Worldwide, more than 20 million patients undergo groin hernia repair annually. The many different approaches, treatment indications and a significant array of techniques for groin hernia repair warrant guidelines to standardize care, minimize complications, and improve results. The main goal of these guidelines is to improve patient outcomes, specifically to decrease recurrence rates and reduce chronic pain, the most frequent problems following groin hernia repair. They have been endorsed by all five continental hernia societies, the International Endo Hernia Society and the European Association for Endoscopic Surgery. 
An expert group of international surgeons (the HerniaSurge Group) and one anesthesiologist pain expert was formed. The group consisted of members from all continents with specific experience in hernia-related research. Care was taken to include surgeons who perform different types of repair and had preferably performed research on groin hernia surgery. During the Group's first meeting, evidence-based medicine (EBM) training occurred and 166 key questions (KQ) were formulated. EBM rules were followed in complete literature searches (including a complete search by The Dutch Cochrane database) to January 1, 2015 and to July 1, 2015 for level 1 publications. The articles were scored by teams of two or three according to Oxford, SIGN and Grade methodologies. During five 2-day meetings, results were discussed with the working group members leading to 136 statements and 88 recommendations. Recommendations were graded as "strong" (recommendations) or "weak" (suggestions) and by consensus in some cases upgraded. In the Results and summary section below, the term "should" refers to a recommendation. The AGREE II instrument was used to validate the guidelines. An external review was performed by three international experts. They recommended the guidelines with high scores. 
The risk factors for inguinal hernia (IH) include: family history, previous contra-lateral hernia, male gender, age, abnormal collagen metabolism, prostatectomy, and low body mass index. Peri-operative risk factors for recurrence include poor surgical techniques, low surgical volumes, surgical inexperience and local anesthesia. These should be considered when treating IH patients. IH diagnosis can be confirmed by physical examination alone in the vast majority of patients with appropriate signs and symptoms. Rarely, ultrasound is necessary. Less commonly still, a dynamic MRI or CT scan or herniography may be needed. The EHS classification system is suggested to stratify IH patients for tailored treatment, research and audit. Symptomatic groin hernias should be treated surgically. Asymptomatic or minimally symptomatic male IH patients may be managed with "watchful waiting" since their risk of hernia-related emergencies is low. The majority of these individuals will eventually require surgery; therefore, surgical risks and the watchful waiting strategy should be discussed with patients. Surgical treatment should be tailored to the surgeon's expertise, patient- and hernia-related characteristics and local/national resources. Furthermore, patient health-related, life style and social factors should all influence the shared decision-making process leading up to hernia management. Mesh repair is recommended as first choice, either by an open procedure or a laparo-endoscopic repair technique. One standard repair technique for all groin hernias does not exist. It is recommended that surgeons/surgical services provide both anterior and posterior approach options. Lichtenstein and laparo-endoscopic repair are best evaluated. Many other techniques need further evaluation. Provided that resources and expertise are available, laparo-endoscopic techniques have faster recovery times, lower chronic pain risk and are cost effective. There is discussion concerning laparo-endoscopic management of potential bilateral hernias (occult hernia issue). After patient consent, during TAPP, the contra-lateral side should be inspected. This is not suggested during unilateral TEP repair. After appropriate discussions with patients concerning results tissue repair (first choice is the Shouldice technique) can be offered. Day surgery is recommended for the majority of groin hernia repair provided aftercare is organized. Surgeons should be aware of the intrinsic characteristics of the meshes they use. Use of so-called low-weight mesh may have slight short-term benefits like reduced postoperative pain and shorter convalescence, but are not associated with better longer-term outcomes like recurrence and chronic pain. Mesh selection on weight alone is not recommended. The incidence of erosion seems higher with plug versus flat mesh. It is suggested not to use plug repair techniques. The use of other implants to replace the standard flat mesh in the Lichtenstein technique is currently not recommended. In almost all cases, mesh fixation in TEP is unnecessary. In both TEP and TAPP it is recommended to fix mesh in M3 hernias (large medial) to reduce recurrence risk. Antibiotic prophylaxis in average-risk patients in low-risk environments is not recommended in open surgery. In laparo-endoscopic repair it is never recommended. Local anesthesia in open repair has many advantages, and its use is recommended provided the surgeon is experienced in this technique. 
