Unusual metastasis of hepatocellular carcinoma to the esophagus

This report describes a case of metastatic hepatocellular carcinoma (HCC) presenting as a polypoid mass in the lower esophagus. The patient was a 63-year-old man with HCC. An endoscopic examination revealed a pedunculated polypoid mass, about 3 cm in diameter, at the lower part of the esophagus. The biopsy specimen obtained from the tumor revealed that the mass consisted of a pseudoglandular arrangement of tumor cells, and the tumor was diagnosed as metastatic HCC. There were no symptoms due to esophageal tumor. He died of progressive hepatic failure. Cases of premortem-diagnosed esophageal metastasis from HCC are extremely rare.     

Superficial neuroendocrine carcinoma of the esophagus

A 50‐year‐old man underwent subtotal esophagectomy for a superficial ulcerated tumor, 1.8 cm in length, located in the middle third of the esophagus. Histological examination of the resected specimen showed a stage I infiltrating neuroendocrine carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, neuron‐specific enolase, synaptophysin, protein gene product 9.5 and carcinoembryonic antigen. Postoperative cisplatin‐based chemoradiation therapy was administered. Fourteen months after surgery, widely metastatic disease was noted and the patient died 3 months later.     

Preoperative chemoradiotherapy and surgery for locally advanced esophageal basaloid squamous carcinoma: report of successful

A 58-year-old Japanese man complained of dysphagia, and esophagography and endoscopy showed a 7.5-cm-long protruding tumor in his middle esophagus. Biopsy diagnosed the lesion as basaloid squamous carcinoma. We assessed the tumor as T3N0M0 stage II. Preoperative chemoradiotherapy was started, consisting of 3 weeks of intravenous chemotherapy with 10 mg/day cisplatin and 750 mg/day 5-fluorouracil and concurrent total 45-Gy external irradiation applied to the tumor. We evaluated the effectiveness as a partial response and performed curative resection with radical esophagectomy 23 days after the completion of chemoradiotherapy. The pathological findings showed necrosis and degeneration over two-thirds of the tumor. Postoperatively, he returned to physical labor and has had no evidence of recurrence for 5 years. Although basaloid squamous carcinoma of the esophagus is associated with poor prognosis because of its highly malignant potential, preoperative chemoradiotherapy followed by radical esophagectomy may allow for the possibility of improving the prognosis of a fatal process.     

Esophageal carcinosarcoma with intramural metastasis

A case of esophageal carcinosarcoma is described herein. A 58-year-old man presented with dysphagia and was admitted to our hospital. Imaging studies revealed a type 3 tumor in the upper intrathoracic esophagus with direct invasion to the left main bronchus. Analysis of a biopsy specimen revealed carcinosarcoma. The patient underwent esophageal bypass and chemoradiotherapy. Eight months after surgery, he died of esophago-bronchial fistula. Autopsy examination revealed liver metastasis, peritoneal dissemination and intramural metastasis. The sarcomatous component was predominant in the intramural and liver metastatic lesions.     

Neoadjuvant chemotherapy with a combination of irinotecan and cisplatin in advanced gastric cancer--a case report

We report a case of advanced gastric carcinoma successfully treated with a combination of irinotecan and cisplatin as neoadjuvant chemotherapy. The patient, a 78-year-old man, had type 2 gastric cancer, which had metastasized to the paraaortic lymph nodes. He was treated with irinotecan, 70 mg on day 1 and day 15, and cisplatin, 80 mg on day 1. The course was repeated every 4 weeks. Two courses of treatment resulted in a marked reduction of both the primary tumor and lymph nodes. Subsequently, the patient underwent curative surgery consisting of total gastrectomy, splenectomy, and D3 lymph node dissection. No surgical complications were observed. On microscopic examination, only a few tumor cells were detected in the granulation tissues of the resected stomach and in the lymph nodes. This would be the first case to demonstrate the effectiveness and the safety of irinotecan and cisplatin used in the neoadjuvant setting for treatment of advanced gastric carcinoma.     

Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine: Case report

Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as thirdline chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partialtumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.     

