A POT1 Founder Variant Associated with Early Onset Recurrent Melanoma and Various Solid Malignancies.

POT1 (Protection of Telomeres 1) is a key component of the six-membered shelterin complex that plays a critical role in telomere protection and length regulation. Germline variants in the POT1 gene have been implicated in predisposition to cancer, primarily to melanoma and chronic lymphocytic leukemia (CLL). We report the identification of POT1 p.(I78T), previously ranked with conflicting interpretations of pathogenicity, as a founder pathogenic variant among Ashkenazi Jews (AJs) and describe its unique clinical landscape. A directed database search was conducted for individuals referred for genetic counselling from 2018 to 2023. Demographic, clinical, genetic, and pathological data were collected and analyzed. Eleven carriers, 25 to 67 years old, from ten apparently unrelated families were identified. Carriers had a total of 30 primary malignancies (range 1-6); nine carriers (82%) had recurrent melanoma between the ages of 25 and 63 years, three carriers (27%) had desmoid tumors, three (27%) had papillary thyroid cancer (PTC), and five women (63% of female carriers) had breast cancer between the ages of 44 and 67 years. Additional tumors included CLL; sarcomas; endocrine tumors; prostate, urinary, and colorectal cancers; and colonic polyps. A review of a local exome database yielded an allelic frequency of the variant of 0.06% among all ethnicities and of 0.25% in AJs. A shared haplotype was found in all carriers tested. POT1 p.(I78T) is a founder disease-causing variant associated with early-onset melanoma and additional various solid malignancies with a high tumor burden. We advocate testing for this variant in high-risk patients of AJ descent. The inclusion of POT1 in germline panels for various types of cancer is warranted.

The Effects of Primary Tumor Location on Survival after Liver Resection for Colorectal Liver Metastasis in the Mediterranean Population.

(1) Background: There is an abundance of literature available on predictors of survival for patients with colorectal liver metastases (CRLM) but minimal information available on the relationship between the primary tumor location and CRLM survival. The studies that focus on the primary tumor location and CRLM survival exhibit a great deal of controversy and inconsistency with regard to their results (some studies show statistically significant connections between the primary tumor location and prognosis versus other studies that find no significant relationship between these two factors). Furthermore, the majority of these studies have been conducted in the West and have studied more diverse and heterogenous populations, which may be a contributing factor to the conflicting results. (2) Methods: We included patients who underwent liver resection for CRLM between December 2004 and January 2019 at two university-affiliated medical centers in Israel: Carmel Medical Center (Haifa) and Rabin Medical Center (Petach Tikvah). Primary tumors located from the cecum up to and including the splenic flexure were labeled as right-sided primary tumors, whereas tumors located from the splenic flexure down to the anal verge were labeled as left-sided primary tumors. (3) Results: We identified a total of 501 patients. Of these patients, 225 had right-sided primary tumors and 276 had left-sided primary tumors. Patients with right-sided tumors were significantly older at the time of liver surgery compared to those with left-sided tumors (66.1 + 12.7 vs. 62 + 13.1, p = 0.002). Patients with left-sided tumors had slightly better overall survival rates than those with right-sided tumors. However, the differences were not statistically significant (57 vs. 50 months, p = 0.37 after liver surgery). (4) Conclusions: The primary tumor location does not significantly affect patient survival after liver resection for colorectal liver metastasis in the Mediterranean population.

Short- and Long-Term Outcomes in Elderly Patients Following Hand-Assisted Laparoscopic Surgery for Colorectal Liver Metastasis.

