Intractable Ulcer Research Articles

Analysis of Toll-like receptor 2, 4, 6 and 9 genome DNA mutations in patients with tractable and intractable gastric mucosal diseases

The possible involvement of Toll-like receptor (TLR) genome DNA in the prolongation and relapse of inflammatory intestinal diseases and alcoholic hepatic diseases has been reported. In this study, we examined the relationship of mutations of the TLR 2, 4, 6 and 9 genomic DNA to recurrent or intractable gastritis or gastric ulcers. The subjects were 32 patients, including 6 with H. pylori (Hp)-positive gastritis, 4 with Hp-negative gastritis, 10 with Hp-positive tractable gastric ulcer, 5 with Hp-positive recurrent gastric ulcer after Hp eradication, and 7 with Hp-negative easily recurrent gastric ulcer after Hp eradication. Gastric mucosal tissue and peripheral blood specimens were collected from each of the patients. DNA was extracted from the tissue and blood specimens and subjected to electrophoresis by the PCR method, using the oligonucleotide primers of TLR 2, 4, 6 and 9. The gastric mucosal tissue specimens were collected endoscopically from the sites of the lesions. Subsequently, the presence or absence of genomic DNA mutations in the blood and tissue specimens was examined using a DNA sequencer. TLR 2, 4, 6 or 9 DNA mutations were not observed in any of the gastric mucosal or peripheral blood specimens obtained from patients with tractable gastritis or gastric ulcer, or from those with intractable gastric ulcer who were Hp-positive or Hp-negative or had become Hp-negative after eradication therapy. These data suggest that mutations of the TLR 2, 4, 6 and 9 genome DNA may not be involved in the recurrence, delayed healing or intractability of gastritis and gastric ulcers.

The Superficial Cervical Artery Flap: Twenty Years' Experience and Development of the Flap

The superficial cervical artery (SCA) is a superficial branch of the transverse cervical artery. The SCA supplies the upper part of the trapezius muscle. Since 1986, we have harvested SCA flaps for the reconstruction of neck scar contractures and intractable ulcers of the parietal region. We developed the SCA flap for use as a skin flap in 1990, and in 1993 we succeeded in harvesting it as a free flap. We first employed the flap with a musculocutaneous pedicle, but later we developed the flap as a muscle pedicled flap and a vascular pedicled flap. Moreover, we have successfully employed the flap as a "Super-thin flap," and as microvascular augmented flaps for harvesting extremely large flaps safely. In the 1980s and early 1990s the concept of "perforator flaps" was unknown, but the SCA is now considered to be a perforator. Thus, we can call the flap the SCA perforator (SCAP) flap. The SCAP flap has a wide rotation arc and low donor-site morbidity, and our clinical studies clearly show that it is useful for reconstruction.

Intractable Gastrointestinal Ulcers with Bleeding in Behcet's disease-A Case Report with H2-Blocker-Resistance but Successfully Treated with Systemic Steroid and Cytotoxic Agents

A 54-year-old male suffering from repeated massive gastro-duodenal bleeding ulcers, since April 2001, was reported. The ulcers seemed to be resistant to conventional H2-blocker treatment. In the meanwhile, colon ulcer with active bleeding was also present simultaneously. He was diagnosed as having Behcet's disease since three years ago with manifestations of recurrent oral ulcers, genital ulcers, erythema nodosum and folliculitis. Hematemesis, massive tarry stool, bloody stool, high fever, oral ulcers and diffuse lower abdominal pain were noted at this episode. An endoscopic examination revealed active gastric ulcer, duodenal ulcer, and polypoid lesions with ”punch-out” ulcers in the colon. Due to treatment failure with H2-blocker in the previous several bleeding ulcer episodes, methylprednisolone pulse, followed with cyclophosphamide, was prescribed for rescue of active ulcer bleeding. Patient responded well to such management. The endoscopy and colonoscopy one month later after treatment showed complete healing of gastric ulcer and granulation polypoid lesions of colon. There was no more ulcer bleeding up to now in Aug 2004.

Chronic vulval ulceration — another immune reconstitution inflammatory syndrome?

