Liver adenosquamous carcinoma invading the esophagogastric junction - a case-report and a review of the literature

A case of adenosquamous carcinoma of the liver involving the esophago-gastric junction is reported. The preoperative diagnosis of a submucosal tumor of the cardia of the stomach was made following a barium meal study, gastrofiberscopy, ultrasonography, and computed tomography. At surgery, a tumor was found measuring 6x5 cm in diameter and involving the left lobe of the liver, lower esophagus and cardia of the stomach, and the origin of the tumor was unclear. Post-operative histopathology revealed that the tumor contained two different malignant components of glandular and squamous cells. An adenosquamous carcinoma originating in the liver was suspected, since the cancer cells did not involve the esophago-gastric mucosa and were mainly located in the S2 of the liver. Despite aggressive adjuvant chemotherapy, the patient died of a recurrence in the liver seven months later. This seems to be the first documentation of adenosquamous carcinoma of the liver invading the esophago-gastric junction.     

Aggressive recurrence of gastric cancer as a granulocyte-colony-stimulating factor-producing tumor

A 62-year-old Japanese man presented with a 1-month history of inter-digestive epigastralgia. His family history included a sister with gastric cancer. Gastroendoscopy and gastrography demonstrated a type-2 tumor in the upper region of the stomach. CT scan and fluorodeoxyglucose–positron emission tomography (FDG–PET) scan demonstrated gastric cancer and its metastatic lymph nodes. The patient underwent total gastrectomy with splenectomy and extended lymph node dissection. Although postoperative adjuvant chemotherapy by S-1 was started, the deteriorating condition of the patient prevented drug administration and even eating meals. On the 19th postoperative day (POD), FDG–PET scan of the body demonstrated new uptake in the liver and lymph node around the aorta. Without any sign of infection, leukocytosis developed around the 30th POD. On the 49th POD, remarkable uptake in the whole upper abdomen was detected on FDG–PET scan. Finally, leukocyte count increased to 125,200 and granulocyte colony stimulating factor (G-CSF) was elevated to 28 pg/ml on the 54th POD. The patient died of multiple liver metastases and carcinomatous peritonitis only 56 days after surgery. G-CSF-producing tumor is a rare but aggressive disease, particularly as recurrent tumor. If leukocytosis is detected in relation to a non-lympho hematopoietic malignant tumor, G-CSF-producing tumor should be considered and FDG–PET scan is recommended for early detection. Chemotherapy for G-CSF-producing tumor must be conducted as soon as possible.     

Successful treatment with cetuximab combination chemotherapy in a case of FOLFOX-refractory rectal cancer with previously unresectable multiple liver metastases leading to complete resection

Most colorectal cancer patients with liver metastases are not resectable upon initial diagnosis. Recently, chemotherapy improves overall survival of initially unresectable patients by allowing tumor downstaging and complete resection. We report a FOLFOX-refractory rectal cancer patient with unresectable multiple liver metastases, whose tumors could be downstaged and completely resected after initiation of FOLFIRI with cetuximab. Case: A 41-year-old male demonstrated rectal cancer with unresectable multiple liver metastases. He was treated by FOLFOX4 therapy as first-line chemotherapy. After initiating 14 courses, he was treated by FOLFIRI with cetuximab because of disease progression. After initiation of chemotherapy, radiographic examination demonstrated remarkable reduction of primary rectal tumor and metastatic liver tumors. He underwent complete rectal tumor resection after 13 courses of chemotherapy, and metastatic liver tumor resection after 18 courses of chemotherapy.     

Prognostic factors influencing survival of patients with advanced colorectal cancer: hepatic-artery infusion versus systemic intravenous chemotherapy for liver metastases

