Closed loop ileus caused by a defect in the broad ligament: A case report.

BACKGROUND: Closed loop ileus caused by entrapment of bowel in a defect of the broad ligament is a rarity. Only a few cases have been reported in the literature. CASE SUMMARY: We present the case of a 44-year-old, healthy patient with no prior history of abdominal surgery who developed a closed loop ileus due to an internal hernia secondary to a defect in the right broad ligament. She first presented to the emergency department with diarrhea and vomiting. As she had had no previous abdominal surgery, she was diagnosed with probable gastroenteritis and discharged. The patient subsequently returned to the emergency department due to a lack of improvement in her symptoms. Blood tests showed an elevated white blood cell count and a closed loop ileus was diagnosed on an abdominal computer tomography scan. Diagnostic laparoscopy revealed an internal hernia entrapped in a 2 cm large defect in the right broad ligament. The hernia was reduced and the ligament defect was closed using a running, barbed suture. CONCLUSION: Bowel incarceration through an internal hernia may present with misleading symptoms and laparoscopy may reveal unexpected findings.

Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells.

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.

Hernia after retroperitoneoscopic adrenalectomy, case report.

We report the first case of a previously undocumented complication after posterior retroperitoneal adrenalectomy (PRA). Extensive diagnostic procedures for persisting abdominal pain led to diagnosis of an incisional hernia (IH) approximately 2.5 years after surgery for a pheochromocytoma of the right adrenal gland. Thus, IHs need to be recognized as a potential complication after PRA, particularly if the symptoms are non-specific. The differential diagnosis of an IH after PRA includes a type of spontaneous lumbar hernia due to a pre-existing weakness of the abdominal wall however the treatment for both type of hernias is similar by mesh repair. A possible risk factor for IH after PRA might be obesity, due to different factors including difficulties in closing the fascia in depth under subcutaneous tissue.

Effectiveness of hemostatic agents in thyroid surgery for the prevention of postoperative bleeding.

Postoperative bleeding remains one of the most frequent, but rarely life-threatening complications in thyroid surgery. Although arterial bleeding is the main cause of postoperative hemorrhage, most often no actively bleeding vessel can be found during revision. Therefore, the coagulation technique for larger vessels may play a minor role, and hemostatic agents could be of higher importance. In this descriptive, retrospective study, data of 279 patients with thyroid surgery (total of 414 thyroid lobectomies) were collected. We reviewed the electronic medical record by analyzing the histological, operative, laboratory and discharge reports in regards to postoperative bleeding. Of the 414 operated thyroid lobes, 2.4% (n = 10) bled. 1.4% (n = 6) needed reoperation while the other 1.0% (n = 4) could be treated conservatively. Hemostatic patches were applied 286 (69.1%) times. Of the 128 (30.9%) patch-free operated sides, 4.7% (n = 6) suffered postoperative bleeding. Tachosil® alone was used 211 (51.0%) times and bleeding occurred in 1.4% (n = 3). Without statistical significance (p = 0.08) the use of Tachosil® seems to help preventing postoperative bleeding. The combination with other patches doesn't appear to be more efficient.

High-resolution standardization reduces delay due to workflow disruptions in laparoscopic cholecystectomy.

