How Does Omitting Additional Surgery After Local Excision Affect the Prognostic Outcome of Patients With High-risk T1 Colorectal Cancer?

OBJECTIVE: To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC). BACKGROUND: It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures. METHODS: Patients who had received LE for T1 CRC at the Japanese Society for Cancer of the Colon and Rectum institutions between 2009 and 2016 were analyzed. Those who had received additional surgical resection and those who did not were matched one-on-one by the propensity score-matching method. A total of 401 propensity score-matched pairs were extracted from 1975 patients at 27 Japanese Society for Cancer of the Colon and Rectum institutions and were compared. RESULTS: Regional lymph node metastasis was observed in 31 (7.7%) patients in the LE + surgery group. Comparatively, the incidence of oncologic adverse events was low in the LE-alone group, such as the 5-year cumulative risk of local recurrence (4.1%) or overall recurrence (5.5%). In addition, the difference in the 5-year cancer-specific survival between the LE + surgery and LE-alone groups was only 1.8% (99.7% and 97.9%, respectively), whereas the 5-year overall survival was significantly lower in the LE-alone group than in the LE + surgery group [88.5% vs 94.5%, respectively ( P = 0.002)]. CONCLUSIONS: Those who had decided to omit additional surgery at the dedicated center for CRC treatment presented a small number of oncologic events and a satisfactory cancer-specific survival, which may suggest an important role of risk assessment regarding nononcologic adverse events to achieve a best practice for each individual with high-risk T1 tumors.

The impact of combined PD-L1 positive score on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: Nivolumab is recommended for patients with advanced esophageal squamous cell carcinoma (aESCC) refractory or intolerant to fluoropyrimidine- and platinum-based chemotherapy regardless of the tumor proportion score (TPS). However, the role of combined positive score (CPS) in predicting nivolumab efficacy remains unclear. We aimed to study whether TPS or CPS is a more suitable biomarker for predicting nivolumab efficacy in these patients. METHODS: We retrospectively collected data from patients with aESCC treated with fluoropyrimidines and platinum and subsequently received nivolumab monotherapy between January 1, 2014 and September 15, 2020. Next, we evaluated the efficiencies of TPS and CPS in predicting the clinical response to nivolumab using PD-L1 IHC 22C3 pharmDx assay. RESULTS: This study included 50 patients (CPS groups: ≥ 10/1-10/ < 1, n = 24/18/8, respectively; TPS groups, ≥ 10%/1%-10%/ < 1%, n = 17/8/25, respectively). The median progression-free survival was 3.2, 2.5, and 1.5 months in the ≥ 10, 1-10 [hazard ratio (HR) vs. CPS of ≥ 10 group, 1.01; p = 0.98; adjusted HR, 1.33; p = 0.56], and < 1 CPS groups (HR vs. CPS of ≥ 10 group, 3.44; p = 0.006; adjusted HR, 1.67; p = 0.41), respectively. For the patients with CPS of ≥ 10/1-10/ < 1 and TPS of ≥ 10%/1%-10%/ < 1%, the objective response rate was 30%/25%/0% and 36%/0%/19% and the disease control rate was 60%/50%/12% (p = 0.06) and 65%/40%/38% (p = 0.30), respectively. CONCLUSIONS: This study suggests that a CPS of < 1 is not a strong predictor of efficacy but can predict the absence of response to nivolumab in patients with aESCC.

Biological characterization of adipose-derived regenerative cells used for the treatment of stress urinary incontinence.

OBJECTIVE: To assess the characteristics of adipose-derived regenerative cells, and provide supportive data explaining the mechanism of efficacy observed for the use of these cells in the treatment of stress urinary incontinence. METHODS: Adipose tissues were harvested by abdominal liposuction from healthy donors and patients with stress urinary incontinence. Adipose-derived regenerative cells were isolated from tissues using the Celution system, and assessed for their characteristics and ability to differentiate into smooth muscle cells. RESULTS: Adipose-derived regenerative cells isolated by the Celution system developed into fibroblastic colonies. Flow cytometric analysis of adipose-derived stem cell markers showed that adipose-derived regenerative cells were positive for CD34 and CD44, and negative for CD31. Immunofluorescence staining after differentiation showed that colony-forming cells were positive for alpha-smooth muscle actin, calponin and desmin, which are smooth muscle cell markers. A cytokine release assay showed that adherent cells secreted cytokines associated with angiogenesis, including vascular endothelial growth factor-A, angiopoietin-2 and placental growth factor. CONCLUSIONS: Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence.

