Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

Skeletal muscle in patients with cancer undergoes many morphological changes due to immuno-inflammatory factors of tumor origin or treatment.T he latest event of these changes is cancer cachexia. Aim of the study is to identify myopathic features in skeletal muscle biopsies from weight stable patients with colorectal cancer and without cachexia or asthenia / weakness, that could possibly provide new diagnostic and prognostic cancer biomarkers. Morphometric analyses and immunohistochemical studies were performed on intraoperative muscle biopsies from patients with colorectal cancer and from weight stable patients undergoing surgery for benign non-inflammatory conditions. A rectus abdominis biopsy was taken in all patients and controls.A correlation between histopathologic findings and clinical characteristics, circulating inflammatory biomarkers and markers of muscle necrosis,surgery data and cancer phenotype were investigated.. Forty four patients (21male/23 female) and 17 controls (6 male/11 female) (p=NS) were studied. In cancer patients’biopsies we observed asubclinical myopathy characterized by an abnormal distribution of myonuclei, which are localized inside the myofiber rather than at the periphery, and by the presence of regenerating muscle fibers. The percentage of myofibers with internalized nuclei is significantly higher in patients (median= 9%, IQR= 3.7-18.8) than in controls (median= 2.7%, IQR= 1.7-3.2) ( p=0.0002). In patients we observed an inverse correlation between the number of centronucleated fibers and the presence of node metastasis (N+)(ρ)=-0.64 (p=0.002). Patients affected with colorectal cancer display early sign of a myopathy, characterized by centronucleated and regenerating myofibers. This myopathy appears to be associated with an early stage of neoplasia and it could be an adaptive response of muscle to cancer. We hope a future application of these findings as a possible early diagnostic and prognostic biomarker of neoplasia

Mesenteric-Portal Vein Resection during Pancreatectomy for Pancreatic Cancer

The aim of the present study was to determine the outcome of patients undergoing pancreatic resection with (VR+) or without (VR 12) mesenteric-portal vein resection for pancreatic carcinoma. Between January 1998 and December 2012, 241 patients with pancreatic cancer underwent pancreatic resection: in 64 patients, surgery included venous resection for macroscopic invasion of mesenteric-portal vein axis. Morbidity and mortality did not differ between the two groups (VR+: 29% and 3%; VR 12: 30% and 4.0%, resp.). Radical resection was achieved in 55/64 (78%) in the VR+ group and in 126/177 (71%) in the VR 12 group. Vascular invasion was histologically proven in 44 (69%) of the VR+ group. Survival curves were not statistically different between the two groups. Mean and median survival time were 26 and 15 months, respectively, in VR 12 versus 20 and 14 months, respectively, in VR+ group . In the VR+ group, only histologically proven vascular invasion significantly impacted survival , while, in the VR 12 group, R0 resection and tumor\u2019s grading significantly influenced long-term survival. Vascular resection during pancreatectomy can be performed safely, with acceptable morbidity and mortality. Long-term survival was the same, with or without venous resection. Survival was worse for patients with histologically confirmed vascular infiltration

Collision of ductal adenocarcinoma and neuroendocrine tumor of the pancreas: a case report and review of the literature

Background: Simultaneous occurrence of exocrine and neuroendocrine tumors of the pancreas is very infrequent. We report a patient with an endocrine tumor in the pancreatic-duodenal area and extensive exocrine carcinoma involving the whole pancreas. Case presentation: A 69-year-old woman was hospitalized in May 2016 for epigastric pain and weight loss. Her past medical history revealed an undefined main pancreatic duct dilation that was subsequently confirmed at CT scan (23 mm) and endoscopic ultrasound. There was no evidence of pancreatic masses, but the cephalic portion of the main pancreatic duct presented hypoechoic nodules. A diagnosis of the main-duct intraductal papillary mucinous neoplasm was made, and the patient underwent total pancreatectomy. Pathological examination showed a collision tumor constituted by a ductal adenocarcinoma involving the whole pancreas and a neuroendocrine tumor located in the duodenal peripancreatic wall and the head of the pancreas. There was one peripancreatic lymph node metastasis from the ductal adenocarcinoma and eight node metastases from the neuroendocrine tumor. These findings suggested a diagnosis of collision of neuroendocrine and ductal adenocarcinomas of the pancreas. The postoperative course was uneventful. Conclusions: The coexistence of pancreatic endocrine and exocrine tumors is very uncommon. When present, problems in differential diagnosis may arise between mixed exocrine-endocrine carcinoma or the collision of separate tumors