In this study of 232 patients with histologically confirmed large bowel carcinoma, patient- and tumor-related characteristics were examined and their effect on prognosis was determined. Serum alkaline phosphatase and albumin concentrations, symptom duration prior to diagnosis of the primary tumor, and the status of the primary tumor showed the strongest relationship to survival after diagnosis of surgically noncurable disease. Patients who had normal serum alkaline phosphatase and albumin concentrations, patients whose symptoms lasted over 12 months before diagnosis, and patients whose primary tumor had been resected before diagnosis of noncurable disease had a good prognosis. Performance status, weight loss, sex, presence of liver metastasis, hemoglobin concentration, and absolute lymphocyte or monocyte counts in the peripheral blood, at time of diagnosis of surgically noncurable disease, were significant factors when examined individually. One hundred seventy-nine patients with metastatic colorectal cancer confined to the liver were selected from 601 patients who received chemotherapy for advanced colorectal cancer over 10-year periods to compare the efficacy of hepatic-artery infusion therapy with that of intravenous 5-fluoropyrimidine--containing chemotherapy. The two groups were similar with respect to prognostic factors. The hepatic-artery infusion chemotherapy produced a higher response rate than intravenous chemotherapy, but did not result in significant prolongation of survival.     

Granulocyte colony-stimulating factor production and rapid progression of gastric cancer after histological change in the tumor

Granulocyte colony-stimulating factor (G-CSF)-producing malignancies are thought to be rare and associated with advanced disease and poor prognosis. Here, we report on a 77-year-old patient with G-CSF-producing gastric cancer. We observed this patient from the stage prior to the diagnosis of gastric cancer when leukocyte count was normal to the stage of advanced disease associated with remarkable leukocytosis. Immunohistochemical analysis demonstrated G-CSF expression in the advanced-stage, poorly differentiated adenocarcinoma, but not in the early-stage, well-differentiated adenocarcinoma. G-CSF receptor was not detected to be expressed in the advanced-stage tumor. Based on these results it appears that a histological change in the tumor may influence G-CSF production and the concomitant rapid progression in gastric cancer.     

A case of postoperative rapid brain metastasis originating from stage II a cervical adenosquamous cell carcinoma

Cerebralmetastases from primary cervical carcinomas are very rare with a repeated incidence of 0. 5-1. 2% in various studies. A 46-year-old woman was initially diagnosed and treated for FIGO clinical stage II a cervical carcinoma. She was two gravid, two para. When 40 years old, she had a right hemicolectomy and chemotherapy, due to colon cancer. Her mother also had colon cancer, cervical cancer, and stomach cancer. She had habitually smoked ten/day for 26 years. First, she went to the outpatient clinic, due to abnormal vaginal bleeding. She had a biopsy of her cervix and was diagnosed with cervical cancer. She underwent a radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Pathological diagnosis was adenosquamous cell carcinoma of uterine cervix with extensive LVSI and pelvic lymph node metastasis (right internalil iac LN), myometrial invasion (depth 10 mm), anterior vaginal wall metastasis, but no metastasis of vaginal stump. She came to our hospital for radiotherapy. The woman received concurrent chemoradiotherapy(CCRT)with weekly CDDP 30 mg/m2 as adjuvant therapy. Shortly after CCRT, she was diagnosed with multiple metastases to the bone, liver, lung, and brain. She received palliative radiotherapy and eventually died four months after being diagnosed. The extremely rapid progression of this patient's disease is unusual. To our knowledge, this is one of the most aggressive cases of cervical adenosquamous cell carcinoma documented.     

Thymic squamous cell carcinoma producing granulocyte colony-stimulating factor associated with a high serum level of interleukin 6

Granulocyte colony-stimulating factor (G-CSF)-producing thymic carcinoma is extremely rare. A-66-year-old man presented with an anterior mediastinal mass, and underwent surgical biopsy. He had marked leukocytosis, and his serum levels of G-CSF and interleukin-6 were elevated. Histologically, the tumor consisted of squamous cell carcinoma, which showed positive immunoreactivity for G-CSF. He was treated with thoracic radiotherapy, and chest imaging revealed a marked reduction of tumor size. He was doing well at 8 months after tumor diagnosis.     

A case of liver metastasis from gastric cancer responding to S-1/CDDP chemotherapy, allowing partial gastrectomy and left hepatectomy

