Israel Medical Association Journal

Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor with an increasing incidence in Western countries. Predominantly affecting older individuals, MCC represents less than 1% of malignant skin tumors.

Objectives: To characterize the clinical presentation, therapeutic interventions, and follow-up outcomes of MCC patients. To promote heightened clinical awareness regarding the early recognition and diagnosis of MCC.

Methods: We conducted a retrospective cohort study analyzing medical records of MCC patients at the Shaare Zedek Medical Center between 2015–2022. From 19 initially identified patients, 17 met the inclusion criteria. Data collection included demographic, epidemiological, clinical, and pathological characteristics.

Results: The study included 17 patients, predominantly of Jewish origin, with a mean age of 70.06 years; 58.8% female. Medical co-morbidities included 64.7% hypertension and 35.3% diabetes. MCC tumors were predominantly left-sided (58.8%), with varied locations including limbs, trunk, and face. Surgical treatment consisted of excision and primary closure (64.7%) or skin grafting (23.5%). The average tumor diameter was 3.41 cm clinically and 3.83 cm pathologically. Lymph node involvement occurred in 29.4% of cases; 23.5% showed metastatic disease at diagnosis, with metastases diffused in different body areas. Kaplan-Meier survival analysis showed no statistically significant differences across most variables, except for a significantly lower survival rate in patients with ischemic heart disease (P = 0.009).

Conclusions: Our study reveals unique characteristics of MCC, predominance of female patients, and a slightly younger average diagnosis age compared to existing literature. The 2-year survival rate in our cohort was 82%. The study underscores the importance of early detection and diagnosis of MCC, thereby enhancing clinical awareness and improving patient outcomes.

In the 1950s, ionizing radiation to the scalp was commonly used in Israel as a treatment for tinea capitis. Decades later, epidemiological studies identified an increased incidence of head and neck malignancies, particularly basal cell carcinoma, as well as intracranial tumors such as meningiomas among individuals who underwent this therapy in childhood. In addition to the oncologic risk, irradiated scalp skin presents significant reconstructive challenges due to chronic skin atrophy, hypovascularity, fibrosis, and impaired wound healing. In this study, we present our clinical experience with a modified, skin-sparing surgical protocol for managing reconstruction post excision of non-melanoma skin cancer of the scalp in patients previously irradiated for tinea capitis. The surgical strategy is tailored according to lesion size, depth, periosteal involvement, and scalp tissue quality. It incorporates components of the reconstructive ladder as appropriate. We present three representative cases highlighting key surgical challenges and considerations in this complex population.

Mohs micrographic Surgery (MMS) is a specialized surgical technique for removal of skin tumors. It achieves the highest cure rates of any available treatment. At the same time, it spares healthy tissue and thus provides superior cosmetic and functional results. The technique is indicated mainly for tumors on the head and neck. Other bodily areas including the trunk and extremities have been found to be indications for MMS as well. These indications have been defined by a collaborative work of major dermatology and dermatologic surgery organizations. Knowledge of these indications, in particular on areas other than the head and neck, is prudent for appropriately managing these tumors.

Neuroendocrine tumors (NETs) are a group of rare, heterogenous neoplasms that maintain unique morphologic and clinical features of neuroendocrine neoplasia and account for approximately 0.5% of all newly diagnosed malignancies. NETs are divided into two groups based on their histopathological morphology: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Well differentiated NETs are classified as G1, G2, or G3 based on their proliferation rate, whereas NECs are highly proliferative and poorly differentiated by definition [1]. Neuroendocrine neoplasms can occur almost anywhere in the body; however, they are most often seen in the gastrointestinal tract, pancreas, and lungs [2]. The extrahepatic bile duct is one of the rarest primary sites for NETs, accounting for 0.1% to 0.2% of NETs of the gastrointestinal tract [3]. Signet ring cell bile duct NETs are extremely uncommon and have no established incidence and prognosis due to their rarity. There is sparse information available regarding these tumors, and only a few cases have been reported in the literature to date. In this report, we presented the clinical course and surgical management of a 31-year-old female patient with a Klatskin signet ring cell NET.

