Abnormal lymphatic phenotype in a CRISPR mouse model of the human lymphedema-causing Connexin47 R260C point mutation.

Connexin proteins form gap junctions controlling exchange of ions and small molecules between cells and play an important role in movement of lymph within lymphatic vessels. Connexin47 (CX47) is highly expressed in lymphatic endothelial cells and CX47 missense mutations, i.e., R260C, cosegregate with primary lymphedema in humans. However, studies utilizing CX47 knockout mice have failed to demonstrate any lymphatic anomalies. To unravel the lymphatic consequences of expressing a mutant CX47 protein, we used CRISPR technology to create a mouse carrying a Cx47 missense mutation (Cx47R259C) equivalent to the human CX47R260C missense mutation associated with human primary lymphedema. Intradermal Evans Blue dye injection identified a 2-fold increase in regional lymph nodes in homozygous Cx47R259C mice compared to wildtype, particularly in the jugular region (4.8 ± 0.4 and 2.0 ± 0.0, respectively, p<0.01). Associated lymphatic channels were increased in Cx47R259C mice and mesenteric lymph reflux occurred in homozygous Cx47R259C mice but not in wildtype. Contractility of superficial cervical lymphatics, assessed by pressure myography, was reduced in homozygous Cx47R259C mice compared to wildtype. In conclusion, our data are the first to demonstrate a role for the Cx47 protein in lymphatic anatomy and function. This phenotype is similar to that found with other valve deficient mouse mutants, e.g., in Foxc2. Of significance, this study is the first to use CRISPR technology to develop a pre-clinical model of primary lymphedema and demonstrates the importance of distinguishing between lack of and presence of mutant protein when developing clinically relevant animal models for translation of pre-clinical findings.

Grynfelt hernia.

Lumbar hernias are very uncommon conditions. Less than 300 cases have been reported in the literature. They result from defects in the posterolateral abdominal wall. The authors report their experience with four lumbar hernias managed at the "Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo" from 1973 to 1993. Age ranged from 54 to 63 years. Three were female, two had right hernias and two had left ones. All patients were treated surgically. Three were repaired by simple suture. The main complications were early recurrence (one case) and infections (one case). In one, a prosthetic mesh (polypropylene) was used to repair the defect, and the recovery was uneventful. Surgical treatment is always indicated in Grynfelt hernia. Approximation of the muscles by primary nonabsorbable suture, grafts or prosthesis are very adequate therapeutic options for lumbar hernias.

[Grynfelt's hernia. A case report and review of the literature]. / Hérnia de Grynfelt. Relato de caso e revisão da literatura.

Lumbar hernias are rare lesions. They involve the extrusion of visceral contents through a defect in the posterolateral abdominal wall. Only 250 a 300 cases had been reported in the literature. They occur most often in the superior lumbar triangle (Grynfelt's hernia). All lumbar hernias must be treated with surgery and the preferable surgical approach is done retroperitoneally. Primary repair, autologous tissue or prosthetic material may be used to obliterate the defect. The authors report a case of Grynfelt's hernia in which polypropylene mesch was placed pre-peritonially.

[Mesenteric cyst]. / Cisto mesentérico.

Mesenteric cysts are rare abdominal tumors. Their incidence varies in different papers from one in 27,000 to one in 250,000 hospital admissions. Five patients with mesenteric cysts were treated at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo between November 1982 and October 1992. The most common location was in the small bowel (60%). All of them were treated by surgery. One case was found incidentally. Treatment of choice is enucleation. It was realized in two cases (40%). The others had segmental bowel resection.

[Traumatic wounds of the esophagus]. / Ferimentos traumáticos de esôfago.

Thirty four (75.5%) individuals sustained gunshot wounds, nine (20%) stab wounds, while two (4.4%) suffered blunt trauma. Thirty four patients (75%) displayed severance of the cervical portion of the esophagus, seven (15.5%) of the thoracic segment and only four (8.8%) had injuries on the abdominal portion. The cervical esophagus was surgically approached through oblique left side cervicotomy with primary suture and drainage with Penrose drain. A postero-lateral right side thoracotomy was employed for lesions of the upper and intermediate portion of the thoracic esophagus. When the lower portion of the esophagus was injured, a left side thoracotomy was employed. When the injury involved less than half of the perimeter of the esophagus suturing with ample drainage was adopted. In more extensive injuries involving over half of the perimeter total esophagectomy was the treatment of choice. In abdominal esophageal injuries laparotomy, suture and drainage were performed. Complications occurred in 40% of all patients. Seven patients died though only one from direct consequences of the esophageal injury. The authors believe that an early surgical approach for traumatic esophageal injuries is the best procedure. Primary suture and drainage score the best results. Other measures (esophagectomy, esophagostomy, gastrostomy) should be adopted only when the injury is either extensive or mediastinal contamination is present.

