Small bowel metastases in non-small cell lung cancer

A case report of stage I adenocarcinoma of the lung in a 43-year-old female with recurrence in the small bowel and liver 11 months after pneumonectomy is presented. In addition, a cohort of 733 patients with non-small cell lung cancer (NSCLC) in all pretreatment stages (stages I-IV) with a total of 218 autopsies are evaluated, and the literature on the topic is reviewed, in order to define the frequency of metastases from NSCLC to the small bowel. There were 10 cases with and 208 cases without small bowel involvement among 218 consecutive autopsies (autopsy rate, 30%,). The frequency of small bowel involvement was 4.6% (95%, confidence interval, 2.2-8.3%), and all were in patients with adenocarcinoma of the lung. All patients with small bowel involvement at autopsy had also other concurrent metastatic sites as well and the following were the most frequent: adrenals (90%, of cases), mediastinal lymph nodes (80%), liver (70%), pleura (60%), contralateral lung (60%), bones (60%), and brain (50%). Significantly more metastatic sites were observed in patients with than without small bowel involvement, both totally (P = 0.0001) and with respect to number of extrathoracic (P = 0.0001) and intrathoracic (P = 0.01) metastatic sites. In conclusion, small bowel involvement in NSCLC is relatively infrequent. As a unique finding, over-representation of patients with poorly differentiated tumors (P = 0.03) and patients having solid carcinoma with mucus formation after histologic subtyping (P = 0.04) among cases with small bowel involvement was observed. This indicates, that small bowel metastases is an epiphenomonen of NSCLC tumors with certain biological characteristics, although as yet undiscovered, which leads to a high metastatic potential. If such biological characteristics could be identified, they may be used in the selection of treatment options for individual patients, e.g. indicating a need for adjuvant or neoadjuvant chemotherapy in addition to surgery in resectable or marginally resectable NCSLC patients.     

Management of small bowel adenocarcinoma

Small bowel adenocarcinoma is a relatively rare malignancy. Only limited information is available on the incidence, prognosis, and role of chemotherapy in the treatment of this disease. We present a review of currently available clinical data to assist the practicing oncologist in the treatment of these patients. Approximately 5,300 new cases and 1,100 deaths from small bowel adenocarcinoma are reported annually in the United States. Increased incidence is seen in patients with Crohn's disease, hereditary nonpolyposis colorectal cancer, and familial adenomatouspolyposis. Factors associated with poor prognosis are age > 75 years, lack of surgical resection, advanced stage, and tumor arising in the duodenum. The median survival of patients with localized, locally advanced, and metastatic disease is 50.1, 22.2, and 8.6 months, respectively. Few data exist on the use of (neo)adjuvant or palliative chemo(radio)therapy in this setting. Fluorouracil (5-FU)based chemotherapy, as a single agent or in combination with others, has been used in most case series. Duodenal adenocarcinoma accounts for more than 50% of all cases of small bowel adenocarcinoma. Resectability is the key prognostic factor, along with age, performance status, tumor location, and presence of distant metastasis. Although the activity of 5-FU-based regimens has been documented, the assessment of clinical benefit is hindered by the lack of prospective, randomized data.     

Duodenal Carcinoma Diagnosed by Hypotonic Duodenography and Small Bowel Enema

A case of adenocarcinoma of the third part of the duodenum is described. Presenting symptoms were abdominal pain and iron deficiency anaemia. Two barium meal series failed to adequately demonstrate the lesion, which was finally diagnosed by combined hypotonic duodenography and small bowel enema.     