(1) Background: Hand-assisted laparoscopic surgery (HALS) has engendered growing attention as a safe procedure for the resection of metastatic liver disease. However, there is little data available regarding the outcomes of HALS for colorectal liver metastasis (CRLM) in patients over the age of 75. (2) Methods: We compare the short- and long-term outcomes of patients >75-years-old (defined in our study as "elderly patients" and referred to as group 1, G1), with patients <75-years-old (defined in our study as "younger patients" and referred to as group 2, G2). (3) Results: Of 145 patients, 28 were in G1 and 117 were in G2. The most common site of the primary tumor was the right colon in G1, and the left colon in G2 (p = 0.05). More patients in G1 underwent laparoscopic anterior segment resection compared with G2 (43% vs. 39% respectively) (p = 0.003). 53% of patients in G1 and 74% of patients in G2 completed neoadjuvant therapy (p = 0.04). The median size of the largest metastasis was 32 (IQR 19-52) mm in G1 and 20 (IQR 13-35) mm in G2 (p = 0.001). The rate of complications (Dindo-Clavien grade ≥ III) was slightly higher in G1 (p = 0.06). The overall 5-year survival was 30% in G1 and 52% in G2 (p = 0.12). (4) Conclusions: Hand-assisted laparoscopic surgery for colorectal liver metastasis is safe and effective in an elderly patient population.

Tumor burden in patients with early and intermediate-stage hepatocellular carcinoma undergoing liver resection: a retrospective multicenter study on clinical and oncological outcomes.

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, liver resection (LR) is recommended for early-stage (BCLC-A) hepatocellular carcinoma (HCC) but not for intermediate-stage (BCLC-B). This study aimed to assess the outcomes of LR in these patients using a subclassification tumour burden score (TBS). METHODS: All consecutive patients that underwent LR for BCLC-A and BCLC-B HCC between 01/2010 and 12/2020 in 4 tertiary referral centers were included. Clinical outcomes and overall survival (OS) were assessed in relation to TBS and BCLC stages. RESULTS: Among 612 patients included, 562 were classified as BCLC-A and 50 as BCLC-B. The incidence of overall postoperative complications (56.0 vs 41.5%, p = 0.053) and mortality (0 vs 1.6%, p = 1.000) were similar between BCLC-A and BCLC-B patients. OS was significantly higher for BCLC A/low TBS than BCLC B/low TBS (p = 0.009), while patients with medium and high TBS had similar OS, irrespective of BCLC stage (respectively p = 0.103 and p = 0.343). CONCLUSIONS: Patients with medium and high TBS had comparable OS and DFS, irrespective of BCLC A or B stage, and postoperative morbidity was comparable. These results highlight the need for refinement of the BCLC staging system, and LR could be considered for selected intermediate stage (BCLC-B) according to the tumour burden.

The Importance of Segment 4 Anatomy on Outcomes Following Living Donor Left Lateral Segmentectomy.

BACKGROUND: During left lateral section (LLS) resection for live liver donation, the vascular inflow and the bile drainage of segment 4 (S4) are compromised. We investigated the long-term changes of S4 after donation and their potential prognostic impact on living liver donors. MATERIALS AND METHODS: This was a retrospective analysis of 42 consecutive left lateral (LLS, S2/3) liver resections for living donation. RESULTS: There were 25 female and 17 male donors. Median age was 33 y and median body mass index was 26. Median LLS, S2/3, volume was 262 cc, and median sS4 volume was 160 cc. Complications were encountered in three donors (7%). An independent extrahepatic S4 artery (S4A) (with a proximal left heptic artery or a right hepatic artery origin) was identified in 41% of the donors. Ligation of the independent S4A was not associated with the rate of post resection liver dysfunction, complications, or the degree of S4 atrophy. Having a dominant S4 portal triad pedicle feeding the right anterior sectors, segment 5/8, of the liver was associated with increased parenchymal damage as evidenced by a higher peak of alanine aminotransferase but was not associated with postoperative complications. The median degree of atrophy of S4 at 1 y post donation as noted on imaging was 66%. The presence of a dominant S4 portal triad pedicle and the peak alanine aminotransferase early postoperatively were both predictors of the degree of S4 atrophy post donation. CONCLUSIONS: The presence of an independent S4A or dominant S4 portal triad pedicle feeding the liver right anterior sectors, segment 5/8, should not be a contraindication for left lateral segment living donation.

The Diagnostic Yield and Implications of Targeted Founder Pathogenic Variant Testing in an Israeli Cohort.