Hyperosmolar hyperglycemic nonketotic coma after chemoradiotherapy for esophageal cancer

A 73-year-old man was diagnosed with a type 2 tumor in the middle third of his esophagus by upper esophagogastrointestinal examination and an esophagogram; the tumor was diagnosed as squamous cell carcinoma by endoscopic biopsy. Computed tomography (CT) revealed that the tumor had invaded his descending aorta. He was diagnosed with T4b/N0/M0 stage IIIc [Union for International Cancer Control (UICC), 7th edition] esophageal cancer. He had no previous history of diabetes mellitus. We treated him with concurrent chemoradiotherapy using cisplatin and 5-fluorouracil. Fourteen days after the entire course of chemoradiotherapy, he became confused and entered into sudden coma, which was diagnosed as hyperosmolar hyperglycemic nonketotic coma. With vigorous intravenous infusion of half-saline and insulin, he recovered from the coma 36 h after onset. Hyperosmolar hyperglycemic nonketotic coma is a severe complication that is difficult to treat and can be induced by chemoradiotherapy. It must be diagnosed early and treated appropriately.     

Complete regression of advanced esophageal cancer with abdominal bulky lymph node metastasis treated by concurrent chemoradiotherapy using docetaxel, cisplatin, and 5-fluorouracil

In an attempt to improve survival of patients with locally advanced esophageal cancer, chemoradiotherapy consisting of cisplatin, 5-fluorouracil (5-FU), and irradiation has recently been used. For such patients, concurrent chemoradiotherapy using docetaxel in combination with cisplatin and 5-FU has been introduced and is under evaluation. We herein report an esophageal cancer patient with concomitant distant lymph node metastasis in whom a complete response was achieved by chemoradiation therapy. A 46-year-old man was diagnosed as having stage IV A esophageal cancer with synchronous bulky metastasis in the celiac lymph node, and concurrent chemoradiotherapy was started. Chemotherapy consisting of docetaxel (30 mg/m² on days 1, 8), cisplatin (60 mg/m² on day 1), and 5-FU (200 mg/m²/day, continuous infusion on days 1–14) was performed for 2 cycles. At the same time, irradiation therapy (1.8 Gy/day on 1–5 days every week for 6 weeks) was employed for both local and metastatic lesions. Although the patient experienced severe hematological toxicity throughout the course, chemoradiotherapy resulted in complete regression of both local and metastatic disease. Subsequently, he was followed as an outpatient without any maintenance therapy, and he has been free of disease for 38 months after completion of the combination therapy. Thus, concurrent chemoradiotherapy may be effective for esophageal cancer, even with visceral metastasis.     

Combined modality therapy for basaloid squamous carcinoma of the esophagus

A 61 year-old woman came to our hospital with dysphasia that had persisted for 2 months. Endoscopy and barium swallow showed a protruding tumor, about 6.0 cm long, in the midportion of the esophagus. A biopsy specimen showed squamous cell carcinoma of the esophagus. Computed tomography (CT) scan revealed adventitial involvement and lymph node metastases beneath the carina. After 2 courses of chemotherapy with cisplatin (CDDP) 100 mg for 1 day, 5-Fluorouracil (5-FU) 800 mg for 5 days, and leucovorin 30 mg for 5 days, complete regression of the tumor was observed by endoscopy and barium esophagography. Transthoracic esophagectomy with lymph node dissection was performed. Histologically, the muscle layers of the resected esophagus had been replaced by fibrous tissue; however, small foci of basaloid squamous carcinoma (BSC) were found in the submucosa. Six months after surgery, a CT scan revealed a metastatic lymph node around the right main bronchus. Chemotherapy and radiotherapy resulted in the disappearance of the metastasis. The patient has survived for more than 3 years since surgery with a good quality of life.     

Pancreatic carcinoma with brain metastases: case report and literature review

The case of a patient developing multiple brain metastases from carcinoma of the exocrine pancreas has been described. A 56-year-old man with stage IV pancreatic cancer attained a clinical and radiographic response while receiving the G-FLIP chemotherapy regimen (biweekly gemcitabine, irinotecan, 5-fluorouracil, leucovorin and cisplatin). After 4 months of therapy, he developed gait imbalance and weakness in the right hand. An MRI of the brain showed multiple 1-2 mm enhancing nodules in the cerebral hemispheres and pons. A subsequent biopsy confirmed that these were pancreatic carcinoma metastases. The patient experienced a rapid deterioration in his neurological status and died 3 days after brain biopsy. Previously reported cases of brain metastases from pancreatic cancer are reviewed.     