[Esophagoplasty with bypass using an isoperistaltic gastric tube in the treatment of cancer of the thoracic esophagus: study of 13 cases]. / Esofagoplastia com tubo gástrico isoperistáltico em derivação no tratamento do câncer do esôfago torácico: estudo de 13 casos.

In order to relieve complete obstruction of the thoracic esophagus due to spinocellular carcinoma, thirteen patients, all of them in good or at least regular general conditions were submitted to a bypass using a isoperistaltic gastric tube. The disease itself was treated by radiotherapy after surgery. Only one patient died at the hospital due to an error in the radiotherapy schedule. Cervical fistula was observed in six patients seven days after surgery; local treatment was enough for complete healing in five out of six. In one patient surgery was performed in order to repair the anastomotic area. Stenosis was observed in three patients but in all cases it was possible to overcome it by endoscopy. With the progress of the disease other complications were observed such as hemoptysis and respiratory distress. The survival rate was nine months (running between five and sixteen) but it should be noted that swallow capacity was maintained until death. The employed of a bypass of isoperistaltic gastric tube seems to be a desirable alternative in the treatment of esophageal cancer because it allows the reestablishment of deglutition before any treatment such as radiotherapy alone or combined with surgery.

[Recurrent inguinal hernia: study of 87 cases]. / Hérnias inguinais recidivadas: estudo de 87 casos.

A retrospective analysis is made of the data of 87 patients with recurrent inguinal hernias operated at the Hospital das Clínicas of the University of São Paulo in a period of six years. As it happened with other authors, frequency of recurrence was: direct hernia (43.5%), indirect hernia (50%), the less often seen mixed form (3.9%), and crural hernia (2.6%). They discuss local and systemic etiopathogenic factors, strain in the early postoperative period being indicated as a major factor, responsible for 43.1% of the cases. More than half of recurrences (48/85) occurred in the first year, some occurring after a longer period of time (30.6% after three years). The mostly used repair techniques were modified Bassani's technique (suture of the transverse arch to the inguinal ligament) and the Lotheissen-McVay technique, in 46.1% and 42.5% of the cases, respectively. In 9 of the 85 cases, tightening the deep inguinal orifice was enough. Analysis of the rate of surgical failure was difficult, as patients did not routinely return for follow-up visits.

[Prevention of infection in closure surgery in colostomies. Double-blind study with tinidazole]. / Profilaxia das infecções na cirurgia de fechamento de colostomia. Estudo duplo-cego com tinidazol.

A comparative double-blind study of tinidazole vs placebo was conducted in order to assess the prophylaxis of post-surgical abdominal infections in 40 patients undergoing closure colostomy surgery. During three days the patients were kept on a low residue diet, and underwent a colon mechanical cleansing. About 10 to 12 hours prior to surgery the patients were given placebo or tinidazole in tablets of identical appearance; the dose of tinidazole was of 2 g (4 tablets) in a single oral dose. Evaluation performed after surgery showed that in the tinidazole group occurred two surgical mild infections (10%), while in placebo group occurred nine infections (45%)--four of them severe and one very severe, showing a significative difference between the two groups (p less than 0.05). In placebo group 21 bacteria were isolated, 3 of them were anaerobic; only two aerobic species were identified in the tinidazole group (p less than 0.001). No adverse reactions were reported in both groups. The authors concluded that in this study, tinidazole showed a prophylactic effect on post-surgical abdominal infections in patients who underwent closure colostomy surgery.

[Cystic dilatation of the intrahepatic bile ducts (Caroli's disease)]. / Dilatação cística das vias biliares intrahepáticas (moléstia de Caroli).

Congenital cystic dilatation of the intrahepatic biliary ducts, known as Caroli's disease, is rarely recognized in general surgical practice and often overlooked. Until now little more than a hundred cases have been described although modern diagnostic procedures disclose more frequently new ones. Three patients with this anomaly have been treated by the authors during the past years and the different aspects concerning diagnosis and treatment are discussed and compared with existing information. In all three patients colic pain in the upper abdomen was the first symptom reported in the first years of life. In one patient jaundice and fever were associated with the abdominal pain and cholangitis developed a secondary biliary cirrhosis. Somatic underdevelopment, consequence of the cirrhosis in this child was observed. In two patients an intrahepatic hepaticojejunostomy was performed and a left hepatectomy in the third. In the two older children intrahepatic gallstones were found; in the younger one no stones were found inside the dilated ducts.