Gastrointestinal carcinoma and sarcoma surgery

A number of advances in both earlier diagnostic imaging and better treatment options for patients with intra-abdominal malignancies have occurred. Frequently such newer therapies rely on the integration of established surgical and radiation approaches potentially with newer chemotherapies and immunomodulators. Unfortunately, with further study some newer therapies have proven less beneficial than initially suggested. Keeping up with the data supporting newer alternatives, and determining which therapies to provide patients can be a challenge. Nonetheless, integrating newer study data into beneficial therapeutic algorithms and understanding the molecular basis and rationale for new therapies remains a critically important role for treating physicians. To help provide busy clinicians and trainees with a current update for the management of intra-abdominal malignancies, this special issue of Translational Gastroenterology and Hepatology provides succinct reviews relevant to both diagnosis and treatment for patients with abdominal sarcoma or adenocarcinoma

Interleukin-6/ GP80-dependent pathways role in physiologic cachexia during liver regeneration after partial hepatectomy

poster abstractLiver has a unique capacity to regenerate its mass after tissue loss. Many of the cytokines and growth factors were shown to be critical in liver regeneration. Studies with interleukin-6 (IL-6) – deficient mice demonstrated that IL-6 plays central role in hepatocyte proliferation via activating signal transducer and activator of transcription 3 (STAT3). The biological activities of IL-6 are potentiated when it binds to an 80 kDa IL-6 (IL-6Ra) receptor located on target cells. IL-6 and Il-6Ra complex then associates with another glycoprotein, gp130, to initiate intracellular signaling. Another of many IL-6 functions is metabolic control of the body. Increased activation of IL6 and STAT3 due to acute body injury, such as partial hepatectomy, causes metabolic dysregulation associated with sustained muscle and adipose tissue loss, a condition called physiologic Cachexia. Two lines of trangenic mice with conditional knockout of gp 80 in the liver and conditional knockout of gp 80 in the muscle were generated to investigate the role of Il6 in liver regeneration and concomitant muscle wasting after partial hepatectomy. Here, we report that specific interruption of IL-6 pathway in the liver was presented with normal liver regeneration but associated with increased animal mortality after partial hepatectomy. Conversely, specific abrogation of IL-6 pathway in muscle lead to increased liver regeneration that did not increase muscle or adipose tissue wasting. These findings suggest that IL-6 pathway may play a central role in the liver regeneration and muscle wasting axis

Role for targeted resection in the multidisciplinary treatment of metastatic gastrointestinal stromal tumor

The management of advanced gastrointestinal stromal tumors (GISTs) has evolved in the modern era due to the discovery of c-kit mutations and the development of tyrosine kinase inhibitors (TKIs). Until the advent of TKIs such as imatinib, the median survival reported for patients with advanced GIST was 19 months. Although surgery is the treatment of choice for resectable primary GIST, its role in cases of recurrence and metastasis remains to be unclear. This review outlines the potential beneficial role of repeat surgical resection in the multidisciplinary treatment of advanced GIST in the era of TKIs

A Surgery Trainee’s Guide to Writing a Manuscript

Publishing clinical and research work for dissemination is a critical part of the academic process. Learning how to write an effective manuscript should be a goal for medical students and residents who hope to participate in publishing. While there are a number of existing texts that address how to write a manuscript, there are fewer guides that are specifically targeted towards surgery trainees. This review aims to direct and hopefully encourage surgery trainees to successfully navigate the process of converting ideas into a publication that ultimately helps understanding and improves the care of patients

Multimodal Action of Mas Activation for Systemic Cancer Cachexia Therapy

Cancer cachexia remains a largely intractable, deadly condition for patients with no approved, effective therapies. However, research progress over the past few decades demonstrates that cachexia is a disease with specific, targetable mechanisms. New work by Murphy and colleagues in this issue of Cancer Research suggests that activation of the alternative renin–angiotensin system with the nonpeptide Mas receptor agonist AVE 0991 holds promise for reducing muscle wasting in cancer. Their cell studies demonstrate on-target activity in skeletal muscle cells, whereas their mouse results suggest potentially more important systemic effects

Integrating therapies for surgical adult soft tissue sarcoma patients

Sarcomas are an uncommon group of over 50 different individual histological malignancies arising from mesenchymal (non-epithelial or connective) tissues. Overall, they constitute 1% of human malignancies with an annual incidence rate of fewer than 5 patients per million. Sarcoma may arise from any mesenchymal cell lineages including fat, muscle, or other connective tissues. Due to the rarity of these groups of malignancies, many subtypes were, and still today, are managed as a single entity. This review focused on soft tissue sarcomas with an emphasis on how to integrate therapies for patients with this rare disorder. The role for surgical resection in cure and palliation as well as the relative benefits of adjuvant therapies such as chemotherapy and radiation therapy are discussed

Biliary Bypass with Laparoscopic Choledochoduodenostomy

Laparoscopic choledochoduodenostomy (LCDD) is employed to treat many benign biliary diseases when endoscopic or percutaneous techniques are not feasible. We describe our technique for LCDD, which utilizes common bile duct transection and an end-to-side biliary-enteric anastomosis. This procedure includes the following elements: isolation and transection of the common bile duct, mobilization of the duodenum (Kocher maneuver), inspection of the common bile duct, and end-to-side biliary-enteric anastomosis. Key details and pitfalls are discussed. Over a 5-year period, LCDD was performed on 18 patients. Indications included intractable abdominal pain (10) and choledocholithiasis (8). The majority of patients, 83%, tolerated the operation well with no complications. There was one postoperative intra-abdominal abscess and two anastomotic strictures, one in the immediate postoperative period and the other 9 months after the operation. The median length of stay was 4 days (IQR 3.0–5.3), and there was minimal blood loss. Based on our experience, LCDD with transection and end-to-side biliary-enteric anastomosis is a safe and effective biliary bypass technique

Protecting Ideas: Ethical and Legal Considerations when a Grant’s Principal Investigator Changes

Ethical issues related the responsible conduct of research involve questions concerning the rights and obligations of investigators to propose, design, implement, and publish research. When a principal investigator (PI) transfers institutions during a grant cycle, financial and recognition issues need to be addressed to preserve all parties’ obligations and best interests in a mutually beneficial way. Although grants often transfer with the PI, sometimes they do not. Maintaining a grant at an institution after the PI leaves does not negate the grantee institution’s obligation to recognize the PI’s original ideas, contributions, and potential rights to some forms of expression and compensation. Issues include maintaining a role for the PI in determining how to take credit for, share and publish results that involve his or her original ideas. Ascribing proper credit can become a thorny issue. This paper provides a framework for addressing situations and disagreements that may occur when a new PI continues the work after the original PI transfers. Included are suggestions for proactively developing institutional mechanisms that address such issues. Considerations include how to develop solutions that comply with the responsible conduct of research, equitably resolve claims regarding reporting of results, and avoid the possibility of plagiarism