Antifibrotic effects of cyclosporine A on TGF-ß1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1α.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-ß1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-ß1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α). In addition, in primary myofibroblast-like cells that were obtained from a patient with pulmonary fibrosis, treatment with CsA and an HIF-1α inhibitor (HIFi) decreased the expression levels of α-smooth muscle actin and fibronectin, which indicated that CsA and HIFi promote dedifferentiation of myofibroblasts. In mice intratracheally administered CsA or HIFi at an early fibrotic stage [7, 8, and 9 d postinstillation (dpi) of bleomycin], marked alleviation of lung fibrosis was observed at 14 dpi. These results suggest that CsA exhibits antifibrotic effects by degrading HIF-1α and that the CsA-HIF-1α axis provides new insights into therapeutic options for the treatment of IPF.-Yamazaki, R., Kasuya, Y., Fujita, T., Umezawa, H., Yanagihara, M., Nakamura, H., Yoshino, I., Tatsumi, K., Murayama, T. Antifibrotic effects of cyclosporine A on TGF-ß1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1α.

Reconstruction of elbow skin and soft tissue defects using perforator-pedicled propeller flaps.

BACKGROUND: The elbow is a challenging region to reconstruct functionally. Several closure methods for elbow wounds have been reported, including flap surgery. Here, we present the results obtained using a propeller flap pedicled by a posterior ulnar recurrence artery perforator (PURAP) or a radial collateral artery perforator (RCAP) for functional reconstruction of soft tissue defects in elbows. METHODS: Twenty-four patients with an average age of 27.0 years (range, 9-52 years) underwent elbow soft tissue reconstructions between 2005 and 2015. Twenty-one patients were male and three were female. Among them, 18 patients received a PURAP flap transfer and six received a RCAP flap transfer. The frequent soft tissue defects were due to release of a postburn scar contracture in 12 patients, trauma in ten patients. Functional results were obtained by measuring range of motion (ROM). RESULTS: The mean follow up time was 10.1 months (range, 4-22 months). The flaps ranged in size from 3 × 5 cm to 16 × 6 cm. Nearly all flaps survived with only one showing partial necrosis. 16 and 8 patients achieved ranges of motions of 0-5 and 6-15 degree extension and 130-145 degree flexion. CONCLUSIONS: With the aims of easy flap harvest, primary donor site closure, skin texture match, and avoiding vascular anastomosis, both PURAP and RCAP were employed. Both flap transfer techniques were safe and effective for elbow soft tissue reconstruction. It is important to ensure that the skin defect and flap design are closely matched.

Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38.

Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAPKs)-c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)-are activated in various types of cells in response to cellular stresses such as apoptotic stimuli and inflammatory waves. In animal models of SCI, inhibition of either JNK or p38 has been shown to promote neuroprotection-associated functional recovery. Here, we provide an overview on the roles of SAPKs in SCI and, in particular, the pathological role of p38 will be discussed as a promising target for therapeutic intervention in SCI.

Prospective open-label randomized comparative, non-inferiority study of two initial antibiotic strategies for patients with nursing- and healthcare-associated pneumonia: Guideline-concordant therapy versus empiric therapy.

BACKGROUND AND OBJECTIVE: The nursing- and healthcare-associated pneumonia guideline, proposed by the Japan Respiratory Society, recommends that patients at risk of exposure to drug-resistant pathogens, classified as treatment category C, be treated with antipseudomonal antibiotics. This study aimed to prove the non-inferiority of empirical therapy in our hospital compared with guideline-concordant therapy. METHODS: This was a randomized controlled trial conducted from December 2011 to December 2012. Patients were randomized to the Guideline group receiving guideline-concordant therapy, and the Empiric group treated with sulbactam/ampicillin or ceftriaxone. The primary endpoint was in-hospital relapse of pneumonia and mortality within 30 days, with a predefined non-inferiority margin of 10%. The secondary endpoints included duration, adverse effects, and cost of antibiotic therapy. RESULTS: One hundred and eleven patients were assigned to the Guideline group (n = 55) and the Empiric group (n = 56; 3 of which were excluded). The incidence of relapse and death within 30 days was similar in the Guideline and the Empiric groups (31% vs. 26%, risk difference -4.5%, 95% CI -21.5% to 12.5%). While the duration of antibiotic therapy was slightly shorter in the Guideline group than in the Empiric group (7 vs. 8 days), there were no significant differences in adverse effects or cost. CONCLUSIONS: The efficacy of empiric therapy was comparable to guideline-concordant therapy, although non-inferiority was not proven. The administration of broad-spectrum antibiotics to patients at risk of exposure to drug-resistant pathogens may not necessarily improve the prognosis. TRIAL REGISTRATION: UMIN000006792.

Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis.

BACKGROUND: Various signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis. METHODS: Mice received a single dose of 3 mg/kg body weight of bleomycin (BLM) and were sacrificed at designated days post-instillation (dpi). Lung homogenates and sections from mice in the early inflammatory phase were subjected to phospho-protein array analysis and immunofluorescence studies, respectively. Bronchoalveolar lavage fluid (BALF) from mice was subjected to an enzyme-linked immunosorbent assay (EIA) for interleukin (IL)-6 and evaluation of infiltrated cell populations. The effects of endogenous and exogenous IL-6 on the BLM-induced apoptotic signal in A549 cells and type 2 pneumocytes were elucidated. In addition, the effect of IL-6-neutralizing antibody on BLM-induced lung injury was evaluated. RESULTS: Phospho-protein array revealed that BLM induced phosphorylation of molecules downstream of the IL-6 receptor such as Stat3 and Akt in the lung at 3 dpi. At 3 dpi, immunofluorescence studies showed that signals of phospho-Stat3 and -Akt were localized in type 2 pneumocytes, and that BLM-induced IL-6-like immunoreactivity was predominantly observed in type 2 pneumocytes. Activation of caspases in BLM-treated A549 cells and type 2 pneumocytes was augmented by application of IL-6-neutralizing antibody, a PI3K inhibitor or a Stat3 inhibitor. EIA revealed that BLM-induced IL-6 in BALF was biphasic, with the first increase from 0.5 to 3 dpi followed by the second increase from 8 to 10 dpi. Blockade of the first increase of IL-6 by IL-6-neutralizing antibody enhanced apoptosis of type 2 pneumocytes and neutrophilic infiltration and markedly accelerated fibrosis in the lung. In contrast, blockade of the second increase of IL-6 by IL-6-neutralizing antibody ameliorated lung fibrosis. CONCLUSIONS: The present study demonstrated that IL-6 could play a bidirectional role in the pathogenesis of lung fibrosis. In particular, upregulation of IL-6 at the early inflammatory stage of BLM-injured lung has antifibrotic activity through regulating the cell fate of type 2 pneumocytes in an autocrine/paracrine manner.

Therapeutic effect of lung mixed culture-derived epithelial cells on lung fibrosis.

Cell-based therapy is recognized as one of potential therapeutic options for lung fibrosis. However, preparing stem/progenitor cells is complicated and not always efficient. Here, we show easily prepared cell populations having therapeutic capacity for lung inflammatory disease that are named as 'lung mixed culture-derived epithelial cells' (LMDECs). LMDECs expressed surfactant protein (SP)-C and gave rise to type I alveolar epithelial cells (AECs) in vitro and in vivo that partly satisfied type II AEC-like characteristics. An intratracheal delivery of not HEK 293 cells but LMDECs to the lung ameliorated bleomycin (BLM)-induced lung injury. A comprehensive analysis of bronchoalveolar fluid by western blot array revealed that LMDEC engraftment could improve the microenvironment in the BLM-instilled lung in association with stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 signaling axis. SDF-1 enhanced both migration activity and differentiating efficiency of LMDECs. Further classification of LMDECs by flow cytometric study showed that a major population of LMDECs (LMDEC(Maj), 84% of total LMDECs) was simultaneously SP-C(+), CD44(+), CD45(+), and hematopoietic cell lineage(+) and that LMDECs included bronchioalveolar stem cells (BASCs) showing SP-C(+)Clara cell secretory protein(+)stem cell antigen (Sca)1(+) as a small population (1.8% of total LMDECs). CD44(+)-sorted LMDEC(Maj) and Sca1(+)-sorted LMDECs equally ameliorated fibrosis induced by BLM like LMDECs did. However, infiltrated neutrophils were observed in Sca1(+)-sorted LMDEC-treated alveoli that was not typical in LMDEC(Maj)- or LMDEC-treated alveoli. These findings suggest that the protective effect of LMDECs against BLM-induced lung injury depends greatly on that of LMDEC(Maj). Furthermore, the cells expressing both alveolar epithelial and hematopoietic cell lineage markers (SP-C(+)CD45(+)) that have characteristics corresponding to LMDEC(Maj) were observed in the alveoli of lung and increased approximately threefold in response to BLM instillation. Taken together, LMDECs newly classified in the present study are easily culture expanded and have a potential role in future regenerative cell therapy for pulmonary fibrosis.