O6-methylguanine DNA methyltransferase and glucose transporter 2 in foregut and hindgut gastrointestinal neuroendocrine neoplasms.

BACKGROUND: Streptozocin (STZ) is used for treating both pancreatic (PanNET) and gastrointestinal (GI-NET) neuroendocrine tumors but its therapeutic efficacy is relatively low in GI-NETs. Therefore, it has become pivotal to select GI-NET patients who could benefit from STZ treatment. STZ is transported via the glucose transporter 2 (GLUT2) into the cells and the loss of O6-methylguanine DNA methyltransferase (MGMT) also increases its therapeutic efficacy. Therefore, GLUT2 high and MGMT low status could be the surrogate markers of STZ. METHODS: In this study, we examined the MGMT and GLUT2 status in gastrointestinal neuroendocrine neoplasm (NEN). We studied 84 NEN cases: 33 foregut and 37 hindgut GI-NETs and 14 gastrointestinal neuroendocrine carcinomas (GI-NECs). RESULTS: In GI-NETs, MGMT scores of ≥2 and ≥ 3 were 77% (54/70) and 56% (39/70), respectively, and GLUT2 scores of ≥4 and ≥ 6 were 30% (21/70) and 4.3% (3/70), respectively. Methylation-specific polymerase chain reaction revealed that MGMT promoter methylation was detected only in 2/14 GI-NECs but none of the included GI-NETs. GLUT2 (GLUT2 score) and MGMT immunoreactivity (MGMT and H-scores) were both significantly correlated with Ki-67 labeling index (GLUT2 score: P = 0.0045, ρ = - 0.4570; MGMT score: P = 0.0064, ρ = - 0.4399; H-score: P = 0.0110, ρ = - 0.4135) and MGMT immunoreactivity were significantly correlated with GLUT2 immunoreactivity (MGMT score: P = 0.0198; H-score, P = 0.0004, ρ = 0.5483) in hindgut NETs, but not in foregut NETs. However, discrepancies from the above correlation between GLUT2 and MGMT immunoreactivity were detected in several GI-NET cases which could be potential candidates for STZ therapy. CONCLUSION: The evaluation of MGMT and GLUT2 status could provide an important information in planning STZ therapy in GI-NET patients.

Variations in clinical features and oncologic behaviors of T1 colorectal cancer according to tumor location.

BACKGROUND: Different genetic characteristics according to tumor location result in variations in survival rates and treatment responses in advanced colorectal cancer (CRC). However, the effects of tumor location during early CRC are still unclear. METHODS: Patients with T1 CRC treated between 2003 and 2019 were enrolled from a prospectively collected database. Patients were once divided into four groups, then combined into two groups (right- and left-sided CRC) according to the tumor location, and clinical features and oncologic behaviors were compared. RESULTS: In total, 458 patients were analyzed. Right-sided CRC had a lower incidence of polypoid type tumor than left-sided CRC (36/126 (28.6%) vs 186/332 (56.0%), p < 0.001). There were no differences in tumor size, pathological grade, pT1 substage and lymphovascular invasion between right- and left-sided CRC. Overall, lymph nodal involvement was observed in 42/458 (9.1%) patients. Right-sided CRC had a lower rate of patients with lymph nodal involvement than left-sided CRC (6/126 (4.8%) vs 36/332 (10.8%), p = 0.04). CONCLUSION: The present study revealed that there were significant differences in the macroscopic type and the incidence of lymph node involvement between right- and left-sided CRC. The clinical features and oncologic behaviors of T1 CRC are possible to vary according to tumor location.

Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose-derived regenerative cells: Outcome of the ADRESU study.

