Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases; however, its inherent high toxicity has led to the development of more powerful and safer thalidomide analogs, including lenalidomide and pomalidomide. These are new generation IMiDs that exhibit direct antitumor activity as well as anti-inflammatory/immunomodulatory properties, and are FDA-approved for the treatment of several hematological malignances. Here we investigated the potential therapeutic effects of lenalidomide and pomalidomide in several experimental murine models of autoimmune/inflammatory diseases: 2,4,6-trinitrobenzene sulfonic acid- and dextran sulfate sodium-induced inflammatory bowel disease and type II collagen-induced arthritis. Lenalidomide displayed a strong therapeutic effect in all these models of autoimmune/inflammatory diseases, while the effect of pomalidomide was less pronounced. In vitro experiments confirmed the immunosuppressive effect of both IMiDs on the proliferative response of stimulated human lymphocytes and on the balance of secreted cytokines toward an anti-inflammatory profile. We conclude that lenalidomide may offer a therapeutic opportunity against autoimmune/inflammatory diseases.
Arthritis, Experimental ; Arthritis, Rheumatoid* ; Cytokines ; Dextran Sulfate ; Humans ; In Vitro Techniques ; Inflammatory Bowel Diseases* ; Lymphocytes ; Models, Theoretical* ; Thalidomide ; Therapeutic Uses

Background/Aims: Per oral endoscopic myotomy (POEM) has been increasingly used for achalasia in Latin America, where Chagas disease is prevalent, and this makes POEM more challenging. The aim of this study was to determine the learning curve for POEM in Latin America. Methods: Patients undergoing POEM in Latin America with a single operator were included from a prospective registry over 4 years. Non-linear regression and cumulative sum control chart (CUSUM) analyses were conducted for the learning curve. Results: A total of 125 patients were included (52% male; mean age, 59 years), of which 80 had type II achalasia (64%), and 38 had Chagas disease (30%). The average pre-procedure and post-procedure Eckardt scores were 6.79 and 1.87, respectively. Technical success was achieved in 93.5% of patients, and clinical success was achieved in 88.8%. Adverse events occurred in 27 patients (22%) and included bleeding (4 patients), pneumothorax (4 patients), mucosal perforation (13 patients), mediastinitis (2 patients), and leakage (4 patients).
The CUSUM chart showed a median procedure time of 97 min (range, 45-196 min), which was achieved at the 61st procedure. Procedure duration progressively decreased, with the last 10 procedures under 50 min approaching a plateau (p-value <0.01). Conclusions Mastering POEM in Latin America requires approximately 61 procedures for both POEM efficiency and to accomplish the procedure within 97 minutes.

Background/Aims: Per oral endoscopic myotomy (POEM) has been increasingly used for achalasia in Latin America, where Chagas disease is prevalent, and this makes POEM more challenging. The aim of this study was to determine the learning curve for POEM in Latin America. Methods: Patients undergoing POEM in Latin America with a single operator were included from a prospective registry over 4 years. Non-linear regression and cumulative sum control chart (CUSUM) analyses were conducted for the learning curve. Results: A total of 125 patients were included (52% male; mean age, 59 years), of which 80 had type II achalasia (64%), and 38 had Chagas disease (30%). The average pre-procedure and post-procedure Eckardt scores were 6.79 and 1.87, respectively. Technical success was achieved in 93.5% of patients, and clinical success was achieved in 88.8%. Adverse events occurred in 27 patients (22%) and included bleeding (4 patients), pneumothorax (4 patients), mucosal perforation (13 patients), mediastinitis (2 patients), and leakage (4 patients).
The CUSUM chart showed a median procedure time of 97 min (range, 45-196 min), which was achieved at the 61st procedure. Procedure duration progressively decreased, with the last 10 procedures under 50 min approaching a plateau (p-value <0.01). Conclusions Mastering POEM in Latin America requires approximately 61 procedures for both POEM efficiency and to accomplish the procedure within 97 minutes.

