Expression of autophagy-related proteins Beclin-1 and LC3A and proliferation marker Ki-67 in calculous and acalculous human gallbladder epithelium.

BACKGROUND: Autophagy is an inducible intracellular process that has been studied mostly in cancer and less in inflammatory diseases. To establish the relation between cholecystitis (calculous and acalculous) and autophagy, we studied the expressions of immunohistochemical markers Beclin-1, LC3A, and Ki-67 in gallbladder epithelium and their significance in the induction of autophagy. METHODS: Adult human gallbladder tissues were obtained from 100 patients (45 male, 55 female) who underwent cholecystectomy. According to the findings, the patients were divided into two groups: group A (calculous gallbladder: 24 male, 46 female; mean age 52.6 ± 16.0 years) and group B (acalculous gallbladder: 21 male, nine female; mean age 65.3 ± 12.4 years). The expressions of immunohistochemical markers Beclin-1, LC3A, and Ki-67 in gallbladder epithelium were studied using immunohistochemistry techniques. RESULTS: Beclin-1 expression was correlated with LC3A expression in group A with increased Beclin-1 expression promoting LC3A expression (p =0.0001). In group B, the LC3A expression did not follow Beclin-1 expression (p =0.09). The mean percentage of Beclin-1 expression in group A patients was 23.8 % compared to group B patients, where the corresponding percentage was only 17.3 %. Corresponding mean percent expressions of LC3A in groups A and B were 38.9 % and 50.7 %, respectively. The expression of Ki-67 was higher in group A patients compared to group B patients. The mean percentage of Ki-67 expression in group A patients was 3.75 %, whereas, in group B patients, it was only 0.5 % (statistically significantly different; p =0.0003). CONCLUSION: In the epithelium of calculous cholecystitis, overexpression of LC3A is related to Beclin-1 overexpression, which reinforces the view that Beclin-1 promotes autophagy in stone cholecystitis. HIPPOKRATIA 2019, 23(2): 64-69.

Increased B7H4 tissue expression correlates with high CA19.9 serum levels and a worse prognosis of pancreatic adenocarcinoma.

Pancreatic cancer (PC) is a leading cause of cancer death worldwide, especially in Western societies. Its aggressive nature and poor prognosis increase the need for identifying new and more accurate diagnostic and prognostic tools. We studied 41 patients who had undergone radical surgical resection for PC, investigated B7H4 protein expression in the PC tissue specimens of these patients by immunohistochemistry and analyzed several clinical and pathological features. The positive expression of the B7H4 antigen was associated with a negative impact of chemotherapy with gemcitabine on patient survival and also correlated with high CA19.9 serum levels and poorly differentiated tumors. Moreover, patients that overexpressed B7H4 antigen had worse prognosis compared to the ones that did not overexpress B7H4. B7H4 antigen is a negative prognostic marker for PC patients and also seems to express resistance of PC patients to chemotherapy with gemcitabine.

B7H4, HSP27 and DJ-1 molecular markers as prognostic factors in pancreatic cancer.

OBJECTIVES: Pancreatic cancer (PC) is one of the most lethal tumors of the gastrointestinal tract. The ability to predict which patients would benefit most from surgical intervention and chemotherapy would be a great clinical tool. A large number of potential markers have been identified lately in pancreatic cancer and their clinical utilities as prognostic tools are under investigation. METHODS: We recruited 41 patients who had undergone radical surgical resection for PC between 2003 and 2010. To investigate the prognostic factors, we evaluated 3 possible markers: B7H4, HSP27 and DJ-1 protein expressions in the tissue specimens of these 41 patients by immunohistochemistry and analyzed the clinical and pathological features of these specimens. RESULTS: The expression of the three antigens was independently associated with a negative impact of chemotherapy with gemcitabine on patient's survival. Moreover, patients who overexpressed B7H4 had worse prognosis than the ones who did not. CONCLUSIONS: B7H4, DJ-1 and HSP27 may be used in the future as prognostic markers that express resistance of pancreatic cancer patients to chemotherapy with gemcitabine.