OBJECTIVES: To report the outcome of the ADRESU study, a multicenter, single-arm, investigator-initiated clinical trial to confirm the efficacy and safety of regenerative treatment for male patients with stress urinary incontinence. METHODS: The participants were male patients with mild-to-moderate stress urinary incontinence persisting for >1 year after prostatectomy. Autologous adipose-derived regenerative cells were isolated using the Celution system from adipose tissue obtained by liposuction. Adipose-derived regenerative cells and mixture of adipose-derived regenerative cells with adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The primary end-point was the proportion of patients with improvement of the urine leakage volume at 52 weeks (or last visit within 52 weeks). Improvement of leakage volume was defined as a decrease from baseline >50% by the 24-h pad test. A total of 10 secondary end-points were set. RESULTS: A total of 45 patients satisfying the eligibility criteria were enrolled. The primary end-point was met; the proportion of patients with improvement in leakage volume at 52 weeks was 37.2% (95% confidence interval 23.0-53.3%). No serious adverse events with causal relationships to the adipose-derived regenerative cells were encountered. There was a progressive improvement in secondary end-points. In the King's Health Questionnaire, improvement of quality of life scores showed greater improvement in responders, as compared with non-responders. CONCLUSIONS: Findings from the ADRESU study suggest the efficacy and safety of regenerative treatment for male patients with mild-to-moderate stress urinary incontinence.

Risk factor analysis for adverse events and stent dysfunction of endoscopic ultrasound-guided choledochoduodenostomy.

BACKGROUND AND AIMS: Although the technique of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is becoming standardized, its safety issues have not been sufficiently investigated. Therefore, we aimed to identify factors associated with adverse events and stent patency in EUS-CDS. METHODS: Consecutive patients who underwent EUS-CDS between September 2003 and July 2017 were included. Technical/clinical success, adverse events and stent dysfunctions were analyzed retrospectively. RESULTS: A total of 151 patients underwent EUS-CDS. In nine patients, procedures were discontinued before puncture. Technical and clinical success rates were 96.5% (137/142) and 98.5% (135/137), respectively. The adverse event rate was 20.4% (29/142). As a risk factor for peritonitis, plastic stents (PS) showed a significantly high odds ratio (OR) compared with covered self-expandable metal stents (CSEMS; OR, 4.31; P = 0.030). CSEMS cases showed a significantly longer patency period than PS cases (329 vs 89 days; HR, 0.35; P < 0.001). As a risk factor for early stent dysfunction (within 14 days), stent direction to the oral side showed a significantly high OR (OR, 43.47; P < 0.001). In cases with oblique-viewing EUS, double penetration of the duodenum occurred at significantly higher frequency than in cases with forward-viewing EUS (7.0 vs 0.0%; P = 0.024). CONCLUSIONS: Plastic stents and stent direction to the oral side were risk factors for peritonitis and early stent dysfunction, respectively. Using covered self-expandable metal stents and changing stent direction to the anal side seemed appropriate to prevent peritonitis and early stent dysfunction.

Treatment of male stress urinary incontinence using autologous adipose-derived regenerative cells: Long-term efficacy and safety.

OBJECTIVES: To investigate the long-term efficacy and safety of periurethral injection of autologous adipose-derived regenerative cells for the treatment of post-prostatectomy stress urinary incontinence. METHODS: A total of 13 patients with persistent stress urinary incontinence after prostate surgery (radical prostatectomy, 10 patients; holmium laser enucleation of the prostate, three patients) underwent periurethral injection of adipose-derived regenerative cells and were followed up for >4 years. A 24-h pad test was carried out for four consecutive days in each evaluation period, and changes in the mean daily leakage volume during the 4 days from baseline to 60 months after treatment were evaluated. RESULTS: The mean follow-up period was 69 months (range 55-72 months). The mean leakage volume/24 h in all patients changed from 260.7 g to 152.7 g. Urinary incontinence progressively improved up to 12 months after treatment in 10 patients, who maintained improvement up to the final assessment, with the mean daily leakage volume decreasing from 281.5 g to 119.0 g (reduction rate 57.7%). The other three patients showed no improvement at 1 year and at the final assessment. After the perioperative period, significant adverse events or prostate-specific antigen increase were not observed during long-term follow up. CONCLUSIONS: The present findings suggest that periurethral injection of autologous adipose-derived regenerative cells is a safe and feasible treatment modality with long-term efficacy for patients with male stress urinary incontinence caused by urethral sphincter deficiency.