Efficient design of a latissimus dorsi musculocutaneous flap to repair large skin defects of the upper back.

Closing large skin defects of the upper back is a challenging problem. We have developed an efficient design for a latissimus dorsi musculocutaneous flap for reconstruction in this region. The longitudinal axis of the skin island was designed to be perpendicular to the line of least skin tension at the recipient site so that primary closure of the flap donor site changed the shape of the recipient site to one that was easier to close. We used this method for four patients with skin cancers or soft-tissue sarcomas of the upper back in 2011 and 2012. The size of skin defects after wide excision ranged from 11 × 10 to 25 × 20 cm(2) , and all skin defects could be covered by the flaps and all wounds of donor site could be closed without skin grafts. No wound complications occurred in any patient. Functional and aesthetic outcomes were satisfactory in all patients. This flap design is effective for reconstructing large skin defects of the upper back.

Flow-through fibula flap using soleus branch as distal runoff: a case report.

The flow-through fibula flap utilizing the soleus branch as a distal runoff has not yet been reported. We herein present a patient with left tibial adamantimoma in whom wide resection of the tumor resulted in a segmental tibial defect 22 cm in length. The defect was successfully reconstructed with a flow-through free fibula osteocutaneous flap using the soleus branch of the peroneal artery as a distal runoff. The short T-segment of the peroneal artery was interposed to the transected posterior tibial artery. The soleus branch has a constant anatomy and a larger diameter than the distal stump of the peroneal artery. Short interposed flow-through anastomosis to the major vessels is much easier and more reliable than the conventional methods. We believe that our method represents a versatile option for vascularized fibula bone grafting for extremity reconstruction.

Vastus lateralis muscle flaps for monitoring buried anterolateral thigh flaps.

Postoperative monitoring of buried anterolateral thigh flaps is difficult with standard methods. Although a monitoring skin flap based on a second cutaneous perforator is often used, it requires tedious dissection of 2 sets of perforators and cannot be used when a second perforator is absent. We present 2 patients who underwent head and neck reconstruction with buried anterolateral thigh flaps, which were monitored with a small, externalized segment of the vastus lateralis muscle accompanying the main skin island. Both flaps survived, and the monitoring muscle flaps remained pink throughout the postoperative period until removal. For monitoring, a vastus lateralis muscle flap has several advantages over a skin flap. This method obviates the need for dissecting a second cutaneous perforator and allows reliable monitoring regardless of the number of available cutaneous perforators. We believe this method is a versatile option for monitoring buried anterolateral thigh flaps.

Relationship between pharyngeal or esophageal reconstruction and esophageal pressure after swallowing.

BACKGROUND: High-resolution manometry, which measures esophageal luminal pressure changes after swallowing, could shed more light on food-transport dynamics after pharyngeal/esophageal reconstruction. This prospective cohort study assessed the influence of two head-and-neck and esophageal tumor-resection and reconstruction approaches on esophageal pressure. METHODS: The cohort consisted of 17 patients who underwent esophageal/pharyngeal resection/reconstruction for cancer and then participated in postoperative high-resolution manometry. Five healthy controls also underwent manometry for comparison. RESULTS: Partial pharyngectomy with patch grafts associated with smooth and continuous esophageal/pharyngeal movement. By contrast, surgery that removed the thoracic esophagus led to complete loss of peristalsis and poor food transport. CONCLUSIONS: High-resolution manometry effectively characterized the changes in food-transport dynamics caused by pharyngeal/esophageal resection/reconstruction. These findings suggest that continuous and smooth movement of the pharynx and esophagus is important for swallowing and high resolution manometry could be useful in patients after pharyngeal/esophageal resection/reconstruction.

Applying the Microvascular Anastomotic Coupler Device to End-to-side Venous Anastomosis in Reconstructive Surgery.