Xenotransplantation of hepatocytes in rats with acute liver failure using sirolimus for immunosuppression.

This study aimed to evaluate the effect of sirolimus (SRL; rapamycin) as an immunosuppressant during xeno transplantation (XT) of rabbit hepatocytes into male Wistar rats with acute liver failure (ALF; n = 72). Isolated rabbit hepatocytes were transplanted intrasplenically into rats within 24 h of chemically induced ALF. Treatment groups received monotherapy with either cyclosporine (CsA) 20 mg/kg or SRL 0.20 mg/kg, or combination therapy with CsA 20 mg/kg + SRL 0.20 mg/kg for 14 days post-transplant. One control group with ALF received no treatment and a second group with ALF received only XT. Surviving rats were euthanized after 14 days, with concurrent blood sampling and organ retrieval for morphological evaluation. Survival rates at 14 days were: no XT/no treatment, 0%; XT alone, 29%; XT + CsA, 79%; XT + SRL, 33%; and XT + CsA + SRL, 33%. Liver morphology showed statistically superior liver regeneration for groups on SRL therapy. It is concluded that, in this hepatocyte XT model, SRL offered no survival advantage for ALF management so CsA still maintains a central role in attempts to develop alternative solutions for ALF.

Impact of breast cancer surgery on the self-esteem and sexual life of female patients.

Patient satisfaction with cosmetic outcome and the psychological impact of breast cancer surgery were evaluated. A total of 207 patients with primary breast cancer, treated with either breast-conserving surgery (n = 83), modified radical mastectomy without reconstruction (n = 108), or mastectomy with delayed breast reconstruction (n = 16) rated their cosmetic outcome and satisfaction following surgery, and the impact of surgery on their self-esteem and sexual life, by questionnaire. Patients undergoing breast-conserving surgery were most satisfied with their surgery and body image, followed by those treated with mastectomy with delayed reconstruction. Although diagnosis of breast cancer had a negative impact on the psychology of all patients, those undergoing breast-conserving surgery or mastectomy with delayed reconstruction were more satisfied and reported a lower impact on their self-esteem and sexual life versus those who only had mastectomy. Diagnosis of breast cancer has a negative psychological impact on the patient, but the type of surgery has a significant role in post-operative self-esteem and sexual life.

Port-site metastasis of extrahepatic bile duct carcinoma after laparoscopic cholecystectomy without evidence of a primary tumour.

A 75-year-old man suffering from symptomatic cholelithiasis underwent laparoscopic cholecystectomy using the four-port technique. No malignancy was observed in the resected gall-bladder and the patient exhibited a good postoperative course. Eleven months postoperatively he presented with two subcutaneous tumours: one at the port-site on the right anterior axillary line (at the position of the vacuum drain) and the other at the subumbilical port-site. The patient underwent an incisional biopsy, which revealed metastatic adenocarcinomas of the primary extrahepatic duct, with no evidence of a primary tumour or other distant metastasis. The patient underwent wide excision of the subcutaneous tumours. Six months later he again presented with subcutaneous tumours at the same positions. Magnetic resonance imaging of the abdomen revealed only the subcutaneous tumours. The patient again underwent wide excision of the subcutaneous tumours, followed by radiotherapy. At a 21-month follow-up the patient was symptom-free. Magnetic resonance imaging of the abdomen and magnetic resonance cholangiopancreatography results were normal, and there was no evidence of other metastasis. Four months later the patient died from metastatic disease of the abdomen.

Primary adrenal hydatid cyst: a case report.

A rare case of primary adrenal hydatid cyst is reported in a 56-year-old male. The cyst was discovered incidentally. The only symptom was hypertension. Partial excision of the gland and pericystectomy were performed. Surgical treatment was also therapeutic for the hypertension.