[Diagnosis of pancreatic neuroendocrine tumor led to diagnosis of multiple endocrine neoplasia type 1:a report of two cases].

Two cases of multiple endocrine neoplasia type 1 are reported. In both cases, computed tomography (CT) showed hypervascular lesions of the pancreas. Endoscopic ultrasound showed multiple lesions in the pancreas, and each case was diagnosed as pancreatic neuroendocrine tumor by EUS-FNA. In addition to a pancreatic neuroendocrine tumor, case 1 had hyperparathyroidism and case 2 had a history of parathyroid tumor. Furthermore, case 1 had a family history of pancreatic tumor and case 2 had a family history of pancreatic tumor and parathyroid resection. From these indications, multiple endocrine neoplasia type 1 was diagnosed by genetic testing. As demonstrated in these two cases, it is important to consider multiple endocrine neoplasia type 1 when diagnosing pancreatic neuroendocrine tumor.

Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol.

BACKGROUND: Male stress urinary incontinence is a prevalent condition after radical prostatectomy. While the standard recommendation for the management of urine leakage is pelvic floor muscle training, its efficacy is still unsatisfactory. Therefore, we have focused on regenerative therapy, which consists of administering a periurethral injection of autologous regenerative cells from adipose tissue, separated using the Celution® system. Based on an interim data analysis of our exploratory study, we confirmed the efficacy and acceptable safety profile of this treatment. Accordingly, we began discussions with Japanese regulatory authorities regarding the development of this therapy in Japan. The Ministry of Health, Labour and Welfare suggested that we implement a clinical trial of a new medical device based on the Pharmaceutical Affaires Act in Japan. Next, we discussed the design of this investigator-initiated clinical trial (the ADRESU study) aimed at evaluating the efficacy and safety of this therapy, in a consultation meeting with the Pharmaceuticals and Medical Device Agency. METHODS: The ADRESU study is an open-label, multi-center, single-arm study involving a total of 45 male stress urinary incontinence patients with mild-to-moderate urine leakage persisting more than 1 year after prostatectomy, in spite of behavioral and pharmacological therapies. The primary endpoint is the rate of patients at 52 weeks with improvement of urine leakage volume defined as a reduction from baseline greater than 50% by 24-h pad test. Our specific hypothesis is that the primary endpoint result will be higher than a pre-specified threshold of 10%. DISCUSSION: The ADRESU study is the first clinical trial of regenerative treatment for stress urinary incontinence by adipose-derived regenerative cells using the Celution® system based on the Japanese Pharmaceutical Affaires Act. We will evaluate the efficacy and safety in this trial to provide an adequate basis for marketing approval with the final objective of making this novel therapy widely available for Japanese patients. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical information Network Clinical Trial Registry (UMIN-CTR Unique ID: UMIN000017901 ; Registered July 1, 2015) and at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02529865 ; Registered August 18, 2015).

A case of API2-MALT1-positive gastric MALT lymphoma with concomitant diffuse large B-cell lymphoma.

API2-MALT1 translocation-positive gastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphoma is thought to transform to diffuse large B-cell lymphoma (DLBCL) rarely. A 69-year-old man presented with epigastralgia. Esophagogastroduodenoscopy showed multiple ulcerations in the stomach. Endoscopic biopsies revealed MALT lymphoma, with Helicobacter pylori infection. The patient underwent eradication therapy with no improvement, and was thereafter followed without additional therapy at his request. Twelve years after initial diagnosis, follow-up computed tomography (CT) showed multiple nodules in bilateral lungs, and a needle biopsy revealed MALT lymphoma, the same as in the stomach and API2-MALT1 translocation was found. Because he again refused additional therapy, follow-up was continued. 15 years after initial diagnosis, CT showed lymphadenopathy at the splenic hilum. At first we suspected disease progression of gastric MALT lymphoma, however a needle biopsy revealed DLBCL without API2-MALT1. Thus, the tumor at the splenic hilum was finally diagnosed as a de novo DLBCL as a second malignancy. Although treatment with rituximab given his age and his wishes was attempted, he died of DLBCL 15 years after the initial diagnosis. We experienced an API2-MALT1-positive gastric MALT lymphoma with concomitant DLBCL, not transformed to DLBCL over a 15-year clinical course.