BACKGROUND: Microsurgical vascular anastomosis plays an important role in successful free-tissue transfer. The Microvascular Anastomotic Coupler Device (MACD) aims to simplify anastomosis and decrease the time spent on this step, thereby reducing surgeon stress and improving the overall quality of the surgery, especially when venous end-to-side anastomosis is required. Our comparative retrospective cohort study aimed to determine the effect of this widely used device on anastomosis times and complications in head and neck/esophageal reconstruction cases involving venous end-to-side anastomosis using the internal jugular vein as the recipient vessel. METHODS: All consecutive patients who underwent head and neck/esophageal reconstruction with hand-sewn or MACD-mediated venous end-to-side anastomosis using the internal jugular vein by three experienced microsurgeons in our tertiary-care hospital in 2012-2020 were identified. Venous anastomosis times and venous trouble cases were recorded. RESULTS: Of the 191 cases, 44 and 147 underwent hand-sewn and MACD-mediated anastomosis respectively. The average venous anastomosis times of these groups were 31 and 11 minutes, respectively. Venous trouble was observed in two hand-sewn (4.5%) and four MACD (2.7%) cases, respectively. Vein twisting and improper coupler placement were the causes in the latter four cases. CONCLUSIONS: This study confirmed that MACD simplifies end-to-side venous anastomosis and reduces the time spent on this procedure. Also, for safer anastomosis, it is necessary to pay attention to preventing twisting and improper coupler placement when using MACD. We believe the MACD can improve the quality of reconstructive surgery.

[Retrospective analysis of pemetrexed plus cisplatin chemotherapy for elderly advanced non-small-cell lung cancer].

BACKGROUND: The efficacy of pemetrexed(PEM)plus cisplatin(CDDP)therapy for chemotherapy-naive non-squamous cell lung cancer has been reported, but the effectiveness of such a regimen for elderly patients is unknown. PURPOSE: The aim of this study is to examine the efficacy and toxicity of CDDP plus PEM therapy for elderly patients, retrospectively. METHODS: We performed a retrospective analysis of six patients 75 years old or older with non-squamous lung cancer, who underwent CDDP plus PEM therapy from June 2009 to May 2010. RESULTS: The mean age was 79. 2 years old(range, 76-82), gender: 3 males/3 females; stage: III B/IV; 1/5, pathology: all patients had adenocarcinoma without epidermal growth factor receptor (EGFR)mutation, line: first/third; 5/1. The scheduled chemotherapy of four courses was completed in four patients. The overall response rate was 50%, and the disease control rate was 83%. Grade 3/4 neutropenia and thrombocytopenia were observed in 1/2 and 1/1 patients, respectively, but no blood transfusions were needed. Severe myelosuppression was shown in patients who were impaired in renal function. Grade 3 nausea or anorexia was also observed in 50%of patients. Therefore, two patients were terminated in one courses of therapy and long-term hospitalization for them was needed. CONCLUSION: Although CDDP plus PEM therapy for elderly patients has sufficient patients compliance because of its tolerable myelosuppression, it is necessary to pay attention to deterioration in renal function and to care for nausea during chemotherapy.

A Cosmetic Surgical Approach Effectively Reconstructed Facial Nerve Paralysis.

In general, facial nerve palsy is treated by reconstructive surgeons, and the role of cosmetic surgeons is largely seen as secondary. The present report describes a case of refractory facial nerve palsy that arose after malignant parotid-tumor resection and high-dose radiotherapy, and that we reconstructed with a combination of cosmetic and reconstructive procedures. The procedures consisted of facelift techniques (lateral SMASectomy, creation of a nasolabial fold with three suture loops anchored at the temporal fascia, and frontal lift), a new wrinkle-removing technique wherein the frontal-muscle function was disrupted, and excision of surplus skin to rejuvenate the face. The outcomes were good, including at 1 year after surgery, and the 71-year-old patient expressed considerable satisfaction. The frontalis muscle resection effectively removed the wrinkles, helped balance the left and right sides, and permitted anti-aging surgery. This procedure has permanent effects, unlike other methods (eg, botulinum-toxin injections) that serve to weaken facial muscle function. It is notable that despite the high-dose radiotherapy the patient had received and the resulting extensive subcutaneous-tissue adhesion, our surgical protocol was relatively easy to perform as well as highly effective. Thus, even static reconstruction can give great hope and satisfaction to patients with facial nerve palsy.

Pyogenic spondylodiscitis of the lumbar spine related to anastomotic fistula after surgery for esophageal cancer: a case report.