Przetrwała hipoglikemia hiperinsulinemiczna współistniejąca z nieaktywnym wyspiakiem trzustki

The most common cause of hyperinsulinaemic hypoglycaemia in adult is insulinoma. Although nesidioblastosis is a rare but well-recognised disorder of persistent hypoglycaemia in infants, it is extremely rare in adults. We present a case of a 59-year-old woman with small neuroendocrine tumour of the tail of the pancreas, diagnosed by CT scans and MRI, and hypoglycaemic syndrome. Laparoscopic distal pancreatectomy was performed, and pathologic examination showed a well-differentiated, non-functioning endocrine tumour of the pancreas and diffuse nesidioblastosis in the remnant gland. In the early postoperative period, recurrent hypoglycaemia occurred in spite of oral diazoxide therapy. Plasma proinsulin levels were extremely high. 18F-DOPA positron emission tomography showed a pathologic uptake of tracer in the head and the uncinate process of the pancreas. Subtotal pancreatectomy was suggested but the patient refused operation: she is taking diazoxide 100 mg three times daily. Coexistence of nesidioblastosis with a neuroendocrine tumour makes preoperative diagnosis and management of severe hypoglycaemia more difficult. Nesidioblastosis should be considered in differential diagnosis of hypoglycaemic syndrome, but histological examination is necessary for a definitive tissue diagnosis. (Endokrynol Pol 2015; 66 (4): 356–360)    Najczęstszą przyczyną hipoglikemii hiperinsulinemicznej u osób dorosłych jest insulinoma. Chociaż przetrwała hipoglikemia hiperinsulinemiczna to rzadkie, lecz łatwo rozpoznawalne zaburzenie przetrwałej hipoglikemii u noworodków, bardzo rzadko występuje u osób dorosłych. Autorzy badania przedstawiają przypadek 59-letniej kobiety z niewielkim guzem neuroendokrynnym ogona trzustki, zdiagnozowanym dzięki tomografii komputerowej oraz rezonansowi magnetycznemu, oraz zespołem hipoglikemicznym. Wykonano laparoskopową dystalną pankreatektomię, a badanie patologiczne wykazało wysoko zróżnicowanego, nieaktywnego, endokrynnego wyspiaka trzustki oraz rozlaną przetrwałą hipoglikemię hiperinsulinemiczną w pozostałej części gruczołu. We wczesnym okresie pooperacyjnym wystąpiła nawracająca hipoglikemia, mimo stosowania doustnego leczenia diazoksydem. Stężenie proinsuliny w osoczu był bardzo wysoki. Pozytonowa tomografia emisyjna z 18F-DOPA wykazała patologiczną absorpcję znacznika w głowie i wyrostku haczykowatym trzustki. Sugerowano subtotalną pankreatektomię, lecz pacjentka nie zgodziła się na operację: przyjmowała dawkę 100 mg diazoksydu trzy razy dziennie. Współistnienie przetrwałej hipoglikemii hiperinsulinemicznej z nowotworem neuroendokrynnym utrudnia diagnostykę przedoperacyjną i leczenie ciężkiej hipoglikemii. Przetrwała hipoglikemia hiperinsulinemiczna powinna być brana pod uwagę w diagnozie różnicującej zespół hipoglikemiczny, lecz badanie histologiczne jest niezbędne do definitywnej diagnozy tkanek. (Endokrynol Pol 2015; 66 (4): 356–360)