BACKGROUND: Optimal resource utilization in high-cost environments like operating theatres is fundamental in today's cost constrained health care systems. Interruptions of the surgical workflow, i.e. microcomplications (MC), lead to prolonged procedure times and higher costs and can be indicative of surgical mistakes. Reducing MC can improve operating room efficiency and prevent intraoperative complications. We, therefore, aimed to evaluate the impact of a high-resolution standardized laparoscopic cholecystectomy protocol (HRSL) on operative time and intraoperative interruptions in a teaching hospital. METHODS: HRSL consisted of a detailed stepwise protocol for the procedure, supported by a teaching video, both to be reviewed as mandatory preparation by each team member before surgery. Audio-video records of laparoscopic cholecystectomies were reviewed regarding type, frequency and duration of MC before and after implementation of HRSL. RESULTS: Thirty-nine (20 control and 19 HRSL) audio-video records of laparoscopic cholecystectomies with a total duration of 51.36 h (28.92 pre 22.44 post) were reviewed. The majority of operations (86%) were performed by teams who had completed less than 10 procedures together previously. Communication-related interruptions and instrument changes accounted for the majority of MC. Median frequency and duration of MC were 95 events/h and 15.6 min/h, respectively, of surgery pre-intervention. With HRSL this was reduced to 76 events/h and 10.6 min/h of operating. In multivariable analysis, HRSL was an independent predictor for shorter delay and lower frequency of MC [percentage decrease 27% (95% CI 18-35%), resp. 30% (95% CI 19-40%)]. Procedure-related risk factors for the longer delay due to MC in multivariable analysis were less experience of the surgeon and intraoperative adhesiolysis. CONCLUSIONS: HRSL is effective in reducing delays due to MC in a teaching institution with limited team experience. These findings should be tested in larger potentially cluster-randomized controlled trials. The trial has been registered with clinicaltrials.gov: NCT03329859.

Do you want to participate in a clinical study as a healthy control? - Risk or benefit?

A healthy woman volunteered to participate as "healthy control" in a study. An increased level of procalcitonin (PCT) was detected and remained elevated on follow-up measurements. As calcitonin levels were elevated as well, thyroid ultrasound was performed which revealed nodes in both thyroid lobes, one of them showing metabolic activity in positron emission tomography-computed tomography scan. To exclude a malignant thyroid cancer despite the negative findings in a fine needle aspiration the patient underwent thyroidectomy and a medullary thyroid carcinoma (MTC) was detected in the right lobe. MTC is a rare endocrine tumor with a poor prognosis once having spread, therefore early detection remains a priority for the outcome. Screening parameter is serum calcitonin, in absence of infection the pro-hormone PCT can be used as a screening parameter as well with high sensitivity.

Absence of myeloperoxidase and CD8 positive cells in colorectal cancer infiltrates identifies patients with severe prognosis.

Colorectal cancer (CRC) infiltration by cells expressing myeloperoxidase (MPO) or CD8 positive T lymphocytes has been shown to be independently associated with favorable prognosis. We explored the relationship occurring between CD8+ and MPO+ cell CRC infiltration, its impact on clinical-pathological features and its prognostic significance in a tissue microarray (TMA) including 1,162 CRC. We observed that CRC showing high MPO+ cell infiltration are characterized by a prognosis as favorable as that of cancers with high CD8+ T cell infiltration. However, MPO+ and CD8+ CRC infiltrating cells did not synergize in determining a more favorable outcome, as compared with cancers showing MPOhigh/CD8low or MPOlow/CD8high infiltrates. Most importantly, we identified a subgroup of CRC with MPOlow/CD8low tumor infiltration characterized by a particularly severe prognosis. Intriguingly, although MPO+ and CD8+ cells did not co-localize in CRC infiltrates, an increased expression of TIA-1 and granzyme-B was detectable in T cells infiltrating CRC with high MPO+ cell density.

OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer.

BACKGROUND: OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. METHODS: OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. RESULTS: OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40(high)/CD8(high) infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40(low)/CD8(high), OX40(high)/CD8(low) or OX40(low)/CD8(low) infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40(high)/CD8(high) density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. CONCLUSIONS: OX40(high)/CD8(high) density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers.

Internal hernia in late pregnancy after laparoscopic Roux-en-Y gastric bypass.