We describe a patient who developed intractable chronic vulval ulceration that we believe was related to immune reconstitution following treatment of HIV infection with highly active antiretroviral treatment (HAART). Immune reconstitution inflammatory syndrome should be considered in the differential diagnosis of unexplained vulval ulceration that arises after starting HAART.

Aluminum foil treatment combined with basic fibroblast growth factor (bFGF) for gangrene of the fingertip caused by collagen disease

Although basic fibroblast growth factor (bFGF) is used for the treatment of various intractable ulcers, there have been no reports of using it for gangrene of the fingertips caused by collagen diseases. We successfully treated gangrene as a result of malignant rheumatoid arthritis with aluminum foil combined with bFGF.

General session III Moderated by Takehisa Iwai: Muscular Flap Treatment for Intractable Ulcer with Artificial Vessel Exposure After a Surgery for Thoracic Aortic Aneurysm

Aim: To heal an exposed artificial vessel due to mediastinitis after the replacement of thoracic aortic aneurysm.Methods: The exposed vessel is washed thoroughly, wrapped in a muscular flap, and a free skin graft is grafted over it to close.Results: An 81‐year‐old male repeatedly had mediastinum after the replacement of aneurysm, and it was not cured with muscular fillings, and a rubor on the chest developed to a subcutaneous hematoma. The lesion was closed with a patch on the artificial vessel, the mediastinal abscess was washed, and the opening was closed by using latissimus dorsi muscular flap and split‐thickness skin graft. No recurrence has occurred for 3 years. A 69‐year‐old male developed mediastinitis after the replacement of thoracic arch aortic aneurysm, and the wound reopened and the vessel exposed. Because conservative treatment did not help, pectoralis major muscular flaps with the perforating branches of the internal thoracic artery and vein as the pedicle were elevated from the both sides, filled the mediastinal space and a split‐thickness skin graft was grafted. No recurrence has occurred for one year.Conclusions: Artificial vessels that developed infections are usually removed. However, we had good results by washing the lesion and wrapping it with muscular flap. By considering the size of surgical invasion and high death rate associated with the re‐replacement of artificial vessel or the opening of omentum, utilization of muscular flap should be considered as the first choice treatment.

Oxygen Hyperbaric Pressure Therapy (OHPT) for Decubitus Ulcers

Aim: Although oxygen hyperbaric pressure therapy (OHPT) for intractable ulcers is covered by national insurance, few studies have reported its use in the treatment of decubitus ulcers. In this study, we used OHPT as part of conservative treatment, and obtained good results.Methods: Five inpatients received a 60‐min session of 100% oxygen in a Hyperbaric Oxygen ChamberR(Kawasaki Engineering Co., Kobe, Japan) at 2 ATA for 10 days. The clinical response was evaluated by four parameters, the difference in the area of ulcer wounds before and after treatment, changes in inflammatory responses, state of wound infection, and histological findings.Results: OHPT was effective in reducing the area of ulcer wounds in four patients. Three patients, in whom blood tests had shown inflammatory responses (increases in WBC and CRP) before treatment, showed improvement. Two patients, in whom wound cultures were positive for MRSA, became negative after treatment. However, the patients varied in granulation tissue proliferation during treatment. The possible mechanisms underlying these changes were, first, improvement of tissue hypoxia by hyperbaric oxygen supply to ischemic tissue, leading to the above‐described reduction in wound area and improvement in inflammatory responses, and second, inhibition of bacterial growth due to an increase in active oxygen species, leading to the disappearance of wound infection.Conclusions: The results of this study suggest that OHPT is a very useful option in the conservative treatment of decubitus ulcers.