BACKGROUND: Pyogenic spondylodiscitis is an extremely rare complication of esophagectomy for esophageal cancer. CASE PRESENTATION: A 70-year-old Japanese man, with a previous medical history of type 2 diabetes mellitus, coronary artery disease, and laryngeal cancer, received neoadjuvant chemotherapy and underwent thoracoscopic esophagectomy with gastric tube reconstruction for advanced esophageal cancer. Cervical esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. However, partial necrosis in the gastric tube developed to form refractory anastomotic fistula. Two months after the initial surgery, debridement and free jejunal transfer reconstruction with the pectoralis major muscle flap were performed. Although the postoperative course of the second surgery was uneventful, the patient complained of severe lower back pain and fever. The patient was diagnosed with pyogenic spondylodiscitis according to the results of the magnetic resonance imaging. Enterobacter cloacae were isolated from the arterial blood culture. Sensitive antibiotics were administered continuously, and the patient required to use a lumbar corset for 2 months. Subsequently, his physiological signs and symptoms had completely disappeared. CONCLUSION: To the best of our knowledge, this case study is the first study that reported pyogenic spondylodiscitis of the lumbar spine, a complication of cervical anastomotic fistula after surgery for advanced esophageal cancer.

Optic Canal Decompression with a Lateral Approach for Optic Nerve Injury Associated with Traumatic Optic Canal Fracture.

Optic canal fracture (OCF) is a traumatic injury that requires urgent intervention because it can induce optic nerve damage and visual impairment. Despite the severity of OCF, a standard treatment method has not been established. In this article, we report a case of OCF and traumatic optic nerve injury in which visual acuity was recovered by releasing the optic canal using an unconventional lateral approach. A 43-year-old man presented with right lateral ethmoid fracture, right orbit blowout fracture, and OCF. The visual acuity was "hand motion" before surgery. Decompression was performed 10 hours after injury by approaching the right optic canal laterally from a coronal incision in front of the right ear, cutting along the border of the sphenoid bone, and scraping away some of the sphenoid wing and zygomatic bone. Steroid pulse therapy was added. Eventually, the visual acuity improved to 0.2 and the intraocular pressure decreased to 16.0 mm Hg. Compared with conventional methods, this method associates with better safety because (1) it causes relatively little bleeding and cerebrospinal fluid leak; (2) once the sphenozygomatic suture is identified, the distance to the optic canal is relatively short; and (3) if the fracture point is on the outer optic canal, the fracture line can be observed directly. Steroid pulse therapy may also have contributed to the good visual outcome. This is the first report of a novel lateral approach to OCF that is safe, effective, and only requires plastic surgery skills.

A Completely Unique Branching Pattern of the Facial Artery.

This case report describes a recent case where a patient with hypopharyngeal cancer underwent resection and reconstruction with a free jejunum flap and the surgeons found a rare variation in the branching pattern of the common carotid artery. Specifically, the left facial artery arose directly from the common carotid artery, whereas the left superior thyroid artery arose from the facial artery. This branching pattern has not been reported previously. Although this is a hitherto unique case, head and neck and reconstructive surgeons should be aware of the possibility that this branching pattern may be present because it could complicate the outcomes of both neck dissection and reconstruction by free tissue transfer.

Second Free Flap Surgery for Skull Base Tumors: Case Report and Literature Review.

Tumors of the skull base, such as meningiomas, tend to recur. With progress in free vascularized flap surgery, an increasing number of studies are investigating skull base reconstruction with free flaps after tumor removal. In this report, we discuss the results of second free flap surgery after skull base reconstructive surgery. We retrospectively analyzed data from patients treated at our center during the period from 2013 through 2017. All four patients identified had skull base anaplastic meningioma and had undergone radiotherapy. In all cases, the flap and donor blood vessel were sourced from sites that differed from those used in the previous surgeries. No complications developed, such as cerebrospinal fluid leakage, meningitis, wound infection, wound hemorrhage, or flap necrosis. Because the first flap was found to be unviable, it was difficult to preserve and was removed. Essential points in preventing complications are anchoring at the appropriate site, pinprick testing of the created flap, and use of multilayered countermeasures to prevent cerebrospinal fluid leakage.

Relationship Between Performance Improvement in Activities of Daily Living and Energy Intake in Older Patients With Hip Fracture Undergoing Rehabilitation.