Effects of Tissue Component Volumes on Vascular Resistance in Free Flaps.

Background A successful free flap transfer is achieved, in part, by having a thorough understanding of vascular anatomy and blood flow dynamics. We previously reported that vascular resistance differs by type of free flap. To test the hypothesis that the difference reflects the proportion of tissue components within free flaps, we calculated blood flow and vascular resistance for free flaps in which we determined the volume of each tissue component. Methods Measurements and calculations were made for 40 free flap transfers performed at our hospital: 7 radial forearm flaps, 14 anterolateral thigh flaps, and 19 rectus abdominis myocutaneous flaps. Results The vascular resistance of free flaps was inversely related to the volume of each tissue component. Univariate regression analysis revealed that muscle volume correlated most closely with resistance (r = 0.881), followed by skin (r = 0.622), and fat (r = 0.577). Multiple regression analysis confirmed the relationship between combined muscle and fat volume and resistance (R2 = 0.865). Conclusions A strong inverse correlation exists between vascular resistance and combined muscle and fat tissue volume in flaps. It may be helpful to consider these relationships when making decisions regarding choice of free flap and recipient vessels.

Post-operative pulmonary and shoulder function after sternal reconstruction for patients with chest wall sarcomas.

BACKGROUND: Sternal resection is occasionally required for patients with malignant tumors, particularly sarcomas, in the sternal region. Few reports have described post-operative respiratory and shoulder function after sternal resection for patients with bone and soft-tissue sarcomas. METHODS: Eight consecutive patients with bone and soft tissue sarcomas requiring sternal resection were the focus of this study. Chest wall was reconstructed with a non-rigid or semi-rigid prosthesis combined, in most cases, with soft tissue flap reconstruction. Clinical outcomes investigated included complications, shoulder function, evaluated with Musculoskeletal Tumor Society-International Symposium of Limb Salvage system, and respiratory function, evaluated by use of spirometry. RESULTS: The anterior chest wall was reconstructed with non-rigid strings for 3 patients and with polypropylene mesh for 5. There were no severe post-operative complications, for example surgical site infection or pneumonia. All 3 patients with non-rigid reconstruction experienced paradoxical breathing, whereas none with polypropylene mesh did so. Post-operatively, FEV(1)% was unchanged but %VC was significantly reduced (p = 0.01), irrespective of the reconstruction method used (strings or polypropylene mesh). Shoulder function was not impaired. CONCLUSIONS: Among patients undergoing sternal resection, post-operative shoulder function was excellent. Pulmonary function was slightly restricted, but not sufficiently so to interfere with the activities of daily living (ADL). Paradoxical breathing is a slight concern for non-rigid reconstruction.

Non-rigid reconstruction of chest wall defects after resection of musculoskeletal tumors.

PURPOSE: We analyzed the techniques used and the complications occurring in chest wall reconstruction after resection of musculoskeletal tumors to identify the optimal reconstruction method. METHODS: The medical records of 50 patients with primary or metastatic malignant tumors requiring chest wall full thickness resection were retrospectively reviewed. The surgical technique and rate of postoperative complications were investigated, and the factors influencing complications were identified. RESULTS: Flap transfer was used in 23 cases (46 %). For skeletal reconstruction, a prosthetic mesh was used in 19 cases. In 18 recent cases, no prosthetic mesh was used, and patients were treated using only suture stabilization. Postoperative complications were recognized in 11 cases (22 %). The analysis of factors influencing the development of complications identified the use of preoperative adjuvant chemotherapy (p < 0.05), the bone as the primary site (p < 0.05), an anterolateral location (p = 0.081) and resection of ≥ 3 ribs (p = 0.077) as significant factors. No significant difference in the rate of complications was noted between the groups divided based on whether mesh was used. CONCLUSION: We used non-rigid reconstruction for full thickness resection of the chest wall, and achieved good postoperative outcomes with no grade 4 complications or perioperative mortality. Non-rigid reconstruction using flap transfers and careful respiratory management is a useful method for treating patients requiring chest wall full thickness resection.