Founder pathogenic variants (PVs) are prevalent in Israel. This study investigated the current practice of offering cancer patients two-step genetic testing, starting with targeted testing for recurring founder PVs, followed, if negative, by next-generation sequencing. A total of 2128 subjects with cancer or a positive family history underwent oncogenetic testing with a panel of 51 recurring PVs at a tertiary medical center in March 2020-January 2023. Those with a known familial PV (n = 370) were excluded from the analysis. Among the remainder, 128/1758 (7%) were heterozygous for at least one variant, and 44 (34%) carried a PV of medium-high penetrance (MHPV). Cancer was diagnosed in 1519/1758 patients (86%). The diagnostic yield of founder MHPV testing was 2% in cancer patients and 4% in healthy individuals with a positive family history. It was higher in Ashkenazi Jews than non-Ashkenazi Jews and Arabs, but not over 10% for any type of cancer, and it was significantly higher in younger (<40 years) than older (>50 years) individuals (7% vs. 1%). Eighty-four of the heterozygotes (66%), mostly Ashkenazi Jews, harbored a low-penetrance variant (LPV) not associated with the diagnosed cancer, usually APC c.3902T>A. These findings question the advantage of two-step testing. LPVs should not be included in targeted testing because this can lead to an overestimation of the yield, and their detection does not preclude further comprehensive testing.

The Association between Preoperative Vitamin D Levels and Postoperative Complications in Patients Undergoing Colorectal Liver Metastasis Surgery.

(1) Background: Over the past several years, there has been a renewed interest with regard to the effect of pre-operative vitamin D levels on post-surgical outcomes. Pre-operative vitamin D deficiency has been associated with many negative post-operative outcomes. However, the role of vitamin D in postoperative outcomes in colorectal liver metastasis (CRLM) resection is relatively uninvestigated. Our study investigated the correlation between preoperative vitamin D levels and postoperative complications in patients undergoing resection for CRLM. (2) Methods: We retrospectively examined the post-operative course of 109 patients, who were evaluated based upon preoperative vitamin D levels: the first group had vitamin D levels less than 25 nmol/L (VIT D < 25 nmol/L) (n = 12) vs. the second group who had vitamin D levels equal to or greater than 25 nmol/L (VIT D ≥ 25 nmol/L) (n = 97). (3) Results: Patients with lower pre-operative vitamin D levels (VIT D < 25 nmol/L) had significantly higher rates of blood transfusions (33.3% vs. 10.3%, p = 0.01), post-operative surgical complications (50% vs. 17.5%, p = 0.009), and infectious complications (25% vs. 7.2%, p = 0.04). However, there was no difference in overall survival seen between the two groups. (4) Conclusions: The results of our study indicate that patients with preoperative vitamin D deficiency (defined as preoperative vitamin D levels less than 25 nmol/L) may have an increased risk of postoperative complications in patients undergoing liver surgery for metastatic colorectal cancer.

Radiological and pathological assessment with EOB-MRI after Y90 radiation lobectomy prior to liver resection for hepatocellular carcinoma.

BACKGROUND: Radiation lobectomy (RL) utilizes Yttrium-90 (Y90) radioembolization for achieving tumor control and inducing contralateral lobe hypertrophy. Our objective was to evaluate the chronological changes occurring radiologically and histopathologically after Y90 RL. METHODS: We retrospectively reviewed 22 patients with chronic liver disease who underwent Y90 RL prior to planned liver resection for hepatocellular carcinoma. Gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (EOB-MRI) was performed every 3 months. RESULTS: Future liver remnant volume (FLRV) significantly increased up to 9 months after Y90 RL. Gd-EOB-DTPA uptake in the treated lobe experienced a 40% reduction in enhancement ratio (ER) during ensuing first 3 months, and never recovered. The reduced ER in the non-tumoral parenchyma was significantly correlated with increased FLRV and FLR (r = 0.41 and r = 0.35, respectively; both p < 0.01). Histopathological evaluation of non-tumor liver tissue found features of sinusoidal obstruction syndrome as an early change after Y90 RL (median 5.7 months) and parenchymal collapse as a late change (mean 11 months). DISCUSSION: The reduced uptake of Gd-EOB-DTPA at 3 months post Y90 RL correlates with a significant increase in FLRV prior to liver resection. EOB-MRI evaluation at 3 months can guide future plan of action after Y90 RL.

