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A 59-year-old man presented with a 6-week history of pain in the thumb.

He also reported having a cough, weight loss, and a history of heavy smoking. Physical examination revealed swelling, redness, and tenderness over the first right metacarpal and a mass (10 cm in diameter) fixed to the thorax. Laboratory tests revealed a C-reactive protein level of 123 mg per liter and a leukocyte count of 34109 per liter. A radiograph of the hand showed osteolysis of the first metacarpal (Panel A, arrow), and a chest radiograph showed a solid mass of the thoracic wall expanding into the subpleural space (Panel B, long arrow) and a tumor in the hilus of the right lung (Panel B, short arrow). A specimen of the metacarpal lesion obtained through needle aspiration was negative for bacteria. The final diagnosis was lung adenocarcinoma with osseous lesions of the hand and ribs. The patient received palliative care.

In a recent study that analyzed data from the GeoSentinel Surveillance Network (which consists of 42 specialized travel or tropical-medicine sites located around the world) on 25,867 returned travelers over a 9-year period (from 1996 to 2005), of the 2902 clinically significant pathogens that were isolated, approximately 65% were parasitic, 31% bacterial, and 3% viral. Six organisms (giardia, campylobacter, Entamoeba histolytica, shigella, strongyloides, and salmonella species) accounted for 70% of the gastrointestinal burden.

Clinical Pearls - What are the clinical manifestations of Giardia lamblia infection? Giardia lamblia (also called Giardia intestinalis or Giardia duodenalis) is highly contagious (ingestion of as few as 10 to 25 cysts may cause disease), with persons becoming infected through the ingestion of cysts in contaminated food or water. However, person-to-person transmission is possible. The clinical manifestations range from mild intestinal problems that resolve spontaneously to complex symptoms that last up to several weeks, such as protein-losing enteropathy, postinfectious fatigue, chronic diarrhea, abdominal pain, nausea, and weight loss. In children, the disease can cause growth and cognitive impairment as a result of iron and micronutrient deficiencies. - What is the natural history, typical clinical course, and methods to diagnose amebiasis? E. histolytica and E. moshkovskii are pathogenic in humans, causing amebiasis. The parasite is acquired through the ingestion of food or water contaminated with fecal cysts. After it has been ingested, the cyst emerges in the terminal ileum as an active trophozoite, which migrates to the colon where it colonizes the mucus layer. Invasion may take days to years after the initial infection and is characterized by fever, abdominal pain, and bloody dark-brown diarrhea. However, 90% of cases are asymptomatic and self-limiting. Symptomatic disease occurs when trophozoites invade the mucosa and submucosa, and some trophozoites enter the portal circulation and disperse to the liver and other soft organs. Disease of the right

colon is common and is associated with the following serious complications: strictures, rectovaginal fistulas, bowel obstruction, toxic megacolon, perforation, peritonitis, and death. Only 1% of clinical cases of amebiasis involve the liver. Several stool antigen assays specific for E. histolytica are commercially available to make an accurate diagnosis of intestinal or hepatic amebiasis on the basis of the Gal/GalNAc lectin. Microscopic examination of the stool is no longer performed for amebiasis because of its low sensitivity and specificity; with microscopy, it is easy to confuse E. histolytica with the identically appearing and much more common nonpathogenic parasite E. dispar.

Morning Report Questions Q: What are the manifestations of strongyloides infection? A: Strongyloides stercoralis (threadworm) is the most dominant species causing infection in humans. Third-stage filariform larvae penetrate the skin (usually the foot) of the human host, reach the lungs via the blood circulation, and enter respiratory pathways. From there, they migrate upward through the trachea, are swallowed, and finally reach the small intestine, where they mature into adult egg-laying female worms. Female worms embed in the submucosa of the duodenum, where they produce dozens of eggs per day. These hatch in the gut lumen, and the first-stage rhabditiform larvae either are passed out in the feces and develop into infective third-stage larvae or remain in the gastrointestinal tract of the human host and start a new infection cycle (autoinfection). Autoinfection can result in persistent infection for decades. More than 50% of patients with a chronic infection are asymptomatic. For a subset of patients with disease, the symptoms include erythematous pruritus, skin eruptions, larva currens, abdominal pain, diarrhea, and weight loss. In travelers presenting with eosinophilia or elevated IgE levels, strongyloides should be considered in the differential diagnosis. In immunocompromised persons, strongyloidiasis can cause a hyperinfection syndrome owing to the reproductive capacity of the parasite inside the host. In cases of disseminated disease, the hyperinfection syndrome can be associated with a mortality rate of close to 90%. Q: What is the natural history and clinical presentation of schistosomiasis? A: Schistosomiasis is a common chronic helminth disease caused by intravascular parasitic schistosoma trematode worms. The three most important species in humans are Schistosoma hematobium, S. mansoni, and S. japonicum. Schistosome transmission requires the contamination of water by egg-containing feces or urine, a specific freshwater snail as intermediate host, and human contact with water inhabited by the intermediate host snails. Schistosome larvae (cercariae) emerge from the snails and penetrate human skin, thereby instigating infection. A maculopapular eruption consisting of discrete