Asymptomatic colonic metastases from primary squamous cell carcinoma of the lung with a positive fecal occult blood test

We describe a 74-year-old man with a colonic metastatic squamous cell carcinoma （SCC） from the lung. His chest X-ray revealed an abnormal shadow in the right upper lobe. Computed tomography （CT） of the chest demonstrated a large lung tumor in the right upper lobe obstructing the right upper bronchus. Bronchoscopy revealed an easy-bleeding tumor in the right upper bronchus that was diagnosed as poorly differentiated squamous cell lung carcinoma. He underwent colonoscopy because he had a positive fecal occult blood test. Colonoscopy revealed a large protruding lesion with central ulceration in the descending colon. Histological examination of the biopsy specimen obtained from the colonic lesion revealed SCC. The lesion was diagnosed as metastatic colonic SCC. He had no abdominal symptoms. He underwent chemotherapy with an infusion of cisplatin 130 mg i.v. day 1, and docetaxel hydrate 100 mg i.v. day 1, repeated every 4 wk, followed by 4 courses of chemotherapy. The primary lesion shrank by less than 10% and was judged to be ＂Partial Response＂ （PR） after 3 courses of treatment. The patient still lived 23 wk after the diagnosis of metastatic colonic SCC. Colonic metastasis of primary SCC of the lung is rare.     

Successful treatment for undifferentiated carcinoma of the esophagus: a case with complete response to chemoradiotherapy

Undifferentiated carcinoma of the esophagus (UEC) is an uncommon esophageal malignancy, and patients with UEC have an especially poor prognosis because of extensive metastasis even at an early stage. A standard treatment regimen for UEC has not yet been established. We have experienced a case with UEC (T2N1, stage II) that achieved complete remission by chemoradiotherapy [cisplatin (CDDP) + 5-fluorouracil (5-FU), 50 Gy]. A 67-year-old man with a 4-cm type 1 tumor in the middle thoracic esophagus was diagnosed as UEC (non-small cell type) histologically. Computerized tomographic (CT) scan of the chest showed metastatic lesions at the right recurrent nerve lymph nodes. Although the lesion was diagnosed as T2, N1, and stage II, the patient was judged to be a severe case because surgical control of UEC is almost impossible even at the early stages. Chemoradiotherapy (CRT; CDDP + 5-FU, and radiation) was selected for this case. In the first course of CRT, the patient was given CDDP (20 mg/m²) and 5-FU (700 mg/m²) for 5 days and concurrent external-beam irradiation (30 Gy, 2 Gy/day × 15 days) in the “long-T” field including the cervical and mediastinal lymph nodes. The second course was the same chemotherapy (CDDP 20 mg/m²/day + 5-FU 700 mg/m²/day, 5 days) with externalbeam irradiation (2 Gy/day) for 10 days (5 days/week, 2 weeks). After the first course of CRT, the patient already had achieved complete remission (CR). An upper gastrointestinal endoscopic study showed the tumor had almost disappeared and was covered by normal epithelium. Histological study from the biopsy samples showed there were no viable cancer cells at the lesion. CT scan of the chest showed the metastatic lesions at the right recurrent nerve lymph nodes had reduced. After the second course of CRT had been completed, the patient was discharged from the hospital. The patient is still alive with no cancer relapse at 2.5 years after the treatment. Further studies to clarify the response rate and survival effect of CRT in patients with UEC are expected.     

Endotracheal metastasis from basaloid squamous carcinoma of the esophagus

Endobronchial metastases from extrapulmonary neoplasms are rare events, and there is no report in the literature of metastasis originating from esophageal cancer. Basaloid squamous carcinoma of the esophagus is a rare histologic type that is known to be a biologically aggressive phenotype. We describe a rare case of metachronous endotracheal metastasis originating from esophageal basaloid squamous carcinoma. A 72-year-old Japanese man underwent esophagectomy for stage I esophageal cancer. Pathological diagnosis of the resected specimen was basaloid squamous carcinoma. One year later, a follow-up computed tomography scan displayed a tumor shadow in the tracheal wall. Bronchoscopy revealed a protruding tumor in the tracheal wall, and the pathologic diagnosis of the biopsy specimen was also basaloid squamous carcinoma. According to the diagnosis of metachronous endobronchial metastasis from esophageal basaloid squamous carcinoma, we treated the patient with chemotherapy comprising docetaxel, cisplatin, and 5-fluorouracil followed by chemoradiotherapy, and complete response was achieved. The patient has not suffered a recurrence of the disease for 23 months since the diagnosis of the endobronchial tumor. Careful follow-up is needed to ensure that rare types of metastasis are not missed in cases with biologically aggressive tumors.     