Resection of Small Bowel Adenocarcinoma Liver Metastasis Combined with Neoadjuvant and Adjuvant Chemotherapy Results in Extended Disease-Free Period—A Case Report

Small bowel adenocarcinoma (SBA) is a very rare tumor entity but occurs in up to 5% of patients suffering from familiar adenomatous polyposis (FAP). Because of nonspecific symptoms, diagnosis is usually made with delay, which contributes to high rates of metastatic disease at the time of diagnosis. The overall prognosis of SBA is poor with 5-year survival rates of 15–35%. For localized disease, complete surgical resection is the treatment of choice, whereas systemic chemotherapy is deemed indicated in tumors with metastatic spread. The optimal regimen has not been defined as yet. In October 2001, a 51-year-old woman with attenuated FAP, that had total proctocolectomy in 1994 was diagnosed with a jejunal adenocarcinoma. She subsequently underwent small bowel resection. Because a computed tomography (CT) scan in April 2002 revealed multiple liver metastases, chemotherapy with nine cycles FOLFOX6 was initiated. Afterwards, a small residual lesion in segment VIII was seen in CT scan but could not be identified by PET and at laparotomy in November 2002. In December 2003, again, a lesion was detected in S VIII. This solitary residual liver metastasis was resected in January 2004. Postoperatively, the patient received adjuvant chemotherapy with three cycles (with six applications in each cycle) 5-fluorouracil/folinic acid/irinotecan according to the AIO protocol. To date, more than 3 years after liver resection, the patient is still in complete remission and undergoes regular restaging investigations. Resection of liver metastases from SBA combined with neoadjuvant and adjuvant chemotherapy can result in extended disease-free survival and should undergo further investigation.     

Epoetin alfa and intravenous iron sucrose to treat severe anemia in a patient with chronic radiation enteropathy

We report the case of a patient with a severe chronic radiation enteropathy. She had been dependent on red cell transfusions for many years. On admission, she displayed anemia (8.6 g/dL) resulting from both inadequate EPO production and a functional iron deficiency. A 3-wk IV iron sucrose treatment (200 mg once weekly) resulted in an increased reticulocyte count, but did not raise the hemoglobin (Hb) level. The adjunction of epoetin alpha (10,000 IU three times a week) made it possible to reach the normal range (12.9 g/dL) after a 17-wk treatment. As the anti-anemic treatment discontinued, the Hb level decreased to 11.1 g/dL within 2 wk. Giving EPO again (10,000 IU twice a week) failed to maintain the Hb level, which dropped under basal values (7.8 g/dL). In contrast, a second combination EPO/iron sucrose did restore a normal Hb level and maintained it. This case report supports the combination of EPO and IV iron supplementation in patients with anemia of chronic disease and either an impaired iron absorption or intolerance to oral iron.     

Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature

From post-mortem case records, the small bowel is the most frequent site of metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder involvement occurring in 15% of cases. However, few cases have been documented in living patients and, when found, are associated with a poor prognosis. We report a case of a Caucasian man with metastatic gallbladder and small bowel melanoma from an unknown primary. He presented with diffuse abdominal pain, vomiting and progressive asthenia; subsequently, intestinal obstruction occurred. He had no past history of malignant melanoma and the primary lesion was not found. The multiple lesions, together with the absence of mucosal involvement in both the gallbladder and small bowel, led us to believe that the lesions were metastatic deposits from a probably regressed primary melanoma. It should be emphasized that surgical resection for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed safely. The clinical presentation, diagnosis, treatment and prognosis of previously reported cases of melanoma metastatic to the gallbladder and small bowel are reviewed. The differences between primary and secondary GI tract melanomas are also discussed.     

A case of lung cancer with skin metastases responding to erlotinib

The patient was a 67-year-old female with left lung adenocarcinoma T2N2M1(brain).She received systemic chemothera- py(cisplatin/docetaxel)and stereotactic radiosurgery.She showed a partial response and PET-CT evidenced no new metastasis. So she underwent left pneumonectomy(LtUt S6S8, adenocarcinoma mixed type pT2pN0).One month later, a small nodule appeared on the dorsal surface of her left hand.Excisional biopsy showed adenocarcinoma metastasis of lung cancer. Soon afterward, multiple skin nodules appeared and were diagnosed multiple skin metastases.Erlotinib was administered. After two weeks, skin metastases were reduced significantly, and she was treated with erlotinib on an outpatient basis for 5 months.This is, to our knowledge, the first case in which skin metastases of lung cancer responded to erlotinib.Our experience suggests erlotinib administration at an early treatment has fewer side effects in therapy for metastatic lung cancer.     

