5 cases, whereas the sarcomatous components exhibited complex features. Confirmed by IHC studies, the sarcomatous elements in different cases included rhabdomyosarcomas, malignant fibrous histiocytomas, fibrosarcoma, and poorly differentiated spindle cells without distinctive differentiation. Furthermore, the sarcomatous elements in these 5 neoplasms stained negative for all the epithelial markers we applied for IHC staining, which support the pathologic diagnosis of carcinosarcoma rather than sarcomatoid carcinoma. The presence of transitional zones between carcinomatous and sarcomatous components may support the transformation theory. Four patients with palliative hepatectomy died within 6 months, whereas 1 patient is still alive 21 months after radical resection. The poor prognosis of hepatic carcinosarcoma may be due to their highly invasive and metastatic features. Radical resection of early stage hepatic carcinosarcoma may contribute to a relatively optimistic prognosis.     

成人原发性肝肉瘤四例诊治分析

目的 探讨成人原发性肝肉瘤的临床特点、诊断及治疗.方法 回顾性分析我院自1998年至2008年收治的4例原发性肝肉瘤患者的临床资料,总结其发病特点、检查结果、诊断、治疗及随访.结果 4例患者中男3例,女1例,年龄25～65岁,分别因腹痛、乏力、消瘦及体检发现肿块而就诊,无明显家族史,肝脏酶学检测正常或稍增高,CT表现大多见肝内较大肿块,囊实性为多,密度不均匀,边界欠清,增强后无明显强化或部分强化;分别误诊为肝囊肿、肝癌、肝腺瘤,均行肝叶切除术.术后病理学诊断分别为:恶性间叶瘤(未分化肉瘤)、癌肉瘤、平滑肌肉瘤、恶性纤维组织细胞瘤部分血管肉瘤.现存活3例(已分别为术后4、56、84个月),死亡1例(术中死亡),其中1例术后5年肝内复发.结论 原发性肝肉瘤的诊断容易误诊,确诊需依赖术后病理及免疫组织化学检查.采用以手术治疗为主的综合治疗是延长患者生存期的主要手段.患者的预后与肿瘤的病理类型、分化程度、是否浸润转移及是否手术切除等密切相关.     

An unusual case of hepatic carcinosarcoma

We report a rare case of a hepatic carcinosarcoma with rabdomyosarcomatous differentiation in its sarcomatous component. A 71-year old Caucasian female patient underwent a liver resection for a 4-cm lesion developed on an underlying HCV-related cirrhosis. Post-operative course was uneventful and the patient was discharged 5 days after surgery. At pathology, the tumor presented the features of hepatocellular carcinoma and rhabdomyosarcoma Three months later the patient experienced a liver recurrence, dying 2 months later for systemic disease. The reported case presents several peculiarities, i.e. the female gender, the HCV-related cirrhotic status, and the European origin of the patient. However, the outcome of our case confirms that this neoplasm pursues a highly aggressive course with poor prognosis.     

羟基磷灰石-阿霉素复合物对大鼠肝移植性肿瘤局部切除术后治疗作用的研究

目的探讨大鼠肝移植性肿瘤局部切除术后,局部埋置抗癌复合物羟基磷灰石阿霉素对大鼠存活、肿瘤复发和肝功能的影响。方法制作大鼠Ｗ２５６癌肉瘤肝移植瘤模型。肿瘤局部切除后,各组大鼠分别于肝创缘埋置羟基磷灰石阿霉素（Ａ组）;注射阿霉素水溶液（Ｂ组）和注射生理盐水（Ｃ组）。测定各组大鼠术后１、３、７天的肝功能。观察术后３个月大鼠死亡和肿瘤复发情况。结果Ａ组大鼠术后死亡率（２５％,３／１２）及复发率（３３％,４／１２）均较Ｃ组（８３％,１０／１２和９２％,１１／１２）明显下降（Ｐ＜００１）,而复发率（３３％,４／１２）亦较Ｂ组（７５％,９／１２）降低（Ｐ＜００５）,并且肝功能受损亦较Ｂ组减轻（Ｐ＜００５或Ｐ＜００１）。结论羟基磷灰石阿霉素复合物局部埋置,提高了肝移植瘤大鼠局部切除术后的生存率,降低了肿瘤的复发率,对肝功能损害较轻,有一定的临床意义。     