Two hundred and fifty-one right hepatectomies for living donation: Association between preoperative risk factors, hepatic dysfunction, and complications.

BACKGROUND: Donor safety is essential in living donor liver transplantation. In this study we assessed the association among perioperative factors, liver dysfunction, and complications in 251 consecutives right hepatectomies for living donation. METHODS: Retrospectively collected data from a prospectively assembled cohort of 251 consecutive living donors who underwent right hepatectomy between 1999 and 2020 were evaluated. RESULTS: Median age was 36 years; 54% were men. There was a statistically significant relationship between standardized liver volume by body surface area and the volumes calculated by imaging, weighting, and volume displacement. (r2 = 0.40, r2 = 0.34, and r2 = 0.34, respectively), with the relationship between standardized liver volume and liver volume by imaging being the strongest. The median remnant liver volume was 35%. Fifty-eight donors (23%) developed postoperative hepatic dysfunction, which was associated with increased length of stay (P = .04), and complications (P < .01). Men had a 2.5 times higher chance of developing postoperative hepatic dysfunction. Age >50 years was an independent predictor of increased bilirubin at postoperative day 4 (P < .01), and remnant liver volume was inversely associated with higher peak international normalized ratio (P < .01). Eighty-one donors (32%) experienced complications. Postoperative hepatic dysfunction was associated with 2.4 times higher chances of complications (odds ratio = 2.4, P < .01). CONCLUSION: Early postoperative hepatic dysfunction is associated with the development of post-live liver donor complications. A thoughtful balancing of preoperative risk factors for postoperative hepatic dysfunction may indeed and by association reduce postoperative complications.

The Role of Preoperative Platelet-to-Lymphocyte Ratio as a Predictor for Incisional Hernias after Hand-Assisted Laparoscopic Liver Surgery for Metastatic Colorectal Cancer.

(1) Background: Hand-assisted laparoscopic surgery for liver resection is a globally established technique. In this study, we report on the incidence and risk factors for postoperative incisional hernia (IH) after hand-assisted laparoscopic surgery for colorectal liver metastasis. (2) Methods: This was retrospective analysis of 89 consecutive hand-assisted laparoscopic surgery for colorectal liver metastasis. (3) Results: Participants were 39 females and 50 males. Median age was 65 years, and in 63%, the BMI was ≥25. Postoperative complications were encountered in 18% of the patients. Seven patients (7.8%) had postoperative incisional hernia in the hand port site. There was significantly higher incidence of incisional hernia in overweight patients (BMI ≥ 25) (p = 0.04), and in cases with simultaneous liver and colon resection (p = 0.02). In univariant and multivariant analyses, simultaneous liver and colon resection (p = 0.004 and 0.03, respectively), and platelet-to-lymphocyte ratio ≤ 200 (p = 0.03, 0.04, respectively) were both independent risk factors for developing postoperative incisional hernia. (4) Conclusions: Both simultaneous liver and colon resection, and platelet-to-lymphocyte ratio ≤ 200 are independent risk factors for postoperative incisional hernia after hand-assisted laparoscopic surgery for colorectal liver metastasis.

Coronavirus Disease 2019 Pandemic: Early Observations in Abdominal Organ Transplantation.

The recent COVID-19 outbreak has quickly become a worldwide pandemic emergency. The course of this pandemic is still unknown, with more than 6 million cases identified and over 370 000 deaths globally as of June 1, 2020. The uncertainty and anxiety during this period will have a detrimental effect on the global health system. The organ transplantation field has been negatively affected by the COVID-19 pandemic, especially in regions where the intensity of cases exceeds the available capacity of the health care resources. Recently, scattered data have been published in the English literature, mainly in case reports and letters to the editor, that describe the effect of COVID-19 on donors and recipients of abdominal solid organs. Our objective is to review and draw conclusions from these data.