Delayed perforation of the large bowel due to thermal injury during laparoscopic cholecystectomy.

We report a case of delayed perforation of the large bowel because of thermal injury during a laparoscopic cholecystectomy. A 78-year-old male with symptomatic cholelithiasis underwent a difficult laparoscopic cholecystectomy because of multiple adhesions resulting from two previous cholecystitis episodes. The patient recovered well after surgery and was discharged on post-operative day 2. On postoperative day 10, the patient returned to the hospital with peritonitis. An exploratory laparotomy revealed perforation of the wall of the hepatic flexure of the large bowel, which was centred in a necrotic area 1 cm in diameter. The perforation was sutured and a temporary ileostomy performed, which was closed at a later date. The patient was doing well at a 10-month follow-up review. A delayed rupture of any part of the bowel after laparoscopic surgery can be potentially fatal if not treated during an emergency exploratory laparotomy, even if the clinical signs are not severe.

Laparoscopic cholecystectomy in a patient with situs inversus using ultrasonically activated coagulating scissors. Report of a case and review of the literature.

Situs inversus totalis is a rare defect with a genetic predisposition, which can present difficulties in the management of abdominal pathology, especially in laparoscopic surgery, due to the mirror-image anatomy. Herein, we report on a patient with situs inversus totalis and symptomatic cholelithiasis. The patient had a successful laparoscopic cholecystectomy, using ultrasonically activated coagulating scissors. Diagnostic pitfalls and technical details of the laparoscopic cholecystectomy are discussed and a review of the relevant literature is presented.

Predictive value of risk factors in patients with obstructive jaundice.

Clinical and laboratory parameters that may affect post-operative mortality and morbidity were studied in 215 patients operated on for obstructive jaundice. The cause of the bile duct obstruction was benign disease in 56.7% of patients and malignant disease in 43.3%. Overall postoperative mortality and morbidity rates were 21.9% and 33.5%, respectively. Eight risk factors were shown to be associated with increased mortality: age > 70 years; malignancy; leucocytosis > 15 000 cells/microl and fever > 38.5 degrees C; haematocrit < or = 30%; creatinine > 1.3 mg/dl; albumin < or = 3 g/dl; bilirubin > 20 mg/dl; and serum alkaline phosphatase > 100 IU/l. The simultaneous presence of less than three risk factors was always associated with post-operative survival, but concomitant existence of seven or more risk factors indicated 100% mortality. Understanding the factors related to post-operative morbidity and mortality in patients with obstructive jaundice will better guide appropriate surgical or non-surgical management and lead to improved survival.

Mucocele of the appendix: a report of five cases.

Mucocele of the appendix is an uncommon disorder, characterized by a cystic dilatation of the lumen. It is often diagnosed clinically from signs and symptoms of acute appendicitis or, if it is asymptomatic, as an incidental finding during ultrasonography, computed tomography, and radiographic examinations of the gastrointestinal tract, or laparotomy. The incidence of mucocele ranges from 0.2% to 0.3% of all appendectomy specimens. We report five cases of appendiceal mucocele (all women, aged 19-90 years), who were admitted from January 1993 to January 2003 to our hospital. These cases represent 0.29% of the 1720 appendectomies performed during this period. Three of the patients were symptomatic and had appendectomies. The final diagnosis for mucocele was given at laparotomy. No colon neoplasms were identified during surgery, and subsequent colonoscopic examinations were also negative. The other two patients were asymptomatic of appendiceal tumor. Colonoscopy revealed two colonic malignant tumors in one patient and an adenocarcinoma of the sigmoid colon in the other. Mucocele of the appendix was diagnosed pre-operatively by ultrasound and computed tomography. One of the two patients underwent a right hemicolectomy and sigmoidectomy; the other one underwent an appendectomy, cecostomy and sigmoidectomy. Four of the patients recovered and are doing well today; one patient died on the twenty-fifth postoperative day. The most common symptom of mucocele is abdominal pain, although many patients may be asymptomatic. Mucocele is often associated with concomitant colon cancer, thus patients with this tumor should be systematically checked for other colonic lesions.