少血供兔VX2肝移植瘤模型动脉栓塞后影像与病理分析

目的建立并筛选少血供兔VX2移植性肝癌模型，观察肝动脉化疗栓塞治疗效果及经肝动脉注射碘油沉积情况。方法开腹种植转移瘤于35只新西兰大白兔肝叶，移植成功后经筛选出少血供移植瘤16只，随机分为2组，对照组8只，插管至腹腔干；实验组8只，插管至肝固有动脉或左肝动脉，术后1周进行CT扫描，观察碘油沉积情况，分别取肿瘤进行HE染色及检测VEGF蛋白表达。结果16只少血供VX2移植瘤模型兔插管成功11只，5只失败。对照组成功者5只插管至腹腔干，实验组6只插管至左肝动脉或肝固有动脉，造影发现肿瘤血管稀疏或不可显示，术后CT扫描发现实验组碘油在瘤内呈环形沉积；对照组5只肝移植瘤中VEGF表达阳性2例，弱阳性3例；实验组6只移植瘤中强阳性4例，阳性2例。结论兔肝动脉血管解剖与人相似，超选择至左肝动脉，暂时阻断肿瘤动脉血供后栓塞化疗，对少血供肿瘤治疗效果较好。CT对术后碘油沉积情况检测方便，可靠，有特征性。     

Carcinosarcoma of the prostate with multiple metastases: case report and review of the literature

A case of carcinosarcoma of the prostate in a previously healthy 65-year-old man is reported. The tumor was initially diagnosed as adenocarcinoma, but the prostatectomy specimen showed a 717-g prostate, with evidence of adenocarcinoma and carcinosarcoma without heterologous structures. By 3-month follow-up, local recurrence, and liver, lung, and bone metastases had developed in the patient. He died of disease 10 months postoperatively. Carcinosarcoma of the prostate is a very rare but highly aggressive cancer with limited therapeutic options that should be treated with surgery and managed symptomatically. We believe this article is the forty-second case reported in the literature.     

Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases--activation of cell invasion and migration pathways.

Elucidating the mechanism of liver tumor growth and metastasis after hepatic ischemia-reperfusion (I/R) injury of a small liver remnant will lay the foundation for the development of therapeutic strategies to target small liver remnant injury, and will reduce the likelihood of tumor recurrence after major hepatectomy or liver transplantation for liver cancer patients. In the current study, we aimed to investigate the effect of hepatic I/R injury of a small liver remnant on liver tumor development and metastases, and to explore the precise molecular mechanisms. A rat liver tumor model that underwent partial hepatic I/R injury with or without major hepatectomy was investigated. Liver tumor growth and metastases were compared among the groups with different surgical stress. An orthotopic liver tumor nude mice model was used to further confirm the invasiveness of the tumor cells from the above rat liver tumor model. Significant tumor growth and intrahepatic metastasis (5 of 6 vs. 0 of 6, P=0.015), and lung metastasis (5 of 6 vs. 0 of 6, P=0.015) were found in rats undergoing I/R and major hepatectomy compared with the control group, and was accompanied by upregulation of mRNA levels for Cdc42, ROCK (Rho kinase), and vascular endothelial growth factor, as well as activation of hepatic stellate cells. Most of the nude mice implanted with liver tumor from rats under I/R injury and major hepatectomy developed intrahepatic and lung metastases. In conclusion, hepatic I/R injury of a small liver remnant exacerbated liver tumor growth and metastasis by marked activation of cell adhesion, invasion, and angiogenesis pathways.     