Hand-Assisted Laparoscopic Surgery Is Superior to Open Liver Resection for Colorectal Liver Metastases in the Posterosuperior Segments.

Introduction: Laparoscopic liver resections (LLR) of colorectal metastasis located in posterosuperior segments (1, 4A, 7 and 8) are challenging and highly demanding. The aim of our study is to determine the safety and feasibility of hand-assisted laparoscopic surgery (HALS) in the resections of the posterosuperior lesions and to compare the peri-operative, short-term and long-term outcomes with the open liver resection (OLR) approach. Methods and Results: A retrospective study of patients who underwent either HALS or OLR for metastatic colorectal cancer (mCRC) located in the posterosuperior segments of the liver between 2008 and 2018 in two university affiliated medical centers. Results: A total of 187 patients were identified, of whom 78 underwent HALS and 109 underwent OLR. There was no difference between the HALS and OLR with regard to preoperative factors (age, primary CRC tumor location, number and anatomical distribution of liver metastasis, pre-operative neo-adjuvant treatment, operative time, blood transfusion rate, and resection margins positivity). On the other hand, HALS compared to OLR had a significantly shorter mean hospital stay (4 vs. 6 days; P = 0.003), and a lower total complications rate (25 vs. 47% P = 0.006). Both groups had no 30-day mortality. Also, patients who underwent HALS vs. OLR had similar liver metastases recurrence (55 vs. 51%. P = 0.65) and 5-year survival (47 vs. 45%. P = 0.72). Conclusions: HALS for mCRC located in posterosuperior liver segments is safe and feasible and it is a preferable approach due to its lower complication rate and shorter hospital stay while not compromising survival and disease recurrence.

Laparoscopic Versus Open Simultaneous Resection of Primary Colorectal Cancer and Associated Liver Metastases: A Comparative Retrospective Study.

PURPOSE: The aim was to compare the short-term and long-term outcomes of patients with metastatic colorectal cancer (CRC) undergoing laparoscopic versus open colorectal resection with simultaneous resection for liver metastases. Currently there is a lack of studies that have investigated the oncosurgical aspects and the short and long-term outcomes from these procedures. MATERIALS AND METHODS: A retrospective study of patients who underwent simultaneous resections for CRC and synchronous liver metastases between 2008 and 2019 in 2 university affiliated medical centers. RESULTS: Sixty-three patients were identified of whom 21 had successful laparoscopic simultaneous resections. In 43% of patients, the primary tumor was located in the right colon. The 3-year overall survival and disease-free survival rates were 87% and 48%, respectively. When compared with a separate control group of 42 patients who underwent conventional open resections, the laparoscopic approach was associated with an increased operative time (286 vs. 225 min, P=0.05), but a shorter hospital stay (6 vs. 8 d, P=0.008). CONCLUSIONS: Simultaneous laparoscopic colorectal and parenchymal sparing liver resection for metastatic CRC is safe, feasible, and it is a preferable approach because of better short-term outcome compared with open surgery while not compromising survival and disease recurrence.

Cholecystoduodenal fistula resulting in gallstone ileus: A path paved by stone.

This report showcases the initial management of gallstone ileus which includes proper biliary assessment to assist with operative planning. While an uncommon condition, surgical management is crucial, although methodology may be variable.

Hand-assisted Laparoscopic Surgery for Colorectal Liver Metastasis: Analysis of Short-term and Long-term Results.