A 63-year-old man was found to have an upper abdominal mass, and was referred to our hospital. Endoscopic examination and abdominal CT showed gastric cancer with liver metastasis. A large metastatic tumor of the liver invaded the hepatic hilus, making curative resection impossible. We started chemotherapy using S-1(120 mg/body/day), orally administered for three weeks followed by 2-week rest period, and cisplatin(100mg/body), administered intravenously on day 8 as 1 course. After 5 courses of chemotherapy, the liver tumor reduced markedly and the gastric cancer pathologically disappeared, enabling partial gastrectomy and left hepatectomy. Histological examination showed a well-differentiated adenocarcinoma in the mucosal layer of the resected stomach. A resected specimen of the liver showed a moderately-differentiated adenocarcinoma with signet-ring cells, compatible to liver metastasis from gastric cancer. Bile leakage the remaining liver occurred, but he recovered soon. Gastrointestinal examination revealed another early gastric cancer after seeing him for 2 years on an outpatient basis. We conducted subtotal gastrectomy, and the patient remains alive 30 months after the first operation. This case suggests that S-1/CDDP chemotherapy may reduce the stage of unresectable liver metastasis from gastric cancer and make a curative operation possible.     

Prolonged complete response obtained by single agent S-1 in a case of peritoneal metastasis from gastric remnant cancer

A 58-year-old man underwent cholecystectomy and partial resection of the stomach with the preoperative diagnosis of acute cholecystitis and submucosal tumor of the stomach. The submucosal tumor was found postoperatively to be a T3 stage gastric cancer with well-differentiated phenotype through histopathologic examination of the resected specimen. The patient rejected a subsequent offer of either reoperation or chemotherapy, and underwent close follow-up. Serum tumor markers rose a few months later, and cancer recurrence was confirmed by the finding of a measurable peritoneal metastasis by computed tomography. He was treated with single agent S-1, obtained a complete response 10 months later, and went on to receive the drug for 42 months. He remains disease-free for over 30 months after cessation of S-1. S-1 is recommended as a first-line chemotherapy for recurrent gastric cancer, but the treatment schedule and follow-up schedule after obtaining a complete response remain an issue.     

Cholangiocellular carcinoma that produced both granulocyte-colony-stimulating factor and parathyroid hormone-related protein

A 56-year-old man was admitted to our hospital because of consciousness disturbance. Abdominal computed tomography revealed a large low-density tumor in the left lobe of the liver. He presented with marked leukocytosis and hypercalcemia with high levels of serum granulocyte-colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTH-rP). A diagnosis of cholangiocellular carcinoma (CCC) of the liver was confirmed by histological examination of an autopsy specimen. The tumor cells showed positivity for both G-CSF and PTH-rP with immunohistochemical staining. These results suggest that the tumor was producing both G-CSF and PTH-rP. This paraneoplastic G-CSF and PTH-rP production caused by CCC is very rare. Such cases must be followed up carefully, since tumors associated with paraneoplastic syndrome progress rapidly, resulting in a poor prognosis.     

Durable Response of Human Epidermal Growth Factor Receptor-2-Positive Gastric Adenosquamous Carcinoma to Trastuzumab-Based Chemotherapy

Here, we report a patient with gastric adenosquamous carcinoma (ASC) with human epidermal growth factor receptor-2 (HER2) overexpression who was successfully treated with trastuzumab-based chemotherapy. The patient was a 66-year-old man preoperatively diagnosed with gastric adenocarcinoma with no evidence of distant metastases. On histopathological examination, the curatively resected tumor was identified as ASC with mixed adenocarcinoma and squamous cell carcinoma components. Multiple liver metastases developed 2.5 months after surgery. Because immunohistochemical staining for HER2 was strong in both components, combination chemotherapy with capecitabine, cisplatin, and trastuzumab was initiated. A partial response was confirmed after 6 treatment cycles and PET and CT scans performed after 13 cycles revealed disease resolution with no uptake in the metastatic lesions. No evidence of disease progression has been observed 16 months after initial chemotherapy. This report suggests the potential utility of trastuzumab-based chemotherapy for HER2-positive gastric ASC.Key Words: Adenosquamous carcinoma, Stomach, Human epidermal growth factor receptor-2, Trastuzumab     

A case of adenosquamous carcinoma of lower extrahepatic bile duct

We report a 83-year-old female with bile duct cancer who underwent subtotal stomach preserving pancreatoduodenectomy. Pathologically, her tumor was diagnosed as adenosquamous carcinoma of the lower extrahepatic bile duct with final stage IVb[pT3pN3M(-)].The prognosis of patients with adenosquamous carcinoma of the bile duct is very poor, and the reason is thought to be its tendency to invade the pancreas.Although she was an aged patient, we performed adjuvant chemotherapy using gemcitabine.No recurrence has occurred until this day, 30 months after the operation.This is thought to be an effect of the adjuvant chemotherapy, considering its poor prognosis.     