A case of granulocyte-colony stimulating factor producing ductal adenocarcinoma of the pancreas]

We report a case of pancreatic ductal adenocarcinoma producing granulocyte-colony stimulating factor (G-CSF). A 56-year-old Japanese man was admitted to our hospital with back pain and high fever. An abdominal CT scan revealed masses in the pancreatic body to the tail, and both lobes of the liver. A biopsy specimen of the hepatic tumor demonstrated metastatic poorly differentiated adenocarcinoma. We administered oral S-1 in combination with gemcitabine. However, his general condition gradually worsened, and a high serum level of G-CSF persisted. He died 135 days after admission. The diagnosis of autopsy was pancreatic ductal adenocarcinoma. Immunohistochemical staining showed the presence of G-CSF in tumor cells. The final diagnosis was G-CSF-producing pancreatic carcinoma.     

Esophageal small-cell carcinoma with syndrome of inappropriate secretion of antidiuretic hormone

Small-cell carcinoma (SCC) of the esophagus is rare, and its clinical characteristics remain poorly understood. A 54-year-old man was given a diagnosis of esophageal SCC and underwent esophagectomy. Four months after surgery, he was admitted to our hospital because of rapidly developing hyponatremia. Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) due to extensive recurrence of SCC was diagnosed. Combined chemotherapy with irinotecan and cisplatin has dramatically reduced metastatic tumors, and it was concomitantly effective for SIADH. This case demonstrates that esophageal SCC could induce SIADH as a paraneoplastic syndrome and that the above combined chemotherapy was feasible and effective.     

Brain metastasis from stage I esophageal squamous cell carcinoma after surgery: a case report

Esophageal cancer rarely metastasizes to the brain. The authors experienced a case of esophageal carcinoma which metastasized to the cerebellum as the first presentation. A 61-year-old man was identified as having esophageal carcinoma by esophagogastroduodenoscopy during a medical checkup. Subtotal esophagectomy with dissection of 3 regional lymph nodes was performed. The tumor was 30?×?20?mm² in size, and was revealed to be a moderately differentiated squamous cell carcinoma. The pathological finding was T1b(SM)N0M0 stage?I. Fourteen months after the surgery, the patient complained of nausea. Brain magnetic resonance imaging (MRI) showed a cystic tumor of 42?×?28?×?28?mm³ in size in the central cerebellum. No other metastasis was pointed out. A craniotomy for brain tumor resection was performed, and the histopathological examination revealed that it was a metastatic carcinoma from the esophagus. Gamma knife therapy was added. The patient died of cerebellar metastasis recurrence 24?months after the first surgery.     

Amelanotic primary malignant melanoma of the esophagus: report of a case treated with minimally invasive esophagectomy and adjuvant chemotherapy

Amelanotic primary malignant melanoma of the esophagus (PMME) is extremely rare. We report a case of amelanotic PMME that was accurately diagnosed and subsequently treated by radical resection with adjuvant chemotherapy. A 69-year-old woman was admitted to our hospital because of dysphagia. Endoscopic examination revealed a tumor without pigmentation in the upper thoracic esophagus, and melanosis in the lower thoracic esophagus. Tumor biopsy showed proliferation of malignant spindle cells with conspicuous nucleoli. Immunohistochemically, the tumor cells were positive for melanosomes (HMB45). The tumor was diagnosed as PMME. Positron emission tomography and computed tomography showed accumulation of the tracer only in the primary lesion. The preoperative diagnosis according to the extent of the tumor, whether cancer cells have spread to lymph nodes, and whether metastasis has occurred (TNM) classification was malignant melanoma in the upper third of the esophagus, T2N0M0 stage IIA. The patient underwent minimally invasive video assisted esophagectomy in the prone position with three-field lymph node dissection. On the resected specimen, the malignant cells were positive for HMB45, KIT, and melan-A. Masson-Fontana staining demonstrated no melanin pigmentation. The patient was diagnosed with amelanotic PMME and received adjuvant chemotherapy, consisting of dacarbazine, nimustine, cisplatin, and tamoxifen. The patient showed no systemic metastasis, and is alive 18 months after the operation with no evidence of recurrence.     