Changes in the hepatic perfusion index during the development of experimental hepatic tumours

A model of microscopic liver tumour has been developed in the Fisher rat by intraportal injection of 1.6 x 10(7) Walker 256 carcinosarcoma cells. Rats were studied at 2, 4 and 6 days after the inoculation of live Walker cells. A control group received dead Walker cells. No tumour was visible in control groups at 2, 4 and 6 days after inoculation. Similarly in rats injected with live cells no tumour was visible at 2 days after inoculation but at 4 and 6 days the percentage hepatic replacement was (mean +/- s.d.) 7.0 +/- 2.3 and 27.9 +/- 6.80 respectively. The hepatic perfusion index was significantly raised at 4 and 6 days after inoculation of live cells compared with control animals and those receiving viable cells after 2 days inoculation. Portal flow and portal venous inflow were significantly reduced when the hepatic perfusion index increased but hepatic arterial flow did not alter. Changes in the hepatic haemodynamics were accompanied by increases in the portal and splanchnic vascular resistance and an increase in the amount of arteriovenous shunting through the liver. These findings confirm studies that the hepatic perfusion index is useful in the detection of occult liver metastases but that the change is not a consequence of an increase in the hepatic arterial flow.     

Carcinosarcoma of the lung mis-diagnosed preoperatively as a mediastinal tumor

Carcinosarcoma of the lung is an uncommon tumor and is rarely preoperatively correctly diagnosed. The prognosis of patients with carcinosarcoma is extremely poor, despite treatment. A 79-year-old man was mis-diagnosed preoperatively as having a malignant mediastinal tumor. Excision of the tumor with segmentectomy of the lung revealed it was composed of a variety of carcinomatous and sarcomatous elements, which is a clear manifestation of the histogenetic totipotentiality of carcinosarcoma. He was subsequently treated with adjuvant chemotherapy and irradiation. He remains well at sixteen months after the operation, to date. Here we report this rare true case of a carcinosarcoma, focusing on the difficulty of a correct preoperative diagnosis.     

Carcinosarcoma of the lung mis-diagnosed preoperatively as a mediastinal tumor.

Carcinosarcoma of the lung is an uncommon tumor and is rarely preoperatively correctly diagnosed. The prognosis of patients with carcinosarcoma is extremely poor, despite treatment. A 79-year-old man was mis-diagnosed preoperatively as having a malignant mediastinal tumor. Excision of the tumor with segmentectomy of the lung revealed it was composed of a variety of carcinomatous and sarcomatous elements, which is a clear manifestation of the histogenetic totipotentiality of carcinosarcoma. He was subsequently treated with adjuvant chemotherapy and irradiation. He remains well at sixteen months after the operation, to date. Here we report this rare true case of a carcinosarcoma, focusing on the difficulty of a correct preoperative diagnosis.     

Carcinosarcoma of the esophagus--pattern of recurrence.

Carcinosarcoma of the esophagus is a rare malignant neoplasm, predominantly affecting men in their seventh decade of life. While presenting symptoms and anatomic location of squamous cell and carcinosarcoma of the esophagus are similar, the latter often presents as a large intraluminal polypoid mass on barium esophagram. The more favorable prognosis associated with carcinosarcoma versus other esophageal neoplasms has been attributed to early onset of symptoms, resulting in prompt diagnosis, and a lower propensity for tumor invasion. We report the case of an elderly woman presenting with dysphagia who was initially diagnosed with esophageal leyomyosarcoma. Final tumor pathology showed esophageal carcinosarcoma.     

Decreased angiotensin II receptors mediate decreased vascular response in hepatocellular cancer.