A 38-year-old female was admitted due to recurrent right upper quadrant (RUQ) abdominal pain. Three years prior to admission, the patient complained of a sudden onset of RUQ pain radiating to the right flank area. A month after the onset of pain, she consulted a physician, and she was advised to undergo endoscopy, but she did not comply. Three months after the consultation, an abdominal ultrasound was done, revealing a simple hepatic cyst. She then underwent aspiration of the cyst. However there was no resolution of the pain. A contrast-enhanced abdominal computed tomography (CT) scan revealed a recurrence of the hepatic cyst. Subsequently, she underwent laparoscopic fenestration of the cyst in liver segments VI, VII, and VIII. The biopsy results confirmed that the hepatic cyst was a hydatid cyst caused by Echinococcus granulosus. A month after the procedure, the abdominal pain recurred, and a repeat CT scan revealed another recurrence of the cyst. The patient was advised to undergo open surgery, but she did not consent. The patient denied taking anthelmintic drugs in the past. She did not experience any other symptoms—such as jaundice, nausea, vomiting, anorexia, or weight loss—along with the RUQ pain. She previously worked in Lebanon as a domestic helper for seven years and then moved to Taiwan, where she was employed for three years for the same work. She denied any direct exposure to dogs or sheep. On physical examination, she had a non-tender, firm, palpable mass in the RUQ area of the abdomen measuring 4x4 cm. The rest of the physical examination findings were unremarkable. A contrast-enhanced CT scan of the whole abdomen done two months prior to her admission showed multiple, well-defined, hypodense lesions in the right hepatic lobe. These lesions exhibited mildly enhancing walls and internal septations with rosette or honeycomb appearance. The two largest lesions seen in hepatic segments V and VII measured 8.6 x 6.1 x 5.2 cm and 9.5 x 8.5 x 7.4 cm, respectively (Figure 1). Similar hypodense lesions were seen in the right retroperitoneal space. At least two lesions were visible in the right perirenal space, measuring 8.8 x 6.1 x 6.5 cm and 6.1 x 5.9 x 3.8 cm, and at least two other lesions were visible in the right anterior pararenal space, within the region of the distal ascending colon, measuring 6.0 x 5.5 x 5.4 cm and 7.9 x 6.4 x 5.1 cm (Figure 2). At this point, we diagnosed the patient as having a recurrent hydatid cyst in the right hepatic lobe, with intraperitoneal extension in the right perirenal space and right anterior pararenal space, based on the CT scan findings. After securing medical clearance and administering mebendazole prophylactically at a dosage of 40 mg/kg/day, taken 3 times a day for 7 days prior to surgery, we aimed to sterilize the hydatid cysts and prevent surgical contamination.1 We did an exploratory laparotomy through a reverse L (Makuuchi) skin incision on the right upper abdominal quadrant (Figure 3). We subsequently performed a layered dissection down to the peritoneum. Intraoperatively, we noted adhesions at the posterior segments of the liver, right diaphragm and mid transverse colon. We then meticulously performed adhesiolysis. With extreme caution, we ensured to prevent any spillage of the cystic contents into adjacent structures and the abdominal cavity. Then, we covered the abdomen with abdominal packs soaked in 95% ethanol. Intraoperative liver ultrasonography revealed only one cystic lesion involving hepatic segments V, VI, and VII. The cyst was adherent to the right subdiaphragmatic area. We also noted multiple intraperitoneal cysts: one adherent to the right perirenal area measuring 8 x 6 cm, another adherent to the distal ascending colon and the mid transverse colon measuring 7 x 6 cm, and a third one non-adherent and floating in the anterior pararenal area measuring 4 x 4 cm. Before excising the intrahepatic mother cyst, we aspirated approximately 30-40 ml of cyst fluid and infused the cyst with an equivalent amount of 95% ethanol. After 15 minutes, we reaspirated the infused ethanol. We first carefully excised the intraperitoneal extensions of the cyst, (Figure 4) starting with the cyst in the distal ascending colon, then the cyst in the anterior pararenal area, and finally the right perirenal cyst, taking extreme caution to avoid rupturing the cyst. We then proceeded with the dissection of the hepatoduodenal ligament, where the portal triad is located, to provide access for our Pringle Maneuver. This step was followed by adhesiolysis at the right subdiaphragmatic