Skin-derived precursor cells promote wound healing in diabetic mice.

BACKGROUND: Impaired wound healing as one of the complications arising from diabetes mellitus is a serious clinical issue. Recently, various cell therapies have been reported for promotion of wound healing. Skin-derived precursor cells (SKPs) are multipotent adult stem cells with the tendency to differentiate into neurons. We investigated the potency of promoting diabetic wound healing by the application of SKPs. METHODS: Skin-derived precursor cells isolated from diabetic murine skin were cultured in sphere formation medium. At passage 2, they were suspended in phosphate-buffered saline (PBS), and applied topically to full-thickness excisional cutaneous wounds in diabetic mice. Application of PBS served as controls (n = 21 for each group; n = 42 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 10 and 28 days and then processed, sectioned, and stained (CD31, α-smooth muscle actin, and neurofilament heavy chain) to quantify vascularity and neurofilaments. RESULTS: Wounds treated with SKPs demonstrated a significantly decreased time to closure (18.63 days) compared with PBS-control wounds (21.72 days, P < 0.01), and a significant improvement in percentage closure at 7, 10, 14, and 18 days compared with PBS-control wounds (P < 0.01). Histological analysis showed that the Capillary Score (the number of vessels/mm2) was significantly higher in SKP-treated wounds at day 10 but not at day 28. Nerve Density (the number of neurofilaments/mm2) had increased significantly in SKP-treated wounds at day 28 compared with control group. Some applied SKPs were stained by neurofilament heavy chain, which demonstrates that SKPs directly differentiated into neurons. CONCLUSIONS: Skin-derived precursor cells promoted diabetic wound healings through vasculogenesis at the early stage of wound healing. Skin-derived precursor cells are a possible therapeutic tool for diabetic impaired wound healing.

Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients.

OBJECTIVES: To assess the efficacy and safety of a novel cell therapy for male stress urinary incontinence consisting of periurethral injection of autologous adipose-derived regenerative cells, and to determine the 1-year outcomes. METHODS: A total of 11 male patients with persistent stress urinary incontinence after prostate surgery were included in the study. The Celution system was used to isolate adipose-derived regenerative cells from abdominal adipose tissue obtained by liposuction. Subsequently, these regenerative cells, and a mixture of regenerative cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The 1-year outcomes were assessed using a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography and magnetic resonance imaging. RESULTS: Stress urinary incontinence improved progressively in eight patients during the 1-year follow up, as determined by a 59.8% decrease in the leakage volume in the 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life. One patient achieved total continence. The mean maximum urethral closing pressure and functional profile length increased from 35.5 to 44.7 cmH2O, and from 20.4 to 26.0 mm, respectively. Magnetic resonance imaging showed the sustained presence of the injected adipose tissue, and enhanced ultrasonography showed a progressive increase in blood flow to the injected area in all patients. No significant adverse events were observed peri- or postoperatively. CONCLUSION: Periurethral injection of autologous adipose-derived regenerative cells might represent a safe and feasible treatment modality for male stress urinary incontinence.

Surgical correction of microstomia in a patient with antilaminin 332 mucous membrane pemphigoid.

Microstomia is a term used to describe a small oral aperture. Most of the reported cases are caused by scar contracture after facial trauma, burn injury, and tumor excision. We experienced a rare case of microstomia in a patient with antilaminin 332 mucous membrane pemphigoid, which was an acquired autoimmune disease and showed blisters and erosive lesions mainly on the mucous membranes. The patient had recurrent aphthous stomatitis and presented microstomia caused by scar contracture of oral mucosa. We surgically corrected microstomia by 5-flap Z-plasty for commissuroplasty and 2 Z-plasty of both upper and lower lips for an enlargement of oral aperture. The patient could achieve an enough oral aperture and was satisfied with the result. There was no recurrence of microstomia for 2 years.