General anesthesia is suggested over regional in patients aged 65 and older as it might be associated with fewer complications like myocardial infarction, pneumonia and thromboembolism. Perioperative field blocks and/or subfascial/subcutaneous infiltrations are recommended in all cases of open repair. Patients are recommended to resume normal activities without restrictions as soon as they feel comfortable. Provided expertise is available, it is suggested that women with groin hernias undergo laparo-endoscopic repair in order to decrease the risk of chronic pain and avoid missing a femoral hernia. Watchful waiting is suggested in pregnant women as groin swelling most often consists of self-limited round ligament varicosities. Timely mesh repair by a laparo-endoscopic approach is suggested for femoral hernias provided expertise is available. All complications of groin hernia management are discussed in an extensive chapter on the topic. Overall, the incidence of clinically significant chronic pain is in the 10-12% range, decreasing over time. Debilitating chronic pain affecting normal daily activities or work ranges from 0.5 to 6%. Chronic postoperative inguinal pain (CPIP) is defined as bothersome moderate pain impacting daily activities lasting at least 3 months postoperatively and decreasing over time. CPIP risk factors include: young age, female gender, high preoperative pain, early high postoperative pain, recurrent hernia and open repair. For CPIP the focus should be on nerve recognition in open surgery and, in selected cases, prophylactic pragmatic nerve resection (planned resection is not suggested). It is suggested that CPIP management be performed by multi-disciplinary teams. It is also suggested that CPIP be managed by a combination of pharmacological and interventional measures and, if this is unsuccessful, followed by, in selected cases (triple) neurectomy and (in selected cases) mesh removal. For recurrent hernia after anterior repair, posterior repair is recommended. If recurrence occurs after a posterior repair, an anterior repair is recommended. After a failed anterior and posterior approach, management by a specialist hernia surgeon is recommended. Risk factors for hernia incarceration/strangulation include: female gender, femoral hernia and a history of hospitalization related to groin hernia. It is suggested that treatment of emergencies be tailored according to patient- and hernia-related factors, local expertise and resources. Learning curves vary between different techniques. Probably about 100 supervised laparo-endoscopic repairs are needed to achieve the same results as open mesh surgery like Lichtenstein. It is suggested that case load per surgeon is more important than center volume. It is recommended that minimum requirements be developed to certify individuals as expert hernia surgeon. The same is true for the designation "Hernia Center". From a cost-effectiveness perspective, day-case laparoscopic IH repair with minimal use of disposables is recommended. The development and implementation of national groin hernia registries in every country (or region, in the case of small country populations) is suggested. They should include patient follow-up data and account for local healthcare structures. A dissemination and implementation plan of the guidelines will be developed by global (HerniaSurge), regional (international societies) and local (national chapters) initiatives through internet websites, social media and smartphone apps. 
An overarching plan to improve access to safe IH surgery in low-resource settings (LRSs) is needed. It is suggested that this plan contains simple guidelines and a sustainability strategy, independent of international aid. It is suggested that in LRSs the focus be on performing high-volume Lichtenstein repair under local anesthesia using low-cost mesh. Three chapters discuss future research, guidelines for general practitioners and guidelines for patients. 
The HerniaSurge Group has developed these extensive and inclusive guidelines for the management of adult groin hernia patients. It is hoped that they will lead to better outcomes for groin hernia patients wherever they live. More knowledge, better training, national audit and specialization in groin hernia management will standardize care for these patients, lead to more effective and efficient healthcare and provide direction for future research.