Role of iron in optimizing responses of anemic cancer patients to erythropoietin

Approximately 50% of cancer patients develop anemia. In the past, the only available treatment option for these patients was transfusion. Since the late 1980s, recombinant human erythropoietin (rHuEPO, epoetin alfa [Epogen, Procrit]) has provided a treatment alternative. Controlled clinical trials have shown that rHuEPO increases hemoglobin and hematocrit levels and reduces the need for transfusions in patients with cancer-related anemia. These controlled trials have suggested (as larger, uncontrolled studies) that the improvements in hemoglobin are associated with increases in energy level, functional status, and overall quality of life. However, only about 50% of patients respond adequately to usual doses of rHuEPO. In the chronic renal failure population, functional iron deficiency is the most common cause of inadequate response to rHuEPO. It has been hypothesized that functional iron deficiency may also occur in cancer patients receiving rHuEPO and may account for the lack of response in up to half of those patients. Studies in renal failure patients have shown that administration of intravenous iron can correct functional iron deficiency more effectively than oral iron and may improve response to rHuEPO. Intravenous iron also reduces the total amount of rHuEPO needed to normalize hematocrit and hemoglobin levels, thereby reducing treatment costs. Ongoing clinical trials are evaluating whether IV iron can also improve rHuEPO responsiveness in patients with cancer-related anemia.     

Small bowel metastases from primary carcinoma of the lung

Although about half of all patients with carcinoma of the lung have metastases at initial presentation, only nine with metastases to the small bowel have been previously reported. This study was performed to determine the incidence of occult and clinically apparent metastases of lung cancer to the small intestine. Small bowel metastases were present in 46 of 431 patients with primary lung cancer who underwent autopsy during an 11-year period. These patients had an average of 4.8 metastatic sites. Small bowel metastases were present in 12 of 31 (39.0%) patients with large cell carcinoma, 13 of 108 (12.3%) with adenocarcinoma, six of 73 (8.0%) with small cell carcinoma, 15 of 199 (7.5%) with squamous cell carcinoma, and none of 20 with undifferentiated carcinoma. During the same interval, six of 78 patients undergoing small bowel resection for metastatic tumor had lung cancer primaries. Among the nine previously reported clinical cases of small bowel metastases and the six in this series, 14 were operated upon for small bowel perforation and one for obstruction. Nine patients died perioperatively, and no patient survived longer than 16 weeks. These data demonstrate that the incidence of lung cancer metastases to the small bowel is higher than is clinically apparent. Lung cancer metastases to the small bowel often present as intestinal perforation and indicate a poor prognosis; surgery is indicated for palliation.     

The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease

Celiac disease is associated with an increased risk of small bowel adenocarcinoma. The aims of this study were to investigate the molecular basis, assess outcomes, and identify clinicopathologic characteristics of small bowel adenocarcinoma in celiac disease. Retrospective case control cohort study of all celiac disease patients treated at our institution for small bowel adenocarcinoma and matched control patients with sporadic small bowel adenocarcinoma from July 1960 to November 2002. Mismatch repair (MMR) status was accessed by testing tissue for microsatellite instability (MSI) and for hMLH1 and hMSH2 protein expression. Over a 40-year time period, 18 patients with small bowel adenocarcinoma and celiac disease were treated at the Mayo Clinic. One celiac disease patient was excluded. High-frequency MSI (MSI-H) was identified in 8 of 11 (73%) and 2 of 22 (9%) available small bowel adenocarcinoma specimens in the celiac disease and control groups, respectively. In the celiac disease group, MSI-H was associated with loss of hMLH1 and hMSH2 in 6 and 1 specimens, respectively. Loss of hMLH1 occurred in both control tumors. Stage was associated with celiac disease status (P = 0.018), and 78% of controls were stage III or IV compared with 47% of celiac disease patients. Overall, survival was better (P = 0.025) in the celiac disease group compared with stage-matched controls. Celiac disease patients with small bowel adenocarcinoma had a high incidence defective MMR (73%) compared with controls and had better survival compared with stage-matched controls. In addition, celiac disease patients presented more frequently with early-stage small bowel adenocarcinoma. The better survival and earlier presentation of small bowel adenocarcinoma in celiac disease appears to be biologically associated with defective MMR.     