erythematous, raised lesions that vary in size from 1 to 3 cm may arise at the site of percutaneous penetration by the cercariae. Patients with acute schistosomiasis, or Katayama fever, which usually begins with the deposition of schistosome eggs into host tissues, can present with fever, malaise, myalgia, fatigue, nonproductive cough, diarrhea (with or without blood), hematuria (S. hematobium), and right-upper-quadrant pain. A skin reaction may develop within a few hours after infection in migrants or tourists infected for the first time, although a rash may appear as much as a week later. In cases of infection with S. mansoni and S. japonicum, a T-cell-mediated granulomatous reaction to schistosome eggs leads to fibrosis and chronic disease of the human liver, resulting in the development of severe hepatosplenic schistosomiasis; in cases of S. hematobium, this reaction leads to fibrosis and calcification of the bladder and ureters, which can result in bladder cancer.

TEACHING TOPIC Vaginal Bleeding CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL, Case 14-2013: A 70-Year-Old Woman with Vaginal Bleeding, (https://www.nejm.org/action/doSecureKeyLogin?uuid=7676846&dateTime=2013051 80000&key=0rSCw5hWJYFuQ6MwpDd%2FHHb9duCvOf9ptOHi%2FlfDIO0%3D&uri=/doi/full/ 10.1056/NEJMcpc1209276?query=BUL) R.T. Penson and Others CME Exam

The underlying cause of abnormal vaginal bleeding is age-dependent. Ten percent of premenopausal women with abnormal bleeding have a malignant tumor. In contrast, 75% of women over 70 years of age with postmenopausal bleeding have cancer, and the risk rises with age in postmenopausal women.

Clinical Pearls - What is the typical presentation of carcinosarcoma of the uterus? Postmenopausal vaginal bleeding is the most common manifestation of carcinosarcoma. Patients with carcinosarcoma also frequently present with the classic triad of painful postmenopausal bleeding, an enlarged uterus, and prolapsed tumor visible at the cervical os. - Under what circumstances is surgery not the primary treatment for uterine cancer? In only a few circumstances is surgery not the primary treatment for uterine cancer -- when there is a desire to preserve fertility, high operative risk, and unresectable disease. The goals of surgical treatment are excision of all disease with at least a 1-cm margin and staging of the tumor. The initial spread is to regional lymph nodes;

therefore, standard treatment is a radical total abdominal hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. Endometrial cancers have several potential patterns of spread: direct invasion and expansion of the primary tumor, lymphatic invasion, hematogenous spread, and intraperitoneal dissemination. Because metastasis is common, preoperative combination positron-emission tomography and computed tomography (PET-CT) and a meticulous exploratory laparotomy are standard practice.

Morning Report Questions Q: What features affect the overall prognosis of patients with carcinosarcoma? A: Diagnostic features of malignant mixed mullerian tumor (carcinosarcoma) include the finding of a biphasic malignant tumor that is composed of high-grade carcinoma (most commonly endometrioid or serous) and sarcoma and is typically homologous (arising from mesenchymal tissue normally found in the uterus), although in up to 50% of cases, the tumor has a heterologous component (most commonly rhabdomyosarcoma or chondrosarcoma). There is no transition between the two components. Tumor stage is the most important prognostic factor in these tumors, although histologic features also affect outcome. The finding of serous or clear-cell carcinoma is associated with a more aggressive course. Sarcomatous components adversely affect the overall prognosis of patients with stage I tumors (5-year survival is 30% among patients with heterologous elements as compared with 80% among patients with homologous elements); myometrial and lymphovascular invasion are also associated with a poor prognosis. Q: What are the treatment options for carcinosarcoma? A: Carcinosarcoma is thought to require multiple methods of treatment. Radiation therapy has been shown to reduce the rates of local recurrence in the pelvis but does not increase the survival benefit among patients with carcinosarcoma. Adjuvant chemotherapy has not been shown to have an effect on recurrence rates or progression-free or overall survival among patients with carcinosarcoma. Hormonal therapy is of no use, since estrogen and progesterone receptors do not control tumor growth, even though they are typically present in patients with carcinosarcoma.

QUOTE OF THE WEEK "In our study, more bleeding events of WHO grade 2, 3, or 4 occurred in the no-prophylaxis group than in the prophylaxis group, with a significant increase in the number of days with bleeding events of WHO grade 2, 3, or 4 and a decreased time to the first bleeding event of WHO grade 2, 3, or 4. Virtually all these bleeding episodes were WHO grade 2; only 7 of the 600 patients in the study had a bleeding event of WHO grade 3 or 4. More patients in the no-prophylaxis group

had bleeding events of WHO grade 3 or 4, but this difference was not significant. The results of our study support the need for the continued use of prophylaxis . . . ." S.J. Stanworth and Others, Original Article, "A No-Prophylaxis