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International guidelines for groin hernia management

Establishment of a Novel Human Megakaryoblastic Leukemia Cell Line, MEG-01, With Positive Philadelphia Chromosome

Studies of the biosynthesis and catabolism of various immunoglobulin (Ig) isotypes have revealed that in humans and some animal species, IgA is produced in quantities that exceed those of all other isotypes (1, 2). Thus in an adult, the synthetic rates (rag of Ig/kg body weight/day) are approximately 66 for IgA, 34 for IgG, 7.9 for IgM, 0.4 for IgD, and 0.02 for IgE (2, 3). Serum IgA is derived primarily from the bone marrow, while IgA destined for external secretions is synthesized locally in mucosa-associated tissues and glands. Interestingly, in humans predominantly monomeric IgA from the systemic pool contributes little to external secretions, and vice versa, locally produced polymeric IgA is selectively transported into external secretions, and only small amounts of this IgA enter the circulation (1, 2). Since individual plasma cells secrete immunoglobulins of various isotypes at approximately the same rate, it follows that in humans, IgA-producing cells in the systemic and secretory compartments greatly outnumber those secreting other isotypes. Indeed, enumeration of Ig-producing cells in various tissues indicated that 1-2 m of human intestine contained more Ig-

Regulation of IgA synthesis and immune response by T cells and interleukins.

Historically, human NK cells have been identified as CD3-CD56+CD16+/- lymphocytes. More recently it has been established that CD57 expression defines functionally discrete subpopulations of NK cells. On T cells, CD57 expression has been regarded as a marker of terminal differentiation and (perhaps wrongly) of anergy and senescence. Similarly, CD57 expression seems to identify the final stages of peripheral NK cell maturation; its expression increases with age and is associated with chronic infections, particularly human cytomegalovirus. However, CD57+ NK cells are highly cytotoxic and their presence seems to be beneficial in a number of non-communicable diseases. The purpose of this article is to review our current understanding of CD57 expression as a marker of NK cell function and disease prognosis, as well as to outline areas for further research.

/pdf/functional-significance-of-cd57-expression-on-human-nk-cells-4pemuev0xk.pdf

Functional Significance of CD57 Expression on Human NK Cells and Relevance to Disease

Using peroxidase-antiperoxidase (PAP) method, carcinoembryonic antigen (CEA) was demonstrated in conventionally processed colorectal cancer tissues A new immunohistochemical grading for colorectal cancers based on the mode of the localization was made in an attempt to clarify the factors responsible for elevation of plasma CEA levels in colorectal cancer patients Most of the patients with well differentiated adenocarcinoma, in which CEA was densely distributed along the apical surface but only rarely present along the basolateral surfaces of the carcinoma cells, had very low levels of plasma CEA, whereas all patients showing CEA distribution in the stroma as well as over the entire surfaces of the cancer cells and their cytoplasm showed high plasma CEA levels In addition, there was a good correlation between the grading and presence of the blood vessel and lymphatic invasions Thus, the appearance of CEA in the surrounding stroma, due to abnormal distribution of CEA on the basolateral plasma membrane of cancer cells, may play a significant role in the elevation of plasma CEA levels in colorectal cancer patients

Immunohistochemical study of carcinoembryonic antigen in patients with colorectal cancer. Correlation with plasma carcinoembryonic antigen levels.

Carcinoembryonic antigen (CEA) and secretory component (SC) were localized by peroxidase-labeled antibody immunocytochemistry in normal and abnormal human gastric mucosa. In normal epithelium, both glycoproteins were absent or only faintly present, but in intestinal metaplasia and carcinoma both were prominently present. CEA and SC on the surfaces of metaplastic epithelial cells were polarized. That is, CEA was expressed only on the microvillous surface and SC was expressed only on the basolateral surface. In gastric cancer, CEA and SC were distributed over the entire surface of the neoplastic cells. Thus, deviations from the normal differentiation and maturation of gastric epithelial cells were accompanied by abnormalities in surface expression of CEA and SC. These observations, together with compatible observations previously made in colonic neoplasia (DJ Ahnen, PK Nakane, and WR Brown, Cancer 49:2077, 1982), suggest that loss of polarity of surface membrane components is a characteristic of neoplastic epithelial cells.