Phenytoin-induced lymphocytic chemotaxis, angiogenesis and accelerated healing of decubitus ulcer in a patient with stroke.

We studied the effect of topically applied phenytoin on the healing of a decubitus ulcer in the sacral region of an immobile patient with stroke. Another similar, but smaller, ulcer was treated with conventional treatment only and served as a control. The ulcers were measured once a week and biopsies were taken from the margins before, 1 week and 2 weeks after commencing treatment with phenytoin. Clinically, phenytoin substantially accelerated the rate of healing. Microscopic examination of the biopsies showed increased lymphocytic infiltration of the phenytoin-treated lesion. Anti-CD31 immunohistochemistry revealed dense CD31+ lymphocytic infiltration and increased angiogenesis only in the phenytoin-treated lesion. Our findings suggest that phenytoin enhances wound healing by stimulating lymphocytic chemotaxis and up-regulation of angiogenesis.

Catheter knots in the urinary tract.

The use of catheters in the urinary tract, both in children and adults, has not been without complications. Many procedures performed in the urinary tract, including urethral or suprapubic catheterization of the bladder, urethrography, and ureteral catheterization, have showed complications, one of which is the formation of catheter knots. This complication, although very rare, yet it is very annoying. In this study, we searched (in winter 2002, employing Medline) and reviewed published reports of urinary tract catheter knots, and present measures for prophylaxis, diagnosis and proper management of this rare complication.

Intestinal transplantation for the treatment of desmoid tumors associated with familial adenomatous polyposis.

BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis (FAP) are locally invasive. Often occurring in the mesentery of the intestine, they sometimes recur after resection. Complications can include intestinal failure and dependence on parenteral nutrition. We describe 9 patients who underwent intestinal transplantation for the treatment of desmoid tumors associated with FAP. METHODS: Records of patients undergoing intestinal transplantation for desmoid tumors at 2 transplant centers were reviewed for patient age, sex, type of graft, procedure date, tumor site, desmoid complications, medications, extracolonic manifestations, status at follow-up, and length of survival. RESULTS: Nine patients with FAP and intestinal failure caused by desmoid tumors were treated with isolated intestinal (n = 6), multivisceral (n = 2), or combined liver-intestinal transplantation (n = 1). Desmoid tumors recurred in the abdominal walls of 2 patients. Two patients died: one as a result of sepsis, the other because of a rupture of a mycotic aneurysm of the aortic anastomosis. One graft lost to severe rejection was replaced with a second intestinal graft. Eleven to 53 months after transplantation, 7 patients were alive, well, independent of parenteral treatment, and leading apparently normal lifestyles. CONCLUSIONS: Transplantation of the intestine alone or as part of a multivisceral transplantation may help rescue otherwise untreatable patients with complicated desmoid tumors.

Levels of mycophenolic acid and its glucuronide derivative in the plasma of liver, small bowel and kidney transplant patients receiving tacrolimus and cellcept combination therapy.

In order to help assess the usefulness of mycophenolate mofetil (MMF) as an immunosuppressive agent in recipients of organs other than kidneys, we measured the trough levels of the active metabolite of MMF, mycophenolic acid (MPA), and its inactive glucuronide derivative (MPAG), in the plasma of liver (n = 83) and small bowel transplant patients (n = 15) receiving MMF in combination with tacrolimus. These levels were compared with a group of renal transplant patients (n = 25) receiving the same drug regimen. All patient groups were otherwise comparable except the small bowel patient group which contained more pediatric patients (average age 18.7 +/- 3.9 years), and, therefore, received a higher average drug dose (in mg/kg). Despite this, these patients displayed the lowest levels of MPA of any group (0.39 +/- 0.08 microg/ml, P < 0.001 vs. 1.10 +/- 0.17 microg/ml for liver transplant patients, P < 0.001 or 2.46 +/- 0.37 microg/ml for renal transplant patients, P < 0.001). There were no statistically significant differences in MPAG levels between any of the groups. Although preliminary, these data demonstrate significant transplanted organ-specific differences in MMF pharmacology and/or bioavailability, and suggest the need for separate evaluation of MMF dosing for each transplant type.