OBJECTIVE: The authors' objective was to determine the origin of the diminished pressor responsiveness of angiotensin II infusion in hepatoma by evaluating angiotensin II receptor status in normal liver, hepatoma tumor, and cultured hepatocytes and H4IIE cells. SUMMARY BACKGROUND DATA: Hepatocellular cancer is a highly vascular tumor, where the neovasculature is unique in that it arises only from the hepatic arterial circulation, whereas normal liver has both hepatic arterial and portal venous blood supply. The tumor neovasculature is also characterized by an abnormal vascular reactivity to vasoconstrictors, including the response to angiotensin II. The altered response of tumor vasculature to angiotensin II offers a potential therapeutic opportunity for modulation of tumor blood flow. However, the origin of the decreased vascular response is unknown. METHODS: The authors evaluated the hepatic vascular response to angiotensin II infusion by determining hepatic arterial blood flow to normal liver and to tumor by means of radioactive microspheres. The angiotensin II receptor status in the normal liver, hepatoma tumor, and cultured hepatocytes and H4IIE cells was determined br radioligand binding analysis and in cryostat sections derived from normal liver and hepatoma tumor by means of in situ binding analysis with biotinylated angiotensin II. RESULTS: Angiotensin II infusion decreased the hepatic arterial flow to normal liver and increased hepatoma to liver flow ratio. The number of angiotensin II receptors in normal liver was significantly higher than that in hepatoma (239 +/- 20 fmol/mg protein in normal liver vs. 162 +/- 15 fmol/mg protein in hepatoma) without a change in the affinity (4.4 +/- 0.8 nM in normal liver vs. 4.7 +/- 1.2 nM in hepatoma). H4IIE cells and primary hepatocytes had low receptor density. In situ binding analysis revealed that angiotensin II receptors were mainly on the smooth muscle cells of the neovasculature. CONCLUSIONS: The data suggests that the diminished vascular response to angiotensin II hepatoma may relate a loss of angiotensin II receptor on tumor neovasculature.     

A case of inflammatory pseudotumor of the liver hilum successfully treated with aggressive hepatectomy

Inflammatory pseudotumor (IPT) of the liver is a rare, benign tumor. When the tumor involves the hepatic hilum, however, the clinical course of the patient becomes problematic because of obstructive jaundice and portal hypertension. Complete removal of the tumor sometimes is difficult when the hepatic hilum is extensively involved, and liver transplantation becomes necessary for such an unresectable tumor. This report concerns a 7-year-old boy who presented with obstructive jaundice and portal hypertension owing to an inflammatory pseudotumor of the hepatic hilum and was treated successfully with aggressive hepatectomy, vascular reconstructions of both the portal vein and the hepatic artery, and biliary reconstruction. The patient was discharged after 39 days of hospitalization. Eight months later, portal vein obstruction was detected and treated successfully with percutaneous transhepatic balloon dilatation of the obstructed site. The liver has continued to function well for 11 months after the tumor resection.     

保留肝V、Ⅵ段的肝右叶巨大肝癌切除术

位于肝Ⅶ、Ⅷ段的巨大肿瘤,如果左半肝体积足够大,选择右半肝切除术相对比较容易实施。但当左半肝体积不足时,为了避免术后肝功能衰竭,必须保留肝V、Ⅵ段组织,手术难度明显增大。2012年7月26日,我科对1例肝Ⅶ、Ⅷ段巨大肝癌患者成功实施了保留肝V、Ⅵ段的肝癌切除术,效果良好。     

A case of true carcinosarcoma in bladder diverticulum]

We report a case of carcinosarcoma arising from a bladder diverticulum. A 71-year-old male was referred to our hospital for macroscopic hematuria. Two diverticula were identified in the left wall of the urinary bladder, one of which showed a broad-based tumor. The bladder tumor was resected using a transuretheral approach and the tumor was histologically diagnosed as leiomyosarcoma. The patient underwent partial resection of the bladder including the two diverticula and the tumor. Pathological examination revealed that the resected specimen was composed of three elements, transitional cell carcinoma (G3), squamous cell carcinoma, and leiomyosarcoma. Thus, the patient was diagnosed with carcinosarcoma. He died 5 months after surgery to remove the panperitonitis carcinomatosa. This case is the 38th reported case of bladder carcinosarcoma in Japan.     