Immunohistochemistry of Gastric Carcinomas and Associated Diseases: Novel Distribution of Carcinoembryonic Antigen and Secretory Component on the Surface of Gastric Cancer Cells'

Leu 7 immunoreactivity was demonstrated with the indirect peroxidase-labelled antibody method on frozen and paraffin-embedded tissue sections of human digestive organs. Anti-Leu 7 monoclonal antibody, which allegedly detects mononuclear cells with natural killer or killer activity, recognized lymphoid cells among intestinal epithelial cells and in the germinal centres of solitary lymphoid follicles of small and large intestine, and a few in gallbladder, liver and the lamina propria of the intestine. In addition, peripheral nerve fibres, endocrine cells in the gut and pancreas and carcinoid and islet cell tumours were also positively stained. At the ultrastructural level, Leu 7 antigen was localized on the plasma membrane of granulated lymphoid cells in the gut mucosa and on the secretory granules of intestinal endocrine cells. In normal pancreas, Leu 7 immunoreactivity was demonstrated in most cells containing pancreatic polypeptide and in many cells containing somatostatin or glicentin. Insulin-containing cells, however, lacked Leu 7 immunoreactant. These findings were obtained in both frozen sections and paraffin-embedded sections. The possible cross-reactivities of monoclonal antibodies are discussed as they raise an important caveat in immunohistochemical studies using these antibodies.

Distribution of Leu 7 (HNK-1) antigen in human digestive organs: an immunohistochemical study with monoclonal antibody.

Purpose
No consensus has been reached on the use of prostheses in a potentially infected operating field. In this study, we evaluated the validity of a mesh prosthesis for the repair of incarcerated groin hernias with intestinal resection.

Prosthetic repair of an incarcerated groin hernia with small intestinal resection

Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor. We report on a patient who underwent hepatectomy for malignant HEH associated with abdominal pain due to rapid progression. An 83-year-old man was admitted to Nippon Medical School Hospital because of acute, severe upper abdominal pain. Seven months before admission, a hepatic tumor, 3 cm in diameter, had been detected in the left lateral sector. The diagnosis was hepatic cavernous hemangioma. Abdominal ultrasonography revealed a heterogeneous hyperechoic tumor with a smooth border, 6 cm in diameter, in the left lateral sector (segment 3). Contrast-enhanced computed tomography of the abdomen showed that the tumor was enhanced from the early to the late phase. Abdominal angiography revealed a cotton wool-like appearance of the tumor. The diagnosis was hepatic cavernous hemangioma. A malignancy could not be ruled out because of the tumor's rapid growth, which had caused abdominal pain. Left hepatectomy was performed. Histopathological examination showed necrosis throughout the tumor. Slightly pleomorphic neoplastic cells with rounded, spindle-like nuclei and scant cytoplasm were sporadically found in vascular channels. Intracytoplasmic lumina occasionally contained red cells. Neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34. The Mib-1 index was high. The tumor was diagnosed as malignant HEH. The postsurgical course was uneventful, and the patient was discharged on postoperative day 11. After 3 months, multiple metastatic tumors appeared in right hepatic lobe. Transcatheter arterial chemoembolization was performed.

Malignant hepatic epithelioid hemangioendothelioma with abdominal pain due to rapid progression.

An 80-year-old woman was admitted to our hospital with severe chest and back pains after vomiting. Computed tomography (CT) of the chest revealed left-sided pneumothorax and pleural effusion. Some food was drained from an inserted chest tube, and we diagnosed spontaneous esophageal rupture (Boerhaave's syndrome). A left thoracotomy was performed 7 hours after the onset of symptoms. A 3-cm perforation was discovered in the lateral wall of the distal esophagus. The perforation was repaired with a primary two-layered closure and covered with pericardial fat. The patient had a good postoperative course and was discharged 1 month after surgery. This case suggests the importance of early surgical treatment, even in elderly patients with spontaneous esophageal rupture.

Yoshinobu Shioda

Papers

Immunohistochemistry of Gastric Carcinomas and Associated Diseases: Novel Distribution of Carcinoembryonic Antigen and Secretory Component on the Surface of Gastric Cancer Cells'

Distribution of Leu 7 (HNK-1) antigen in human digestive organs: an immunohistochemical study with monoclonal antibody.

Prosthetic repair of an incarcerated groin hernia with small intestinal resection

Malignant hepatic epithelioid hemangioendothelioma with abdominal pain due to rapid progression.

Successful treatment of a spontaneous esophageal rupture in an elderly patient: a case report.