Resection of cholangiolocellular carcinoma successfully responding to neoadjuvant hepatic arterial infusion chemotherapy - report of a case

A 78-year-old man who had hepatitis C was examined by computed tomography(CT)because of prostate cancer, and was found to have a liver tumor 8. 0 cm in size at S4/S8. The view of the liver tumor was enhanced by CTHA image and washed out by CTAP image. It was suspected to have invaded the RHV and MHV. The pathological examination of the liver biopsy sample revealed cholangiocellular carcinoma or cholangiolocellular carcinoma. Hepatic arterial infusion chemotherapy with gemcitabine and cisplatin was performed. The size of the tumor reduced to 6. 0 cm and the invasion to the RHV was no longer evident. Hepatic resection for the middle two segments was performed after 3 months of chemotherapy. After a histological examination of the resected specimen, the patient was given the final diagnosis of cholangiolocellular carcinoma. Over 50% of the tumor was estimated as necrosis by chemotherapy, indicating that the gemcitabine and cisplatin regimen was remarkably effective. The patient is alive with no evidence of recurrence.     

Solitary Adrenal Metastasis in a Patient with Sigmoid Colon Cancer; Report of a Case

A 73-year-old man had sigmoidectomy for sigmoid colon cancer in December 2001. Although he was followed regularly with chemotherapy, his serum carcinoembryonic antigen (CEA) increased on August 2002. Abdominal computed tomography and magnetic resonance imaging showed a right adrenal mass and no other abnormality. The preoperative diagnosis was a solitary adrenal metastasis from sigmoid colon cancer; the lesion was removed in September 2002. On pathology, adrenal metastasis was confirmed. Although the patient’s serum CEA normalized soon thereafter, 12 months after adrenalectomy, the CEA again increased; the patient had local recurrence of the resected adrenal lesion and liver metastasis. Therefore, the patient was given systemic chemotherapy, but his condition deteriorated, and he died 38 months after adrenalectomy. Adrenal metastasis from colorectal cancer is not unusual; however, a solitary metastasis is rarely found and resected surgically. As surgical treatment of the metastatic lesion could improve patients’ prognosis to some extent if it is detected early, the possibility of adrenal metastasis should be kept in mind when colorectal cancer patients are followed.     

胃癌患者血清G—CSF和C—反应蛋白的检测及其临床意义

目的：探讨胃癌患者血清粒细胞集落刺激因子（Ｇ－ＣＳＦ）和Ｃ－反应蛋白（ＣＲＰ）水平的变化其临床意义。方法采用ＥＬＩＳＡ法测定４７例胃癌患者血清Ｇ－ＣＳＦ和ＣＲＰ水平,并与胃良性肿瘤组和正常对照组进行比较分析。结果胃癌患者血清Ｇ－ＣＳＦ和ＣＲＰ水平明显增高（Ｐ〈０．０１）,并与疾病的临床分期和肿瘤的分化程度有关（Ｐ〈０．０５）,病灶切除后血清Ｇ－ＣＳＦ和ＣＲＰ水平明显降低（Ｐ〈０．０１）。结论血清Ｇ     

Increased expression levels of cyclin-dependent kinase inhibitor p27 correlate with good responses to platinum-based chemotherapy in non-small cell lung cancer

In order to determine whether expression of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer (NSCLC) correlates with chemotherapeutic response, resected tumors from 22 patients with recurrent lung cancer who had undergone complete resection and received chemotherapy after the initial tumor recurrence were subjected to p27 immunostaining. Histological examination of the resected tumors revealed 14 adenocarcinomas, 7 squamous cell carcinomas and one adenosquamous cell carcinoma. Fifty percent or less and over 50% of the cells in the resected tumors of 11 patients each (groups 1 and 2, respectively) were p27-immunopositive. All but one patient received platinum-based chemotherapy after recurrence. Only one in group 1 achieved a partial response (PR) in chemotherapy whereas 2 and 4 in group 2 achieved complete and PRs, respectively. The chemotherapy response rate of group 2 (54%) was significantly higher than that of group 1 (9%, p=0.022). The times to recurrence after tumor resection of the 2 groups did not differ significantly (log-rank p=0.23, Wilcoxon p=0. 32), but survival after chemotherapy of group 2 was significantly better than that of group 1 (log-rank p=0.045, Wilcoxon p=0.028). It is suggested that high p27 expression levels in tumors may predict the good responses to platinum-based chemotherapy for NSCLC.     