Intracellular delivery of liposome-encapsulated prolidase in cultured fibroblasts from prolidase-deficient patients

Prolidase is a cytosolic exopeptidase whose deficiency causes the development of a rare autosomal recessive disorder known as Prolidase Deficiency (PD). The main manifestations of PD are intractable ulcerations of the skin, recurrent infections and mental retardation. At this time only a hazardous and expensive chronic therapy based on blood transfusions is the suggested treatment for PD. The aim of this work was to investigate the capability of utilizing liposomes as enzyme carriers: these vesicular systems have been recently evaluated as protein carriers for their potential in terms of “in vivo” localization, drug release and for protein stabilization in biological fluids. Liposomes were prepared, with a 1:1 PC:Col molar ratio with or without DSPE-PEG, by a thin-film hydration. Ex-vivo experiments were performed, incubating prolidase loaded liposomes with cultured fibroblasts from PD patients and from controls, to determine the amount of active enzyme delivered to cells. Evaluation of liposomes toxicity on cultured skin fibroblasts showed that liposomes did not interfer with cellular growth. Results showed that all the active prolidase encapsulated in the liposomes was completely vehiculated inside fibroblasts after 6 days incubation. SEM analysis suggests that prolidase is vehiculated inside the cell through liposome endocytosis.

胆嚢十二指腸瘻を合併した難治性十二指腸潰瘍に対し腹腔鏡下手術を行った1例

胆嚢十二指腸瘻を合併した難治性十二指腸潰瘍に対し腹腔鏡下手術を行った1例

口腔粘膜の難治性潰ようおよび不明熱を呈した先天性無痛無汗症の１例

口腔粘膜の難治性潰ようおよび不明熱を呈した先天性無痛無汗症の１例

Bright leaves, dark leaves.

The 20th century has been called the “Century of the Surgeon,” and surely it was. But who would we nominate to be the “Surgeon of the Century?” I want to place in nomination the name of a surgeon who worked in Europe and America. He developed a number of new surgical procedures, lived in four different countries during his surgical career, and studied and worked with two stalwarts in medicine. He worked in the laboratory of Ludwig Aschoff, a pioneer in pathology, and was a surgical resident and later colleague of Ernst Ferdinand Sauerbruch, an early leader in thoracic surgery. He was president of the German Surgical Society, even though he was not living in Germany at the time. He published more than 400 scientific articles in several surgical fields and in three different languages. He was editor or coeditor of 14 scientific journals, was author or coauthor of 27 books, and wrote 15 book chapters. He did pioneering research in the pathogenesis of gastric ulcer, diseases of the lungs and thorax, the origin of pulmonary emphysema, and on tuberculosis in bone and joints. In 1931, he did the first successful pneumonectomy in a human. He developed a technique for extrapleural pneumothorax for tuberculosis. Ironically, he was stricken by tuberculosis before the development of effective drug therapy, but he survived. He worked on techniques to deal with the difficult duodenal stump when partial gastrectomy was the accepted definitive therapy for intractable peptic ulcer disease. In 1937, he performed a resection of the gastric cardia and did an invaginated anastomosis. Proximal gastrectomy was well known to produce severe disabling esophagitis, but his patient did not develop it. This was to become a defining moment in his career. He left Germany, his homeland, never to live there again, and lived in Turkey, the United States, and in Switzerland. He counted among his patients Nobel Prize winners Albert Schweitzer, Albert Einstein, and pioneering radiologist Gustav Buckey. In 1955, he saw a patient with symptomatic reflux esophagitis and, recalling his 1937 patient, plicated the fundus of the stomach around the distal esophagus. This procedure not only set the stage for the best and most successful surgical treatment for reflux esophagitis—“heartburn”—but placed the surgeon’s name in the vocabulary of every general surgeon and gastroenterologist in the world. This man’s name is, of course, Rudolf Nissen. Why did a surgeon this successful entitle his biography, Helle Blatter, Dunkle Blatter—Bright Leaves, Dark Leaves (Fig. 1)? 4 Why did he leave his homeland, never to live there again? Why did he choose to live in Basel, Switzerland, for the last part of his life? How was he able to accomplish so much? What effect did his success have on his family? Rudolf Nissen was born in 1896 in Neisse, Silesia, to Dr Franz Nissen and Margarethe Borchert Nissen. Silesia was then a part of Prussia, Germany, but now is in Poland. His father, Franz Nissen, was a successful general surgeon in this quiet, tolerant city on the edge of the Carpathian Mountains. Two years after Rudolf ’s birth, his father built a clinic and hospital in Neisse. The family lived on one of the upper floors of the building, so Rudolf grew up in close contact with surgery and was inevitably drawn to it. He went to school at the katholische humanistisches Gymnasium, or Catholic high school in Neisse. The discipline of Prussia and of this school undoubtedly contributed to his strong work ethic and self-control. Perhaps, also, Immanuel Kant’s concept of “oughtness” was drilled into him at home and in school. As a young man, Rudolf thought he might like to become a painter. His father knew Fritz Erler, and sent his son to study with him at the Breslau Art Institute so that he could evaluate Rudolf ’s talent. It is likely Franz Nissen had given Erler instructions. Fritz concluded that Rudolf Nissen had enough talent to “earn his bread as a painter, but not the butter to go on it.” Rudolf began his medical studies in Breslau and then Munich, in 1913 and 1914. He volunteered for the German army to fulfill his one-year military service obligaPresented as the Presidential Address at the Texas Surgical Society, 2001.