A Phase II Trial of Irinotecan and Cisplatin in Patients with Metastatic Neuroendocrine Tumors

The role of systemic chemotherapy in the treatment of patients with metastatic neuroendocrine tumors is controversial. While combination regimens containing cisplatin and etoposide have activity against more aggressive neuroendocrine tumor variants, such regimens appear to have little efficacy in patients with well-differentiated neuroendocrine tumor subtypes. The combination of irinotecan and cisplatin is active both against small cell lung cancer and in upper gastrointestinal malignancies but has not been prospectively evaluated in patients with metastatic neuroendocrine tumors. We therefore assessed the efficacy of an irinotecan/cisplatin combination in patients with this disease. Eighteen patients with metastatic neuroendocrine tumors (excluding small cell carcinoma) were treated with irinotecan, 65 mg/m², and cisplatin, 30 mg/m², administered weekly for 2 of every 3 weeks. Patients were followed for evidence of toxicity, response, and survival. The toxicities associated with this regimen were mild and included myelosuppression, nausea, and diarrhea. Only one radiologic response was observed among four patients with poorly differentiated neuroendocrine tumors. No radiologic responses were observed in 14 patients with well-differentiated tumors. The median overall survival duration of patients treated with this regimen was 11.4 months. We conclude that while the combination of irinotecan and cisplatin may have activity in aggressive neuroendocrine tumor subtypes, this combination is inactive in patients with well-differentiated neuroendocrine tumors. This work received financial support from Pfizer Corporation, M. H. Kulke is supported in part by NIH grants K23 CA 093401 and K30 HL04095 and gifts from Dr. Raymond and Beverly Sackler, the Stephen and Caroline Kaufer fund for neuroendocrine tumor research, and the Caring for Carcinoid Foundation.     

Complete cure of metastatic gastric cancer treated with combination chemotherapy using S-1

A 65-year-old man had gastric cancer with liver and lung metastases, and received three cycles of FLEP (5-fluorouracil, leucovorin, etoposide, cisplatin) chemotherapy on June, 2001. The primary lesion became scar ulceration and adenocarcinoma tissue was recognized by biopsy pathologically. The lung metastases and lymph node metastases disappeared. The metastatic liver lesion decreased more than 95% in size and was judged partial response. Thereafter he received only oral administration of 100mg S-1 (70mg/m2). The metastatic liver lesion was shown to have disappeared on CT of the abdomen and was judged complete response, on June, 2002. Since then, he was receiving S-1 and continued to be complete response for two and half years until June, 2004. The clinical trial of S-1 as an adjuvant therapy for patients with advanced gastric cancer, who underwent curative resection, is ongoing in a multicenter study. Although the outcome is still unknown, the effect of S-1 for adjuvant chemotherapy may be also promising. We think that S-1 is useful as an adjuvant therapy and maintenance therapy of prior treatment including surgical resection.     

A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus,gastroesophageal junction,and gastric cardia

PURPOSE: The incidence of adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia has been rising in the face of limited treatment options for patients with metastatic disease. With the emergence of data to suggest that single agent docetaxel and irinotecan carry antineoplastic effects in this setting, we determined the response rate of these agents when given in combination. PATIENTS AND METHODS: Forty-six patients with metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia were evaluated. Patients received docetaxel 50 mg/m2/d and irinotecan 130 mg/m2/d intravenously at 21-d intervals with a tumor assessment after 2 cycles. Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d intravenously at 21-d intervals. RESULTS: The response rate for the entire cohort was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses. Five of these 12 responses were observed in patients treated at the higher chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia and fevers, a dose reduction was incorporated into the protocol, and the remainder of the cohort was treated at the lower dose. All except 4 of the 15 observed grade 4 toxicities occurred at the higher dose, and these toxicities included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in addition to neutropenia and fevers. There were no grade 5 toxicities. The median survival for the entire cohort was 7.3 mo. CONCLUSION: The combination of docetaxel and irinotecan provides modest antineoplastic activity among patients with adenocarcinoma of the esophagus, esophagogastric junction, and gastric cardia. Doses of docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d at 21-d intervals provide an acceptable safety profile, but higher doses appear to result in unacceptable toxicity.