Behavioral alterations in iron deficiency

This review has examined recent evidence from human studies that iron deficiency adversely affects behavior by impairing cognitive function, producing noncognitive disturbances, and limiting activity and work capacity. The body of research taken as a whole provides increasingly persuasive arguments for intensifying efforts to prevent and treat iron deficiency anemia. Cognitive Function. There is reasonably good evidence that mental and motor developmental test scores are lowered among infants with iron deficiency anemia. Although the research on cognitive function in iron-deficient older children and adults is sparse and diverse, it suggests that there may be alterations in attentional processes associated with iron deficiency. Iron therapy has not yet been shown effective in completely correcting the observed disturbances. Although some aspects of cognitive function seem to change with iron therapy, lower developmental, IQ, and achievement test scores have still been noted after treatment. Noncognitive Disturbances. A variety of noncognitive alterations during infant developmental testing has also been observed, including failure to respond to test stimuli, short attention span, unhappiness, increased fearfulness, withdrawal from the examiner, and increased body tension. Exploratory analyses suggest that such behavioral abnormalities may account for poor developmental test performance in infants with iron deficiency anemia. These studies indicate the fruitfulness of examining noncognitive aspects of behavior, such as affect and activity, in addition to specific cognitive processes. Activity and Work Capacity. There has been a steady accumulation of evidence that iron deficiency anemia limits maximal physical performance, submaximal endurance, and spontaneous activity in the adult, resulting in diminished work productivity with attendant economic losses. The mechanisms underlying these effects, the extent to which anemia or iron deficiency separate from anemia is responsible, and the counterpart in infants and children remain to be established.     

Primary malignant melanoma of the small bowel: a case report and review of the literature

Although small bowel involvement by malignant melanoma is most frequently metastatic, a primary origin at this site has been reported in rare cases. The biological and clinical features of these cases have not yet been summarized. Here, another case of small bowel melanoma is described, and a review of the existing literature is given. An 81-year-old man presented with anemia and gastrointestinal bleeding. A tumor of the ileum was detected by video capsule endoscopy and removed by segment resection. Histological examination revealed a malignant melanoma of the ileum. Another primary site could be excluded by clinical and radiographic examination. The patient felt well five months after surgery. Only 18 cases of primary small bowel melanoma (including the present one) have been reported to date. A literature review reveals that this rare neoplasm is associated with a slight predilection for the male gender, a predilection for the ileum and a poor prognosis.     

The Royal Marsden experience of a small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil.

The purpose of this study was to review the efficacy of a protracted venous infusion of 5-fluorouracil (PVI 5-FU)-based chemotherapy in advanced small bowel adenocarcinoma. Data on all patients with small bowel malignancy who were seen at a single institution over a 5-year period were retrieved from the gastrointestinal unit and hospital databases, and these cases were reviewed. Eight patients with advanced small bowel adenocarcinoma received PVI 5FU-based chemotherapy. The overall response rate in assessable patients was 37.5% (3/8). The median overall survival was 13 months (range 1-28), and progression-free survival was 7.8 months (range 0-15). Overall, the treatment was well tolerated and symptomatic benefit was seen. In conclusion, PVI 5-FU has activity in this disease. This should be assessed either as a single agent or as part of a combination regimen such as epirubicin/cisplatin/PVI FU (ECF) in a multicentre randomized study.     

A case report of primary adenocarcinoma of small intestine

This is an account of a case of primary adenocarcinoma of the small intestine with peritoneal dissemination successfully treated with chemotherapy. A 64-year-old woman was admitted with a complaint of severe abdominal distension. Abdominal computerized tomography revealed a bowel obstruction with tumor and the remarkable small bowel dilation of oral side of tumor. The tumor was found at surgery to be at the ileum 15 cm proximal from the ileocecal region. Peritoneal dissemination was recognized around the ileocecal region, so ileum partial resection was performed for the primary cancer lesion and dissemination region. Pathological diagnosis of the resected specimen was adenocarcinoma with lymph nodes metastasis. The peritoneal dissemination consisted of metastatic adenocarcinoma from small intestine. After an operation, internal use of S-1 was performed as adjuvant chemotherapy. But a recurrent lesion at the ovarium was detected 6 months after surgery. The patient was subsequently treated with resection of the ovarium. For lung metastasis, the combination chemotherapy with mFOLFOX6 + bevacizumab was administered. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed as advanced cancer because of few characteristic symptoms. So carcinoma of the small intestine usually has a poor prognosis.     