Background: Signet ring cell carcinoma (SRCC) is classified as an undifferentiated gastric carcinoma with poor prognosis. Early SRCCs are associated with improved prognosis.

Objectives: To describe the outcomes of incidental SRCC.

Methods: In this case series, 900 medical charts of patients with SRCC were screened to identify patients with incidental SRCC, defined as diagnosed in random, non-focal-lesion-targeted biopsies.

Results: Six patients were diagnosed with incidental SRCC and underwent gastrectomy. The final pathology of five patients revealed one or more small foci of early SRCC without lymphovascular invasion. Only one patient had no evidence of malignancy. The median follow-up after surgery was 4.2 years (50 months, range 37–90 months). No deaths or recurrences were recorded during the follow-up period. These results resemble the reported survival rate for early SRCC.

Conclusions: An aggressive surgical approach in incidental gastric SRCC patients is recommended, as they have a chance for long-term survival.

Background: Surgical resection is the only curative option for gastric carcinoma (GC). Minimally invasive techniques are gaining popularity.

Objectives: To present a single-surgeon's experience in transitioning from an open to a minimally invasive approach, focusing on surgical and oncological outcomes.

Methods: We conducted a retrospective analysis including distal gastrectomy patients 2012–2020 operated by a single surgeon. Two cohorts were compared: open (ODG) and laparoscopic distal gastrectomy (LDG).

Results: Overall, 173 patients were referred for gastrectomy during the study years. We excluded 80 patients because they presented with non-GC tumors, underwent proximal or total gastrectomy, or underwent palliative surgery. Neoadjuvant treatment was administered to 62 patients (33.3%). Billroth 1 was the preferred method of reconstruction (n=77, 82.8%), followed by Roux-en-Y (n=12, 13%). Fifty-one patients (54.8%) underwent LDG, 42 (45.2%) underwent ODG. The LDG group had significantly shorter lengths of stay (6 days, interquartile range [IQR] 1–3 5–8 vs. 5 days, IQR 1–3 4–6, P = 0.001, respectively), earlier return to oral feeding (1 day, IQR 1–3 1–3 vs. 2 days, IQR 1–3 1–3.2, P < 0.001), and earlier removal of drains (4 days, IQR 1–3 3–5.2 vs. 5 days, IQR 1–3 3.5–6.7, P < 0.001). Overall lymph node yield was 30 (IQR 1–3 24–39) and was similar among groups (P = 0.647).

Conclusions: Laparoscopic techniques for resection of distal GC are feasible and safe, leading to good perioperative outcomes and adequate lymph node yield.

Background: Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results.

Objectives: To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome.

Methods: We reviewed charts of patients who were diagnosed with stage I–III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019.

Results: In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy.

Conclusions: Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.

Intravesicular administration of Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has long been used as adjuvant therapy for treatment of non-muscle invasive bladder carcinoma. BCG is usually well tolerated; however, infectious complications can range from 1–5% of cases. Infectious complications of BCG [1] can be divided into localized disease, which is considered a late onset disease occurring 3 months following treatment such as cystitis, Epididymo-orchitis, and pyelonephritis. Another form is a systemic disease, which is an early onset manifestation including sepsis syndrome that usually occurs directly after treatment and is the most common form of disseminated BCG infection.

Hypereosinophilia is defined as the absolute eosinophilic count of above 1500 cells/µL in the peripheral blood on two separate tests taken during one month and/or the pathological confirmation of hypereosinophilia. There are many conditions that are associated with increased eosinophil counts including: parasitic infections, drug reactions, eosinophilic granulomatosis with polyangiitis, allergic reactions, drug reaction with eosinophilia and systemic symptoms (DRESS), primary immunodeficiencies (PID), eosinophilic gastrointestinal diseases (EGID), familial hypereosinophilia, and neoplasms [1]. Molecular classification may be an adjuvant in the classification of hypereosinophilia [2]. Our patient presented with hypereosinophilia as part of a paraneoplastic syndrome.

Background: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response.

Objectives: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry

Methods: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts.