A 27-year-old patient in late pregnancy presented to the department of obstetrics with crampy abdominal pain located in the right flank, 3 years after a laparoscopic Roux-en-Y gastric bypass. Clinical investigation showed tenderness on palpation in the upper abdomen without signs of peritonitis. The cardiotocogram and blood tests were normal. The ultrasound showed a hydronephrosis on the right side, and a pigtail catheter was inserted. The abdominal symptoms did not abate and the abdominal surgeon was consulted 36 hours after admission. Diagnostic laparoscopy was performed promptly because of high suspicion of internal hernia (IH). Laparoscopy showed IH at the mesojejunal intermesenteric defect with a herniated common channel and volvulus of the anastomosis. Conversion to open reduction and complete closure with non-absorbable interrupted sutures was performed. Small bowel resection was avoided. The patient was discharged 10 days after the operation and a healthy boy was born 4 weeks later.

Histone deacetylase inhibitors and colorectal cancer: what is new?

Colorectal cancer is the third most common cancer in humans. Cancer has always been regarded as a disease of genetic defects such as gene mutations and deletions, chromosomal abnormalities, which lead to the loss of function of tumor-suppressor genes and/or gain of function or hyperactivation of oncogenes. Modifications on chromatin are considered to be the result of the opposing activities of histone acetyltransferases and histone deacetylases, which affect gene expression. Targeting histone deacetylases, histone deacetylase inhibitors are promising agents, as in solid tumors they are characterized by relatively low toxicity profile and antiproliferative activities. In colorectal cancer, the current experience is mainly experimental but promising. Histone deacetylase inhibitors are currently being admitted as monotherapy or combination therapy either with the conventional chemotherapy or with other agents. Valproic acid combined with ionization may enhance tumor response. Vorinostat was the first drug of this group used in clinical trial in combination with conventional chemotherapy and managed to stabilize advanced colorectal cancer. Experimental results show that combination therapy of vorinostat and decitabine (DNA methyl transferase inhibitor) may have optimal results. However, patients with colorectal cancer need to be recruited in randomized clinical trials in order to evaluate the potential efficiency of these agents.

Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial.

BACKGROUND: Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis. METHODS/DESIGN: In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5% surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years. DISCUSSION: The results of this randomized controlled trial will have an important impact on current international guidelines for infection control strategies in the hospital. Moreover, the results of this randomized controlled trial are of significant interest for patient safety and healthcare economics. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov under the identifier NCT01790529.

GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer.

PURPOSE: Colorectal cancer infiltration by CD16(+) myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization. EXPERIMENTAL DESIGN: GM-CSF or M-CSF-stimulated peripheral blood CD14(+) cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by (3)H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF-specific antibodies. Clinicopathological features and overall survival were analyzed. RESULTS: GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF-stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1ß and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), "pushing" growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16(+) and CD8(+) cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance. CONCLUSIONS: GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer.

High frequency of CD8 positive lymphocyte infiltration correlates with lack of lymph node involvement in early rectal cancer.

AIMS: A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. METHODS: A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2) was stained for several immunomarkers of the innate and the adaptive immune response. Patients' survival and nodal status were analyzed and correlated with infiltration of the different immune cells. RESULTS: Of all tested markers, only CD8 (P = 0.005) and TIA-1 (P = 0.05) were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect "per se," CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992-0.996; P = 0.009 and OR 0.988; 95% CI 0.984-0.994; P = 0.05, resp.). An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (P < 0.00001). CONCLUSION: Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients' nodal involvement.

Acute thyroid swelling and elevated C reactive protein.

A 34-year-old lady presented with a painful swelling of the left thyroid lobe since 1 week and elevated C reactive protein (CRP) above 100 mg/L. An ultrasound examination revealed a thyroid cyst with partly solid component, suitable with a haemorrhage into a cyst. The serum thyroid stimulating hormone (TSH), as well as peripheral thyroid hormones, was in the normal range. The acute swelling could be well explained by a haemorrhage, but not an elevated CRP. Her medical history was uneventful apart from a tooth extraction 2 weeks ago due to an infection. Therefore, our hypothesis was a haemorrhage into a pre-existing thyroid cyst during bacteraemia caused by the tooth infection. Conservative treatment with the aim of delayed hemithyreoidectomy failed due to a second episode of haemorrhage. During surgical resection pus drained out of the cyst and the histological report afterwards confirmed our tentative diagnosis. The patient was discharged 2 days later.