Successful treatment for solitary brain metastasis from alveolar soft part sarcoma

Following pulmonary metastases, alveolar soft part sarcoma has an unexplained predisposition to metastasize to the brain. Herein, a case of alveolar soft part sarcoma solitarily metastatic to the brain is described. A 23-year old female underwent the resection of alveolar soft part sarcoma from the right thigh. Three years after the surgery, a brain tumor was resected and pathology proved it was a metastatic alveolar soft part sarcoma. She is currently alive and well 6 years after brain surgery. Our report suggests that surgical resection for solitary brain metastasis from alveolar soft part sarcoma is an effective treatment modality.     

Irinotecan-based combination chemotherapy for metastatic small intestinal adenocarcinoma

Metastatic small intestinal adenocarcinoma (SIA) is rare among digestive tract malignancies, and a standard therapy has yet to be established. The present study described a patient who was treated with irinotecan-based chemotherapy. A 67-year-old woman with a long history of anemia was diagnosed as having SIA using small bowel endoscopy. Tumor invasion of the mesentery and multiple metastases to the lungs and peritoneal lymph nodes were detected. Nine courses of chemotherapy, each consisting of bolus infusion of 5-fluorouracil at 500 mg/m(2), plus infusion of irinotecan at 100 mg/m(2) with l-leucovorin at 20 mg/m(2) on days 1, 8 and 15, were administered at 4-weekly intervals postoperatively. After two courses, the metastatic nodules in the lungs showed a decrease in number and size, and this response continued for over 6 months. Adverse events were manageable during this period. The patient succumbed to the disease 12 months after the initial diagnosis. The present results therefore suggest that irinotecan-based chemotherapy is a potential treatment for metastatic SIA.     

Serum levels of soluble transferrin receptor correlate with severity of disease but not with iron stores in patients with malignant lymphomas.

Soluble transferrin receptor levels in serum (s-sTfR) may be useful in differentiating between iron deficiency anemia and anemia of chronic disease. However, there is both theoretical and clinical evidence for elevated s-sTfR levels in patients with various hematological malignancies. In the present study, routine bone marrow aspirations were performed in 82 patients with malignant lymphomas (63 with non-Hodgkin's lymphoma and 19 with Hodgkin's disease). Smears were stained for evaluation of iron stores and graded. Patients were also given a disease score based on bone marrow morphology, erythrocyte sedimentation rate and LDH. s-sTfR levels correlated better with disease score [partial Spearman rank correlation coefficient (r(s)) controlled for iron stores was 0.51 (95% confidence interval 0.39-0.65); p < 0.001] than with iron stores [partial r(s) controlled for disease score was -0.25 (95% confidence interval -0.44 to -0.03); p = 0.027]. This study showed elevated s-sTfR levels in patients with malignant lymphomas without any signs of iron deficiency anemia. The diagnosis of iron deficiency anemia should not be established upon the basis of s-sTfR alone in this group of patients.     

Successful treatment of metastatic pancreatic adenocarcinoma with combination chemotherapy regimens

Pancreatic adenocarcinoma is the fourth leading cause of cancer deaths in the United States. Current 5-year survival is less than 4%, highlighting the dire need for effective treatment. We report the case of a 41-year-old woman who was diagnosed with advanced metastatic well-to-moderately differentiated mucinous adenocarcinoma of the pancreas, involving the liver and peritoneal cavity. She agreed to receive novel combination chemotherapy rather than the standard-of-care treatment. This patient was treated with three unique combination regimens. Complete response of multiple liver and peritoneal metastases and reduction in size with increasing calcification of the pancreatic mass occurred in this patient after 18 months of treatment. This report documents the individual response to effective and well-tolerated treatment regimens integrating available drugs.