area. Because of dense adhesions, there was a diaphragmatic injury, for which we performed phrenicorrhaphy. We then mobilized the right hepatic lobe through careful dissection of the triangular and coronary ligaments. The margins were marked under ultrasound guidance and the Pringle Maneuver was applied intermittently. We then carried out a parenchymal-sparing resection of segments V, VI, and VII. After securing hemostasis, we placed a Jackson Pratt drain in the subhepatic area. At the end of the surgery, we successfully resected hepatic segments V, VI, and VII, which contained an intrahepatic mother cyst with multiple spherical daughter cysts. Additionally, we excised three secondary cysts from the intraperitoneal area. Grossly, the excised specimen showed the right posterior segment of the liver with a surgically resected yellowish multiseptated cyst attached to it. This cyst has a fibrous rim and it contains several variable-sized daughter cysts (Figure 5). The excised intraperitoneal cyst from the distal ascending colon to mid transverse colon area (Figure 6), has a thick wall with a laminated external layer (Figure 7). The histopathological examination of the hydatid cyst showed E. granulosus protoscolices containing four acetabula and an armed rostellum with 30 to 36 hooks (Figure 8) . Sections of the liver showed liver parenchyma that was infiltrated by mononuclear cells. Adjacent to the liver parenchyma, the hydatid cyst wall contains an outer acellular laminated membrane, a germinal membrane, and remnants of the E. granulosus protoscolices, which resembled grains of sand (Figure 9 and 10). Postoperatively, the patient complained of dyspnea and tachypnea. On chest physical examination, we noted decreased breath sounds on the right. A chest x-ray done revealed a right-sided pneumothorax. Pneumothorax can occur during hepatectomy due to the escape of intraperitoneal carbon dioxide gas into the pleural cavity.2 We performed a chest tube thoracostomy insertion, and removed the tube after 5 days, once we observed full expansion of the patient’s right lung. We discharged the patient on the 9th postoperative day and prescribed oral antibiotics and pain relievers as home medications. Cystic echinococcosis (CE) or hydatid disease is a zoonotic parasitic disease caused by infection with the larval stage of the tapeworm E. granulosus. Dogs and other carnivores are definitive hosts, while sheep, cattle, and goats are intermediate hosts. Humans are accidental, intermediate hosts and become secondarily infected by ingesting food or water contaminated with eggs or gravid proglottids that are excreted in the definitive host’s feces. CE is endemic in North and East Africa, South America, China and Central Asia, and the Mediterranean countries.3 4 5 6 This disease has a low prevalence in Southeast Asia, particularly the Philippines.7 In our case, the patient probably acquired the infection when she worked in Lebanon, where echinococcosis is endemic. The liver and the lungs are the most common sites of the disease in humans. The concomitant occurrence of the cyst in the retroperitoneum or other intra-abdominal spaces is extremely rare,8 9 and it is associated with a high mortality and disability rate.10 Abdominal CT scan is a good imaging technique for visualizing wall calcifications in CE,11 and in our patient, enhancing walls and internal septations, which represent the walls of daughter cysts, were seen. Peritoneal seeding or cyst dissemination can occur due to a previous hepatic hydatid cyst surgery or after a spontaneous or traumatic rupture.12 These secondary cysts are formed from the liberated protoscolices caused by rupture of the daughter cysts.13 Although rare, when a cyst ruptures into the peritoneal cavity, it can lead to reactions ranging from mild hypersensitivity reaction to potentially fatal anaphylactic shock.14 A preoperative course of oral albendazole or mebendazole, as in the case of our patient’s medication, sterilizes the cysts and reduces their tension, thereby facilitating the surgery.15 16 It also kills most of the protoscolices within the hepatic hydatid cyst.17 Postoperatively, these drugs significantly reduce the risk of cyst recurrence.16 The prognosis of CE is generally good, and a complete cure is possible with total surgical excision without spillage.18 For hepatic echinococcosis, it is crucial to prioritize radical surgical resection in the initial surgery and preoperative anthelmintic therapy to minimize morbidity and recurrence often linked with conservative surgery.16 19
Cysts ; Echinococcus granulosus