Thrombocytopenia after liver transplantation.

BACKGROUND: Thrombocytopenia after orthotopic liver transplantation (OLT) is a well recognized and prevalent early postoperative complication. The etiology, as well as the effect of this phenomenon on transplant outcome, however, are vague. The aims of this study are to identify factors contributing to thrombocytopenia and to ascertain whether there is any correlation with early rejection and ultimate survival. METHODS: This study examines 541 OLTs (541 grafts in 494 patients) that were transplanted at the University of Miami during the 3-year period from June 1994 to September 1997. The patients with severe postoperative thrombocytopenia (nadir platelet count [PLT] < 20,000/mm3), as well as the whole group of patients, were analyzed. The preoperative PLT, intra-operative platelet transfusion requirements, cross-match, recipient and donor cytomegalovirus (CMV) status, infusion of donor bone marrow cells (DBMC), occurrence of early rejection episodes (in the first posttransplant month), and re-transplantation were factors examined for any association with thrombocytopenia. Total bilirubin (TB) and direct bilirubin (dB), hematocrit, white blood cell count (WBC), aspartate aminotransferase and alanine aminotransferase, determined on the day that platelets reached a nadir (nadir day), were also analyzed. RESULTS: In 90.9% of the cases, there was a 56.5%+/-23.5% fall in platelets in the immediate posttransplant period (first 2 weeks), but the mean PLT exceeded preoperative levels during the 3rd and 4th postoperative weeks. The nadir of the drop in the PLT most commonly occurred on posttransplant day 4. For preoperative PLT, platelet transfusions during the operation, re-transplantation, early rejection, cross-match, and recipient CMV status, there was significant statistical correlation with any degree of postoperative thrombocytopenia. Four of these factors, preoperative PLT, intra-operative platelet transfusions, re-transplantation, and early rejection, were found to be independently associated with thrombocytopenia in general. None of them was found to be independently correlated with severe thrombocytopenia. A statistically significant correlation between bilirubin and WBC on the nadir day and the degree of thrombocytopenia was observed. No correlation was found between infusion of DBMC or donor CMV serology and thrombocytopenia. Both the nadir PLT and the percentage of the platelet fall were independent predictive factors (p<0.01 and 0.005, respectively) of patient and graft survival. CONCLUSIONS: Thrombocytopenia in the immediate posttransplant period is correlated with low preoperative PLT, massive platelet transfusions, and re-transplantation. These factors reflect a poor preoperative condition. There is also a correlation with allograft dysfunction, rejection, and poorer patient and graft survival. A rise in the mean PLT after the 2nd postoperative week reflects proper graft function.

Donor peripheral blood stem cell infusions in recipients of living-related liver allografts.

BACKGROUND: In this pilot study, donor peripheral blood stem cell (DPBSC) infusions were performed in three recipients of living-related liver transplants (LRLT). METHODS: DPBSCs were obtained by leukapheresis after mobilization with granulocyte-colony-stimulating factor (Filgrastim). Donor leukapheresis was performed on the 5th postoperative day, and half of the DPBSCs were infused into the recipient on the day of collection. The second half of the pheresed product was cryopreserved for delayed administration. RESULTS: Results from preliminary studies of chimerism in LRLT recipients, at 20 weeks posttransplant, suggested that the levels of donor cells detected in LRLT recipients treated with DPBSC infusions may be higher than those observed for recipients of cadaver donor liver allografts and vertebral body marrow infusions. CONCLUSIONS: The results of this pilot study indicate that administration of mobilized DPBSC to recipients of LRLT is a feasible procedure for both donor and recipient.