nesidioblastosis coexisting with non functioning islet cell tumour in an adult

The most common cause of hyperinsulinaemic hypoglycaemia in adult is insulinoma. Although nesidioblastosis is a rare but well-recognised disorder of persistent hypoglycaemia in infants, it is extremely rare in adults. We present a case of a 59-year-old woman with small neuroendocrine tumour of the tail of the pancreas, diagnosed by CT scans and MRI, and hypoglycaemic syndrome. Laparoscopic distal pancreatectomy was performed, and pathologic examination showed a well-differentiated, non-functioning endocrine tumour of the pancreas and diffuse nesidioblastosis in the remnant gland. In the early postoperative period, recurrent hypoglycaemia occurred in spite of oral diazoxide therapy. Plasma proinsulin levels were extremely high. 18F-DOPA positron emission tomography showed a pathologic uptake of tracer in the head and the uncinate process of the pancreas. Subtotal pancreatectomy was suggested but the patient refused operation: she is taking diazoxide 100 mg three times daily. Coexistence of nesidioblastosis with a neuroendocrine tumour makes preoperative diagnosis and management of severe hypoglycaemia more difficult. Nesidioblastosis should be considered in differential diagnosis of hypoglycaemic syndrome, but histological examination is necessary for a definitive tissue diagnosis. (Endokrynol Pol 2015; 66 (4): 356–360

Extra-gastrointestinal stromal tumor of the pancreas: case report and review of the literature

Primary extra-gastrointestinal stromal tumor (EGISTs) arising in the pancreas is extremely rare: only 20 cases have previously been reported in the English literature from 2000 to 2013. We reported a case of EGIST of the pancreas in a 69-year-old woman who presented with abdominal pain and with a solid, heterogeneously enhancing neoplasm in the uncinate process of the pancreas, revealed preoperatively by an abdominal computed tomography scan. A diagnosis of neuroendocrine tumor was suggested. Positron emission tomography with 68Ga-DOTATOC did not show pathological accumulation of the tracer in the pancreas. The patient underwent enucleation, under ultrasonic guidance, of the pancreatic tumor that emerged to the surface of the pancreas. Histopathology and immunohistochemical examination confirmed the final diagnosis of EGIST of the pancreas (CD117+), with one mitosis per 50 high-power fields. Although rarely, GIST can involve the pancreas as a primary site, and this tumor should be considered in the differential diagnosis of pancreatic neoplasms

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival

Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia

Demonstration in human cadavers of feasibility of ileoproctostomy performed entirely through a transanal route

Innovative surgical techniques are frequently developed in animal models before of trials in surgical patients. However, these experimental approaches do not permit a perfect evaluation of feasibility due to obvious anatomical differences between humans and animals. The Body Donation Program of the University of Padua has recently developed studies of feasibility on human cadavers of new surgical approaches. Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an innovative kinf of surgery which utilizes a flexible endoscope to enter the abdominal, pelvic or thoracic cavities through the body’s natural orifices and then through an internal incision. Skin incisions are thus unnecessary and, as a consequence, tissue trauma, postoperative pain, and incision-related complications are minimized and less anaesthesia is required. The aim of the present study was to verify in human cadavers the technical feasibility of a new NOTES technique, i.e., ileoproctostomy performed entirely through a transanal access. This surgical procedure was previously performed only in a porcine model. The procedure was carried out in three human cadavers (two males and a female). One cadaver was fresh. The other cadavers were fixed through infusion of Thiel’s solution through the larger arteries. A Transanal Endoscopic Microsurgery (TEM) device and endoscopic instruments were utilized. The study demonstrated that ileoproctostomy through a transanal access is technically feasible in humans. The principal steps of the procedure were: placement of the TEM device; rectal perforation above the peritoneal reflection; peritoneoscopy using a standard gastroscope; grasping the small bowel with retrieval forceps and pulling it through the rectal hole; suturing the ileum and the rectum together with two semi-circular continuous sutures utilizing the TEM device; opening the ileal loop from the rectal side followed by endoscopic exploration. Although still at an experimental stage, ileoproctostomy through a transanal access is technically feasible in humans. In planning new procedures, a fundamental step is represented by feasibility tests on donated corpse