Effect of blood flow occlusion on laser hyperthermia for liver metastases

BACKGROUND: Interstitial laser hyperthermia (ILH) is an in situ ablative technique for the treatment of colorectal liver metastases. A significant factor limiting tumor destruction is hepatic blood flow. Modulation of hepatic blood flow may increase the size of tumor necrosis achieved. Our aim was to investigate the effect of blood flow occlusion on ILH-induced necrosis in both tumor and normal liver tissue. MATERIALS AND METHODS: A model of colorectal liver metastases in male inbred CBA mice was used. ILH was applied to normal liver and tumor tissue using a bare optical quartz fiber from an SYL500 Nd:YAG surgical laser generator, with and without hepatic blood flow occlusion, and the extent of necrosis was studied. Tumor blood flow was assessed by laser Doppler flowmetry and scanning electron microscopy. RESULTS: Hepatic blood flow occlusion resulted in a significant reduction in blood flow in normal liver tissue (37.9% +/- 5.8, P < 0.001) and in the periphery of the tumor (17.5% +/- 7.8, P < 0.001). It did not affect the blood flow in the center of the tumor (13.4% +/- 4.3, P = 0.07). ILH of normal liver tissue, at low power (2 W), with hepatic blood flow occlusion, resulted in a significant increase in the diameter of necrosis. This effect was not seen when higher power (5 W) was used in normal liver. No significant effect was noted within tumor tissue at either power setting. CONCLUSION: The overall effect of hepatic blood flow occlusion in ILH-induced tissue necrosis appears to be negligible in tumor tissue. Its main applicability appears to be at the tumor-host interface, where a decrease in blood flow may lead to higher temperatures and therefore to a greater degree of tumor cell destruction.     

Internal radiotherapy for hepatic metastases II: The blood supply to hepatic metastases

Given that metastatic hepatic malignancy remains as a significant cause of death, with a median survival after diagnosis of only 7 months despite treatment, there exists a need for some effective treatment modality. Internal radiotherapy in the form of yttrium-90 microspheres infused into the hepatic artery appears to be a promising method of therapy. One criterion required for the success of this treatment is that of a differentially greater arterial supply to tumor as opposed to liver tissue. This arterial hypervascularity of tumor has been demonstrated before. However, some conflict has been reported as to the maintenance of this state as tumor size increases. Using 15 micrometers Cobalt-57 microspheres for studying salivary adenocarcinoma implants in DA rat livers, these experiments have demonstrated a constant blood flow in the tumor periphery of 3.9 times that within the normal hepatic parenchyma, regardless of tumor size. Also demonstrated is a progressive decrease in central tumor arterial blood flow after a tumor diameter of 6 mm has been exceeded. Arterial hypervascularity of liver tissue adjacent to the tumor has been demonstrated while an intermediate zone of liver tissue appeared hypovascular, suggesting the presence of shunting. In three humans with metastatic liver disease, hepatic artery infusion of particulate radiotracer has demonstrated the peripheral tumor hypervascularity and relative central tumor hypovascularity with good correlation obtained with the images of the metastases on conventional colloidal hepatic scintigraphy. This method allows assessment of the patient's suitability for internal radiotherapy by enabling assessment of the tumor vascularity and the degree of potentially dangerous extrahepatic irradiation.     

Intermittent hepatic arterial or portal occlusion reduces liver tumor growth

The effect of repeated, intermittent hepatic vascular occlusion on liver tumor growth was studied in 32 rats. An adenocarcinoma was inoculated in the left liver lobe. After 8 days, the tumor size was measured and then, in three groups, the hepatic artery was occluded intermittently during 5 days for 15 min, 1 hr, or 2 hr daily, respectively. The tumor growth after 6 days in these groups was compared with that in a group where instead the portal vein was occluded intermittently during 5 days for 15 min, and with that in a group of sham-operated control rats. In the control rats, the tumor volume (mean +/- SEM) increased from 0.16 +/- 0.03 to 1.34 +/- 0.15 cm3 during the 6 days of experiment. It was found that repeated, intermittent occlusion of the hepatic artery or the portal vein, retarded the liver tumor growth to 30-60% of the growth rate in sham-operated controls (P less than or equal to 0.015). The 15-min daily hepatic artery or portal vein occlusion was found to reduce the tumor growth rate as much as daily hepatic artery occlusion for 2 hr. It is suggested that short, daily, intermittent hepatic vascular occlusions might be efficient in the palliative treatment of liver malignancy.