Increased expression levels of p53 correlate with good response to cisplatin-based chemotherapy in non-small cell lung cancer

In order to determine whether expression of the tumor suppressor gene p53 in non-small cell lung cancer (NSCLC) correlates with chemotherapeutic response, resected tumors from 18 patients with recurrent lung cancer who had undergone complete resection and received chemotherapy after the initial tumor recurrence were subjected to p53 immunostaining. Histological examination of the resected tumors revealed 11 adenocarcinomas, 6 squamous cell carcinomas and one adenosquamous cell carcinoma. Group 1 was 50% (n=9) p53-immunopositive. All patients received cisplatin-based chemotherapy after recurrence. No patient in group 1 achieved response to chemotherapy whereas 2 and 3 in group 2 achieved complete and partial responses, respectively. The chemotherapy response rate of group 2 (56%) was significantly higher than that of group 1 (0%, p=0.009). The times to reoccurrence after tumor resection of group 2 was significantly better than that of group 1 (log-rank p=0.019, Wilcoxon p=0.042), and survival after chemotherapy of group 2 was also significantly better than that of group 1 (log-rank p=0.023, Wilcoxon p=0.034). It is suggested that high p53 expression levels in tumors correlate with both good response to cisplatin-based chemotherapy and good survival of patients with advanced NSCLC.     

Experience with the management of primary endodermal sinus tumor of the mediastinum

Ten male patients with extensive primary endodermal sinus tumor of the mediastinum were treated with chemotherapy (with or without surgical excision and radiation therapy) between 1977 and 1985. Three patients, treated with cyclophosphamide-vincristine-based chemotherapy, died 1.5, 2.5, and 6.0 months, respectively, after initial diagnosis. Of the seven patients treated with cisplatin-based chemotherapy, one patient died of septicemia at 2.5 months after diagnosis and was disease-free at autopsy examination. Three other patients died of progressive disease at 7.0, 13.0, and 14.0 months, respectively. The three survivors remain alive at 17.0, 31.0, and 40.0 months from diagnosis; all are without evidence of disease. Of the three patients who underwent excision of the residual mediastinal tumor after cisplatin-based chemotherapy, persistent local disease was found in two patients. One of these two patients died of recurrent disease. All surviving patients had surgical resection of the tumor either before or after cisplatin-based chemotherapy, with or without radiotherapy and the timing of therapeutic interventions was guided by changes in the serum alpha-fetoprotein concentrations after initial therapy and during follow-up. Our experience suggests that the optimal management of patients with primary mediastinal endodermal sinus tumor requires an aggressive multidisciplinary approach guided by the extent of the tumor and the serum tumor marker levels.     

Granulocyte-colony stimulating factor-producing esophageal carcinoma: serum level as a marker for monitoring the effects of treatment

We report here a case of granulocyte-colony stimulating factor (G-CSF)-producing esophageal carcinoma in a 66-year-old man. The International Union Against Cancer (UICC) staging was IV A, and a diagnosis of moderately differentiated squamous cell carcinoma was made, based on histopathology. The diagnosis was based on marked leukocytosis (41 500 leukocytes/mm³) and an elevated serum level of G-CSF (154 pg/ml). Immunofluorescent histochemistry and northern blot analysis confirmed the expression of G-CSF protein in cancer cells and its mRNA in cancer tissue. We paid special attention to any change in serum G-CSF levels during aggressive cancer treatment. Subtotal esophagectomy induced a significant decrease in G-CSF level. Adjuvant chemo-radiotherapy, targeting celiac lymph node metastasis, and radiotherapy, targeting solitary lung metastasis, together effectively maintained a low serum G-CSF level, despite a recurrence of the tumor in the lungs, in the form of multiple metastases, with an increase in serum G-CSF levels. The patient's clinical course suggested that serum G-CSF would be a useful marker for monitoring the effects of treatment on G-CSF-producing carcinoma. Received: November 26, 1999 / Accepted: June 28, 2000