Atypical and aggressive upper gastrointestinal ulceration associated with aspirin abuse.

Unusual resistance to treatment in 5% to 7% of 1,845 peptic ulcers examined under endoscopy from 1987 to 1996 prompted a search for unusual causes. Although some ulcers were caused by Zollinger-Ellison syndrome (ZES), an atypical clinical course in other patients, especially with those with multiple ulcers, suggested abuse of aspirin. Patients who did not have ZES were questioned closely regarding aspirin use and were tested for serum salicylate to detect surreptitious abuse. The authors identified 37 patients with aspirin-related ulcers but otherwise intact upper gastrointestinal tracts. There were 12 men and 25 women aged 18 to 73 years; 18 admitted to current aspirin abuse (>1 g/d), but 19 denied it despite objective evidence from elevated serum salicylate (8.4 +/- 1.2 mg/dL). The clinical presentation was atypical, with only 10 patients having single ulcers, whereas 27 had 83 multiple or multiorgan ulcers. Overall, there were 32 duodenal, 57 gastric, and 4 esophageal ulcers. Omeprazole healed 64% of ulcers, but despite follow-up maintenance with H2 receptor antagonists, all ulcers recurred rapidly, often in a new location. Thirty of 37 patients had serious complications: 18 bled; 9 had pyloric and 2, duodenal stenosis; 2, esophageal strictures; and 2, perforation. Six patients who stopped using aspirin healed easily. The 80% who did not stop on advice after diagnosis were considered abusers. Patients with aspirin abuse have atypical, often multiple, intractable ulcers with many complications. These ulcers differ from conventional Helicobacter pylori peptic ulcers and also from those found in patients with ZES. Unless aspirin use is stopped, these ulcers remain incurable and dangerous.

Bilateral Amputation for Intractable Venous Ulceration

Bilateral Amputation for Intractable Venous Ulceration

Advances in venous surgery: SEPS and phlebectomy for chronic venous insufficiency.

Chronic venous insufficiency (CVI) and its complications of chronic pain, intractable ulceration, and infection are important conditions to treat by modern surgical techniques. As early as the 1930s, perforating veins with outward flow were implicated in the pathogenesis of this condition. Recognition that such outward flow promotes leukocyte adhesion and activation as the principal microcirculatory cause for the cutaneous changes has explained the importance of perforating vein interruption? Because of disability of CVI, surgeons and patients reluctantly tolerated the open Linton perforator interruption operation with its morbid knee-to-ankle incisions. It was tolerated because it worked. Modifications to reduce the morbidity of the procedure eliminated two of the three incisions used in the explorations of the 1930s. Other modifications such as DePalma's modification of the incisions further reduced wound complications. However, the most significant surgical alteration was to utilize the endoscopic techniques introduced in Europe by Fischer and Hauer. Very quickly it was obvious that the endoscopic technique minimized postoperative complications. Application of endoscopic perforator interruption to varicose vein surgery validated the safety of the procedure but did not contribute to knowledge about treating CVI.