Results: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5–57) months.

Conclusions: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.

Background: For locally advanced rectal cancer patients a watch-and-wait strategy is an acceptable treatment option in cases of complete tumor response. Clinicians need robust methods of patient selection after neoadjuvant chemoradiation.

Objectives: To predict pathologic complete response (pCR) using computer vision. To analyze radiomic wavelet transform to predict pCR.

Methods: Neoadjuvant chemoradiation for patients with locally advanced rectal adenocarcinoma who passed computed tomography (CT)-based simulation procedures were examined. Gross tumor volume was examind on the set of CT simulation images. The volume has been analyzed using radiomics software package with wavelets feature extraction module. Statistical analysis using descriptive statistics and logistic regression was performed was used. For prediction evaluation a multilayer perceptron algorithm and Random Forest model were used.

Results: In the study 140 patients with II–III stage cancer were included. After a long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. CT-simulation images of tumor volume were extracted with 850 parameters (119,000 total features). Logistic regression showed high value of wavelet contribution to model. A multilayer perceptron model showed high predictive importance of wavelet. We applied random forest analysis for classifying the texture and predominant features of wavelet parameters. Importance was assigned to wavelets.

Conclusions: We evaluated the feasibility of using non-diagnostic CT images as a data source for texture analysis combined with wavelets feature analysis for predicting pCR in locally advanced rectal cancer patients. The model performance showed the importance of including wavelets features in radiomics analysis.

Background: Heart transplantation (HT) success rate is limited by a high incidence of cancer post-HT. Data on kidney cancer following solid organ transplantation, especially HT, are limited, and only a few cases have been reported.

Objectives: To report a unique case series of detected kidney cancer following HT.

Methods: Between 1997 and 2018, 265 patients who underwent HT were enrolled and prospectively followed in the HT registry of the Sheba Medical Center.

Results: The series included 5 patients, 4 men and a woman (age range 35–50 years at HT). The patients were diagnosed with kidney tumors 6–11 years after HT (age range at diagnosis 40–72 years). Two of the men were identical twin brothers. At HT four patients received induction therapy with anti-thymocyte globulin and all received an initial immunosuppressive regimen based on cyclosporine. All male HT recipients had a history of heavy smoking. Two male patients developed allograft vasculopathy, but all had preserved heart function. The 72-year-old woman developed a kidney tumor of the native kidney 5 years after re-HT and kidney transplantation. Two patients had features of multifocal papillary renal cell carcinoma (RCC) and eventually underwent bilateral nephrectomy, while another patient underwent left partial nephrectomy with preserved renal function.

Conclusions: To the best of our knowledge, this is the first case series study describing kidney tumors following HT. With the improving outcomes and life expectancy of HT patients, a better understanding of the factors that determine cancer risk is of the utmost importance and may have a major impact on the non-cardiac surveillance.

Background: Pancreatic injuries during nephrectomy are rare, despite the relatively close anatomic relation between the kidneys and the pancreas. The data regarding the incidence and outcome of pancreatic injuries are scarce.

Objectives: To assess the frequency and the clinical significance of pancreatic injuries during nephrectomy.

Methods: A retrospective analysis was conducted of all patients who underwent nephrectomy over a period of 30 years (1987–2016) in a large tertiary medical center. Demographic, clinical, and surgical data were collected and analyzed.

Results: A total of 1674 patients underwent nephrectomy during the study period. Of those, 553 (33%) and 294 patients (17.5%) underwent left nephrectomy and radical left nephrectomy, respectively. Among those, four patients (0.2% of the total group, 0.7% of the left nephrectomy group, and 1.36% of the radical left nephrectomy) experienced iatrogenic injuries to the pancreas. None of the injuries were recognized intraoperatively. All patients were treated with drains in an attempt to control the pancreatic leak and one patient required additional surgical interventions. Average length of stay was 65 days (range 15–190 days). Mean follow-up was 23.3 months (range 7.7–115 months).

Conclusions: Pancreatic injuries during nephrectomy are rare and carry a significant risk for postoperative morbidity.