BACKGROUND: There is scant data regarding the outcomes of hand-assisted laparoscopic surgery (HALS) for colorectal liver metastasis (CRLM). The aim of this study is to report our experience and analyze the short-term and long-term results. MATERIALS AND METHODS: Retrospective study of patients undergoing HALS for CRLM in 2 university affiliated medical centers. RESULTS: Two hundred and thirty-eight liver procedures were performed on 145 patients including 205 parenchymal sparing resections and 33 anatomic resections. The median number of metastases was 1 (range: 1 to 8), 38 patients (26.2%) had 3 or more metastases, and 41 patients (28.3 had a bi-lobar disease. The tumor size was 20 (2 to 90) mm, and 52 patients (36.6%) had a tumor larger than 30 mm. Nighty-nine patients (67.8%) received neoadjuvant chemotherapy. In 8 patients (5.5%) the laparoscopic liver resection was combined with ablation, and 16 patients (11%) underwent a synchronous resection of colorectal cancer. The median operative time, blood loss during surgery, and postoperative hospital stay were 163 minutes, 300 mL, and 4 days, respectively. The median modified Iwate complexity score was 4 (0 to 10) and the conversion rate to open surgery was 5.5%. The overall and major complication rates were 23.8% and 3.6%, respectively. The mortality rate was 0.7%. R0 resections were achieved in 91% of patients. Median overall survival for all the cohort (intend to treat) was 59 months, and the 8- and 10-year overall survival rates were 47.3% and 24.9%, respectively. CONCLUSIONS: This study shows that HALS is a safe and efficacious treatment for selected patients with CRLM.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.

Limited upper midline incision for major hepatectomy in adults: safety and feasibility.

Objectives: Optimal incision for major hepatectomy remains controversial. In this study, we described our experience with a limited upper midline incision (UMI) for major hepatectomy. The objective was to analyze the feasibility and safety of UMI in major hepatectomy. Material and Methods: Fifty-seven consecutive patients who underwent major hepatectomies performed via an UMI were compared to a control group of 36 patients who underwent major hepatectomies with a conventional incision (CI). Results: In 85% of the patients, the indication was malignancy, with a median tumor size of 6 cm. Fifty-three percent of the patients had underlying chronic liver disease, and liver fibrosis was found in 61% of the patients. Ninteen percent of the patients had previous upper abdominal surgery. Twenty- six patients underwent left hepatectomy, 20 patients had right hepatectomy and 11 patients trisegmentectomy. Additional combined surgical proce- dures were performed in 42% of the patients. Median operative time was 323 minutes, estimated blood loss was 500 ml, and median post-operative hospital stay was seven days. Surgical complications occurred in 22 patients (39%). 5-year overall survival was 67%. When compared with the control group with CI, patients with UMI had no statistical difference on operative time, estimated blood loss, length of hospital stay, complication rate, and overall survival. Conclusion: Major hepatectomies can be safely performed through UMI. This approach should be considered as a reasonable option in addition to conventional and laparoscopic approaches for major hepatectomies.

Hand-assisted Laparoscopic Repeat Hepatectomy for Secondary Liver Neoplasm.

BACKGROUND: Hand-assisted laparoscopic surgery is a widely accepted alternative to an open approach. The use of this technique in repeat liver resection is limited due to technical difficulties caused by postsurgical adhesions. We aimed to assess the feasibility and safety of hand-assisted laparoscopic repeat hepatectomy (HALRH). MATERIALS AND METHODS: This was a retrospective study of the medical files of patients who had undergone HALRH between 2010 and 2017 in 2 university-affiliated medical centers. RESULTS: Sixteen patients with repeat hepatectomy were included with a median age of 67.5 years. The first liver resection was a traditional laparotomy for 9 patients and hand-assisted laparoscopic surgery for 7 patients. The conversion rate to open surgery was 6%. The median operative time, blood loss during surgery, and postoperative hospital stay were 166 minutes, 400 mL, and 7 days, respectively. R0 resections were achieved in 88% of patients. The median number of tumors and tumor size were 1 and of 25 mm, respectively. There were no mortalities or major complications postoperatively. For patients with colorectal liver metastases, the median follow-up and overall survival were 21 and 43 months, respectively. CONCLUSION: The findings suggest HALRH to be safe and feasible. Future ERAS guidelines should evaluate this approach for liver surgery.