腐骨除去によりロ腔鼻腔ろう孔を生じた骨軟化症の１例

A rare case of osteomalacia with an oronasal fistula developing after sequestrectomy is presented. The patient was a 45-year-old woman who was referred to our hospital because of an intractable ulcer at the midline of the hard palate. She had an edentulous maxilla and wore a poorly fitting complete maxillary denture. Oral examination showed ulceration with a sequestrum under the prosthesis. Removal of the sequestrum extending from the oral cavity to the nostrils resulted in an oronasal fistula of the hard palate. The case was finally diagnosed as osteomalacia based on the results of radiographic and serum chemical examinations. In this patient, continuous pressure caused by the poorly fitting maxillary denture induced the sequestrum in the hard palate, which was thin and fragile because of osteomalacia.

Enzyme loaded biodegradable microspheres in vitro: ex vivo evaluation

Prolidase is a naturally occurring enzyme involved in the final stage of protein catabolism. Deficient enzyme activity causes prolidase deficiency (PD), a rare autosomal recessive inherited disorder whose main manifestations are chronic, intractable ulcerations of the skin, particularly of lower limbs. Although several attempts have been made towards the treatment of this pathology, a cure for this disease has yet to be found. The purpose of this work is to evaluate the possibility of enzyme replacement therapy through prolidase microencapsulation in biodegradable microspheres. The poly( d,l-lactide-co-glycolide) (PLGA) prolidase loaded microparticulate systems have been prepared utilizing the w–o–w double emulsion solvent evaporation method. They have been characterized “in vitro” by morphological analysis, total protein content and an in vitro dissolution test of active protein. “Ex vivo” evaluation of prolidase activity from the microspheres has been performed on cellular extracts of cultured skin fibroblasts from healthy subjects (controls) and from patients affected by PD. The results reported in this work on prolidase from pig kidney (available on the market) demonstrate the positive role of microencapsulation as a process of enzymatic activity stabilization inside PLGA microspheres achieving both in vitro and ex vivo active enzyme release. This formulation can be proposed as a parenteral depot drug delivery system.

消毒薬使用中止で劇的に改善した難治性し端潰よう

消毒薬使用中止で劇的に改善した難治性し端潰よう

熱傷はん痕後の皮膚悪性腫ようの２例

The auther report two cases arising of skin cancer on the burn scar. A 72-year-old Japanese woman got burnt in the frontal scalp, when she was 3 years old. The tumor was an easiely bleeding nodule measuring 14×14×8 mm in size. Histological examination revealed a keratotic Basal Cell Carcinoma. Wide excision of the lesion and local skin flap were performed. Second case was an 86-year-old woman who had a burn on the left thigh during a neonatal period. It has grown up to the intractable ulceration in 1995 and it became hemorrhagic. The biopsy specimen showed that the ulcer is a squamous cell carcinoma. It was removed widely under the general anesthesia, and the skin graft was carried out in 1999. [Skin Cancer (Japan) 2001; 16: 233-236]

逆行性Ｖｅｎｏｎｅｕｒｏａｄｉｐｏｆａｓｃｉａｌ ｆｌａｐを用いて治療した足関節周囲皮膚欠損の２例

We successfully treated skin defects around the ankle joint by the reverse venoneuroadipofascial (V-NAF) flap in 2 patients. The V-NAF flap is the fasciocutaneus flap supplied by accompanying arteries of the cutaneous vein and cutaneous nerve. Case 1 was a 54-year-old female suffering rheumatoid arthritis for 30 years. Intractable ulcer at the medial malleolar region of the right ankle joint occurred 2 years ago and has enlarged. The skin defect was covered with reverse V-NAF flap (16×6cm) and the donor site was covered with skin graft. No recurrence of the ulcer was found for 5 months. Case 2 was a 23-year-old male with 50 degrees equinus contracture of the left ankle after rupture of the popliteal artery. He received ankle fusion and developed skin defect in front of the ankle joint. This defect was covered with V-NAF flap (10×5cm) and the donor site closed primarily. Wounds healed without any problems. The reverse V-NAF flap is considered the treatment of choice to cover skin defects around the ankle joint. The advantages of this flap are as follows; it is reliable, there is no need for microvascular anastomosis, and harvesting is easy without the need to sacrifice major arteries.

Clinical Evaluation of Operation for Intractable Leg Ulcer due to Primary Varicose Veins

Clinical Evaluation of Operation for Intractable Leg Ulcer due to Primary Varicose Veins