HNF6 and HNF4α expression in adenocarcinomas of the liver, pancreaticobiliary tract, and gastrointestinal tract: an immunohistochemical study of 480 adenocarcinomas of the digestive system.

Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and humans. However, little is known about the prevalence of HNF6 and HNF4α expression in carcinomas of the hepatobiliary tract and pancreas. We aimed to reveal the diagnostic utility of HNF6 and HNF4α immunolabelling in adenocarcinomas of these organs. We investigated HNF6 and HNF4α expression by immunohistochemistry using a total of 480 adenocarcinomas of the digestive system, including 282 of the hepatobiliary tract and pancreas and 198 of the gastrointestinal tract. HNF6 expression was primarily restricted to intrahepatic cholangiocarcinomas (CCs) (63%, n=80) and gallbladder adenocarcinomas (43%, n=88), among others. Notably, small duct intrahepatic CCs almost invariably expressed HNF6 (90%, n=42), showing stark contrast to a low prevalence in large duct intrahepatic CCs (10%, n=21; p<0.0001). HNF6 expression was infrequent in extrahepatic CCs (9%, n=55) and pancreatic ductal adenocarcinomas (7%, n=58), and it was rare in adenocarcinomas of the gastrointestinal tract [oesophagus/oesophagogastric junction (EGJ) (2%, n=45), stomach (2%, n=86), duodenum (0%, n=25), and colorectum (0%, n=42)]. In contrast, HNF4α was widely expressed among adenocarcinomas of the digestive system, including intrahepatic CCs (88%), extrahepatic CCs (94%), adenocarcinomas of the gallbladder (98%), pancreas (98%), oesophagus/EGJ (96%), stomach (98%), duodenum (80%), and colorectum (100%). HNF6 was frequently expressed in and almost restricted to intrahepatic CCs of small duct type and gallbladder adenocarcinomas, while HNF4α was expressed throughout adenocarcinomas of the digestive system. HNF6 immunolabelling may be useful in distinguishing small duct intrahepatic CCs from other types of CC as well as metastatic gastrointestinal adenocarcinomas.

A Shaped Pectoralis Major Muscle Flap under Indocyanine Green Fluorescence Angiography for Sternal Wound Infection.

The treatment of a sternal wound infection is challenging because it requires radical debridement and reconstruction with a well-vascularized flap. The defects after debridement are three-dimensionally complex, especially if synthetic grafts are involved. Although the pectoralis major muscle (PMM) flap is useful for reconstruction, it is difficult to fill up the complex dead space surrounding the vascular prosthesis when using a conventional PMM flap. Herein, we describe a new technique of splitting and shaping the PMM flap to fit the complex defect. Intraoperative indocyanine green fluorescence angiography was used to assess dynamic blood flow of the PMM supplied by internal mammary artery perforators. This technique allows the PMM flap to be split and shaped to securely fit the dead space, which may improve the healing rate.

Negative pressure wound therapy for a large skin ulcer following repair of huge myeloschisis with kyphosis in a newborn.

BACKGROUND: In surgery of repair for spina bifida, various skin plastic techniques are sometimes necessary due to large skin defect or subsequent ulcers in cases when approximation on the midline is difficult. CASE REPORT: A baby was born with a large skin defect due to huge lumbar myeloschisis and kyphosis, which was repaired 2 days after birth using Limberg's skin flap at the peak of kyphosis. Skin ischemia around the tip of the flap gradually enlarged and resulted in a large skin ulcer. We performed negative pressure wound therapy (NPWT) using a Vacuum Assisted Closure (V.A.C.®) therapy system for 4 weeks which shrank the ulcer remarkably. Subsequently, a pedicle skin flap without graft was performed to cover the rest of the ulcer, which adapted well without CSF leakage postoperatively. CONCLUSION: A combination treatment of NPWT and skin plastic surgery was successfully performed for a very young infant with spina bifida. NPWT could be another useful option for the treatment of ulcer following spina bifida repair surgery, though surgeons should carefully confirm that there is no CSF leakage before and during the procedure.