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Background During laparoscopic cholecystectomy, common bile duct (CBD) injury is a rare but severe complication. To reduce the risk of injury, near-infrared (NIR) fluorescent cholangiography using indocyanine green (ICG) has recently been introduced as a novel method of visualizing the biliary system during surgery. To date, several studies have shown feasibility of this technique; however, liver background fluorescence remains a major problem during fluorescent cholangiography. The aim of the current study was to optimize ICG dose and timing for NIR cholangiography using a quantitative intraoperative camera system during open hepatopancreatobiliary (HPB) surgery. Subsequently, these results were validated during laparoscopic cholecystectomy using a laparoscopic fluorescence imaging system. Methods Twenty-seven patients who underwent NIR imaging using the Mini-FLARE image-guided surgery system during open HPB surgery were analyzed to assess optimal dosage and timing of ICG administration. ICG was intravenously injected preoperatively at doses of 5, 10, and 20 mg, and imaged at either 30 min (early) or 24 h (delayed) post-injection. Next, the optimal doses found for early and delayed imaging were applied to two groups of seven patients ( n  = 14) undergoing laparoscopic NIR fluorescent cholangiography during laparoscopic cholecystectomy. Results Median liver-to-background contrast was 23.5 (range 22.1–35.0), 16.8 (range 11.3–25.1), 1.3 (range 0.7–7.8), and 2.5 (range 1.3–3.6) for 5 mg/30 min, 10 mg/30 min, 10 mg/24 h, and 20 mg/24 h, respectively. Fluorescence intensity of the liver was significantly lower in the 10 mg delayed-imaging dose group compared with the early imaging 5 and 10 mg dose groups ( p  = 0.001), which resulted in a significant increase in CBD-to-liver contrast ratio compared with the early administration groups ( p  < 0.002). These findings were qualitatively confirmed during laparoscopic cholecystectomy. Conclusion This study shows that a prolonged interval between ICG administration and surgery permits optimal NIR cholangiography with minimal liver background fluorescence.

De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes ( p -value = 1.00 × 10 −5 ) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes ( p -value = 5.01 × 10 −4 ) in contrast to predicted benign de novo mutations. One gene we identify, RBM5 , is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men ( p -value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility. Germline de novo mutations can impact individual fitness, but their role in human male infertility is understudied. Trio-based exome sequencing identifies many new candidate genes affecting male fertility, including an essential regulator of male germ cell pre-mRNA splicing.

Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve sentinel lymph node (SLN) mapping of breast cancer. We performed a randomized clinical trial to assess the value of blue dyes when used in combination with NIR fluorescence. We also preliminarily examined the possibility of performing SLN mapping without radiotracers. Clinical trial subjects were 24 consecutive breast cancer patients scheduled to undergo SLN biopsy. All patients received standard of care using 99(m) technetium-nanocolloid and received 1.6 mL of 500 μM ICG injected periareolarly. Patients were randomly assigned to undergo SLN biopsy with or without patent blue. To assess the need for radiocolloids to localize the SLN or SLNs, the surgeon did not use the handheld gamma probe during the first 15 min after the axillary skin incision. SLN mapping was successful in 23 of the 24 patients. No significant difference was found in signal-to-background ratio between the groups with and without patent blue (8.3 ± 3.8 vs. 10.3 ± 5.7, respectively, P = 0.32). In both groups, 100 % of SLNs were radioactive and fluorescent, and in the patent blue group, only 84 % of SLNs were stained blue. In 25 % of patients, the use of the gamma probe was necessary to localize the SLN within the first 15 min. This study shows that there is no benefit of using patent blue for SLN mapping in breast cancer patients when using NIR fluorescence and 99(m) technetium-nanocolloid. NIR fluorescence imaging outperformed patent blue in all patients.

Background Trocar site hernia (TSH) is a known complication of laparoscopic cholecystectomy (LC). Gallbladder extraction is typically performed through the umbilical or epigastric trocar port. However, data on the incidence of TSH in relation to the extraction site is limited. This study aimed to evaluate the need for surgical repair of TSH following gallbladder extraction through the umbilical versus epigastric trocar port. Methods A retrospective cohort study was conducted across two Dutch general hospitals. It assessed the occurrence of TSH after LC and examined commonly described risk factors in relation to the TSH location. Results Among 2 377 patients that underwent LC, the extraction site of the gallbladder was known in 1756 patients. Gallbladder extraction was performed via the umbilical trocar port in 929 (53%) of cases and via the epigastric trocar port in 827 (47%) of cases. TSH repair was required in 36 (2.1%) patients, with a higher incidence in patients with gallbladder extraction through the umbilical trocar port (3.2%) compared to the epigastric trocar port (0.7%), ( p  < 0.001). Conclusion The need for operative repair of a TSH after a LC is significantly reduced when the gallbladder is retrieved through the epigastric trocar site port compared to the umbilical trocar site port.

Objective:In early cervical cancer, a total pelvic lymphadenectomy is the standard of care, even though most patients have negative nodes and thus undergo lymphadenectomy unnecessarily. Although the value of sentinel lymph node (SLN) mapping in early-stage cervical cancer has not yet been established, near-infrared (NIR) fluorescence imaging is a promising technique to perform this procedure. Near-infrared fluorescence imaging is based on invisible NIR light and can provide high sensitivity, high-resolution, and real-time image guidance during surgery.Methods:Clinical trial subjects were 9 consecutive cervical cancer patients undergoing total pelvic lymphadenectomy. Before surgery, 1.6 mL of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected transvaginally and submucosally in 4 quadrants around the tumor. Patients were allocated to 500-, 750-, or 1000-μM ICG:HSA concentration groups. The Mini-FLARE imaging system was used for NIR fluorescence detection and quantitation.Results:Sentinel lymph nodes were identified in all 9 patients. An average of 3.4 ± 1.2 SLNs was identified per patient. No differences in signal to background of the SLNs between the 500-, 750-, and 1000-μM dose groups were found (P = 0.73). In 2 patients, tumor-positive lymph nodes were found. In both patients, tumor-positive lymph nodes confirmed by pathology were also NIR fluorescent.Conclusions:This study demonstrated preliminary feasibility to successfully detect SLNs in cervical cancer patients using ICG:HSA and the Mini-FLARE imaging system. When considering safety, cost-effectiveness, and pharmacy preferences, an ICG:HSA concentration of 500 μM was optimal for SLN mapping in cervical cancer patients.

Introduction A primary fibroid (leiomyoma) arising from both ovaries is rare and can be difficult to diagnose as a result of the low incidence and its indistinctive presentation. A literature review on the diagnostic and therapeutic approach of this rare benign tumour is presented. We describe a case of bilateral primary ovarian fibroid with an unusual presentation to illustrate our recommendations for treatment. Case presentation A 37-year-old woman was admitted with symptoms of acute severe abdominal pain. She had a history of faint abdominal discomfort. Due to the acute deterioration of the abdominal pain a diagnostic laparoscopy was performed. A tumour arising from both ovaries was seen and a biopsy was taken in order to decide on further therapy. Histology showed a fibroid for which excision by a second laparoscopic intervention was planned. Due to excessive adhesions conversion to laparotomy was necessary. Conclusion We recommend that in the case of an abnormal adnexal mass, particularly in women who want to preserve their fertility, frozen section histology be performed laparoscopically. A frozen section diagnostic procedure, instead of a regular biopsy, seems to be a useful tool during an elective diagnostic laparoscopic procedure in order to prevent potential morbidity as a result of possible future laparoscopy or even laparotomy. Previous laparoscopic procedures can cause massive adhesions that could impede a subsequent laparoscopic approach.