OBJECTIVE: To analyze whether sufficient energy intake (EI) improves performance of activities of daily living (ADL) in patients with hip fracture admitted to rehabilitation hospitals. The adequate amount of EI for improving performance of ADL in patients with hip fracture remains unknown. METHODS: This retrospective cohort study included all patients with hip fracture (n=234) admitted to rehabilitation hospitals in Japan. The inclusion criteria for this study were age >65 years and body mass index <30.0 kg/m2. Patients who were transferred to an acute hospital and those with missing case data were excluded. According to the amount of EI, the patients were classified into energy sufficiency and shortage groups (EI/total energy expenditure ≥1.0 and <1.0, respectively). The Functional Independence Measure (FIM) and FIM gain were used to evaluate the patient disability level and change in patient status in response to rehabilitation. Finally, FIM gain was calculated as the discharge FIM score minus the admission FIM score. RESULTS: The final analysis targeted 202 patients-53 (26.2%) were in the energy shortage group and 149 (73.8%) were in the energy sufficiency group. The energy sufficiency group had a greater FIM gain than the energy shortage group (mean, 25.1±14.2 vs. 19.7±16.4; p=0.024). Furthermore, sufficient EI in the first week since admission (ß=0.165; 95% confidence interval, 0.392-5.230; p=0.023) was an independent factor of FIM gain. CONCLUSION: Among elderly patients with hip fracture admitted to rehabilitation hospitals in Japan, the amount of EI during the first week after admission was an independent factor of FIM gain.

A Novel Tube-Drainage Technique of Negative Pressure Wound Therapy for Fistulae after Reconstructive Surgery.

BACKGROUND: Patients with head and neck or esophageal cancer who undergo resection and reconstructive surgery sometimes develop fistulae that exhibit delayed wound healing. We developed a novel negative pressure wound therapy (NPWT) that employs a Penrose drain. This case series report describes its effect on the wound healing and treatment duration of cancer patients with postoperative fistulae. METHODS: This consecutive case series consisted of all patients from February 2014 to February 2017 who underwent resection and reconstruction for head and neck or esophageal cancer and who then developed a fistula that was treated with either NPWT or a second flap that did not resolve the fistula or led to fistula recurrence and was then treated with NPWT. A Penrose drainage tube was inserted into the fistula, and a NPWT device was applied. RESULTS: Eleven patients (10 males, 1 female; mean age, 67.4 years) underwent NPWT for fistulae that arose after tumor resection and reconstruction (n = 6) or after fistula reconstruction (n = 5). The resection was for esophageal (n = 4), laryngeal (n = 3), oral (n = 2), and hypopharyngeal (n = 2) cancer. In 9 cases, 1 week of NPWT led to rapid and complete wound healing. In 2 cases, complete healing occurred after 3-4 weeks of NPWT. CONCLUSIONS: Our NPWT applies continuous negative pressure inside the fistula only and dramatically promoted fistula healing. This approach may work by cleaning the fistula and promoting mucosal surface adhesion. It is particularly effective when the tissue surrounding the fistula is soft due to fresh tissue transfer.

Phlegmonous gastritis associated with advanced esophageal cancer.

Phlegmonous gastritis is a rapidly progressive bacterial infection of the stomach wall. It has a high mortality rate and aggressive treatment, either with antibiotics or surgical resection, is required. Here, we report an extremely rare case of phlegmonous gastritis associated with advanced esophageal cancer. A 65-year-old Japanese man was urgently admitted to the hospital due to pyrexia and gastrointestinal symptoms. Abdominal computed tomography revealed widespread diffuse thickening of the gastric wall. On endoscopic examination, an ulcerative mass was detected at the lower thoracic esophagus, and a markedly elevated submucosal lesion was present in the middle of the stomach body. Biopsy specimens taken endoscopically from the esophageal tumor confirmed a diagnosis of squamous cell carcinoma. Gastric biopsy cultures were positive for Streptococcus viridans, leading to a diagnosis of phlegmonous gastritis associated with esophageal cancer. After the patient's condition improved with preoperative antibiotic administration, we performed a thoracoscopic esophagectomy, a total gastrectomy and a reconstruction of the gastrointestinal tract using a pedicled right colon. Histological examination of the resected specimen confirmed that the gastric mass was compatible with a phlegmon.