High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor.

BACKGROUND: Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). METHODS: A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. RESULTS: MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-. CONCLUSIONS: High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC.

Missed diagnosis of a gallstone ileus: an incomplete laparoscopy due to a putative ventriculoperitoneal shunt infection.

A 90-year-old woman presented with abdominal pain and vomiting. Initial investigations revealed diffuse abdominal tenderness and fever, combined with leucocytosis and marked elevation of C reactive protein levels. Abdominal CT demonstrated segmental bowel wall thickening in the jejunum near the tip of a ventriculoperitoneal (VP) shunt, which had been placed 17 years before because of hydrocephalus. Pneumobilia was present but no ectopic gallstone was detected at the initial analysis and there were no signs of mechanical ileus. Immediate laparoscopy was performed to exclude small bowel ischaemia. Owing to purulent ascites the VP shunt was externalised, supposing VP shunt infection with reactive jejunitis to be the main problem. Antibiotic treatment was then administered and the remaining part of the shunt was removed 6 days later. However, clinical signs of intestinal obstruction have been aggravated. Therefore, a laparoscopy was repeated 3 days later and a gallstone ileus was diagnosed. After enterolithotomy through a minilaparotomy, the patient was fully recovered.

Lung resection in hematologic patients with pulmonary invasive fungal disease.

BACKGROUND: Pulmonary invasive fungal disease is a frequent complication in patients with hematologic malignancies. Surgical resection in addition to antifungal therapy is an option for selected cases but often feared because of immunosuppression. METHODS: We analyzed the outcome of 71 patients undergoing lung resection for pulmonary invasive fungal disease. Most patients had leukemia, 44 underwent high-dose chemotherapy, and 18 underwent stem cell transplantation. RESULTS: On the day of surgery, 44 patients were neutropenic, and 41 had a platelet count < 50 × 109/L. Forty-five nonanatomic (atypical) resections and 26 lobectomies were performed. Fungal infection was histologically proven in 53 patients. Reoperation was needed in four patients (bronchial stump dehiscence, persistent air leak, chylothorax, and seroma). Minor complications at the site of surgery occurred in 14 patients. In only two, there was an uncontrolled disseminated fungal infection. Overall, mortality at 30 days was 7% (five of 71). Long-term survival was mainly influenced by the underlying hematologic disease. CONCLUSIONS: Lung resection is a therapeutic option for hematologic patients with pulmonary fungal infection. Despite immunosuppression, the perioperative morbidity and mortality is acceptable, and, therefore, the prognosis is not determined by the surgical intervention.

Early versus delayed cholecystectomy in patients with biliary acute pancreatitis.

BACKGROUND: In patients with biliary acute pancreatitis (AP), cholecystectomy is mandatory to prevent further biliary events, but timing of cholecystectomy remains a subject of ongoing debate. The objective of the present, retrospective study was to compare the outcomes of early (within 2 weeks after onset of disease) versus delayed cholecystectomy in patients with biliary AP. METHODS: Between January 2000 and December 2005, 112 patients underwent cholecystectomy because of biliary AP. Thirteen patients were excluded from analysis because of necrotizing pancreatitis on the initial computed tomography. Thirty-two were operated within 14 days (group A) and 67 after a longer time period (group B). The primary end point of the study was the rate of biliary complications before cholecystectomy. RESULTS: There were no differences regarding conversion rates to open surgery (6% vs 3%; P = .59), local (3% vs 4%; P = 1.00), or systemic complications (0% vs 3%; P = 1.00), and mean postoperative stay (4.7 vs 5.7 days; P = .40). Nevertheless, a greater rate of recurrent biliary pancreatitis was found in the group undergoing cholecystectomy later (0% vs 13%; P < .03). CONCLUSION: The timing of cholecystectomy seems to have no clinically relevant effect on local or systemic complications, but delaying cholecystectomy is associated with an increase of biliary complications in patients with non-necrotizing biliary AP.